Central Drugs Standard Control Organization

As set forth in the 2019-CTRules and the Hdbk-ClinTrial, the Central Drugs Standard Control Organization (CDSCO) is the regulatory authority responsible for clinical trial oversight, approval, and inspections in India. In accordance with the provisions of the 2019-CTRules, the Drugs Controller General of India (DCGI) heads CDSCO, and is responsible for granting permission for clinical trials to be conducted and for regulating the sale and importation of drugs for use in clinical trials. (Note: The DCGI is commonly referred to as the Central Licensing Authority in the Indian regulations.)

According to IND-59, CDSCO functions under the Directorate General of Health Services (DGHS), which is part of the Ministry of Health and Family Welfare (MOHFW). Per IND-59 and IND-47, as the Central Drug Authority, CDSCO is responsible for approving new drugs, conducting clinical trials, establishing drug standards, overseeing the quality of imported drugs, providing expert advice, and coordinating the state licensing authorities who regulate the manufacture, sale, and distribution of drugs.

Per the DCA-DCR, the Drugs Technical Advisory Board (DTAB) and the Drug Consultative Committee (DCC) advise the DCGI. IND-16 states that the DTAB, a statutory board, is composed of technical experts who advise the central and state governments on technical drug matters and on making rules. The DCC, a statutory committee, consists of central and state drug control officials who advise the central and state governments and the DTAB to ensure drug control measures are enforced throughout India.

Further, as indicated in the Hdbk-ClinTrial, Subject Expert Committees (SECs) comprise experts representing the relevant therapeutic areas that are responsible for reviewing the submitted clinical trial applications, investigators’ brochures, and study protocols. The 2019-CTRules and Order13Jan20 further note that the DCGI may, when required, constitute one (1) or more of these expert committees or group of experts with specialization in relevant fields to evaluate scientific and technical drug-related issues. In accordance with the 2019-CTRules and with the approval of the MOHFW, Order13Jan20 establishes the terms of reference that CDSCO will use to constitute the SECs from the groups/panels of approximately 550 medical experts with specialization in relevant fields, including the existing members of the SECs from various government medical colleges and institutions. Additionally, per Notice31Jan24, CDSCO’s SEC Division is responsible for conducting meetings to evaluate IND proposal submissions. Refer to Scope of Assessment section for additional

Please note: India is party to the Nagoya Protocol on Access and Benefit-sharing (IND-29), which may have implications for studies of investigational products developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see IND-45.

Contact Information

According to IND-58 and IND-70, CDSCO contact information is as follows:

Central Drugs Standard Control Organization
Directorate General of Health Services (DGHS)
Ministry of Health and Family Welfare
Government of India
FDA Bhavan, ITO, Kotla Road
New Delhi 110002
India
Phone: +91-11-23216367 (CDSCO)/23236975
Fax: +91-11-23236973
E-mail: dci@nic.in

Liberia Medicines and Health Products Regulatory Authority

As per the LMHRA-Act, the LibCTReg, and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) is the regulatory authority responsible for clinical trial approvals, oversight, and inspections. According to the LMHRA-Act, the LMHRA operates as an autonomous government agency that reports to the President of the Republic of Liberia. In addition to its role in authorizing clinical trials, the LMHRA-Act indicates that the LMHRA’s responsibilities also include drug and health care product registration, inspections, import/export control, licensing, quality control, advertising and promotion, and pharmacovigilance and post-marketing surveillance.

Per LBR-30, the Clinical Trials Unit within LMHRA’s Pharmacovigilance & Clinical Trials Department is responsible for coordinating all aspects of clinical trials in Liberia including:

• Receiving and assessing all clinical trial applications submitted to the LMHRA
• Conducting good clinical practice (GCP) inspections of trial sites and GCP training for inspectors and the study team to ensure compliance that is in line with LMHRA regulatory requirements and international best practices
• Reviewing all reports from clinical trial sites and advising management on appropriate regulatory actions
• Investigating the conduct of clinical trials
• Suspending or stopping clinical trials (depending on the magnitude of the offense)
• Serving as secretariat for the Scientific Advisory Committee (SAC) on clinical trials
• Reviewing importation permits for investigational products (IPs) that are required for the conduct of clinical trials
• Conducting pre-submission meetings to discuss issues related to application processes
• Reviewing all reports (safety reports, quarterly reports, Serious Adverse Events (SAE) reports and final or close-out reports) from clinical trial studies conducted

Per the LibCTReg, the LMHRA can establish advisory committees for the review of clinical trial applications and for post-approval safety and compliance issues, if needed, and especially in the event of new/emerging technologies. According to LBR-29, the LMHRA has established an SAC to provide technical support to review clinical trial applications.

Other Considerations

Please note: Liberia is party to the Nagoya Protocol on Access and Benefit-sharing (LBR-3), which may have implications for studies of IPs developed using certain non-human genetic resources (e.g., plants, animals, and microbes). For more information, see LBR-17.

Contact Information

Per LBR-19, the LMHRA contact information is as follows:

Liberia Medicines and Health Products Regulatory Authority (LMHRA)
2^nd & 3^rd Floors Clay Building
Sekou Toure Avenue
Mamba Point
Monrovia, Liberia
Phone: (+231) 777-140-555 or (+231) 888-140-555
Email: info@lmhra.gov.lr

Overview

In accordance with the 2019-CTRules and the Hdbk-ClinTrial, the Drugs Controller General of India (DCGI), who heads the Central Drugs Standard Control Organization (CDSCO), is responsible for reviewing and approving clinical trial applications for all new drugs, investigational new drugs (INDs), and imported drugs to be registered in India. Additionally, per the 2019-CTRules, the G-ICMR, and IND-31, the DCGI and a DCGI-registered ethics committee (EC) must approve a clinical trial application prior to the sponsor (also known as applicant) initiating the trial, except in the case of non-regulatory academic/research clinical trials that only require EC approval. Refer to the Scope of Review section for detailed information on non-regulatory academic/research clinical requirements. (Note: The DCGI is commonly referred to as the Central Licensing Authority in the Indian regulations.)

As per the 2019-CTRules and the Hdbk-ClinTrial, the scope of the DCGI assessment includes a review of applications for IND and new drug clinical trials, global clinical trials (GCTs), and post marketing studies (Phases I-IV). Per Notice18Feb20, which clarifies information provided in IND-31, the 2019-CTRules are only applicable to new drugs and investigational new drugs. (Note: the Hdbk-ClinTrial has not yet been updated to fully align with the 2019-CTRules.)

The 2019-CTRules defines a “new drug” as:

• A drug, including active pharmaceutical ingredients or phytopharmaceutical drugs, that has not been used in the country to any significant extent
• A drug that has already been approved by the DCGI and is now proposed to be marketed with modified or new claims
• A fixed dose combination of two (2) or more drugs, individually approved for earlier specific claims, and which are now proposed to be combined for the first time in a fixed ratio, or, if the ratio of ingredients in an already marketed combination is proposed to be changed
• A modified or sustained release form of a drug, or novel drug delivery system of any drug approved by the DCGI
• A vaccine, recombinant Deoxyribonucleic Acid (r-DNA)-derived product, living modified organism, monoclonal antibody, cell, or stem cell derived product, gene therapeutic product, or xenografts intended to be used as a drug

Per the 2019-CTRules and IND-31, the above listed drugs, excluding the modified/sustained drug forms and biological drug products, will be deemed new for four (4) years from the date of first approval. The modified/sustained drug forms and biological products including vaccines should always be viewed as new drugs. See also IND-6 for additional information on the revised definition of “new drug” under the 2019-CTRules.

The 2019-CTRules defines an IND as a new chemical or biological entity or a product having therapeutic indication but that has never been tested on human beings, and as also noted in IND-31, has not been approved as a drug for marketing in any country.

In addition, according to IND-31, the DCGI review and approval process may be conducted in parallel with the institutional or independent EC review for each clinical trial site. However, per the 2019-CTRules and the Hdbk-ClinTrial, CDSCO must confirm that the EC approvals for each participating site have been obtained per the protocol prior to approving the initiation of the study. (See the Scope of Review section for more information.)

Clinical Trial Review Process

As set forth in the 2019-CTRules and the Hdbk-ClinTrial, the DCGI is responsible for reviewing and approving clinical drug applications. The evaluation timeline is dependent upon whether the investigational drugs under review are developed outside India, or discovered, researched, and manufactured in India. (Refer to the Timeline of Review section for detailed CDSCO timeline information.)

Per the Hdbk-ClinTrial, upon receipt of an application (via Form CT-04 which is found in the 2019-CTRules), a CDSCO official is responsible for conducting the initial administrative review. If the application is deemed complete, the official forwards the application along with a summary of the evaluation and a statement referring the proposal to a Subject Expert Committee (SEC) for further technical review. If the proposal is not accepted by the SEC, the sponsor may request additional consideration of the proposal by the Technical Committee. Otherwise, only the SEC’s recommendations are required for the DCGI (CDSCO) to issue a final decision to the Technical or Apex Committee. Additionally, per Notice31Jan24, CDSCO’s SEC Division is responsible for conducting meetings to evaluate IND proposal submissions. See the Submission Process section for CDSCO submission requirements.

Per the Hdbk-ClinTrial, SECs are usually comprised of six (6) experts representing various therapeutic areas, including pharmacologists/clinical pharmacologists, and medical specialists. However, Order13Jan20, issued in accordance with the 2019-CTRules, indicates that SECs will be comprised of eight (8) medical experts, specifically one (1) pharmacologist and seven (7) medical specialists. Per the Hdbk-ClinTrial, SECs are responsible for advising CDSCO with in-depth evaluations of non-clinical data (including pharmacological and toxicological data) and clinical trial data (Phases I-IV) provided by the sponsors for approval. The 2019-CTRules further notes that the DCGI may, when required, constitute one (1) or more of these expert committees or group of experts with specialization in relevant fields to evaluate scientific and technical drug-related issues.

Additionally, per Order13Jan20, SECs will evaluate and advise the DCGI on proposals in various categories for the approval of new drug and clinical trial applications. These include the following: new drug substances of chemical and biological origin including vaccines and r-DNA derived products; subsequent approval of new drug and biological products including vaccines and r-DNA derived products already approved in the country; global clinical trials; fixed dose combinations of two (2) or more drugs to be introduced for the first time in the country; causality analysis, drug safety, or any other technical matter requiring expert advice in the opinion of the Ministry of Health and Family Welfare (MOHFW) or the DCGI. See Order13Jan20 for the complete terms of reference required to constitute SECs.

Once an SEC has completed its review, the Hdbk-ClinTrial indicates that the committee sends its comments via email to CDSCO. CDSCO will then compile any written SEC comments requiring sponsor clarification or modification and sends this feedback to the sponsor. The sponsor must submit a written reply to CDSCO, which is also sent to the SEC for review.

Following receipt of the sponsor’s response, the DCGI (CDSCO) will issue a final decision by official communication (permission, rejection, or resubmission) to the Technical or Apex Committee. In the case of a sponsor’s request for reconsideration, CDSCO will review the resubmitted application and send it to the SEC again, or, to the Technical Committee per the sponsor’s request. Following the SEC’s review, the DCGI (CDSCO) will send a final decision to the Technical or Apex Committee. If CDSCO rejects the reconsideration request, the agency will send a letter to the sponsor to communicate this decision. Refer to the Hdbk-ClinTrial for additional timeline information.

Per the 2022-CTRules-3rdAmdt, which amends the 2019-CTRules, upon obtaining approval from the DCGI, the sponsor must notify CDSCO via Form CT-06A (see 2022-CTRules-3rdAmdt) prior to initiating the clinical trial. The DCGI will then record the information provided on this form and it will become part of the official record known as the approval of the DCGI. The DCGI grants permission to initiate a clinical trial via either Form CT-06 (see 2019-CTRules) or as an automatic approval via Form CT-4A (see 2019-CTRules). 2022-CTRules-3rdAmdt further states that when the DCGI approves a clinical trial of a new drug already approved outside India per the 2019-CTRules, the sponsor must also notify CDSCO via Form CT-06A, and this record will become part of the official record known as the guaranteed approval of the DCGI.

Per the 2019-CTRules, the DCGI’s permission to initiate a clinical trial granted via either Form CT-06 or as an automatic approval via Form CT-4A will remain valid for two (2) years from the date of its issue, unless extended by the DCGI as noted in the 2019-CTRules and IND-31.

In addition, per the 2019-CTRules, an investigator should not implement any deviations from or changes to the protocol without the sponsor’s agreement and after obtaining the EC’s prior review and documented approval or favorable opinion of the amendment. All protocol amendments should be submitted to the DCGI in writing along with the EC approval letter. Similarly, the G-ICMR indicates that the EC must review and approve any protocol amendments, major deviations, or violations prior to those changes being implemented.

The 2019-CTRules explains that the exception to this requirement is when it is necessary to eliminate an immediate hazard to the trial participant or when the changes involved are only logistical or administrative in nature. In this case, the EC as well as the DCGI must be notified immediately of all such exceptions. The DCGI should be notified of administrative or logistical changes or minor amendments in the protocol within 30 days.

The Hdbk-ClinTrial and the 2019-CTRules also note that application reviews should be based on the following evaluation parameters:

• Assessment of risk versus benefit to the patients
• Innovation vis-à-vis existing therapeutic option
• Unmet medical need in the country
• Safety/dosage/investigational tests (e.g., pharmacogenetic tests)
• Any additional information or study(ies) needed before marketing approval for inclusion in package insert/ summary product characteristic (SmPC) post marketing

See IND-46 for additional information on conducting clinical trials in India. For specific guidelines regarding gene therapy and stem cell therapy clinical trials, see the G-GeneThrpy and the G-StemCellRes.

(See the Submission Process and Submission Content sections for detailed submission requirements.)

Waiving Local Clinical Trials

As delineated in the 2019-CTRules and IND-31, the DCGI, with the approval of the Central Government, may waive the requirement to conduct a local trial for a new drug already approved outside India. Order7Aug24, in accordance with Rule 101 in the 2019-CTRules, further specifies that the United States, the United Kingdom, Japan, Australia, Canada, and the European Union are the countries for which the DCGI may waive a local clinical trial for applications requesting permission to conduct a clinical trial and for applications requesting permission to import or manufacture new drugs in the following new drug categories:

• Orphan drugs for rare diseases
• Gene and cellular therapy products
• New drugs used in pandemic situations
• New drugs used for special defense purpose
• New drugs having significant therapeutic advance over the current standard care

The 2019-CTRules explains that for applications to request permission to import or manufacture a new drug, a local clinical trial may be waived if the following conditions are met:

• The new drug is approved and marketed in the countries specified by the DCGI in Order7Aug24, and no major unexpected serious adverse events have been reported, or
• The DCGI has already granted permission to conduct a Global Clinical Trial with the new drug that is currently ongoing in India and this new drug has also been approved for marketing in one (1) of the countries to be specified by the DCGI in Order7Aug24, and
• There is no probability or evidence, on the basis of existing knowledge, of any difference in the metabolism of the new drug by the Indian population, or any factor that may affect the pharmacokinetics, pharmacodynamics, and safety and efficacy of the new drug, and
• The applicant has committed in writing to conducting a Phase IV clinical trial to establish the new drug’s safety and efficacy per the DCGI-approved formulation

For countries that do not meet the waiver eligibility requirements, the 2019-CTRules states that these applications must be approved by the DCGI within 90 working days from the date of application receipt. Refer to the Manufacturing & Import section for detailed information on import requirements for new drugs already approved outside of India. See also IND-6 for additional information on local clinical trial waivers to import or manufacture new drugs under the 2019-CTRules.

Overview

In accordance with the LMHRA-Act, the LibCTReg, and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) is responsible for reviewing, evaluating, and approving applications for clinical trials using registered or unregistered investigational products (IPs). According to the G-LibClinTrial, proposed clinical trials of registered medicines may include changes to indications, new methods of administration, or new combinations, etc. The G-LibClinTrial specifies that the scope of the LMHRA’s assessment includes all clinical trials (Phases I-IV). In addition, per the LibCTReg and the G-LibClinTrial, the National Research Ethics Board of Liberia (NREB) and LMHRA reviews may be conducted in parallel. However, the G-LibClinTrial and the G-NREB specify that the LMHRA will only issue final approval once NREB (ethics committee (EC)) approval is obtained.

Clinical Trial Review Process

According to LBR-30, the LMHRA’s Clinical Trials Unit within the Pharmacovigilance & Clinical Trials Department is responsible for coordinating all clinical trial activities. According to LBR-29, the LMHRA has established a Scientific Advisory Committee (SAC) to review clinical trial applications.

Per the G-LibClinTrial, the LMHRA will only process an application upon receipt of a completed application and the prescribed fees. Upon receipt, the LMHRA screens the clinical trial application package for completeness and must inform the applicant in writing about the validity of the application or the formal grounds for non-acceptance of the application. After validating the application package is complete, the LMHRA conducts a scientific assessment of the application.

During the clinical trial scientific assessment process, the LibCTReg and G-LibClinTrial also explain that relevant clinical trial decisions, reports, or information from other national regulatory authorities or regional and international bodies can be recognized or used by the LMHRA. The LibCTReg further specifies that the scope/extent of utilization of relevant clinical trial decisions, reports, or information from other national regulatory authorities or regional and international bodies will be at the sole discretion of the LMHRA. In such instances, business and company secrets must remain confidential.

The LibCTReg also states that the LMHRA must inform the NREB if it is in possession of information bearing on other clinical trials which is of significance to the board's assessment of the clinical trial on which it is to issue an expert opinion; this applies especially to information on aborted or otherwise prematurely discontinued investigations. In such instances, business and company secrets must remain confidential. Also, the LMHRA must ensure that the list of approved and rejected clinical trial applications as well as summary of evaluation reports and status of approved clinical trials are publicly available and periodically updated.

Per G-LibClinTrial, all applications must be evaluated with the same set of criteria based on up-to-date scientific knowledge and ethics standards, regardless of the applicant. The LMHRA may also request additional documents or changes through a query letter. Once a query has been raised and issued to the applicant, the process stops when the LMHRA receives a written response to the query. If the LMHRA requires changes to the application, the applicant must modify the application within an established timeline, or it will be rejected.

As indicated in the G-LibClinTrial, the LMHRA must issue a clinical trial certificate indicating the LMHRA clinical trial number to the applicant upon application approval. The clinical trial certificate may contain conditions required by the LMHRA with respect to the conduct or reporting of the trial. If the application is rejected, the applicant can submit a written appeal to the LMHRA’s Managing Director. Moreover, the information provided in a clinical trial application must not be disclosed by the LMHRA to a third party except with the written consent of the applicant or in accordance with the directive of the LMHRA Board of Directors.

Per the LibCTReg and the G-LibClinTrial, under certain circumstances, the LMHRA may accept an expedited application and review process for clinical trials (e.g., epidemics or other urgent public health interests requiring fast use of new medicines or health products and/or fast gathering of health product information). The LibCTReg also notes that in the case of emergency situations, the LMHRA may also make exemptions to the documentation requirements for the submission of clinical trial applications. Refer to 2.3 of the G-LibClinTrial for additional information on how to submit an expedited clinical trial application package. In the case of trials involving human participants, per the G-LibClinTrial, the applicant must provide proof of current, relevant, and appropriate study insurance for all participants or professional indemnity insurance for investigators as part of the application submission package to be sent to the LMHRA.

As delineated in the LibCTReg, any amendments to approved clinical trial documentation, trial arrangements, and the IPs referenced in the application must be classified and processed as determined by the LMHRA in the corresponding guidelines. The G-LibClinTrial explains that depending on the nature of the change, trial amendments are regarded as substantial or non-substantial/minor amendments. Amendments to a clinical trial are regarded as “substantial” when they are likely to have significant impact on the safety or physical or mental integrity of the trial participants and/or the scientific value of the trial. Any substantial amendments to the clinical trial protocol, clinical trial arrangements, or the IP or related product deemed to be an amendment must be approved by the LMHRA and the NREB before such amendments are carried out. Written NREB approval is also required before the LMHRA can reach a decision on an amendment. The LMHRA should respond within 20 calendar days upon receipt of the NREB’s written decision. The LMRHA may reject or accept the changes, or recommend a revision of the sponsor’s classification.

Per the G-LibClinTrial, non-substantial/minor amendments, by comparison, can be implemented immediately by the sponsor and should always be documented and notified to the LMHRA and the NREB. However, in order to allow the LMHRA to exercise its clinical trial oversight function, the sponsor should ensure that the LMRHA is aware of a non-substantial amendment(s) as soon as possible. For example, progress reports including safety data as well as annual updates of the investigator's brochure (IB) are not considered amendments per se, and therefore, do not have to be notified as substantial amendments to the LMHRA. However, the sponsor has to verify whether the data presented requires a change to the documentation submitted with the request for clinical trial authorization. If this amendment is substantial, the rules for notification of substantial amendments apply to these changes. See the G-LibClinTrial for additional amendment requirements. See the Submission Process section for amendment submission requirements.

Per the LibCTReg, the LMHRA’s written approval of a clinical trial with IPs involving human participants is based on the conclusion that the anticipated therapeutic and public benefits justify the risk and may be continued only if compliance with this requirement is permanently monitored. An LMHRA authorization may only be refused if:

• The documents submitted are incomplete up to the expiration of an appropriate deadline given to the applicant for their supplementation
• The documents submitted, especially the data on the IP(s) and the trial protocol including the investigator's brochure (IB), do not comply with the current state of scientific knowledge, and especially, the clinical trial is unsuitable for providing proof of IP(s) safety or efficacy, or
• In the case of trials involving human participants, the documentation requirements (see Section 1 (4) of LibCTReg), particularly insurance coverage for trial participants, are not fulfilled
• The LMHRA is in possession of findings which indicate that the testing facility is not suitable to conduct the clinical trial
• The LMHRA is of the opinion that the number of clinical trial participants to be recruited in the trial is not scientifically justified, or
• The requirements provided for in the general conditions and special preconditions for conducting a clinical trial (see Chapter II (Sections 1-2) of LibCTReg) are no longer fulfilled

The LibCTReg indicates that in a clinical trial of an IP consisting of a genetically modified organism, consisting of a combination of genetically modified organisms, or containing such organisms, unjustifiable harmful effects on the health of third persons and the environment are not to be expected when the trial is conducted according to the state of scientific knowledge in relation to the trial’s purpose.

(See the Submission Process and Submission Content sections for detailed submission requirements and the Timeline of Review section for additional LMHRA timeline information.)

The LibCTReg further explains that a clinical trial authorization must be suspended by the LMHRA for a limited period of time if at least one (1) of the following is true:

• It becomes known that one (1) of the grounds for refusal previously indicated existed at the time the trial authorization was issued (see also Chapter II (Section 5 (3)) of LibCTReg)
• The conditions surrounding the clinical trial do not correspond to the information contained in the authorization application
• The facts presented give reason to doubt the safety or the scientific basis of the clinical trial

Per the LibCTReg, the LMHRA must withdraw a clinical trial authorization when scientific justification for resuming the trial is not provided to address the reasons previously indicated for suspension. The LMHRA must also immediately inform the NREB through a written communication stating the grounds for its action. Before a decision is taken, the applicant must be allowed a deadline of 10 working days to submit a statement, unless the LMHRA orders the immediate interruption of the clinical trial. The lodging of an objection and an action to rescind the withdrawal or the order to suspend the authorization should not have a suspensive effect. If the authorization to conduct a clinical trial is withdrawn or suspended, the clinical trial may not be continued. Also, if the LMHRA, in the context of its activities, becomes aware of facts which justify the assumption that one (1) or more of the investigators or the sponsor or the sponsor’s representative no longer fulfills their obligations with regard to the proper conduct of the clinical trial, the LMHRA must immediately inform this individual(s) and must order remedial measures to be taken by the individual(s).

Pursuant to Part VIII of the LMHRA-Act, the LibCTReg states that any person(s), institution(s), corporate entity(ies), their designees, or legal representatives who violates the clinical trial authorization procedures, the serious adverse event notification requirements, and/or the suspension/withdrawal provisions delineated in the LibCTReg will be liable to pay administrative fines. See the LibCTReg for details.

Inspection

As stated in the LibCTReg, the LMHRA should inspect a clinical trial to ensure that the general public is adequately protected against the adverse event risks related to a clinical trial with IP(s); and, to confirm that the PI and the sponsor, including the sponsor’s representatives, are strictly adhering to the specific and general conditions to which the trial was authorized. The G-LibClinTrial also indicates that the LMHRA may inspect clinical trial sites and/or the sponsor's/contract research organization (CRO)’s premises and/or the manufacturer’s premises to ensure that the clinical trials comply with good clinical practice (GCP) provisions before, during, or after the trial is conducted.

Per the LibCTReg and the G-LibClinTrial, NREB representatives may accompany the LMHRA during clinical trial site inspections, or, per the LibCTReg, they may choose to do the inspections independently. The G-LibClinTrial also notes that the LMHRA may include other relevant regulatory authorities in the inspection. The PI and/or the sponsor/CRO and/or the manufacturer must be notified in writing of the inspection unless the LMHRA has reasonable cause to believe that the approved protocol is being violated. In this case, an unannounced inspection may be conducted. Following these inspections, the LMHRA must prepare an inspection report, and the report will be made available to the PI and/or sponsor while safeguarding the confidential aspects. The report may also be made available to the NREB and other regulatory authorities upon their request.

Additionally, the LibCTReg specifies that the LMHRA may also:

• Request additional information
• Inspect any resources that are deemed by the LMHRA to be related to the clinical trial and that may be located at the trial site, the sponsor´s and/or CRO’s facilities, or other establishments deemed appropriate by the LMHRA
• Suspend or stop a clinical
• Withdraw the authorization to conduct a clinical trial, if the LMHRA is of the opinion that the safety of the trial participants may be compromised, that the scientific reasons for conducting the trial have changed, or if the integrity of the data is compromised

Central Drugs Standard Control Organization

As per the 2019-CTRules, IND-43, and IND-42, a sponsor (also known as applicant) is responsible for a paying a fee to the Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO), to submit a clinical trial application. (Note: The DCGI is commonly referred to as the Central Licensing Authority in the Indian regulations.)

The 2019-CTRules and IND-43 specify that Form CT-04 should be accompanied by one (1) of the following officially mandated fees:

• 3,00,000 Rupees for Phase I (human) clinical trials
• 2,00,000 Rupees for Phase II (exploratory) clinical trials
• 2,00,000 Rupees for Phase III (confirmatory) clinical trials
• 2,00,000 Rupees for Phase IV clinical trials
• 50,000 Rupees for reconsideration of application for permission to conduct clinical trial

According to the 2019-CTRules, the sponsor must also submit a fee of 5,000 Rupees per product with an application for permission to manufacture or import the investigational product (IP) to be used in a clinical trial.

In addition, the 2019-CTRules states that no fee is required to be paid along with the clinical trial application if a trial is being conducted by an institution or an organization wholly or partially funded or owned by the Central Government of India or one of India’s state government institute(s).

See also IND-31 for additional information on CDSCO fee requirements.

In addition, IND-24 indicates that for applications submitted to the National Single Window System (NSWS) portal (IND-3), users should pay any required fees directly to CDSCO or any other ministry/department/state responsible for processing the application via the NSWS portal (IND-3). At this time, however, per IND-14, only a few CDSCO steps and processes (e.g., medical device related registration, manufacturing/import applications and drug manufacturing/import applications) have been moved to the NSWS portal (IND-3).

Payment Instructions

As described in the 2019-CTRules and IND-43, payment must be made electronically via the Bank of Baroda, Kasturba Gandhi Marg, New Delhi-110001, any other Bank of Baroda branch, or any other bank approved by the Ministry of Health and Family Welfare (MOHFW) via the State Bank of India’s SBIePay payment gateway, which is accessed from the SUGAM portal (IND-59). The payment should be credited to: Head of Account, 0210-Medical and Public Health, 04-Public Health, 104-Fees and Fines per the 2019-CTRules, also known as the head of Fees & Fines, according to IND-42.

According to IND-43 and IND-42, once the user validates the payment information in the SUGAM portal (IND-59), the payment request is redirected to the SBIePay payment gateway. When the payment is submitted, the bank payment gateway will confirm that the payment was successful, and the user will be redirected to the online payment status page in the SUGAM portal (IND-59) to view the e-Challan (payment receipt).

IND-43 and IND-42 also specify that the online payment will take two (2) to three (3) days to be credited to the National Portal of India’s Payment & Account Office. Therefore, users are requested to initiate online payments at least three (3) days prior to submitting an application to CDSCO. Refer to IND-43 and IND-42 for detailed fee requirements and online payment instructions via the SUGAM portal (IND-59).

(Note: Although the fees listed in IND-43 are correct, the SUGAM portal (IND-59) and associated documentation as well as CDSCO’s Pre-Screening Checklist (IND-32) have not yet been aligned with the 2019-CTRules in terms of referencing the new application form (CT-04). However, the ClinRegs team is regularly monitoring the CDSCO website for new developments and will post the most current sources as they become available.)

Liberia Medicines and Health Products Regulatory Authority

The LibCTReg and the G-LibClinTrial require proof of payment of the clinical trial application fee in the application dossier. Per LibCTReg and LBR-39, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) charges a non-refundable fee to submit a clinical trial application for authorization. As delineated below, authorization fees vary depending on the phase and institution conducting the study:

• Industry Funded (Phase I): $25,000 USD
• Industry Funded (Phase II): $20,000 USD
• Industry Funded (Phase III): $15,000 USD
• Clinical Research Organization (CRO) Funded Phase I: $10,000 USD
• CRO Funded Phase II: $8,000 USD
• CRO Funded Phase III: $6,000 USD
• Investigator/Local Phases III & IV: $2,500 USD
• Academic Research Trial (Individual): $2,000 USD
• Amendment (Substantial) to Clinical Trial Protocol: $1,000 USD

Payment Instructions

No information is available regarding payment instructions.

Overview

As delineated in the 2019-CTRules and IND-31, India has a decentralized process for the ethical review of clinical trial applications, and requires ethics committee (EC) approval for each trial site. Because there is no national EC in the country, ECs are based at either institutions/organizations, or function independently, and must meet the requirements set forth in the 2019-CTRules and the G-ICMR. Prior to initiating and throughout the duration of a trial, every trial site must be overseen by an EC registered with the Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO). (Note: The DCGI is commonly referred to as the Central Licensing Authority in the Indian regulations.)

Ethics Committees for Biomedical and Health Research

Per the 2019-CTRules, CDSCO requires institutions that intend to conduct biomedical and health research to have an EC that reviews and oversees this type of research study. In addition, CDSCO has also established a separate registration and monitoring system for ECs that review biomedical and health research. See the Scope of Review section for additional information on biomedical and research study requirements.

Ethics Committee Composition

Pursuant to the 2019-CTRules and the G-ICMR, an institutional/independent EC should be multidisciplinary and multi-sectorial, representing a mixed gender and age composition. ECs that review clinical trial applications and those that review biomedical and health research share the same composition criteria including affiliations, qualifications, member specific roles and responsibilities, as well as terms of reference and review procedures.

The 2019-CTRules and the G-ICMR state that an EC should appoint from among its members a chairperson (from outside the institution) and a member secretary (generally from inside the institution). The other members should represent a balance of affiliated and non-affiliated medical/non-medical and scientific/non-scientific persons, including the lay public. Per the 2019-CTRules and the G-ICMR, preferably 50% of the members should not be affiliated with the institution.

As per the 2019-CTRules and the G-ICMR, the composition should include the following:

• Chairperson from outside the institute (Vice Chairperson (optional))
• One (1) to two (2) basic medical scientists (preferably one (1) pharmacologist)
• One (1) to two (2) clinicians from various institutions
• Legal expert(s) or retired judge
• One (1) social scientist/representative of non-governmental voluntary agency
• One (1) philosopher/ethicist/theologian
• One (1) lay person from the community
• Member secretary (Alternative Member secretary optional)
• One (1) member whose primary area of interest/specialization is non-scientific
• At least one (1) member independent of the institution/trial site

Additionally, per the 2019-CTRules, EC members are required to:

• Be familiar with key clinical regulatory requirements as delineated in the 2019-CTRules and the G-ICMR that reference both the Declaration of Helsinki (IND-63) and the most recently updated International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (IND-41)
• Have post-graduate qualifications and experience in their fields if representing basic medical scientists/clinicians
• Represent the specific patient group as much as possible based on the research area requirement

Terms of Reference, Review Procedures, and Meeting Schedule

As delineated in the 2019-CTRules and the G-ICMR, EC members should be made aware of their roles and responsibilities. The terms of reference should also include a statement on terms of appointment including duration and conditions; policy for removal/replacement; resignation procedure; meeting frequency; payment of processing fee to EC for review; honorariums to members and invited experts; maintenance of EC documentation and communication records, etc. Each committee should specify these terms in its own standard operating procedures (SOPs) that should be made available to each member.

In addition, per the 2019-CTRules and the G-ICMR, members should have no conflict of interest, and should voluntarily withdraw from the EC while making a decision on an application if a proposal evokes a conflict of interest. The G-ICMR indicates the term of membership is generally two (2) to three (3) years, and may be extended.

In terms of training, the G-ICMR also specifies each member must:

• Provide a recent signed Curriculum Vitae (CV) and training certificates on human research protection and good clinical practice (GCP) guidelines, if applicable
• Either be trained in human research protection and/or GCP at the time of induction into the EC, or undergo training and submit training certificates within six (6) months of appointment (or as per institutional policy)
• Be willing to undergo training or update their skills/knowledge during their tenure as an EC member

Further, if required, the 2019-CTRules and the G-ICMR, state subject experts could also be invited to offer their views, which must be recorded; however, the experts would not have any voting rights. Only members independent of the trial and the trial sponsor (also known as applicant) should vote/provide opinions in study related matters. In addition, all records must be safely maintained after the completion or termination of the study for at least five (5) years from the date of the trial’s completion or termination (both hard and soft copies).

The G-ICMR specifies that all EC members should review all proposals. Members should be given at least one (1) week to review the proposal and related documents, except in the case of expedited reviews. The Member Secretary should screen the proposals for their completeness and categorize them into three (3) types according to risk level: exemption from review, expedited review, or full committee review. An investigator cannot decide that a protocol falls in the exempted category without an EC review. Per the 2019-CTRules and the G-ICMR, a minimum of five (5) members is required for the quorum.

For detailed EC procedures and information on other administrative processes, see the 2019-CTRules, the G-ICMR, and IND-5. See also IND-27 and IND-28 for the Indian Council of Medical Research (ICMR)’s research conduct policies.

Overview

Per the G-ACRE-IRB and the G-NREB, all research involving human participants should be reviewed by an ethics committee (EC). According to the NatResHlthPlcy, Liberia has two (2) ethics committees (ECs): the National Research Ethics Board of Liberia (NREB) and the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB) (formerly known as the University of Liberia-Pacific Institute for Research and Evaluation Institutional Review Board (UL-PIRE-IRB)).

National Research Ethics Board of Liberia

As explained in the G-NREB, the NREB is an advisory institution that reports to the Ministry of Health (MoH), and its members are appointed by the Minister of Health. According to LBR-38, only the NREB has the sole responsibility to review all clinical trial protocols. The G-NREB states that the board ensures all research related protocols within and outside of Liberia are in compliance with internationally recognized ethical standards (including the Belmont Report (LBR-11), the Declaration of Helsinki (LBR-27), the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (LBR-8), and the Council for International Organizations of Medical Sciences (CIOMS’) International Ethical Guidelines for Health-related Research Involving Humans (LBR-2)), as well as Liberia’s applicable regulations and guidelines. In addition, per the G-NREB and LBR-12, the NREB is responsible for reviewing research proposals involving human participants to assess their compliance with ethical principles, regulatory requirements, and international guidelines, and for approving research protocols that meet ethical standards and providing recommendations for addressing any ethical concerns.

Per the NatResHlthPlcy the G-NREB, and LBR-12, the NREB is also responsible for the following (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• Ensuring that researchers obtain informed consent from participants and protect their rights, privacy, and confidentiality
• Evaluating the potential risks and benefits of research projects and ensure that they are justified and minimized
• Developing and disseminating policies, guidelines, and standards for ethical conduct in research
• Providing guidance and support to researchers, research institutions, and ECs on ethical issues related to research involving human participants
• Fostering awareness and understanding of ethical principles and regulatory requirements among stakeholders in the research community
• Conducting training programs, workshops, and seminars to educate researchers, EC members, and other stakeholders on ethical principles and best practices in research ethics
• Building the capacity of research institutions and ECs to effectively review and oversee research involving human participants
• Promoting a culture of ethical conduct and responsible research practices within the research community
• Monitoring compliance with approved research protocols and ethical standards throughout the duration of research projects
• Conducting periodic reviews or audits of research activities to ensure adherence to ethical principles and regulatory requirements
• Investigating and addressing any allegations of research misconduct or breaches of ethical standards
• Establishing guidelines for the review of research for health protocols for use by other review boards
• Giving advice on ethical research issues to the MoH and related government ministries and agencies
• Engaging with the public, policymakers, and other stakeholders to raise awareness of ethical issues in research and foster dialogue on ethical considerations
• Advocating for the protection of research participants’ rights and the promotion of ethical conduct in research at the national and international levels
• Collaborating with relevant government agencies, institutions, and organizations to advance the ethical governance of research
• Establishing and maintaining a repository of all protocols reviewed in the country along with finished research/study reports

Atlantic Center for Research and Evaluation Institutional Review Board

As noted in the G-ACRE-IRB, the ACRE IRB is mandated by the Board of Directors of the ACRE Africa Center. According to LBR-28, the ACRE IRB has the expertise to review clinical research, and some members of the ACRE IRB also serve on the NREB and provide expertise in the review of clinical trial protocols. However, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical research protocols submitted to the ACRE IRB are referred to the NREB.

Ethics Committee Composition

National Research Ethics Board of Liberia

According to the G-NREB, the NREB is composed of 21 members who jointly represent a diverse community with a range of expertise. The G-NREB notes that the majority of the board members are clinicians, scientists, and national subject matter experts. Per LBR-18, the NREB board typically consists of experts in various fields related to research ethics, such as medicine, public health, social sciences, ethics, law, and community representatives. Board members may include researchers, ethicists, healthcare professionals, legal experts, and representatives from government agencies and civil society organizations. LBR-38 further specifies that the NREB membership includes, but is not limited to, a sociologist, an infectious disease scientist, a biologist, a lawyer, a pharmacist, an epidemiologist, a statistician, a bioethicist, a mental health specialist, a health system strengthening specialist, a religious elder, community elders, surgeons, clinicians, and public health specialists.

In addition, per LBR-18, although the NREB organization structure may vary based on its specific mandate, size, and operational requirements, the board typically consists of a chairperson/executive director, a secretariat or administrative staff, ethics review committees/panels, and advisory groups that may provide specialized expertise or support for specific activities or initiatives.

Atlantic Center for Research and Evaluation Institutional Review Board

As specified in the G-ACRE-IRB, the ACRE IRB members (full, regular, and ad-hoc) must be recommended by the ACRE IRB Chair and appointed by the ACRE Board of Directors. The ACRE IRB must be comprised of 12 members with the qualifications and experience, individually and collectively, to review and evaluate the scientific, medical, and ethical aspects of research protocol submissions. The membership must include both scientists and non-scientists from diverse backgrounds to undertake an impartial and adequate review of research proposals. The ACRE IRB membership must include the following:

• Scientists (including, but not limited to, professionals in natural science, social science, and behavioral science)
• Non-scientists (health practitioners, legal experts representing the community, and civil society)

In addition, the ACRE IRB must ensure social inclusivity and gender sensitivity in its membership and recruitment of ad-hoc reviewers. There must be adequate representation by age, gender, community, etc., on the board to safeguard the interests and welfare of all segments of society. ACRE IRB members must be drawn from both public and private institutions within the country.

Terms of Reference, Review Procedures, and Meeting Schedule

National Research Ethics Board of Liberia

Pursuant to the G-NREB, the NREB follows standard operating procedures (SOPs) as well as relevant ethical guidelines and regulations to ensure compliance with research ethics principles and to uphold societal interests. The NREB may seek subject matter expert opinions regarding specific research protocols and/or issues, as long as the experts have no conflict of interest, including participation in the research, financial interest in the outcome, and/or involvement in competing research, among other reasons. NREB members should meet bi-monthly for regular meetings and adhere to the board’s threshold requirement to review a minimum of three (3) complete applications at each meeting. When applicable, the NREB director may also convene ad-hoc meetings. All complete applications submitted by the deadline must be reviewed at the next regularly scheduled meeting if the number of applications meet the threshold. Members are encouraged to attend all meetings and the quorum required for voting is two-thirds of the NREB membership. Members who cannot attend a meeting due to unforeseen reasons must inform the NREB director two (2) weeks prior to the scheduled meeting. If unable to attend, members must also advise the NREB director regarding their views or concerns on specific agenda items one (1) week prior to a scheduled meeting. Meeting agendas and research protocols should be distributed to members no later than three (3) weeks before a regular meeting. Refer to the G-NREB and LBR-12 for detailed committee requirements.

Atlantic Center for Research and Evaluation Institutional Review Board

As delineated in the G-ACRE-IRB, the ACRE IRB Chair must be the head and chief spokesperson of the board and must conduct meetings in accordance with the policies, regulations, and timetable approved by the board. ACRE IRB members must be appointed initially for a term of three (3) years, which must be renewable and is subject to the ACRE IRB Board of Directors’ decision. To maintain continuity in ACRE IRB operations, at least one-third of the membership must be retained at any given time. The outgoing Chair must be an ex-officio member of the incoming ACRE IRB. ACRE IRB members and consultant reviewers must be provided with all relevant SOPs by the Secretariat to guide in the review process of all submitted protocols. ACRE IRB members are required to review, discuss, and consider protocols submitted to the board for evaluation to safeguard the rights, safety, and well-being of study participants; review progress reports and monitor ongoing research studies appropriately; evaluate final reports and outcomes; maintain absolute confidentiality in all document deliberations at board meetings; state conflicts of interest, where applicable; and participate during deliberations. Members with a conflict of interest will recuse themselves from the review of submissions with which they have a conflict, except to answer specific questions posed by the board. Additionally, per LBR-28, ACRE IRB reviews are conducted virtually via the Zoom platform.

The ACRE IRB must convene a meeting every month or when deemed necessary. The Chair, or a delegated board member, must call the meeting to order, provided there is a quorum. If there is no quorum, the meeting must be rescheduled. A quorum must be greater than 50% of the voting board members at any given event. A quorum must consist of regular and/or alternate board members (persons formally selected by the board to substitute for regular members who are unavailable ), and it must include at least one (1) member whose primary background is science related, and one (1) member whose primary background is not science related. Special/independent consultants cannot be used to establish a quorum. Members who are recused from the review of a protocol cannot be used to establish a quorum. A simple majority vote of ACRE IRB members in attendance is required for a protocol to be approved.

The ACRE IRB Chair may invite individuals with competence in special areas to assist in the review of issues that require expertise beyond or in addition to that available on the board. These individuals will be required to sign a confidentiality agreement before they review a protocol or attend a board protocol discussion, however, they are not permitted to vote. The consultant will provide the Chair with a written report to be shared with all reviewers summarizing relevant information.

Refer to the G-ACRE-IRB for detailed information on ACRE IRB administrative processes.

Overview

The primary scope of information assessed by ethics committees (ECs) relates to maintaining and protecting the rights, safety, and well-being of all research participants, especially those in vulnerable populations, in accordance with the requirements set forth in the 2019-CTRules, the G-ICMR, the G-Children, the Declaration of Helsinki (IND-63), and the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (IND-41). (See the Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired sections for additional information about these populations).

The 2019-CTRules and the G-ICMR also state that ECs must ensure an independent, timely, and competent review of all ethical aspects of the research protocols. They must act in the interests of the potential research participants and the communities involved by evaluating the possible risks and expected benefits to participants, and they must verify the adequacy of confidentiality and privacy safeguards. Per the G-Children, ECs providing opinions on studies involving children should also include members with pediatric expertise. The expert(s) may be permanent EC members or invited as subject experts to provide advice and be consulted on an ad-hoc basis.

See also the G-AI-BiomedRes for EC review guidelines for biomedical and health research proposals involving artificial intelligence-based tools and technologies.

Role in Clinical Trial Approval Process

As per the 2019-CTRules, the G-ICMR, and IND-31, the Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO), and a DCGI-registered EC must approve a clinical trial application prior to the sponsor (also known as applicant) initiating the trial, except in the case of non-regulatory academic clinical trials that only require EC approval. (Note: The DCGI is commonly referred to as the Central Licensing Authority in the Indian regulations.) According to IND-31, the DCGI review and approval process may be conducted in parallel with the EC review for each clinical trial site. However, per the 2019-CTRules and the Hdbk-ClinTrial, CDSCO must confirm the EC approvals for each participating site have been obtained per the protocol prior to approving the initiation of the study. (Note: the Hdbk-ClinTrial has not yet been updated to fully align with the 2019-CTRules.)

The 2019-CTRules, the Hdbk-ClinTrial, and IND-31 specify that an EC must grant a separate approval for each trial site to be used, and the DCGI must be informed of each approval. A trial may only be initiated at each respective site after obtaining an EC approval for that site. The 2019-CTRules and IND-31 further state that if a site does not have an EC, it may obtain approval from another site’s EC provided that it is located within the same city or within a radius of 50 kilometers of the trial site. The DCGI should be notified of the EC’s approval within 15 working days of the approval being granted per the 2019-CTRules. Per the 2019-CTRules and IND-31, the EC of each site should notify the DCGI of its approval and provide a copy within 15 working days of making this decision. Refer to IND-36 for the Indian Council of Medical Research (ICMR)’s EC clinical trials application form.

During a clinical trial, per the 2019-CTRules, an investigator should not implement any deviations from or changes to the trial protocol without agreement by the sponsor and after obtaining the EC’s prior review and documented approval or favorable opinion of the amendment. All protocol amendments should be submitted to the DCGI in writing along with the EC’s approval letter.

The 2019-CTRules further states that the exception to this requirement is when it is necessary to eliminate an immediate hazard to the trial participant or when the changes involved are only logistical or administrative in nature. In this case, the EC as well as the DCGI must be notified immediately of all such exceptions. The DCGI should also be notified of administrative or logistical changes or minor amendments in the protocol within 30 days.

As delineated in the 2019-CTRules, ECs also have a continuing responsibility to monitor approved clinical trials and biomedical and health research studies to ensure ethical compliance throughout the study duration.

For all studies, the G-ICMR indicates that ECs must review and approve any protocol amendments, major deviations, or violations at regular intervals.

There is no stated expiration date for an EC approval in the 2019-CTRules or the G-ICMR. However, per the 2019-CTRules, in the event that an EC revokes its approval of a clinical protocol, it must record its reasons for doing so and immediately communicate this decision to the investigator as well as to the DCGI.

Per the 2019-CTRules, the EC must also maintain data, record, registers and other documents related to the functioning and review the clinical trial for a period of five (5) years after completion of the study. For detailed EC review procedures and information on other administrative processes, see the 2019-CTRules, the G-ICMR, IND-5, and IND-27. See also IND-36 for the EC clinical trial application form, and IND-52 for other commonly used EC review forms.

The G-ICMR further states that research during humanitarian emergencies and disasters can be reviewed by an EC through an expedited review and scheduled/unscheduled full committee meetings, and this may be decided by the member secretary on a case-by-case basis depending on the urgency and need. If an expedited review is done, full ethical review should follow as soon as possible. The EC should also closely monitor the conduct and outcome of research. See Section 12.5 of the G-ICMR for additional information on EC review requirements during humanitarian emergencies.

For specific guidelines regarding gene therapy and stem cell therapy clinical trials, see G-GeneThrpy and G-StemCellRes.

Academic Clinical Trials

As defined by the 2019-CTRules, an academic clinical trial is a clinical trial of a drug already approved for a certain claim and initiated by any investigator, academic or research institution for a new indication or new route of administration, or, new dose or new dosage form, where the results of such a trial are intended to be used only for academic or research purposes and not for seeking DCGI approval or regulatory authority approval in any country for marketing or commercial purpose.

The 2019-CTRules and IND-31 specify that an academic clinical trial does not require DCGI approval as long as the following conditions are met:

• The trial is approved by the EC, and
• The data generated is not intended for submission to the DCGI

In addition, per the 2019-CTRules and IND-31, the EC should inform the DCGI about the academic trials it has approved and cases where there could be an overlap between the clinical trial for academic and regulatory purposes. If the DCGI does not comment to the EC within 30 days from receiving EC notification, it should be presumed that DCGI permission is not required. See also IND-6 for additional information on academic trial approval requirements.

IND-25 further explains that a drug import license is not required for EC-approved academic trials that will be using a permitted drug formulation with a new indication, a new route of administration, a new dose, or a new dosage form. See the Manufacturing & Import section for detailed information.

Biomedical and Health Research

According to the 2019-CTRules and the G-ICMR, biomedical and health research is defined as studies that include basic research, applied and operational research, or clinical research designed primarily to increase scientific knowledge about diseases and conditions (physical or socio-behavioral); their detection and cause; and evolving strategies for health promotion, prevention, or the amelioration of disease and rehabilitation.

As discussed in Notice15Sept19 and Chapter IV of the 2019-CTRules, any institution or organization that intends to conduct biomedical and health research involving human participants is required to have an EC to review and oversee the conduct of such research before the study is initiated and throughout its duration. See also IND-28 for ICMR’s biomedical and health research conduct policies, and IND-6 for additional information on the regulation of biomedical and health research under the 2019-CTRules.

The EC must also be registered with the designated authority within the Ministry of Health and Family Welfare (MOHFW)’s Department of Health Research (DHR). Refer to the Oversight of Ethics Committees section for detailed registration requirements.

Multicenter Research

As delineated in the G-ICMR, in a multicenter research study, all of the participating study sites are required to obtain approval from their respective ECs. Each EC may conduct a separate review, or the ECs may decide to designate a main EC, with the others choosing to accept its decision. The study sites also typically follow a common protocol to avoid duplication of effort, wastage of time, and issues arising with communication between committees.

Per the G-ICMR, in the event that sites choose to have separate EC reviews, the following requirements must be met:

• The participating site ECs/Secretariats should establish communication with one another
• If any EC does not grant approval for a study at a site, the reasons must be shared with other ECs and should be considered
• The EC can suggest site-specific protocols and informed consent modifications as per local needs

A separate review may be requested for studies with a higher degree of risk, clinical trials, or intervention studies where conduct may vary depending on the site, or, for any other reason that requires closer review and attention. See the G-ICMR for additional participating site requirements when a primary EC is selected for common EC review.

Per the G-ICMR, when the multicenter research study designates one (1) main EC, the nominated EC members that represent the participating sites may attend the meeting of the elected EC. The designated EC should also be in India and be registered with the relevant authority (either the DCGI or the DHR depending on the type of study). In addition, the decision to conduct a common review is only applicable for ECs in India. In the case of international collaboration for research and approval by a foreign institution, the local participating study sites would be required to obtain approval from a local EC. Refer to the G-ICMR for detailed information on multicenter studies that use the common review practice and involve international collaborations.

The G-ICMR further notes that the local site requirements (e.g., informed consent, research implementation and its monitoring) may be performed by the local EC, which would require good communication and coordination between the researchers and the EC secretariats representing the participating sites.

See the G-MultictrResRev for additional guidelines on streamlining the ethics review process for multicenter biomedical and health research studies conducted by the ICMR or its network of institutions.

Overview

According to the G-ACRE-IRB and the G-NREB, the primary scope of information assessed by ethics committees (ECs) in Liberia relates to maintaining and protecting the dignity and rights of research participants and ensuring their safety throughout their participation in a clinical trial. According to the NatResHlthPlcy, Liberia has two (2) ECs: the National Research Ethics Board of Liberia (NREB) and the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB) (formerly the University of Liberia-Pacific Institute for Research and Evaluation Institutional Review Board (UL-PIRE-IRB)).

The G-ACRE-IRB and the G-NREB also state that the ECs are responsible for ensuring independent, timely, and competent reviews of all ethical aspects of the clinical trial protocol. The ECs must also act in the interests of the potential research participants and the communities involved by evaluating the possible risks and expected benefits to participants, and they must verify the adequacy of confidentiality and privacy safeguards. As per the G-ACRE-IRB, the ACRE IRB must pay special attention to reviewing informed consent and protecting the welfare of certain classes of participants deemed to be vulnerable, including children.

See the G-ACRE-IRB and the G-NREB for detailed ethical review guidelines.

Role in Clinical Trial Approval Process

As per the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) and the NREB must approve a clinical trial application prior to the sponsor or the representative initiating the clinical trial. Per the LibCTReg and the G-LibClinTrial, the NREB and LMHRA reviews may be conducted in parallel. However, the G-LibClinTrial and the G-NREB specify that the LMHRA will only issue final approval once NREB approval is obtained. In addition, per the LibCTReg and the G-LibClinTrial, any substantial amendment to the approved clinical trial research protocol must be approved by the LMHRA and the NREB before such amendments are carried out.

Additionally, per the LibCTReg, the LMHRA must inform the NREB if it is in possession of information bearing on other clinical trials which is of significance to the board's assessment of the clinical trial on which it is to issue an expert opinion; this applies especially to information on aborted or otherwise prematurely discontinued investigations. In such instances, business and company secrets must remain confidential.

National Research Ethics Board of Liberia

Per the G-LibClinTrial and the G-NREB, ethical clearance by the NREB is required as part of the LMHRA clinical trial approval process. As per the G-NREB, a protocol will be reviewed if the number of submitted protocols meets the board’s threshold requirement to review a minimum of three (3) complete applications at each meeting.

As delineated in the LibCTReg, the NREB provides its opinion on the application for a clinical trial in line with its written standard operating procedures (SOPs). According to LBR-20, upon receiving the research proposals, the NREB conducts a preliminary screening to ensure that all required documents and information are included and that the proposals meet the submission requirements. Incomplete or insufficient proposals may be returned to researchers with instructions for revisions or additional information. An ethics review committee/panel composed of experts in relevant fields, such as medicine, public health, ethics, law, and community representatives is then assigned by the NREB, and the committee members review the proposals independently or collectively, depending on the complexity of the research and the availability of resources. The ethics review committee/panel thoroughly evaluates each research proposal based on established ethical review criteria.

Per LBR-31, the NREB follows established ethical review criteria to evaluate research proposals to help ensure that research studies adhere to ethical principles and protect the rights, welfare, and dignity of research participants. The ethical criteria delineated in LBR-31 include informed consent, beneficence, justice, privacy and confidentiality, respect for participants’ rights and dignity, scientific validity and integrity, and compliance with regulatory requirements. See LBR-31 for details.

Per LBR-20, the committee members also assess the ethical implications of the proposed research, including the risks and benefits to participants, the adequacy of the informed consent process, the protection of vulnerable populations, and the equitable distribution of research burdens and benefits. The review process may involve discussions, debates, and deliberations among committee members to reach consensus on the ethical acceptability of the research proposals. See also LBR-23 for additional EC review guidelines.

LBR-20 further explains that the NREB communicates the outcomes of the ethical review process to researchers, including decisions on approval, conditional approval pending revisions, or rejection. Researchers receive feedback and recommendations from the EC to address any ethical concerns raised during the review process and may be required to make revisions to their proposals, provide additional information, or address specific ethical issues before final approval is granted. The LibCTReg also notes that a written permission from the NREB may only be refused if the documents submitted are incomplete up to the expiration of an appropriate deadline given to the applicant for their supplementation; the documents submitted, including the trial protocol, the investigator’s brochure, the modalities for selecting trial participants, and informed consent/assent, do not correspond to the current state of scientific knowledge, and especially, the clinical trial is unsuitable for providing IP(s) proof of safety or efficacy, or; the applicable requirements specified in the general conditions for conducting clinical trials (see Chapter II (Section 1) of LibCTReg) are not fulfilled.

Per the G-NREB, a principal investigator (PI) will be contacted by written communication (letter or email) if the NREB determines that additional materials are required to complete its review. PIs may also be asked to be available for presentations and/or contacted during the meetings. The G-NREB also explains that the NREB should notify PIs in writing of its decision within two (2) weeks following a board meeting, where applicable, following a complete review of the protocols. The NREB will also communicate its decisions to the NREB Secretariat. An approval expiration date is not specified. Pursuant to the G-NREB, PIs may also re-submit previously considered protocols, which will require a full NREB review. Per LBR-20, once all the ethical requirements have been met, the NREB grants final approval for the research proposals to proceed.

As indicated in the G-NREB, for continuing review submissions, PIs must submit review reports to the NREB Secretariat at least eight (8) weeks prior to the approved protocol’s expiration. If the NREB has not reviewed and approved a study’s request by the current expiration date, study activities should cease until the board determines whether continuing the research is in the best interest of all previously enrolled participants. The NREB will also review continuing review submissions prior to the expected expiration date of NREB approval for requests to extend the ethical approval to continue implementation of the research project. See LBR-6 for the NREB Continuing Review Form. See the Progress Reporting section for additional information on continuing review.

Additionally, per LibCTReg, the NREB’s written permission must be withdrawn if the NREB subsequently becomes aware that grounds for a refusal as referred to in the clinical trial authorization procedures (see Chapter II (Section 5 (1)) of LibCTReg) existed at the time the authorization was issued. The authorization must be withdrawn if the NREB becomes aware of the fact that subsequently at least one (1) of the following is true:

• Requirements regarding the suitability of the investigator, the investigator’s deputy, or the trial site are no longer fulfilled
• Trial participants are no longer properly insured or the prerequisites for an exception to the insurance obligation no longer exist
• Modalities for selecting trial participants no longer correspond to the current state of medical knowledge and, especially, the clinical trial is unsuitable for providing proof of the IP(s) safety or efficacy
• Prerequisites for the inclusion of persons pursuant to the general conditions and special preconditions for conducting a clinical trial (see Chapter II (Sections 1-2) of LibCTReg) are no longer fulfilled. The NREB shall inform the LMHRA through a written communication

For protocol amendments, per the G-NREB, the NREB must review and approve any protocol amendments prior to implementation. The NREB secretariat must first consult with the NREB Chair to determine the type of review required (full board review or expedited due to risk). Protocols that pose no or minimal risk to participants, have no formal informed consent process, or are subject to NREB continuing review, may be considered exempt and may qualify for expedited review. Refer to the G-NREB for detailed information on the decision types and various review processes the NREB uses to consider protocol submissions.

Additionally, the G-NREB explains that as a condition of research protocol approval, the NREB requires the PI to provide regular updates to the Secretariat from the date of approval. LBR-20 also notes that researchers are required to report any significant deviations from the approved protocols or ethical concerns that arise during the course of the research to the NREB for review and guidance. The NREB may also provide ongoing monitoring and oversight to ensure continued compliance with ethical standards and regulatory requirements. The G-NREB specifies that the NREB must conduct site visits at appropriate intervals. In certain cases, the site visits may be unannounced to ensure the integrity of the study.

Reviews During Public Health Emergencies

As delineated in the G-CTEmergncy, in the event a public health emergency is declared in Liberia or a neighboring country by the World Health Organization (WHO), the Ministry of Health (MoH), or the National Public Health Institute of Liberia (NPHIL), the NREB will expedite the initiation of research and many processes (i.e., drafting documents, translations, and obtaining approvals) will occur in parallel, rather than sequentially, as is typical during non-emergency situations.

Per the G-CTEmergncy, in addition to the NREB review form (if applicable), the following checklist will be included to streamline fast-tracking of epidemic-related research:

• Identify the research as epidemic or outbreak-related to facilitate fast-tracking
• Specify whether prior research data on the disease exists, referencing relevant local and international studies
• Ensure the inclusion of at least one (1) (preferably two (2)) PIs or co-PIs from the country where the research and review take place
• Provide qualifications of key investigators, including details of their previous experience with outbreak-relevant research
• Indicate if the protocol is part of a multicenter trial. If so, describe the status of ethics approval for the master protocol or the ethics approval from the sponsoring country

The G-CTEmergncy indicates that the NREB will also use the following guidelines to ensure compliance during health emergencies:

• Establish surge capacity for reviews and systems for virtual discussions (via platforms like Zoom)
• Identify core members who will handle the majority of the review burden, providing specialized training in outbreak-related research review to ensure high standards without compromising ethical considerations. Additional members can be called upon as demand increases
• The Director will alert members and determine whether they are available for emergency review
• Identify subject experts (technical and ethical) within the country and abroad who are willing to serve as ad hoc or co-opted members during outbreaks, anticipating the need to review multiple studies in a short time
• Establish a quorum consisting of one-third of NREB members, including pre-identified subject matter experts. If a pre-identified member submits their review but cannot attend the meeting, the member will still count towards the quorum

The G-CTEmergncy further states that revised SOPs will be circulated to all review committee members. Meetings may be virtual or electronic to reduce health risks during highly infectious outbreaks (e.g., COVID-19, Ebola). Protocols should be submitted electronically for efficiency, with hard copies to follow if mandatory. PIs must inform the NREB as early as possible about their intent to submit a high-level overview of their research (e.g., trial of a new medicine or vaccine, observational study, or survey) to prepare the committee for forthcoming protocols. Face-to-face meetings with PIs are not mandatory and may be conducted electronically or virtually if necessary. Also, protocols will be sent to reviewers within 48 hours of submission. Reviewers should complete their reviews within five (5) days during an outbreak. The PI should receive consolidated reviews with suggestions or approval within 10 working days, and should respond to the review within 48 hours. The director of the NREB secretariat will be the primary contact for communication with PIs, and all communications will be documented and archived for future reference.

Atlantic Center for Research and Evaluation Institutional Review Board

Per G-ACRE-IRB, the ACRE IRB’s purpose is to review and certify the ethical acceptability of all research involving human participants conducted in Liberia. However, per LBR-28, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.

Per G-ACRE-IRB, all studies submitted to the ACRE must be approved by the ACRE IRB. This includes all studies conducted by ACRE investigators as well as all research conducted by outside investigators or students and faculty of universities in Liberia. The G-ACRE-IRB is intended to ensure quality and consistency in the ACRE IRB’s review of social, behavioral, clinical, and biomedical research protocols that comply with the Council for International Organizations of Medical Sciences (CIOMS’) International Ethical Guidelines for Health-related Research Involving Humans (LBR-2) and the national ethical guidelines for research on human participants.

According to G-ACRE-IRB, on receipt of a proposal for review, the ACRE IRB Secretariat will preliminarily assess the completeness of the submission. If the submission is incomplete, the Secretariat will inform the PI accordingly and request the additional materials. Once the submission is deemed complete, the Secretariat will notify the PI and distribute the materials to the assigned ACRE IRB members. Exempt studies will be reviewed by all board members; expedited studies will be reviewed by all board members; full review studies will be sent to the entire ACRE IRB membership for review. An expedited study is defined as one which does not require review by a convened ACRE IRB quorum because it has been determined that participants are subject to low risk. Additional information about the various review types can be found in the G-ACRE-IRB. The PI must check the level at which the protocol will be reviewed and confirm the required documents before submitting it for review. Please refer to the G-ACRE-IRB for additional information on the administrative processes relating to proposal submission.

As specified in the G-ACRE-IRB, the ACRE IRB approval will commence on the day the study is approved and will expire within a defined time period based on the risk assessment and regulations. If specific conditions are stipulated in the approval letter, those conditions must be met by the designated date or approval may be withdrawn.

The G-ACRE-IRB also states that the ACRE IRB must review and approve any protocol amendments prior to those changes being implemented. The protocol submission is reviewed either via expedited procedures (for minor changes) or via full ACRE IRB review (for all other changes). The criteria for approval are the same as for initial review. In addition, the ACRE IRB has a continuing responsibility to monitor the approved trial(s) to ensure ethical compliance throughout the study duration. A continuing review is conducted to review progress of an ongoing study, and not just changes made in the study, in order to ensure continued protection of the rights and welfare of research participants. Refer to the G-ACRE-IRB for protocol amendment and continuing review documentation submission and procedural requirements.

Additionally, per the G-ACRE-IRB, a protocol may be selected to undergo post-approval monitoring due to reported complaints and/or requests by the convened EC. Other reasons for post-approval monitoring may include:

• From continuing review or reports from other sources, it is revealed that material changes may have occurred without ACRE IRB approval
• Where an investigator conducting a project has previous records of noncompliance
• Projects involving vulnerable populations that raise cause for concern
• Complex projects involving unusual levels or types of risks to participants
• Upon request by the investigator
• In response to inquiries from external regulatory agencies

The G-ACRE-IRB further notes that if the monitoring reveals serious or continuing noncompliance, the EC Secretariat or EC designee will compile the information regarding the allegation, complaint, or report and submit the information to the EC for further review and processing as needed. See the G-ACRE-IRB for additional information on monitoring procedures, reporting of monitoring results, and noncompliance.

As described in the G-ACRE-IRB, the ACRE IRB is also authorized to suspend or terminate an approved research study for a variety of reasons, including but not limited to:

• Failure to obtain appropriate consent or keep appropriate study-related paperwork
• Conduct of research activities without prior ACRE IRB approval
• Serious adverse event(s)
• Detrimental change in the risk-benefit ratio of the study
• Failure of investigators to complete required training

The convened board is specifically authorized to suspend or terminate approval of research protocols that are not being conducted in accordance with the ACRE IRB’s requirements or that has been associated with serious harm to the participants. The ACRE IRB Chair, or the designee, is authorized to suspend research protocols in emergency situations, such as when the rights, safety, or welfare of research participants are at immediate risk. Refer to the G-ACRE-IRB for detailed information on the board’s process for study suspension/termination, notification of the investigator, the consequences of study suspension/termination, and ACRE IRB requirements for permitting study reinstatement.

As indicated in the G-ICMR, ethics committees (ECs) may charge a reasonable fee to cover the expenses related to optimal functioning to conduct reviews. EC members may also be given reasonable compensation for their time attending EC meetings, and every institution should allocate adequate funds to ensure the smooth functioning of the EC.

National Research Ethics Board of Liberia

As described in the G-NREB, the National Research Ethics Board of Liberia (NREB) must charge a minimal fee for the review of each submission type. Submissions include research protocols, re-submissions, amendments, and continuing reviews. The fee structure is based on the following application types: research protocol, behavioral research, investigational product (IP) (clinical trial), non-clinical trial, or waiver/exemption. Fees specifically associated with conducting a clinical trial involving IPs is based on a project’s scope, duration, sample size, and complexity as well as the types and quantities of IPs, among other criteria. The fees delineated in the G-NREB are as follows:

• Clinical trial: $7,000 USD
• Re-submission: $1,500 USD
• Continuing Review: $1,500 USD
• Amendment: $1,500 USD

Payment Instructions

No information is available regarding payment instructions for the NREB.

Atlantic Center for Research and Evaluation Institutional Review Board

As per the G-ACRE-IRB, the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB) fees for protocol review other than clinical trials are as follows:

• Health, Behavioral and Education Research: $500 USD
• Re-Submission: $500 USD
• Continuing Review: $500 USD
• Amendment: $250 USD
• Foreign Student: $300 USD
• Liberian Student: $100 USD

The fee for non-sponsored research conducted by individual investigators is 50 percent of the sponsored research fee.

Payment Instructions

No information is available regarding payment instructions for the ACRE IRB.

Overview

In accordance with the 2019-CTRules and IND-31, all ethics committees (ECs) that review drug clinical trials are required to register with the Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO), prior to reviewing and approving a clinical trial protocol. (Note: The DCGI is commonly referred to as the Central Licensing Authority in the Indian regulations.) As delineated in Notice15Sept19 and Chapter IV of the 2019-CTRules, all ECs that review biomedical and health research studies are required to register with the designated authority within the Ministry of Health and Family Welfare (MOHFW)’s Department of Health Research (DHR). According to IND-50, the DHR’s Office for Ethics Committee Registration has been designated as the entity responsible for coordinating and monitoring registrations for ECs overseeing biomedical and health research in India. This office will receive applications for registration of ECs and will review and make decisions on EC registrations/re-registrations.

See also IND-69 for an application submission checklist to re-register ECs. Refer to IND-49 for a list of registered ECs, and IND-48 for a list of re-registered ECs.

Registration, Auditing, and Accreditation

Registration Provisions for Clinical Trial Ethics Committees

As specified in the 2019-CTRules and Notice1Aug18, ECs that intend to review clinical trial research protocols must submit Form CT-01 via the SUGAM portal (IND-59) to register with the DCGI. The DCGI, in turn, will review the application within 45 working days from the date of receipt and, if satisfied with the information provided, grant the EC's registration request via Form CT-02. Per 2022-CTRules-3rdAmdt, provided that no communication has been received from the DCGI within the stated period of 45 working days, the EC registration will be deemed granted by the DCGI, and such registration will be regarded as legally valid for all purposes and the applicant will be authorized to initiate a clinical trial in accordance with these rules. 2022-CTRules-3rdAmdt further states that once the EC has obtained provisional approval from the DCGI per the 2019-CTRules, the committee must also notify CDSCO via Form CT-02A, which will become part of the official record known as the guaranteed registration of the DCGI.

Per the 2019-CTRules and IND-53, the EC registration will remain valid for a period of five (5) years from the date of issue, unless suspended or cancelled sooner. The EC may apply for registration renewal via the IND-59 using Form CT-01 and should include all additional required documentation 90 days prior to the registration’s expiration date. The registration will remain in force until the DCGI passes a new registration order as long as the application is received within the specified 90-day deadline. Following the DCGI’s review of the application and inspection report, if any, and provided that there are no changes to the documentation included in the original application, the EC’s request for registration renewal will be granted within 45 working days from the date of application receipt. See also IND-42 and IND-43 for detailed fee requirements and online payment instructions via IND-59.

The 2019-CTRules also states that if the EC fails to comply with any of the registration conditions, the DCGI may, after giving the EC an opportunity to show cause as to why such an order should not be passed, prepare an order in writing to suspend or cancel the EC registration for such period as deemed necessary. The suspended or cancelled EC can appeal to the DCGI within the period specified in the show cause notice, and, after consideration, the DCGI may respond by taking one (1) or more of the following actions:

• Withdraw the notice
• Issue a warning to the EC describing the deficiency or defect observed during an inspection
• Reject the results of the clinical trial
• Suspend for a specified period or cancel the registration, or
• Debar its members to oversee any future trial for a specified period

The aggrieved EC may file an appeal to the Government of India (Central Government) within 60 working days. The Central Government may subsequently pass an order in response to the appeal within 60 working days from the date of the appeal filing.

The EC must also allow CDSCO officials to enter the committee premises to inspect any records, data, documents, or other materials related to a clinical trial. The EC must provide adequate replies to any queries raised by the inspecting authority in relation to the conduct of the trial as noted in the 2019-CTRules.

Registration Provisions for Biomedical and Health Research Ethics Committees

As explained in Notice15Sept19 and IND-51, ECs planning to review biomedical and health research studies are initially required to register on the DHR’s National Ethics Committee Registry for Biomedical and Health Research (NECRBHR) website (IND-51). The NECRBHR facilitates the receipt and processing of application submissions and assists the DHR’s Office of Ethics Committee Registration. An authorized signatory/responsible person must complete the EC Applicant Registration Form (IND-38) and submit it online on the NECRBHR website (IND-51). Once the NECRBHR verifies the application and approves the account registration, the applicant will receive an email with login instructions to apply electronically via the DHR’s NAITIK portal (IND-54). See IND-66 for a checklist of NECRBHR registration requirements.

Per the 2019-CTRules, the EC must submit an application to the NECRBHR using Form CT-01 along with the required information and documentation specified in Table 1 of the Third Schedule of the 2019-CTRules. Upon receipt of the application, the DHR’s Office of Ethics Committee Registration (designated authority) must grant provisional registration to the EC for a period of two (2) years. Final registration will be granted to the EC on Form CT-03 when the DHR has completed its review of the application and the associated documentation. The final registration will remain valid for a period of five (5) years from the date of its issue, unless suspended or cancelled sooner.

The EC may also apply to request registration renewal using Form CT-01 along with the specified documentation at least 90 days prior to the final registration’s expiration date. The final registration will remain in force until the DHR completes its review of the renewal application provided that the following conditions are met:

• The DHR does not require the EC to provide a new set of documents
• There have been no changes in the submitted documents since the final registration was granted, and
• The EC submits a certificate to the DHR validating that the documents have not changed

Following a review of the registration renewal application and further inquiry to confirm there have been no documentation changes, the DHR will renew the EC’s registration on Form CT-03 within 45 working days from the date of application receipt. The renewed registration will remain valid for five (5) years from the date of its issue, unless suspended or cancelled sooner.

The 2019-CTRules further states that if the EC fails to comply with any of the registration conditions, the DHR may, after giving the EC an opportunity to show cause as to why such an order should not be passed, prepare an order in writing to suspend or cancel the EC registration for such period as deemed appropriate. The suspended or cancelled EC can appeal to the DHR, and after consideration, the DHR may respond by taking one (1) or more of the following actions:

• Issue a warning to the EC describing the deficiency or defect observed, which may adversely affect the rights or well-being of the study participants
• Suspend the EC for a specified period or cancel the registration, or
• Debar its members from overseeing any future biomedical health research for a specified period

The aggrieved EC may file an appeal to the Government of India (Central Government) within 45 working days. In response to the appeal, as deemed necessary, and after giving the EC an opportunity to be heard, the Central Government may subsequently pass an order considered appropriate to the case.

(Note: The registration provisions for biomedical and health research ECs in Notice15Sept19 and IND-51 have not yet been aligned with the 2019-CTRules in terms of explaining the application submission process. The 2019-CTRules does not specify that the application submission process is electronic as is stated in Notice15Sept19 and IND-51. Further, only Notice15Sept19 and IND-51 specify that the DHR’s Office of Ethics Committee Registration is the designated authority. However, the ClinRegs team is regularly monitoring the CDSCO website for new developments and will post the most current sources as they become available.)

Additional Provisions for Clinical Trial and Biomedical and Health Research Ethics Committees

In addition to requiring all ECs to register with the relevant regulatory authority (the DCGI or the DHR), the G-ICMR specifies that ECs should be encouraged to seek recognition, certification, and accreditation from established national and international bodies (e.g., the SIDCER-FERCAP Foundation, the Association for the Accreditation of Human Research Protection Programs (AAHRPP), CDSCO, and the Quality Council of India through National Accreditation Board for Hospitals and Healthcare Providers (NABH), etc.). Although voluntary, the G-ICMR states that these certifications and accreditations should be continually updated to help with quality assurance and quality improvement and ensure that ECs comply with best practices to protect research participants.

Overview

There are no applicable regulations or guidance regarding the authorization of ethics committees (ECs) in Liberia. However, per G-NREB, the National Research Ethics Board of Liberia (NREB) is responsible for maintaining a registry of health research ECs and mitigating conflicts among ECs, researchers, and research entities.

Registration, Auditing, and Accreditation

No information is available on registration, auditing, and accreditation requirements.

Overview

In accordance with the 2019-CTRules, the Hdbk-ClinTrial, the G-ICMR, and IND-31, the sponsor (also known as the applicant) is required to submit a clinical trial application to the Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO), to obtain authorization to conduct a clinical trial in India. (Note: The DCGI is commonly referred to as the Central Licensing Authority in the Indian regulations.) The investigator must also obtain ethics committee (EC) approval from a DCGI-registered EC prior to initiating a study. According to IND-31, the DCGI review and approval process may be conducted in parallel with the EC review for each clinical trial site. However, per the 2019-CTRules and the Hdbk-ClinTrial, CDSCO must confirm the EC approvals for each participating site have been obtained per the protocol prior to approving the initiation of the study. (Note: the Hdbk-ClinTrial has not yet been updated to fully align with the 2019-CTRules.)

For specific guidelines regarding gene therapy and stem cell therapy clinical trial submissions, see G-GeneThrpy and G-StemCellRes.

Regulatory Submission

SUGAM Pre-Submission Registration

As explained in IND-42, CDSCO created the SUGAM portal (IND-59) to be used by applicants to apply for no objection certificates (NOCs), licenses, registration certificates, permissions, and approvals. Once submitted, applicants can track their applications, respond to queries, and download CDSCO issued permissions. According to IND-20, importers, Indian agents, foreign enterprises that hold an Indian subsidiary, and corporate users can register on the SUGAM portal (IND-59).

Per IND-42, users are required to complete a registration form requesting access to the SUGAM portal (IND-59) along with uploading the required identification (ID) documentation. IND-42 specifies that the authorized signatory/responsible person in an organization should complete the registration form. After registration is approved, the user is required to submit hard copies of identification (ID), proof of undertaking, and address to the CDSCO office. Registration will be approved by CDSCO only after evaluation of the submitted documents. IND-20 further notes that the email ID provided in the registration form should be an official email ID as all correspondence with CDSCO via the SUGAM portal (IND-59) will be completed using this registered email ID. Additionally, IND-20, the user will receive login credentials on the registered email ID after completion of the verification process from the CDSCO office. For detailed registration instructions, see IND-42 and IND-20.

NSWS Portal Pre-Submission Registration

Per Notice1Jan24, CDSCO launched the National Single Window System (NSWS) portal (IND-3) that will eventually serve as a one-stop shop for all approvals, licenses, registrations, and clearances. IND-24 further explains NSWS portal (IND-3) is a digital platform that is designed to integrate the services provided by various ministries, departments, and states thereby enabling users to identify and apply for regulatory approvals and registrations per their business requirements in a single location. According to IND-14, once the implementation process is completed, various regulatory documents including approvals, applications, and records will be accessible via the NSWS portal (IND-3). At this time, however, per Notice1Jan24 and Notice16Jan24, only a few CDSCO steps and processes (e.g., medical device related registration, manufacturing/import applications, and drug manufacturing/import applications) have been moved to the NSWS portal (IND-3). Per IND-24, while the NSWS portal (IND-3) does not charge a fee for registration, users are required to pay any fees required by CDSCO or any other ministry/department/state to process applications submitted for approval via the NSWS portal (IND-3).

IND-24 indicates that to access the NSWS portal (IND-3) services, users are required to sign up by registering with an email address and mobile phone, and then creating a business profile. As explained in IND-61, to complete the business profile, users are required to have a tax identification number known as a Permanent Account Number (PAN)). According to IND-33, a PAN is issued by the Income Tax Department within the Indian Ministry of Finance. Both domestic and foreign users can apply for a PAN using the appropriate application form.

Per IND-62 and IND-64, the user’s PAN will need to be verified using Digital Signature Certificate (DSC) for the created business profile. The steps involved in this process include adding authorized signatory information, registering the DSC, and verifying the PAN details against the registered DSC. IND-62 and IND-64 also note that users will need to have emBridge software installed on their computers to serve as a connecting link between the NSWS portal (IND-3) and DSC. Please refer to IND-62 and IND-64 for detailed instructions on completing this registration process which is required to apply for approval and registrations. See also IND-4 for a complete list of NSWS portal (IND-3) user guides.

Submissions

As indicated in the Notice15Jan18, all clinical trial application submissions must be submitted electronically via CDSCO’s SUGAM portal (IND-59). Refer to IND-42 for instructions on uploading forms and related documentation via the SUGAM portal (IND-59).

Per IND-7, CDSCO has introduced a new protocol for the submission of regulatory affairs related documents to facilitate the transition from hard copy to soft copy document submission. As explained in Notice12Oct23 and IND-7, effective immediately, CDSCO’s Clinical Research Unit (CRU) Division is requesting that stakeholders submit bulky dossiers, documents, query replies, and similar materials in soft copy format. The soft copies should be submitted in PDF format and ideally less 20 MB on a CD or pen drive to the CRU Division or submitted via email to cru.division@cdsco.nic.in. The files will then be forwarded to the appropriate Division along with the stakeholder’s cover letter.

The DCA-DCR delineates that English should be used for specific documents included in the clinical trial application submission. For the informed consent form and patient information sheet, English and/or the vernacular language of the participant(s) should be used. English should also be used for the package inserts.

In addition, per Notice31Jan24, CDSCO’s Subject Expert Committee (SEC) Division is responsible for conducting meetings to evaluate investigational new drug (IND) proposals. Applicants are requested to submit a copy of their proposal presentation only to the appropriate SEC division via the SUGAM portal (IND-59) after receiving an invitation letter from CDSCO, and well in advance of the scheduled meeting.

Ethics Review Submission

As indicated in the 2019-CTRules, the Hdbk-ClinTrial, the G-ICMR, and IND-31, India requires all clinical trials of drugs involving human participants to be reviewed by a DCGI-registered EC. Because the submission process at individual institutional ECs will vary, applicants should review and follow their institution’s specific requirements. The G-ICMR also specifies that investigators should submit research proposals as soft or hard copies to the EC Secretariat for review in the prescribed format and required documents as per EC standard operating procedures (SOPs).

Overview

In accordance with the LibCTReg and the G-LibClinTrial, the sponsor, the legal representative, the principal investigator (PI), or the sponsor-investigator is responsible for submitting a clinical trial application to the Liberia Medicines and Health Products Regulatory Authority (LMHRA) and obtain written permission from the National Research Ethics Board of Liberia (NREB). However, per the G-NREB, the PI must obtain ethics committee (EC) approval. The LibCTReg and the G-LibClinTrial state that the NREB and LMHRA reviews may be conducted in parallel. Per the G-LibClinTrial and the G-NREB, the LMHRA will only issue final approval once NREB approval is obtained.

Regulatory Submission

As indicated in the LibCTReg and the G-LibClinTrial, the sponsor or the representative should submit the application form and associated documents along with the prescribed fee. Also, per the G-LibClinTrial, four (4) sets of the application should be submitted both electronically and as printed copies to the LMHRA. The clinical trial application and any accompanying material must be submitted in English. If the documents are written in another language, a certified translation is required. Per LBR-29, the sponsor's representative must also submit a power of attorney attesting that the representative is a duly appointed agent.

Additionally, per the LibCTReg and the G-LibClinTrial, any substantial amendment to the approved clinical trial documentation, trial arrangements, and the investigational product must be submitted by the applicant to the LMHRA and the NREB together with the prescribed fee for the evaluation and authorization related to such amendment. Per the G-LibClinTrial, the submitted amendment(s) must be indicated in a signed cover letter identifying the clinical trial, the sponsor (applicant) and must include the possible consequences for the evaluation of the results. The amendment(s) must also be described in a completed Clinical Trial Amendment form (Annex 2 of the G-LibClinTrial), and the new version of the documents identified should include an updated version number and date. Also, the submitted document should clearly present scientific arguments justifying classification of an amendment to the LMHRA and the NREB, and, where applicable, supporting information must be included with the submission.

Per the G-LibClinTrial, the signed cover letter and clinical trial application dossier should be sent to the following:

The Managing Director
Liberia Medicine and Health products Regulatory Authority (LMHRA)
2^nd & 3^rd Floors Clay Building
Sekou Toure Avenue
Mamba Point
Monrovia, Liberia

Ethics Review Submission

National Research Ethics Board of Liberia

As delineated in the LibCTReg, application submissions to the NREB must include all of the information and documents as required for the board’s opinion. According to the G-NREB, PIs must submit typed, dated, and signed submissions electronically and by hard copy to the NREB. The documents should be formatted in standard font size 12, double-spaced, with the pages printed on one (1) side only. The NREB requires 15 comb-bound copies of the full research protocol along with the attachments listed in the G-NREB, and where applicable, an email version that includes the protocol title and the PI’s name. In addition, all protocols must be numbered appropriately and separately from all other supporting documentation (e.g., letters, participant information sheets and consent forms, questionnaires, curriculum vitae(s) (CVs), etc.). Supporting documents should also be numbered separately. Refer to LBR-32 for the NREB Research Protocol Template.

In addition to protocol submission requirements, the G-NREB also specifies that the complete application for ethical review and approval of a proposed health research study should be submitted by a PI to the NREB Secretariat. Applicants should submit the application three (3) weeks prior to the next NREB meeting. Applications submitted by a PI and researchers from foreign institutions must also include a local (resident) Liberian researcher on the research team as well as support letters and CV(s). See the G-NREB for detailed application submission requirements.

Per the G-NREB, NREB submissions should be submitted to the following address:

Director
National Research Ethics Board of Liberia (NREB)
First Floor West, John F. Kennedy Medical Center
Monrovia, Liberia
Email: nreb.liberia.gov@gmail.com

As delineated in the G-CTEmergncy, during a public health emergency in Liberia or in a neighboring country, the NREB requires protocols to be written in English and include, at a minimum, the proposed study, corresponding ethics approval, consent or assent forms, and data collection tools and forms. In addition, along with the usual documents for review (protocols, CVs, Human Subject Certificates, Good Clinical Practice, etc.), the following must be submitted:

• A collaboration letter (in the form of a memorandum of understanding) with sponsor institutions and research funders, including declarations of interest when possible
• A monitoring and safety management plan for the project provided by the PI and study sponsor
• Data-sharing and material transfer agreements for data and biological materials, especially if samples will be exported out of the country, ensuring compliance with the Laws of Liberia (a draft version may be submitted initially)
• Clear procedures for dissemination, publication, co-authorship, co-presentation, and intellectual property rights
• Plans to disseminate findings to the affected community, ensuring continued engagement and trust, especially among research participants
• Depending on the type of research, a local insurance policy for trials and interventions may be required

Atlantic Center for Research and Evaluation Institutional Review Board

As indicated in the G-ACRE-IRB, PIs are required to submit the research protocol as part of an application packet that includes the documentation specified by the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB) submission form (see Article XXV in the G-ACRE-IRB). (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.) According to LBR-28, the ACRE IRB has not reinstated the requirement for PIs to submit eight (8) hard copies of the protocol. Applications should be submitted electronically. See the Submission Content section for additional documentation requirements.

Per the G-ACRE-IRB, all research proposals are to be submitted (either via electronic mail or in person) to:

The IRB Coordinator
Atlantic Center for Research and Evaluation (ACRE)
Ground Floor, Graduate School Building
University of Liberia
Capitol Hill
Monrovia, Liberia

Proposals submitted electronically should be sent to jktegli@yahoo.com and ulpireirb@gmail.com.

Regulatory Authority Requirements

As per the 2019-CTRules, the Hdbk-ClinTrial, IND-32, and IND-35, documentation must be submitted to the Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO), as part of the approval process for investigational new drugs (INDs) will depend upon the type of application, phase of the study, stage in drug development process, and/or objective of the study. Information that may be required is included in the lists below (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• Form CT-04 (the clinical trial application form including sponsor (also known as applicant) name; sponsor nature/constitution and contact information; clinical trials site contact information and details; contact information for person responsible for compensation payment, if any; correspondence address; new drug/investigational new drug name(s) and details (i.e., therapeutic class, dosage form, composition, and indications); clinical trial phase; protocol number with date; and ethics committee (EC) and investigator names)
• Treasury Challan receipt demonstrating payment of corresponding fee or transaction ID
• Chemical and pharmaceutical information
• Animal pharmacology data
• Animal toxicology data
• Human clinical pharmacology data
• Active ingredient information (for INDs and global clinical trials (GCTs))
• Formulation data (for INDs and GCTs)
• Therapeutic class (for INDs and GCTs)
• Regulatory status in India and in other countries
• Proposed study status in other participating countries and any approvals, withdrawals, discontinuation of approval, etc. (for GCTs)
• Affidavit stating study has not been discontinued in any country (for GCTs)
• Prescribing information
• Testing protocol(s) for quality control testing
• Clinical study protocol
• Dosage form
• Justification and schematic diagram/flow chart proposed study and design (for INDs and GCTs)
• Number of patients globally (for GCTs) and number of patients to be enrolled from India (for INDs and GCTs)
• Details of all sites selected and assessment for suitability of sites and investigators (with contact details)
• EC registration status of the selected sites
• Relevance of study, investigational drug, or any specific study aspects to the health care needs of India
• Innovation vis-à-vis existing therapeutic options
• Unmet medical need in the country (as applicable)
• Any India-specific safety/dosage concerns/investigational tests to be done
• Clinical study reports should be submitted per the International Council for Harmonisation (ICH) Common Technical Document (CTD) (IND-68)
• Protocol safety measures per toxicological studies; early clinical studies, approved product insert for marketed product, and published literature
• Investigator’s Brochure (IB)
• Investigational Medicinal Products Dossier (IMPD) (for (GCTs))
• Affidavit stating the IB information is correct and based on facts (for GCTs)
• Source of bulk drugs (for INDs)
• Treasury Challan with Application for Grant of License to Import New Drug or Investigational New Drug for Clinical Trial or Bioavailability or Bioequivalence Study or for Examination, Test and Analysis (CT-16) (IND-11) (for GCTs)
• Sponsor authorization letter (for GCTs)
• Details of biological specimens to be exported and the online application for export no objection certificate (NOC) for biological samples on the SUGAM portal (IND-59) (for GCTs) (See IND-1 for the application form to request a NOC to export biological samples) (Refer to the Specimens topic for more information on specimen import/export)
• Case Report Form (CRF)
• Informed consent form (ICF) and patient information sheet (See Required Elements section for additional information)
• Investigator(s) undertaking
• EC approvals (if available)
• Clinical study report(s)
• Investigator list in India and site address

See the 2019-CTRules, the Hdbk-ClinTrial, IND-32, and IND-35 for detailed DCGI application submission requirements. See also IND-22 for details on the IND-59 approval process for GCTs and IND-31 for clinical trial FAQs. (Note: The Hdbk-ClinTrial has not yet been updated to fully align with the 2019-CTRules.)

Refer to the 2019-CTRules and IND-31 to obtain detailed submission requirements for applications to conduct a clinical trial using an already approved new drug with a new indication, a new dosage form/new route of administration, a modified release dosage form, or a new drug with an additional strength.

Ethics Committee Requirements

Each institutional EC has its own application form and clearance requirements, which can differ significantly regarding the number of copies to be supplied and application format requirements. However, per the G-ICMR, the requirements listed below are basically consistent and shared by all of the Indian ECs:

• Cover letter to the Member Secretary
• Type of review requested
• Application form for initial review (IND-39)
• Informed consent document (in English and the local language(s)) including translation and back translation certificates, if applicable
• Case record form/questionnaire
• Recruitment procedures (e.g., advertisement, notices) if applicable
• Patient instruction card, diary, etc., if applicable
• IB (as applicable for drugs, biological, or device trials)
• Details of funding agency/sponsor and fund allocation, if applicable
• Investigators’ Curriculum Vitaes (CVs)
• Conflict of interest statement, if applicable
• Good Clinical Practice (GCP) training certificate for investigators (preferably within last five (5) years)
• Any other research ethics/other training evidence, if applicable as per EC standard operating procedures (SOPs)
• List of ongoing research studies undertaken by the principal investigator, if applicable
• Investigator’s undertaking statement with all participating investigator signatures
• Regulatory permissions (as applicable)
• Relevant administrative approvals (such as Health Ministry’s Screening Committee (HMSC) approval for international trials)
• Institutional Committee for Stem Cell Research (IC-SCR) Registration (IND-72), if applicable
• Memorandum of Understanding (MoU) in case of studies involving collaboration with other institutions, if applicable
• Clinical trial agreement between the sponsors, investigator, and the head of the institution(s), if applicable
• Clinical trial registration documentation (preferable)
• Insurance policy (it is preferable to have the policy as well as the insurance certificate) for study participants indicating conditions of coverage, date of commencement and date of expiry of coverage of risk (if applicable)
• Indemnity policy, clearly indicating the conditions of coverage, commencement date, and expiry date of risk coverage (if applicable)
• Any additional document(s), as required by EC (such as other EC clearances for multicentric studies)
• Protocol

Furthermore, the ICMR has prepared a generic application for initial review (IND-39) that may be used by the EC. The form is also included in the bulleted list above.

Clinical Protocol

As delineated in the 2019-CTRules, the Hdbk-ClinTrial, and the G-ICMR, the clinical study protocol should include the following elements:

• Title page
• Table of contents
• Brief summary (See G-ICMR)
• Study rationale
• Study objective
• Study design and methodology
• Study population
• Justification of inclusion/exclusion of vulnerable populations (See G-ICMR)
• Participant eligibility and recruitment procedures
• Study assessments
• Study conduct stating the types of activities that would be included (e.g., medical history, type of physical examination, etc.)
• Study treatment
• Ethical consideration
• Study monitoring and supervision
• Investigational product management (See Investigational Products topic for detailed coverage of this subject)
• Data analysis
• Undertaking by the Investigator statement
• Appendices

The G-ICMR also mentions the following requirements:

• Study duration
• Justification for placebo, benefit-risk assessment, plans to withdraw; if standard therapies are to be withheld, justification for the same
• Informed consent procedure and sample of the patient/participant information sheet and informed consent forms including audiovisual recording, if applicable, and informed consent for stored samples
• Plan to maintain the privacy and confidentiality of the study participants
• Adverse events/adverse drug reactions
• For research involving more than minimal risk, an account of management of risk or injury
• Proposed compensation, reimbursement of incidental expenses and management of research related injury/illness during and after research period
• Provision of ancillary care for unrelated illness during the duration of research
• Account of storage and maintenance of all data collected during the trial
• Plans for publication of results while maintaining confidentiality of participants’ personal information/identity

For detailed information on these elements, see the 2019-CTRules, the Hdbk-ClinTrial, and the G-ICMR.

Regulatory Authority Requirements

As set forth in the LibCTReg and the G-LibClinTrial, the sponsor, the legal representative, the principal investigator (PI), or the sponsor-investigator is required to obtain clinical trial authorization from the Liberia Medicines and Health Products Regulatory Authority (LMHRA) and written permission from the National Research Ethics Board of Liberia (NREB). However, per the G-NREB, the PI must obtain ethics committee (EC) approval.

As per the LibCTReg and the G-LibClinTrial, the following documentation must be submitted to the LMHRA (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• Cover letter (signed, witnessed, and notarized) including list of documents submitted and their version numbers and date
• Clinical trial application form including cover page
• Clinical trial protocol (see below for detailed protocol requirements)
• A list of the planned clinical trial sites and the planned number of study participants to be recruited at the sites located in Liberia
• Details of the site(s) where the trial is to be conducted and a duly justified written statement on the suitability of the clinical trial sites adapted to the nature and use of the investigational product (IP) and including a description of the suitability of facilities, equipment, human resources, and description of expertise, issued by the head of the clinic/institution at the trial site or by some other responsible person
• Participant information sheet, informed consent form(s) (ICF(s)) or video(s), or assent form(s) in case of minor(s) or persons under legal disability who are to participate in the trial, and informed consent procedure for clinical trials in humans
• Product information if the IP is registered (summary of product characteristics, patient information leaflet/package insert and labelling)
• Investigator’s Brochure (IB) containing relevant chemical, pharmaceutical, pre-clinical pharmacological and toxicological data, and where applicable, human or animal pharmacological and safety and efficacy clinical data about the IP
• If applicable, synopsis of previous trials with the IP(s)
• If applicable, electronic copies of key, peer-reviewed publications following the International Committee of Medical Journal Editors (ICMJE) recommendations to support the application
• Copy or copies of recruitment advertisement(s), if applicable, and questionnaires
• Investigational medicinal product (IMP) dossier, if applicable
• Product information and certificate of analysis (CoA) for the concomitant and rescue medications
• Good Manufacturing Practice (GMP) certificate issued from the national regulatory authority of the country where the IP is manufactured, translated into English language
• CoA of the IP(s)
• Certificate(s) of accreditation for the central laboratories
• Workload forms for investigators
• Signed declaration by the applicant (includes a commitment to adhere to the ethical principles outlined in the Declaration of Helsinki (LBR-27) and the International Council for Harmonisation (ICH)’s Guideline for Good Clinical Practice E6(R2) (LBR-8)
• Signed declaration by the national PI
• Signed curriculum vitae (CV) for all key staff participating in the conduct of the clinical trial (e.g., PI and/or co-investigators, study coordinator, regional and local monitor, contract research affiliate, etc.)
• Signed declaration(s) by each investigator(s)
• Signed joint financial declaration between the sponsor and the PI
• Signed declaration by the sub-investigators and key staff participating in the trial
• Signed declaration by the regional clinical trial monitor(s)
• Signed declaration by the sponsor/sponsor-investigator
• Proof of registration with the Pan African Clinical Trials Registry (PACTR) (LBR-36) or another World Health Organization (WHO) Primary Registry (LBR-35)
• Active clinical trial insurance (Phase I, II, and III)
• Evidence of Insurance coverage for prospective participants
• Proof of sponsor indemnification for investigators and trial site
• Good Clinical Practice (GCP) certificates for the investigators
• Proof of registration of the key investigators with a professional statutory body, if applicable
• Proof of residence in Liberia for the PI
• Proof of professional indemnity (i.e., malpractice insurance)
• Study budget
• In case of parallel submission, proof of submission of the clinical trial application to the National Research Ethics Board of Liberia (NREB)
• The written permission of the NREB in case of sequential submission, and in case of parallel submission, the updated versions of documents or information as requested by the NREB, for the conduct of the clinical trial, if applicable
• Information on the composition of the Data and Safety Monitoring Board (DSMB)—including the list, terms of reference, and CVs for its members—justifying their expertise as members of the DSMB
• Summary of product characteristics or other professional information for all registered medicines used in the trial, or the international equivalent thereof if the medicines are not registered in Liberia
• Registered IPs should include registered indication or registered dosage regimen
• Recruitment arrangements
• Request for authorization of export of biological samples out of Liberia as well as the respective material transfer agreement, if applicable
• Summary of the clinical trial (100-150 words) to be made publicly available on the LMHRA website
• Proof of payment of the appropriate application fee

Refer to the LibCTReg and the G-LibClinTrial for detailed application requirements and expedited application documentation requirements.

The LibCTReg also notes that in the case of emergency situations, the LMHRA may also make exemptions to the documentation requirements for the submission of clinical trial applications. Refer to 2.3 of the G-LibClinTrial for additional information on how to submit an expedited clinical trial application package.

Ethics Committee Requirements

National Research Ethics Board of Liberia

As indicated in the G-NREB, for clinical trials and biomedical/epidemiological study submissions, the following documents may be included, but are not limited to:

• Full protocol and executive summary (refer to LBR-32 for research protocol template)
• Sponsor’s protocol, if applicable (per LBR-32)
• Signed agreement between sponsors and PI, where applicable
• A statement that the researcher(s) agree to comply with ethical principles set out in relevant guidelines
• IB
• Material Transfer Agreement (MTA) for shipment of specimen(s)/biological material(s) outside of Liberia, where applicable (See also Specimen Import & Export and Consent for Specimen sections)
• Data Sharing Agreement, where applicable
• Administrative information on sponsors of the study
• Signatory page of key persons from the collaborative institutions involved in the study (i.e., Sponsor Signatory Approval Page duly signed, with date, where applicable)
• Written ICF with dates and version number and translations into the local language, where necessary
• Written parental consent form for children under 17 years of age (if study involves minors)
• Written parental consent form and assent form for children under 18 years of age (15-17 years) (if study involves adolescents)
• All forms, documents, and community engagement advertisements to be used in the recruitment of potential participants
• All data collection forms to be used in the research including, but not limited to, case report forms, questionnaires, interview schedules, etc., clearly indicated and dated
• Referral forms for treatment, where applicable
• Study budget
• Study timeline
• Any other information deemed necessary to facilitate the review process
• Current CV(s) of PI and co-investigator(s) if not submitted to the NREB in the preceding 12 months
• Profile on previous study (i.e., Phase I & Phase II studies, where applicable)
• Investigator Agreement (PI’s responsibility), page duly signed with name and date, and current Certificate of Training in GCP for PI(s)
• DSMB membership and charter of work/current member CVs
• Insurance coverage for study participants
• Scientific review approval
• LMHRA approval letter for use of the IPs/devices and clinical trial approval (this should be submitted after the NREB approval)

Atlantic Center for Research and Evaluation Institutional Review Board

Per the G-ACRE-IRB, the following documentation must be submitted along with the application for an initial application review of a protocol for clinical research other than a clinical trial (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.):

• Cover letter
• Protocol summary (Article XXV (Section 25.02) in the G-ACRE-IRB)
• Protocol and/or amendments (including data collection instruments, surveys, tests, questionnaires, debriefing information, etc.)
• IB, where applicable
• Evidence of submission and/or approval from other ECs, where applicable
• Proof of research ethics training (i.e., certificate in human subject protection) by research team members
• ICFs, where applicable
• Questionnaires and other study instruments, where applicable (including interview schedules, recruitment and interview scripts, and recruitment materials (Article XXV (Section 25.02) in the G-ACRE-IRB)
• DSMB and Institutional Biosafety Committee (IBC) records, if applicable
• MTA, if applicable (See also Specimen Import & Export and Consent for Specimen sections)
• Status report for ongoing study (applicable for continuing review)
• Letter of collaboration or support with collaborating entity/researcher(s), if applicable
• Capacity building plan for collaborating agency/researcher, if applicable
• Investigator(s) CVs
• Social corporate responsibility plan for communities, if applicable
• Letter from an appropriate official permitting research activities on their premises, if the research/recruitment will take place in or through schools, businesses, care facilities, or other organizations
• Budget

Clinical Protocol

Liberia Medicines and Health Products Regulatory Authority

Per the G-LibClinTrial, the contents and format of the clinical trial protocol should follow the requirements laid down in LBR-8. Accordingly, LBR-8 requires the following protocol contents:

• General information (protocol title, identifying number, and date; contact information for the sponsor, medical expert, investigator(s), trial site(s), qualified physician(s), and laboratory and/or institutions involved in the study)
• Background information
• Objectives and purpose
• Trial design
• Selection, withdrawal, and treatment of participants
• Assessment of efficacy
• Assessment of safety
• A description of the statistical methods to be used in the trial
• Direct access to source data and documents
• Quality control and quality assurance
• Ethical considerations
• Data handling and recordkeeping
• Publication policy

In addition, as indicated in the G-LibClinTrial, the protocol should contain a statement that the trial will be conducted in compliance with the protocol, GCP, and the applicable regulatory requirements, and signed and dated by both the sponsor/sponsor’s representative and PI to document the investigator’s and sponsor’s agreement to the protocol. If the protocol is not signed and dated by both parties, a corresponding declaration that is signed and dated by both must be provided to the LMHRA with the application.

National Research Ethics Board of Liberia

The LBR-32 requires the following elements to be included in the research protocol template submission:

• Specific aims
• Background and significance of research
• Research locations and collaborating sites
• Study team
• Study design
• Recruitment methods
• Consent process
• HIPAA privacy protections
• Vulnerable populations
• Risks
• Benefits
• Participant privacy
• Data confidentiality
• Data/statistical analysis plan
• Costs and compensation
• Sharing study results
• Research related injuries
• Reportable events
• Regulatory compliance
• Data or specimen banking (repositories)
• Clinical trials
• Device, if applicable
• Drug/biologic

National Research Ethics Board of Liberia/Atlantic Center for Research and Evaluation Institutional Review Board

Per the NatResHlthPlcy, Liberian ECs including the NREB and the ACRE IRB, should structure the research protocol according to the follow format:

• Title
• Investigators’/Researchers’ information including contact addresses
• Abstract/Summary
• Background/Introduction
• Aims and objectives
• Study design and methods
• Data collection, management, and analysis
• Study administration and ethical issues
• Resource requirements
• Study plan
• Supervision
• Dissemination and outcome

For more details, see Annex 2 of the NatResHlthPlcy.

Atlantic Center for Research and Evaluation Institutional Review Board

According to the G-ACRE-IRB, the clinical research protocol should contain the elements included in the ACRE IRB submission form (see Article XXV in the G-ACRE-IRB). The initial protocol submission should also contain:

• Original protocol (including cover sheet, abstract, and research section including the Human Subjects Section)
• Application letter
• ICF and/or assent form
• Sample questions survey
• Investigator(s) CVs
• Qualification of study site(s)
• Protocol budget
• Copy of ACRE IRB approval, if available
• Study design
• Study participation, including informed consent procedures and content/language and participant information sheet content (See also the Documentation Requirements section)

Note: Per the G-ACRE-IRB, for regular renewal or interim modification reviews of a protocol, PIs should attach current consent document(s) and include instruments ONLY if changes are being proposed (Article XXV (Section 25.02) in the G-ACRE-IRB).

Overview

Based on the 2019-CTRules, the Hdbk-ClinTrial, the G-ICMR, and IND-31, the review and approval of a clinical trial application by the Drugs Controller General of India (DCGI), head of the Central Drugs Standard Control Organization (CDSCO), is dependent upon obtaining ethics committee (EC) approval from a DCGI-registered EC prior to initiating a study. (Note: The DCGI is commonly referred to as the Central Licensing Authority in the Indian regulations.) According to IND-31, the DCGI review and approval process may be conducted at the same time as the EC review for each clinical trial site, except in the case of non-regulatory academic clinical trials that only require EC approval. However, per the 2019-CTRules and the Hdbk-ClinTrial, CDSCO must confirm the EC approvals for each participating site have been obtained per the protocol prior to approving the initiation of the study. (Note: the Hdbk-ClinTrial has not yet been updated to fully align with the 2019-CTRules.)

Regulatory Authority Approval

As specified in the 2019-CTRules and IND-31, upon receipt of a clinical trial application , the DCGI has 90 calendar days to evaluate the application for a new drug or an investigational new drug; 90 calendar days to evaluate a new drug already approved outside India; and 30 days to evaluate a drug discovered, researched, and manufactured in India. Per the Hdbk-ClinTrial, upon receipt of an application, a CDSCO official conducts the initial administrative review. If the application is deemed complete, within four (4) weeks following receipt, the official forwards the application along with a summary of their evaluation and a statement referring the proposal to a Subject Expert Committee (SEC) for further technical review.

The 2019-CTRules further notes that the DCGI may, when required, constitute one (1) or more of these expert committees or group of experts with the specialization in relevant fields to evaluate scientific and technical drug-related issues. The committee/group may submit its recommendations within 60 days from the date of the request. See the Scope of Assessment section for more information on SEC composition and review processes.

Once the SEC has completed its review, the Hdbk-ClinTrial indicates that the committee sends its comments via email to CDSCO. CDSCO will then compile any written SEC comments requiring sponsor (also known as applicant) clarification or modification and send this feedback to the sponsor within one (1) week of receipt. The applicant must submit a written reply to CDSCO within four (4) weeks of receiving the comments, which will, in turn, be sent to the SEC for review.

Following receipt of the sponsor’s response, the DCGI (CDSCO) will issue a final decision by official communication (permission, rejection, or resubmission) to the Technical or Apex Committee within 15 days. In the case of a sponsor’s request for reconsideration, CDSCO will review the resubmitted application and send it to the SEC again or to the Technical Committee per the sponsor’s request. Following the SEC’s review, the DCGI (CDSCO) will send a final decision to the Technical or Apex Committee within 15 days. If CDSCO rejects the reconsideration request, the agency will send a letter to the sponsor to communicate this decision. Refer to the Hdbk-ClinTrial for additional timeline information.

See also IND-22 for details on the SUGAM portal (IND-59) approval process for global clinical trials, and IND-46 for additional information on conducting clinical trials in India.

Per the 2022-CTRules-3rdAmdt, which amends the 2019-CTRules, provided that no communication has been received from the DCGI within the stated period of 90 working days, permission to conduct all new drug or investigational new drug clinical trials as well as clinical trials for new drugs already approved outside India will be deemed granted by the DCGI. This permission will be regarded as legally valid for all purposes and the applicant will be authorized to initiate a clinical trial in accordance with these rules. Similarly, per the 2019-CTRules and IND-31, if the DCGI does not respond within 30 days to applications for drugs developed in India, the sponsor may conclude that permission to conduct the trial has been granted. Refer to the Scope of Assessment section for information on obtaining a waiver for an already approved drug. See also the Manufacturing & Import section for detailed information on import requirements for new drugs already approved outside of India.

For specific guidelines regarding gene therapy and stem cell therapy clinical trials, see the G-GeneThrpy and the G-StemCellRes.

(See also the Submission Process and Submission Content sections for detailed submission requirements.)

Ethics Committee Approval

As per IND-9, the EC review and approval process, which occurs at the same time as the DCGI review and approval, generally takes from four (4) to six (6) weeks. Many study sites also have scientific review committees (SRCs) review the scientific justification of the study. Once the SRC approves the study, it is submitted to the EC for its review and approval.

The G-ICMR indicates that EC members should be given enough time (at least one (1) week) to review the proposal and related documents, except in the case of expedited review. While all EC members should review all submitted proposals, each EC may adopt different procedures for protocol review per their standard operating procedures.

Overview

According to the LibCTReg and the G-LibClinTrial, the National Research Ethics Board of Liberia (NREB) and the Liberia Medicines and Health Products Regulatory Authority (LMHRA) reviews may be conducted in parallel. However, per the G-LibClinTrial and the G-NREB, the LMHRA will only issue final approval once NREB approval is obtained.

Regulatory Authority Approval

The LibCTReg and the G-LibClinTrial indicate that upon receipt of a clinical trial application, the LMHRA screens the application package for completeness and must inform the applicant in writing about the validity of the application or the formal grounds for non-acceptance of the application within 10 working days of application receipt. If applicable, the applicant, in turn, must address formal grounds for non-acceptance within 10 working days.

The LibCTReg and the G-LibClinTrial further explain that after validation of a complete clinical trial application, the LMHRA must inform the applicant in writing about the outcome of the scientific assessment of the application within a maximum of 60 working days, or according to the following timeline for the different types of investigational products (IPs), unless otherwise specified by the LMHRA on a case-by-case basis:

• Pharmaceutical IPs: 45 working days
• Biological and biotechnology IPs: 60 working days
• Genetically modified organism IPs: 90 working days

As indicated in the LibCTReg and the G-LibClinTrial, these timelines exclude time taken for the applicant to respond to queries from the LMHRA during the review and decision process. If changes are required and the applicant fails to modify the application within a maximum of 30 working days, the application will be rejected. Per the G-LibClinTrial, during the clinical trial scientific assessment process, the LMHRA may request additional documents or changes through a query letter. Once a query has been raised and issued to the applicant, the process stops when the LMHRA receives a written response to the query. If the LMHRA requires changes to the application, and the applicant fails to modify the application within a maximum of 90 days, the application will be rejected.

As explained in the G-LibClinTrial, the LMHRA must issue a clinical trial certificate indicating the LMHRA clinical trial number to the applicant upon application approval. The clinical trial certificate may contain conditions required by the LMHRA with respect to the conduct or reporting of the trial. If the application is rejected, the applicant can submit a written appeal to the LMHRA’s Managing Director within 60 days of receipt of the rejection notice.

Per the G-LibClinTrial, in the case of expedited clinical trial application reviews, the LMHRA will review the application in no more than 14 working days for approved products and within 21 days for new products.

Additionally, per the G-LibClinTrial, the LMHRA must respond to any substantial clinical trial amendment within 20 calendar days upon receipt of the written decision from the NREB.

Ethics Committee Approval

National Research Ethics Board of Liberia

Pursuant to the G-NREB, principal investigators (PIs) are required to submit new research protocols no later than one (1) month prior to the next bi-monthly board meeting. The NREB should notify PIs in writing of its decision within two (2) weeks following a board meeting, where applicable, following a complete review of the protocols. The G-NREB does not specify an approval expiration date.

The G-NREB explains that for protocol amendments, the NREB Secretariat, in consultation with the Chair, will make a determination regarding the type of review (full board review or expedited given the risk) and will notify the investigator within three (3) weeks upon submission per the board’s decision. Expedited reviews must take no more than three (3) weeks, and if any committee member raises a concern about a protocol that was expedited, the protocol must undergo a full board review.

Refer to the G-NREB for additional information on the various submission types that may be submitted to the board and their corresponding review and approval processes.

Atlantic Center for Research and Evaluation Institutional Review Board

As specified in the G-ACRE-IRB, PIs are required to submit all application materials to the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB) four (4) weeks in advance of the date that a decision is requested. (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.) In the case of full review studies, submission is required four (4) weeks prior to the next scheduled ACRE IRB meeting. The ACRE IRB will convene a special meeting, if necessary, to accommodate the PI’s compliance with an external funding deadline; however, submission is required four (4) weeks prior to the special meeting date.

As specified in the G-ACRE-IRB, the ACRE IRB approval will commence on the day the study is approved and will expire within a defined time period based on a risk assessment and regulations. If specific conditions are stipulated in the approval letter, those conditions must be met by the designated date or approval may be withdrawn. No timeline of review is specified for the ACRE IRB’s review. However, the G-ACRE-IRB states that the clinical research protocol and accompanying documents are approved as they are submitted.

The G-ACRE-IRB states that the ACRE IRB must also review and approve any clinical research protocol amendments prior to those changes being implemented. The clinical research protocol submission is reviewed either via expedited procedures (for minor changes) or via full board review (for all other changes). Refer to the G-ACRE-IRB for clinical research protocol amendment documentation submission and procedural requirements.

Overview

As set forth in the 2019-CTRules, the Hdbk-ClinTrial, the G-ICMR, and IND-31, a clinical trial can only commence in India after the sponsor (also known as applicant) receives permission from the Drugs Controller General of India (DCGI) and approval from the respective ethics committees (ECs). The DCGI is head of the Central Drugs Standard Control Organization (CDSCO) and is commonly referred to as the Central Licensing Authority in the Indian regulations. According to the 2019-CTRules and IND-31, non-regulatory clinical trials intended for academic/research purposes only require institutional EC approval. (See the Scope of Review section for additional details). There is no waiting period required following the sponsor’s receipt of these approvals. (Note: the Hdbk-ClinTrial has not yet been updated to fully align with the 2019-CTRules.)

The 2022-CTRules-3rdAmdt, which amends the 2019-CTRules, further indicates that once the sponsor obtains approval from the DCGI for a new drug, an investigational new drug, or a new drug already approved outside India, the sponsor must notify CDSCO via Form CT-06A prior to initiating the clinical trial. The DCGI will then record the information provided on the form and it will become part of the official record known as the automatic approval of the DCGI.

In addition, per the 2019-CTRules and IND-31, the sponsor is required to obtain approval from the DCGI to manufacture or import investigational products (IPs) and to obtain an import license for the shipment of IPs to be used in the trial. (See the Manufacturing & Import section for additional information.)

As explained in the 2019-CTRules and IND-31, the EC should notify the DCGI about the academic trials it has approved and about cases where there could be an overlap between a clinical trial for academic and regulatory purposes. If the DCGI does not provide comments to the EC within 30 days from receiving EC notification, then it should be presumed that DCGI permission is not required.

For specific guidelines regarding gene therapy and stem cell therapy clinical trials, see G-GeneThrpy and G-StemCellRes.

Clinical Trial Agreement

According to the 2019-CTRules, the sponsor must have an agreement with the investigator, which is to be provided to the EC. Furthermore, the investigator must sign an undertaking to conduct the trial in accordance with the protocol, good clinical practice guidelines, and all applicable requirements, among other things. For more details, see Table 4 (Third Schedule) in the 2019-CTRules.

Clinical Trial Registration

Per the 2019-CTRules, the G-ICMR, and IND-31, it is mandatory for all sponsors to register their clinical trials, including academic trials, with the Indian Council of Medical Research (ICMR)’s Clinical Trials Registry - India (CTRI) (IND-57) before initiating a study. Refer to the Scope of Review and Submission Process sections for further information on academic trials.

According to IND-56, registrants are advised to factor in a minimum of 10 to 15 working days for trial review, verification, and validation and the submission must indicate “Not Yet Recruiting” for the trial’s status. A REF number is issued to those registrants who have successfully submitted a trial to IND-57.

In addition, per IND-10, the ICMR has agreed to adopt the United Nation’s recommendations to register and publicly disclose results from all funded or supported clinical trials. The ICMR, along with other participating healthcare bodies, plans to develop and implement policies that require all trials they fund, co-fund, sponsor, or support to be registered in a publicly available registry. All study results will also be released within specified timeframes on the registry or through scientific journal publications.

See the 2019-CTRules, the Hdbk-ClinTrial, IND-32, and IND-35 for detailed DCGI application submission requirements.

Overview

In accordance with the LMHRA-Act, the LibCTReg, and the G-LibClinTrial, a clinical trial can only commence after the sponsor or the representative receives authorization from the Liberia Medicines and Health Products Regulatory Authority (LMHRA). The LibCTReg and the G-LibClinTrial, in turn, state that the sponsor, the legal representative, the principal investigator (PI), or the sponsor-investigator must obtain written permission from the National Research Ethics Board of Liberia (NREB). In addition, per the G-LibClinTrial, the appointed PI must provide proof of residency in Liberia in the clinical trial application submission package.

As per the G-LibClinTrial, the sponsor or the representative is required to obtain LMHRA approval for the clinical trial before the import of an investigational product (IP) to be used in the trial is authorized. However, parallel submission for approval of the clinical trial and the permit to import the IP is possible if the import permit application is included in the clinical trial application submission package.

In addition, per the LibCTReg, the applicant must inform the LMHRA in writing of the exact clinical trial commencement date (i.e., first patient first visit). If the trial does not begin within 90 calendar days from issuance of the clinical trial certificate, the applicant must show cause for the failure to commence as scheduled and solicit issuance of a new clinical trial certificate. Pursuant to Part VIII of the LMHRA-Act, the LibCTReg delineates that failure to inform the LMHRA of the commencement or not starting the clinical trial within this period will have regulatory implications including, but not limited to, the payment of administrative charges for the re-issuance of the clinical trial certificate on its expiration.

The LibCTReg also states that the sponsor, the investigator, and all of the persons involved in the clinical trial must fulfill the requirements of good clinical practice in accordance with the International Council for Harmonisation’s Guideline for Good Clinical Practice E6(R2) (LBR-8) and the World Health Organization (WHO)'s Guidelines for Good Clinical Practice (GCP) for Trials on Pharmaceutical Products (LBR-25) as determined by the LMHRA. The G-LibClinTrial further specifies that the LMHRA has adopted LBR-8 for use along with the LMHRA guidelines.

Clinical Trial Agreement

While a signed clinical trial agreement is not an official requirement, the G-LibClinTrial states that the protocol should contain a statement that the trial will be conducted in compliance with the protocol, LBR-8, and the applicable regulatory requirements. The protocol should also be signed and dated by both the sponsor or the representative and the PI to document the investigator’s and the sponsor’s agreement to the protocol. If the protocol is not signed and dated by both parties, a corresponding declaration signed and dated by both must be provided to the LMHRA with the application.

Clinical Trial Registration

As delineated in the LibCTReg, the sponsor or the sponsor-investigator must register all clinical trials with a public international database. The G-LibClinTrial further specifies that the LMHRA requires the sponsor or the representative to provide proof of registration with the Pan African Clinical Trials Registry (PACTR) (LBR-36) or another WHO Primary Registry (LBR-35).

Safety Reporting Definitions

In accordance with the 2019-CTRules, the G-ICMR, and IND-42, the following definitions provide a basis for a common understanding of India’s safety reporting requirements:

• Adverse Event (AE) – Any untoward medical occurrence (including a symptom/disease or an abnormal laboratory finding) during treatment with a pharmaceutical product in a patient or a human participant not necessarily related to the treatment
• Adverse Drug Reaction (ADR) – a noxious and unintended response at doses normally used or tested in humans (in cases of approved pharmaceutical products); a noxious and unintended response at any dose(s) (in cases of new unregistered pharmaceutical products); an untoward medical occurrence seemingly caused by overdosing, abuse/dependence and interactions with other medicinal products (in clinical trials)
• Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (SADR) – an AE or ADR that is associated with death, in-patient hospitalization (in case the study was being conducted on outpatients), prolongation of hospitalization (in case the study was being conducted on in-patients), persistent or significant disability or incapacity, a congenital anomaly or birth defect, or is otherwise life threatening. Per IND-42, Important Medical Events may be considered SAEs when they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one (1) of the outcomes listed in this definition
• Unexpected Adverse Drug Reaction – an ADR, the nature or severity of which is not described in the informed consent/information sheet or the applicable product information, such as an investigator’s brochure (IB) for the unapproved investigational product (IP) or package insert/summary of product characteristics for an approved product (G-ICMR)

Safety Reporting Requirements

Per the 2019-CTRules, the sponsor (also known as applicant) and the investigator must forward any SAE/SADR report, after due analysis, within 14 days of the occurrence to the Drugs Controller General of India (DCGI), the ethics committee (EC) Chairman, and the head of the institution where the trial is being conducted. (Note: The DCGI is head of the Central Drugs Standard Control Organization (CDSCO) and is commonly referred to as the Central Licensing Authority in the Indian regulations.)

In the event of an SAE/SADR resulting in death, per the 2019-CTRules, the sponsor or the representative and the investigator must forward the SAE/SADR reports to the DCGI within 14 days of knowledge of this occurrence. The 2019-CTRules and IND-42 also indicate that the EC is also required to forward its report along with its opinion on financial compensation, if any, to be paid by the sponsor or the representative, to the DCGI within 30 days of the incident.

See Table 5 of the 2019-CTRules for details on the data elements required for reporting SAEs/SADRs that occur during a clinical trial.

See the Insurance & Compensation section for additional information on sponsor compensation requirements.

Investigator Responsibilities

As indicated in the 2019-CTRules, the G-ICMR, and IND-42, the investigator must report all SAEs/SADRs to the DCGI, the sponsor or the representative, and the EC, within 24 hours of occurrence. Per the 2019-CTRules, in the event that the investigator fails to report any SAE/SADR within the stipulated period, the investigator is then required to provide reasons for the delay to the DCGI along with the SAE/SADR report for the DCGI’s approval.

In addition, per the G-ICMR, the investigator must submit a report to the DCGI explaining how the SAE/SADR was related to the research within 14 days. According to the 2019-CTRules, the investigator must also promptly report to the EC all changes in the clinical trial activities and all unanticipated problems involving risks to human research participants or others.

Form Completion & Delivery Requirements

As per Notice25Feb21, the investigator, the sponsor or the representative, and the EC must report all SAEs electronically via the SUGAM portal (IND-59). However, follow-up reports pertaining to SAE reports submitted prior to March 14, 2021, will continue to be accepted in paper form. Refer to IND-59 for the SUGAM user manual and video tutorials. See also IND-42 for instructions on how to submit SAE reports (referred to as Due Analysis Reports) via IND-59.

The G-ICMR further states that the investigator may report SAEs/SADRs to the EC through email or fax communication (including on non-working days). Refer to IND-37 for the Indian Council of Medical Research (ICMR)'s EC Serious Adverse Event Reporting Format (Clinical Trials).

Safety Reporting Definitions

According to the LibCTReg, the G-LibPV, and the G-ACRE-IRB, the following definitions provide a basis for a common understanding of Liberia’s safety reporting requirements (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• Adverse Event (or Adverse Experience) (AE) – Any untoward medical occurrence in a participant to whom a medicinal product has been administered, including occurrences which are not necessarily caused by or related to that product, or any abnormal sign (e.g., any abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant’s involvement in the research; AEs encompass both physical and psychological harms
• Adverse Drug Reaction (ADR) – Any noxious and unintended responses in a participant to an investigational medicinal product which is related to any dose administered to that participant. A causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e., the relationship cannot be ruled out
• Serious Adverse Event (SAE) or Serious Adverse Drug Reaction (SADR) – Any untoward medical occurrence that at any dose: results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or may jeopardize the participant’s health and may require medical or surgical intervention based upon appropriate medical judgment (e.g., the development of drug dependency or drug abuse). A causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e., the relationship cannot be ruled out
• Unexpected Adverse Drug Reaction – An adverse reaction where the nature or severity is inconsistent with the applicable product information (e.g., Investigator's Brochure for an unapproved investigational product (IP) or package insert/summary of product characteristics for an approved product)

Safety Reporting Requirements

Per the LibCTReg and the G-LibClinTrial, the principal investigator (PI) or the sponsor should report any SAEs/SADRs suspected to be related to the IP immediately, and in any event, no later than three (3) calendar days after becoming aware of the event to the Liberia Medicines and Health Products Regulatory Authority (LMHRA) and the National Research Ethics Board of Liberia (NREB). Per the G-LibClinTrial, in the case of multicenter trials involving clinical trial sites (in and outside of Liberia), the PI or sponsor must submit all SAEs/SADRs deemed to be related to the IP within 15 calendar days to the LMHRA and the NREB. The PI or the sponsor is also required to indicate the timelines allocated for related investigations.

The G-LibPV provides the following scale by which to assess the severity of AEs/ADRs: Mild, Moderate, Severe, or Fatal. For more details, see Table 2 in G-LibPV. The G-LibPV also provides criteria for determining the link between the intervention and the AEs/ADRs as either certain, probably/likely, possible, unlikely, conditional/unclassified, or un-assessable/unclassified. For more details, see Table 3 in G-LibPV.

Investigator Responsibilities

The G-NREB indicates that investigators are required to submit a report to the NREB for all AEs except those resulting in death within seven (7) calendar days. Investigator(s) must report all deaths that are possibly, probably, or definitely related to the study within 24 hours to the NREB.

Other events that must be reported to the NREB include the following:

• Unanticipated problems involving risks to participants or others
• Non-compliance (including major protocol deviations and non-compliance unrelated to a protocol deviation)
• New information that might affect the willingness of participants to enroll or continue to participate in the study

As indicated in the G-ACRE-IRB, for studies using the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB), the investigator must promptly report any unanticipated problems to the ACRE IRB in accordance with the following guidelines (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.):

• Unanticipated problems that are SAEs must be reported to the ACRE IRB within five (5) business days of the investigator becoming aware of the event. The board strongly recommends that a preliminary report be submitted by the investigator within 48 hours of learning of the SAE with a formal follow-up report submitted within the above timeline
• Any other unanticipated problem should be reported to the ACRE IRB within two (2) weeks of the investigator becoming aware of the problem. The board strongly recommends that a preliminary report be submitted by the investigator within five (5) business days of learning of the unanticipated problem with a formal follow-up report submitted within the above timeline

In addition, per the G-ACRE-IRB, when making a report to the ACRE IRB, the investigator should include the following information:

• The appropriate identifying information for the research protocol, such as the title, the investigator’s name, and the ethics committee (EC) project number
• A detailed description of the AE, incident, experience, or outcome; however, to maintain confidentiality, participants’ names and identifiable information should not be included in the report
• An explanation of the basis for determining that the AE, incident, experience, or outcome represents an unanticipated problem
• A description of any changes to the protocol or other corrective actions that have been taken or are proposed in response to the unanticipated problem

Other Safety Reports

As explained in the G-ACRE-IRB, for studies using the ACRE IRB, the ACRE IRB Executive Committee conducts the initial review of unanticipated problems. This committee is authorized to take the following actions in response to any incident report:

• Conduct an administrative review of the report, including assessing whether the incident constitutes an unanticipated problem
• If a convened ACRE IRB review is needed, the Chair assigns the incident report for review at the next available regularly scheduled ACRE IRB meeting
• Alternately, the ACRE IRB Executive Committee may convene an emergency meeting of the ACRE IRB to review the report
• If the ACRE IRB Executive Committee finds that the rights, safety, and welfare of the participants are jeopardized by the research, the Chair may suspend the research until such time when the full ACRE IRB can convene to review the report. When reviewing a particular incident, experience, or outcome reported as an unanticipated problem by the investigator, the board may determine that the incident, experience, or outcome does not meet the criteria for an unanticipated problem

Following a review of the unanticipated problem report, per the G-ACRE-IRB, the ACRE IRB may require the following actions, in order to protect the ongoing safety of the research participants:

• Modification of participant inclusion or exclusion criteria to mitigate the newly identified risks
• Implementation of additional procedures for monitoring participants
• Modification of informed consent documents to include a description of newly recognized risks
• Addition of provisions about newly recognized risks to previously enrolled participants
• Suspension of enrollment of new participants
• Suspension of research procedures in currently enrolled participants
• Suspension of the entire study
• Termination of approval for the entire study

Per the G-ACRE-IRB, if the solution to an unanticipated problem is to amend the research protocol and/or informed consent forms, then an amendment request must be made to the ACRE IRB. If the changes are minor, they may be reviewed by expedited review procedures. If the changes are major, they must be reviewed and approved by the convened board. Changes made in response to an unanticipated problem must be reviewed and approved by the ACRE IRB before being implemented, except where implementation is necessary to eliminate immediate hazards to research participants.

Form Completion & Delivery Requirements

Liberia Medicines and Health Products Regulatory Authority

As per the G-LibPV, all SAEs/SADRs and SUSARs must be reported on the LMHRA’s Suspected Adverse Drug Reaction Reporting Form (Annex 3 in the G-LibClinTrial).

Atlantic Center for Research and Evaluation Institutional Review Board

Per LBR-28, since all clinical trials protocols submitted to the ACRE IRB are referred to the NREB for review, all AEs/ADRs and SAEs/SADRs are only sent to the NREB.

National Research Ethics Board of Liberia

No information is available on NREB safety reporting forms and delivery requirements.

Interim and Annual Progress Reports

As described in the 2019-CTRules and IND-31, the Drugs Controller General of India (DCGI), who heads the Central Drugs Standard Control Organization (CDSCO), requires the sponsor (also known as applicant) to submit a six (6)-month status report for each clinical trial electronically via the CDSCO’s SUGAM portal (IND-59). The report should clarify whether the trial is ongoing, completed, or terminated. In the case of termination, detailed reasons for such termination must be communicated to the DCGI within 30 working days of the termination. In addition, per the 2019-CTRules, an ethics committee (EC) may periodically request study progress reports from the investigators.

As delineated in the 2019-CTRules, sponsors are also required to submit an annual status report for the clinical trial to the DCGI.

The 2019-CTRules further specifies that in cases where trials have been prematurely discontinued for any reason, including a lack of commercial interest in pursuing the new drug application (NDA), the sponsor should submit a summary report within three (3) months. The summary report should provide a brief description of the study, the number of participants exposed to the drug, dose/duration of exposure, details of adverse drug reactions, if any, and the reason for the study’s discontinuation or non-pursuit of the NDA.

See IND-35 for a Checklist of Notification for Annual Status Report documentation requirements to be included in a global clinical trial application.

Final Report

The final report should comply with the format and content guidelines listed in the 2019-CTRules as follows:

• Title page
• Study synopsis (1 to 2 pages)
• List of abbreviations and definitions
• Table of contents
• EC approval letter(s)
• Study team introduction
• Study objective
• Investigational plan
• Trial participants
• Efficacy evaluation
• Safety evaluation
• Discussion and overall conclusion
• List of references
• Appendices

See the 2019-CTRules for more detailed information on preparing the final report.

See IND-35 for a checklist of documentation requirements to be included in a global clinical trial application pertaining to end of clinical trial notification.

Interim and Annual Progress Reports

Liberia Medicines and Health Products Regulatory Authority

Pursuant to the LibCTReg, the applicant must submit to the Liberia Medicines and Health Products Regulatory Authority (LMHRA) and the National Research Ethics Board of Liberia (NREB) progress reports containing safety updates and duly signed and authenticated Data and Safety Monitoring Board (DSMB) reports, as specified in the corresponding clinical trial guidelines. As specified in the G-LibClinTrial, the applicant must provide a progress report at least annually on the clinical trial to the LMHRA, unless otherwise stipulated in the clinical trial certificate. The report should contain recruitment status, safety updates, and DSMB reports, as well as an update on the use and results collected on biological samples exported out of Liberia, if applicable.

National Research Ethics Board of Liberia

As indicated in the G-NREB, for continuing review submissions, PIs must submit review reports to the NREB Secretariat at least eight (8) weeks prior to the approved protocol’s expiration. See LBR-6 for the NREB Continuing Review Form. Additionally, according to LBR-38, the NREB is also using LBR-24 for continuing review, for annual reports, and as a final report to close a study.

Per the G-LibClinTrial and the G-NREB, research in Liberia should comply with the International Council for Harmonisation's (ICH)’s Guideline for Good Clinical Practice E6(R2) (LBR-8). As part of the country’s compliance with LBR-8, the investigator should submit written summaries of the trial status to the NREB annually, or more frequently, if requested by the board. The investigator should also promptly provide written reports to the sponsor, the NREB, and where applicable, the institution on any changes significantly affecting the conduct of the trial, and/or increasing the risk to participants.

Atlantic Center for Research and Evaluation Institutional Review Board

For clinical research studies using the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB), the G-ACRE-IRB requires the principal investigator(s) (PIs) to submit progress reports (also referred to as continuing review submissions in Liberia) to the ACRE IRB. If no work was conducted on a study during the last approval period, the PIs should explain why (e.g., too busy with other projects; a delay in funding; or unable to hire a graduate student to work on the project). If the PI(s) are closing the study, a copy of any publications or manuscripts resulting from the study should be attached. (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.)

As indicated in the G-ACRE-IRB, the following list provides the required documentation to submit a continuing review to the ACRE IRB:

• A completed Continuing Review form
• A copy of the current informed consent document(s) or any newly proposed consent document(s) if enrollment is ongoing
• A copy of current recruitment material(s) or any newly proposed recruitment material(s) if enrollment is ongoing
• A summary of adverse events and any unanticipated problems involving risks to participants
• Numbers of and reason for withdrawal of participants from the research
• A summary of any relevant information about risks associated with the research
• Number and demographics of participants enrolled
• Changes in the principal and/or associate investigator(s)
• A summary description of participant experiences
• Research results obtained thus far
• A current risk-benefit assessment based on the study results
• Any new information since the ACRE IRB’s last review

After the Secretary and the Coordinator have determined that the continuing review submission is complete, the documentation must be submitted to the ACRE IRB and reviewed by the convened board, or by the expedited reviewer(s), if necessary, for an expedited review.

Final Report

Liberia Medicines and Health Products Regulatory Authority

The LibCTReg states that the applicant is required to submit a final clinical trial summary report to the LMHRA. As per the LibCTReg and the G-LibClinTrial, the applicant must notify the LMHRA within 30 business days from the end of a clinical trial. Per the G-LibClinTrial, the end of the trial definition should be documented in the clinical trial protocol.

The LibCTReg and the G-LibClinTrial also indicate that the applicant must submit a closeout report with a copy of the LMHRA-issued disposal certificate to the LMHRA. The G-LibClinTrial specifies this report should be submitted within 90 days from completion of the clinical trial. (See Annex 5 of the G-LibClinTrial for closeout report form).

In addition, per the LibCTReg and the G-LibClinTrial, the applicant must submit a comprehensive end of study report conforming to the ICH’s Structure and Content of Clinical Study Reports (E3) (LBR-37) guidelines, within one (1) year from the trial’s completion.

Per the LibCTReg and the G-LibClinTrial, the end of study report must also contain any adverse events reported by the PIs.

Per LBR-8, the investigator, where applicable, should inform the institution; the investigator/institution should provide the ethics committee with a summary of the trial’s outcome, and the regulatory authority (LMHRA) with any reports required.

National Research Ethics Board

The LibCTReg states that the applicant is required to submit a final clinical trial summary report to the NREB. The applicant must also notify the NREB within 30 business days from the end of a clinical trial.

Additionally, per the LibCTReg, the PI must also inform the NREB of any adverse events as part of the end of study report.

The LibCTReg further specifies that the applicant must submit a comprehensive end of study report to the NREB conforming to the LBR-37 guidelines, within one (1) year from the trial’s completion.

According to LBR-38, the NREB is using LBR-24 for continuing review, for annual reports, and as a final report to close a study.

Atlantic Center for Research and Evaluation Institutional Review Board

Per the G-ACRE-IRB, PI(s) should complete Section 12 (Disposition of Project) of the ACRE IRB Submission Form (Section 25.02 in Article XXV of the G-ACRE-IRB) for the final ACRE IRB review. For the board’s purposes, the project has ended when there is no further participant enrollment, intervention(s), or data collection, and the remaining data are either de-identified or maintained with safeguards. The PI(s) should use this section to describe the disposition of the project and its data and provide a brief summary of their findings.

As per the 2019-CTRules and the G-ICMR, a sponsor (also known as applicant) is defined as an individual, a company, or an institution that takes responsibility for the initiation, management, or financing of a clinical study. The G-ICMR further states that an investigator who independently initiates and takes full responsibility for a trial automatically assumes the role of a sponsor. The 2019-CTRules also indicates that the sponsor may appoint a contract research organization (CRO).

As stated in the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with LMHRA guidelines. Per LBR-8 and the LibCTReg, the sponsor is defined as an individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial.

LBR-8 and the LibCTReg also define a sponsor-investigator as an individual who both initiates and conducts an investigation, and under whose immediate direction the investigational product is administered or dispensed. The term does not include any person other than an individual. The obligations of a sponsor-investigator include both those of a sponsor and those of an investigator.

In addition, per the LibCTReg, the sponsor may hire a contract research organization (CRO) (commercial, academic, or other) to perform one (1) or more of the sponsor’s trial-related duties and functions. LBR-8 further explains that although a sponsor may transfer responsibility for any or all of the sponsor’s obligations to a CRO, the ultimate responsibility for the trial data’s quality and integrity always resides with the sponsor. The sponsor should also ensure oversight of any trial-related duties and functions carried out on its behalf, including trial-related duties and functions that are subcontracted to another party by the sponsor’s CRO. Any trial-related responsibilities transferred to a CRO should be specified in writing. The CRO should implement quality assurance and quality control.

Overview

As stated in the 2019-CTRules, all investigators must possess appropriate qualifications, training, and experience, and should conduct the trials in compliance with Good Clinical Practices (GCPs) and Good Laboratory Practices (GLPs). (See GCLP for the G-ICMR for Good Clinical Laboratory Practices (GCLP), IND-31 for additional laboratory requirement information, and IND-76 for international GCLP guidelines. Investigators should also have access to investigational and treatment facilities as relevant to the protocol.

Per the 2019-CTRules, prior to entering into an agreement with the investigator(s)/institution(s) to conduct a study, the sponsor (also known as applicant) should provide the involved parties with the protocol and an up-to-date investigator’s brochure and allow them sufficient time to review this documentation. The sponsor must also define and allocate all study-related duties and responsibilities to the respective identified person(s) and organization(s) prior to initiating the study.

In addition, per Notice2Dec19, the Central Drugs Standard Control Organization (CDSCO) is preparing a comprehensive database of clinical trial sites and investigators involved in the conduct of global clinical trials in different therapeutic categories by collecting information from various sources. The first phase includes an Excel spreadsheet of sites and investigators involved in global clinical trials (IND-26).

See also IND-28 for the Indian Council of Medical Research (ICMR)’s research conduct policies.

Foreign Sponsor Responsibilities

No information is currently available on foreign sponsor responsibilities.

Data and Safety Monitoring Board

While there are no general requirements for establishing a Data Safety Monitoring Board (DSMB), the G-Children recommends that a DSMB be strongly considered for research involving children in emergency situations.

Multicenter Studies

As delineated in the G-ICMR, in the case of multicenter research studies, all of the participating study sites are required to obtain approval from their respective ethics committees (ECs), which includes the option of each site choosing to accept the review/approval of a primary EC. The study sites also typically follow a common protocol to avoid duplication of effort, wastage of time, and communication issues. See the G-ICMR for additional participating site requirements when a primary EC is selected for common EC review. Also, see the Scope of Review section for additional details.

Further, per the G-ICMR, if a multicenter trial is going to be conducted, the sponsor may organize a coordinating committee or select coordinating investigators. The sponsor must also conduct training for investigators in ethics, GCPs, standard operating procedures (SOPs), and study protocols.

Overview

According to the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with LMHRA guidelines. Per LBR-8, the sponsor is responsible for selecting the investigator(s) and the institution(s) for the clinical trial. Each investigator should be qualified by training and experience and should have adequate resources to properly conduct the trial for which the investigator is selected. LBR-8 also explains that the sponsor should utilize appropriately qualified individuals to supervise the overall conduct of the trial, to handle the data, to verify the data, to conduct the statistical analyses, and to prepare the trial reports.

As indicated in LBR-8, the investigator(s) should be qualified by education, training, and experience to assume responsibility for the proper conduct of the trial, should meet all the qualifications specified by the applicable regulatory requirement(s), and should provide evidence of such qualifications through up-to-date curriculum vitae (CV) and/or other relevant documentation requested by the sponsor, the ethics committee (EC), and/or the regulatory authority(ies) (see section 4 in LBR-8 for detailed investigator requirements).

As stated in the G-LibClinTrial, all investigators must be trained in good clinical practices (GCP) documented by the provision of training certificates not older than three (3) years at the time of application. Any other training or experience from previous clinical trials and patient care as needed for the conduct of the trial must be provided for the investigators to prove their qualifications. The principal investigators (PIs) should have acted as PI or at least as an investigator in at least one (1) prior clinical trial and must provide proof of residency in Liberia in the clinical trial application submission package. The LibCTReg also states that the trial is to be conducted in an appropriate facility by a suitably qualified investigator in a responsible manner and managed by an investigator who can provide evidence of sufficient experience in the conduct of clinical trials as determined by the LMHRA.

Per the G-NREB, PIs are also required to be able to provide a current Certificate of Training in GCP for PIs, be qualified to undertake the particular study, and be knowledgeable in the values and tenets of ethical and regulatory principles and scientific method applications associated with conducting research in human participants.

In addition, the G-LibClinTrial requires the applicant to provide details of the site(s) where the clinical trial is to be conducted and a duly justified written statement on the suitability of the trial sites adapted to the nature and use of the investigational product in the clinical trial application submission package. The statement should include a description of the suitability of facilities, equipment, human resources, and description of expertise, issued by the head of the clinic/institution at the trial site or by some other responsible person.

Furthermore, per LBR-8, the sponsor should obtain the investigator's/institution's agreement to:

• Conduct the trial in compliance with GCP, the applicable regulatory requirement(s), and the approved protocol
• Comply with procedures for data recording/reporting
• Permit monitoring, auditing, and inspection
• Retain the trial related essential documents until the sponsor informs the investigator/institution these documents are no longer needed

The sponsor and the investigator/institution should sign the protocol, or an alternative document, to confirm this agreement.

Foreign Sponsor Responsibilities

No information is available on foreign sponsor requirements.

Data and Safety Monitoring Board

As per the G-LibClinTrial, the sponsor or the representative should provide information on the composition of the Data and Safety Monitoring Board (DSMB) in the clinical trial application submission package. This information should include the list of members, the terms of reference, and the CVs of its members to justify their expertise as members of the DSMB.

LBR-8 further indicates that the sponsor may consider establishing a DSMB (also known as an independent data monitoring committee (IDMC)) to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial. The DSMB should have written operating procedures and maintain written records of all its meetings.

Multicenter Studies

As delineated in LBR-8, in the event of a multicenter clinical trial, the sponsor must ensure that:

• All investigators conduct the trial in strict compliance with the protocol agreed to by the sponsor and are given EC approval
• The case report forms (CRFs) are designed to capture the required data at all multicenter trial sites
• Investigator responsibilities are documented prior to the start of the trial
• All investigators are given instructions on following the protocol, complying with a uniform set of standards to assess clinical and laboratory findings, and completing the CRFs
• Communication among investigators is facilitated

Further, per LBR-8, if the organization of a coordinating committee and/or selection of coordinating investigator(s) are to be used in multicenter trials, their organization and/or selection are the sponsor's responsibility.

Insurance

The G-ICMR specifies that the sponsor (also known as applicant) should provide insurance coverage or a provision in the budget for possible compensation for trial-related injuries. The G-ICMR also states that it is preferable to have the insurance certificate and the policy for study participants. Further, the policy should explain the conditions of coverage, date of commencement, and expiration date for risk coverage (if applicable). In addition, institutional mechanisms must be established to allow for insurance coverage of trial-related or unrelated illnesses (ancillary care).

The 2019-CTRules states that the ethics committee (EC) also requires a copy of the insurance policy or details regarding compensation for participation and for serious adverse events (SAEs) occurring during the study as part of its submission review process.

With regard to indemnity coverage, the G-ICMR states that an indemnity policy must be included in the documentation for EC review. The policy should clearly indicate the conditions of coverage, date of commencement, and coverage expiration date, if applicable.

Compensation

Injury or Death

In accordance with the 2019-CTRules and the G-ICMR, the sponsor is responsible for providing compensation to research participants and/or their legal heir(s) in the event of trial-related injuries, permanent disability, or death. Per the G-ICMR, in the event the investigator/institution becomes the sponsor in a clinical trial, it is the host institution’s responsibility to provide compensation for research-related injury or harm as determined by the ethics committee (EC).

The 2019-CTRules further notes that the sponsor is responsible for compensating the research participant and/or the legal heir(s) if the trial-related injury, death, or permanent disability to a participant is specifically related to any of the following reasons:

• Adverse effects of an investigational product (IP)
• Any trial procedures involved in the study
• A violation of the approved protocol, scientific misconduct, or negligence by the sponsor, the representative, or the investigator
• Failure of the IP to provide the intended therapeutic effect where, the standard care, though available, was not provided to the participant per the protocol
• Not providing the required standard care, though available to the participant per the protocol in the placebo-controlled trial
• Adverse effects due to concomitant medication excluding standard care, necessitated as part of the approved protocol
• Adverse effect on the child in-utero due to a parent’s participation in a trial
• Any clinical trial procedures involved in the study leading to a serious adverse event (SAE/serious adverse drug reaction (SADR)

Per the 2019-CTRules and the G-ICMR, the sponsor must also ensure that participants who suffer any trial-related injuries be provided with free medical treatment for such injuries as long as required per the opinion of the investigator (and the EC per the G-ICMR), or until such time it is established that the injury is not related to the clinical trial, whichever is earlier. Per the 2019-CTRules, if the sponsor or the representative fails to provide medical management, the Drugs Controller General of India (DCGI), after a hearing, must issue a written order to suspend or cancel the study or restrict the sponsor, including the representative, from conducting any further clinical trials or taking any other action for such period deemed appropriate for this case. (Note: The DCGI is head of the Central Drugs Standard Control Organization (CDSCO) and is commonly referred to as the Central Licensing Authority in the Indian regulations.)

In the case of a trial-related injury, the 2019-CTRules and IND-31 state that the sponsor is required to provide complete medical management and compensation to the participant within 30 days of receiving an order from the DCGI. In the event of permanent injury or death, the sponsor is required to provide compensation to the participant or to the legal representative/guardian within 30 days of receiving the DCGI’s order. According to IND-31, compensation and medical management requirements are also applicable in the case of injury or death occurring during an academic trial.

The 2019-CTRules explains that in the case of an SAE resulting in death, the DCGI must constitute an independent expert committee to review the incident and make its recommendations to the DCGI for the cause of death and to provide a quantum of compensation. The sponsor or the representative and the investigator must forward their reports, after due analysis, to the DCGI and the head of the institution where the trial was conducted within 14 days of the occurrence. The EC must forward its report along with its opinion on financial compensation, if any, to be paid by the sponsor or the representative within 30 days of receiving the investigator’s report. The DCGI, in turn, must forward the sponsor, investigator, and EC reports to the expert committee chairperson. Following its review, the expert committee must make its recommendations to the DCGI as to the cause of the SAE resulting in death and the quantum of compensation within 60 days from receiving the DCGI’s submission. The DCGI must then consider the expert committee’s recommendations and issue an order within 90 days to the sponsor or the representative specifying the quantum of compensation required to be paid within 30 days of receiving the order.

In the case of an SAE/SADR resulting in permanent disability or any injury other than death, the 2019-CTRules indicates that the sponsor or the representative and the investigator must forward their reports, after due analysis, to the DCGI, the EC chairperson, and the head of the institution where the trial has been conducted within 14 days of the occurrence. The EC, after due analysis, must forward its report along with its opinion on financial compensation, if any, to the DCGI within 30 days of the event occurrence. The DCGI, in turn, must determine the cause of the injury and issue an order, with the option to constitute an independent expert committee, within 60 days of receipt of the report. The DCGI must issue an order within 90 days of receiving the report indicating the quantum of compensation to be paid by the sponsor or the representative within 30 days of receipt of this order.

In the case of an injury not being permanent in nature, per the 2019-CTRules, compensation should be commensurate with the participant’s loss of wages.

Per the 2019-CTRules, in the event that a sponsor or the representative fails to provide compensation to a research participant for trial-related injuries, or to the legal heir(s) in case of death, the DCGI must, after giving an opportunity to show cause why such an order should not be passed by a written order, suspend or cancel the clinical trial, or restrict the sponsor or the representative from conducting any further clinical trials in India or taking any other action deemed fit given the circumstances.

See the 2019-CTRules and the G-ICMR for detailed information on terms of compensation payment.

Trial Participation

The G-ICMR explains that participants may also be compensated for their time and other expenses (e.g., loss of wages, food supplies, and travel). The EC should approve all payments, reimbursement, and medical services provided. Per the G-ICMR, participants should not be required to pay for any expenses incurred beyond routine clinical care and which are research related including patient work-ups, or interventions associated with treatment. If there are provisions, participants may receive additional medical services at no further cost.

Post-Trial Access

The 2019-CTRules and IND-31 explain that the investigator may recommend the sponsor provide post-trial access to the investigational product (IP) free of cost to the participant for such period as deemed necessary by the investigator and the EC. The sponsor must obtain DCGI approval to initiate this plan. The investigator’s recommendation will be based on the following conditions:

• If the trial is being conducted for an indication for which no alternative therapy is available, and the IP has been determined to be beneficial
• The participant or the legal representative/guardian has consented in writing to use the post-trial IP, and has certified and declared in writing, along with the investigator, that the sponsor must have no liability for post-trial use of the IP

See also IND-6 for additional information on post-trial access to IPs under the 2019-CTRules.

Additionally, per the G-ICMR, the benefits accruing from research should be made accessible to individuals, communities and populations whenever relevant. The EC should consider the need for an a priori agreement between the researchers and sponsors regarding the following:

• Efforts should be made to communicate the findings of the research study to the individuals/communities wherever relevant
• The research team should make plans wherever applicable for post-research access and sharing of academic or intervention benefits with the participants, including those in the control group
• Post-research access arrangements or other care must be described in the study protocol so that the EC may consider such arrangements during its review

G-ICMR further states that if an investigational drug is to be given to a participant post-trial, appropriate regulatory approvals should be in place. In studies with restricted scope, such as student projects, post study benefit to the participants may not be feasible, but conscious efforts should be made by the institution to take steps to continue to support and give better care to the participants.

Insurance

As set forth in the LibCTReg and the G-LibClinTrial, the applicant should include documentation in the clinical trial application submission package to verify active clinical trial insurance that covers phases I, II, and III, proof of professional indemnity (malpractice insurance), and proof of sponsor indemnification for investigators and the trial site. The LibCTReg also notes that an indemnity in the form determined by the Liberia Medicines and Health Products Regulatory Authority (LMHRA) is to be signed by the participant protecting the LMHRA from liability related to an injury or an adverse event which may be sustained by a person, directly or indirectly, as a result of the conduct of the trial and which occurs or reveals itself at the time of the trial or subsequently.

The G-LibClinTrial also specifies that a study insurance certificate and an indemnity provision should be current and valid for the full duration of the trial and follow-up period. If the validity is shorter, a written renewal commitment for the trial duration is required. The certificate should contain a reference to the clinical trial, the clinical trial protocol number, and the countries to which the insurance cover is extended. The insurance cover should be provided from an internationally recognized company. Additionally, the LibCTReg, requires an insurance policy to be in place to provide benefits in the event that a clinical trial participant suffers injury or death related to the study.

Per LBR-29, both clinical trial insurance and indemnification certificates must be included in the clinical trial application dossier in accordance with the African Vaccine Regulatory Forum (AVAREF)’s Clinical Trial Application Checklist (LBR-1). According to LBR-4, the AVAREF was established by the World Health Organization (WHO) in 2006 to promote the harmonization of ethics and regulatory processes in Africa.

In addition, per the G-LibClinTrial, under certain circumstances, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) may accept an expedited application and review process for clinical trials (e.g., epidemics or other urgent public health interests requiring fast use of new medicines or health products and/or fast gathering of health product information). In the case of trials involving human participants, the applicant must provide proof of current, relevant, and appropriate study insurance for all participants or professional indemnity insurance for investigators as part of the application submission package to be sent to the LMHRA. Furthermore, as specified in the LibCTReg and the G-LibClinTrial, the LMHRA has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines. LBR-8 states that if required by the applicable regulatory requirement(s), the sponsor should provide insurance or should indemnify (legal and financial coverage) the investigator/the institution against claims arising from the trial, except for claims that arise from malpractice and/or negligence.

Compensation

Injury or Death

Per LBR-8, the sponsor or the representative is responsible for providing compensation to research participants and/or their legal heirs in the event of trial-related injuries or death.

LBR-8 states that the sponsor's policies and procedures should address the treatment costs of trial participants in the event of trial-related injuries, and when trial participants receive compensation, the method and manner of compensation should comply with applicable regulatory requirement(s). According to LBR-29, the LMHRA does not have a compensation committee.

In addition, per the LibCTReg, any person(s), institution(s), corporate entity(ies), their designees, or legal representative(s) who does not provide insurance coverage for prospective participants as required, and in the course of the research bodily injury or substantial harm results, the person(s), institution(s), corporate entity(ies), their designees, or legal representative(s) commits a first degree misdemeanor consistent with the PenalLaw. The PenalLaw states a person commits a misdemeanor of the first degree if the person recklessly engages in conduct which creates a substantial risk of death or serious bodily injury to another.

Pursuant to Part VIII of the LMHRA-Act, the LibCTReg also specifies that the principal investigator or organization is subject to an action of damages for any Serious Adverse Event (SAE)/Serious Adverse Drug Reaction (SADR) that is life-threatening, or results in persistent or significant disability/incapacity or congenital anomaly/birth defect, during the conduct of a clinical trial. Additionally, any SAE that results in the death of a participant during the conduct of a clinical trial must constitute negligent homicide consistent with the PenalLaw which states that a person is guilty of negligent homicide if the person causes the death of another human being negligently; negligent homicide is a felony of the third degree.

Trial Participation

Per LBR-8, the participant should be provided with information regarding any anticipated prorated payment, if any, for participating in the trial.

Quality Assurance/Quality Control

In accordance with the 2019-CTRules and the G-ICMR, the sponsor (also known as applicant) is responsible for implementing and maintaining quality assurance (QA) and quality control (QC) systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data generated, recorded, and reported in compliance with the protocol, Good Clinical Practices (GCPs), and all applicable laws and regulations.

Monitoring Requirements

As per the 2019-CTRules, the sponsor must permit clinical trial site inspections by the Drugs Controller General of India (DCGI)-authorized officers. The officers may enter the premises and clinical trial site with or without prior notice to inspect, search, or seize any record, statistical result, document, investigational drug, and other related material. The sponsor must also reply to inquiries raised by the inspecting authority in relation to the conduct of the trial. (Note: The DCGI is head of the Central Drugs Standard Control Organization (CDSCO) and is commonly referred to as the Central Licensing Authority in the Indian regulations.)

In addition, as part of its QA system, the 2019-CTRules notes that investigator(s) may provide periodic study progress reports (PSUR), or regulatory officials or sponsor-designated authorized representatives may provide monitoring and internal audit reports to the ethics committee (EC) to support its recurring clinical trial reviews. An audit certificate may be issued, if available.

Furthermore, the 2019-CTRules requires the investigator to sign an undertaking indicating agreement to maintain adequate and accurate records and to make those records available for audit or inspection by the sponsor, the EC, the Central Licensing Authority, or their authorized representatives, in accordance with regulatory provisions and GCP guidelines. The investigator must agree to fully cooperate with any study-related audit conducted by regulatory officials or authorized representatives of the sponsor.

See IND-35 for a checklist of PSUR documentation requirements to be included in a global clinical trial application, and IND-34 for the DCGI’s GCP Inspection Checklist.

Premature Study Termination/Suspension

As delineated in the 2019-CTRules, when the sponsor fails to comply with any provisions of the DCA-DCR and the 2019-CTRules, the DCGI may, after giving an opportunity to show cause and after affording an opportunity of being heard, by an order in writing, implement one (1) or more of the following actions:

• Issue a warning in writing describing the deficiency or defect observed during inspection or otherwise which may affect adversely the right or well-being of a trial participant or the validity of clinical trial conducted
• Reject the results of the clinical trial
• Suspend for such period as considered appropriate or cancel the permission granted in Form CT-06 or in Form CT-4A
• Debar the investigator or the sponsor, including the representatives, from conducting any clinical trial in the future for such period as considered appropriate by the DCGI

The sponsor or the representative may appeal the DCGI’s decision within 60 working days of receipt of the order.

Further, per the 2019-CTRules, in case of studies prematurely discontinued for any reason, including lack of commercial interest in pursuing the new drug application, the sponsor should submit a summary report within three (3) months. The summary report should provide a brief description of the study, the number of patients exposed to the drug, dose and duration of exposure, details of adverse drug reactions, if any, and the reason for discontinuation of the study or non-pursuit of the new drug application.

The 2019-CTRules also indicates that in case of termination of any clinical trial the detailed reasons for such termination must be communicated to the DCGI within 30 working days of such termination.

See IND-35 for a checklist of premature study termination documentation requirements to be included in a global clinical trial application.

Quality Assurance/Quality Control

As specified in the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation (ICH)'s Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines. Per LBR-8, sponsors are responsible for implementing and maintaining quality assurance (QA) and quality control (QC) systems with written standard operating procedures (SOPs) to ensure that trials are conducted and data are generated, recorded, and reported in compliance with the protocol.

Per LBR-8, the sponsor should implement a system to manage quality throughout all stages of the trial process, focusing on trial activities essential to ensuring participant protection and the reliability of trial results. The quality management system should use a risk-based approach that includes:

• During protocol development, identifying processes and data that are critical to ensure participant protection and the reliability of trial results
• Identifying risks to critical trial processes and data
• Evaluating the identified risks against existing risk controls
• Deciding which risks to reduce and/or which risks to accept
• Documenting quality management activities and communicate to those involved in or affected by these activities
• Periodically reviewing risk control measures to ascertain whether the implemented quality management activities are effective and relevant
• In the clinical study report, describing the quality management approach implemented in the trial and summarize important deviations from the predefined quality tolerance limits and remedial actions taken (Refer to the ICH’s Structure and Content of Clinical Study Reports (E3) guidelines (LBR-37))

Pursuant to Part VIII of the LMHRA-Act, the LibCTReg states that any person(s), institution(s), corporate entity(ies), their designees, or legal representatives who violates the clinical trial authorization procedures, the serious adverse event notification requirements, and/or the suspension/withdrawal provisions delineated in the LibCTReg will be liable to pay administrative fines. See the LibCTReg for details.

Monitoring Requirements

Per LBR-8, if or when sponsors perform audits as part of implementing quality assurance, they should consider the following:

• The purpose of the audit should be to evaluate trial conduct and compliance with the protocol, SOPs, good clinical practice (GCP), and applicable regulatory requirements
• The selection and qualification of auditors who are independent of clinical trials/systems to conduct audits; the sponsors should ensure the auditors are qualified by training and experience to conduct audits properly and have appropriate qualifications that should be documented
• Auditing procedures that ensure the auditing of clinical trials/systems is conducted in accordance with the sponsor’s written procedures on what to audit, how to audit, the frequency of audits, and the form and content of audit reports

In addition, per LBR-8, the sponsor should develop a systematic, prioritized, risk-based approach to monitoring clinical trials. The extent and nature of monitoring is flexible and permits varied approaches that improve effectiveness and efficiency. The sponsor may choose on-site monitoring, a combination of on-site and centralized monitoring, or where justified, centralized monitoring. The sponsor should document the rationale for the chosen monitoring strategy (e.g., in the monitoring plan).

Refer to LBR-8 additional audit procedure details.

Premature Study Termination/Suspension

Pursuant to the LibCTReg, if the trial is suspended or terminated before its purpose is achieved, the applicant must convey the reason(s) in writing to the LMHRA and the National Research Ethics Board of Liberia (NREB) within 10 working days and all information must be provided as determined by the LMHRA. The G-LibClinTrial also states that the applicant must inform the LMHRA of a clinical trial suspension or premature termination of a clinical trial within 10 working days and clearly explain the reasons for this decision. LBR-8 further explains that if a trial is prematurely terminated or suspended, the sponsor should promptly inform the investigator(s)/institution(s) and the regulatory authority(ies) of the termination or suspension and the reason(s) for the termination or suspension. The ethics committee (EC) should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor or by the investigator/institution, as specified by the applicable regulatory requirement(s). Additionally, according to LBR-8, if it is discovered that noncompliance significantly affects or has the potential to significantly affect participant protection or reliability of trial results, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions. Further, the sponsor should promptly inform the EC and provide the reason(s) for the termination or suspension.

Electronic Data Processing System

No information is currently available on electronic data processing systems.

Records Management

Per the 2019-CTRules, the sponsor (known as applicant) must keep a record of new drugs manufactured and persons to whom the drugs have been supplied for clinical trial or bioavailability and bioequivalence study or for examination, testing, and analysis. In addition, the 2019-CTRules indicates that the licensed sponsor must maintain records of any imported new drug or substance that indicates the quantity of drug imported, used, and disposed of in any manner including related documentation.

See the Scope of Review section for information on ethics committee management of clinical trial related records.

Electronic Data Processing System

As specified in the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation (ICH)'s Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines.

As per LBR-8, when using electronic trial data processing systems, the sponsor must ensure that the electronic data processing system conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance. Sponsors should base their approach to validate such systems on a risk assessment that takes into consideration the intended use and the potential of the system to affect participant protection and reliability of trial results. In addition, sponsors should maintain standard operation procedures (SOPs) for the systems that cover system setup, installation, and use. The responsibilities of the sponsor, investigator, and other parties should be clear, and the system users should be provided with training in their use. Refer to LBR-8 for additional information.

Records Management

The G-LibClinTrial specifies that the principal investigator (PI) must keep an Investigator Site File (ISF), and the sponsor must keep a Trial Master File (TMF) containing essential documents relating to the clinical trial, which provide verification for the trial conduct and the quality of the data generated, taking into account all trial characteristics. The files must be readily available and directly accessible upon request from the LMHRA. The sponsor and the investigator must archive the contents of the TMF and ISF, respectively, for at least 25 years after the end of the trial including the medical files of study participants.

As set forth in LBR-8, the sponsor should inform the investigator(s)/institution(s) in writing of the need for record retention and should notify the investigator(s)/institution(s) in writing when the trial related records are no longer needed. Sponsor-specific essential documents should be retained for at least two (2) years after the last approval of a marketing application, until there are no pending or contemplated marketing applications, or at least two (2) years have elapsed since the formal discontinuation of the investigational product’s clinical development. The sponsor should inform the investigator(s) and the institution(s) in writing when trial-related records are no longer needed.

In addition, LBR-8 states that the sponsor and investigator/institution should maintain a record of the location(s) of their respective essential documents including source documents. The storage system used during the trial and for archiving (irrespective of the type of media used) should allow for document identification, version history, search, and retrieval. The sponsor should ensure that the investigator has control of and continuous access to the data reported to the sponsor. The investigator/institution should have control of all essential documents and records generated by the investigator/institution before, during, and after the trial. Per LBR-8, the sponsor should ensure the protocol or other written agreement specify that the investigator(s)/institution(s) provide direct access to source data/documents for trial related monitoring, audits, ethics committee review, and regulatory inspection.

As per the G-LibClinTrial, data handling and recordkeeping should be conducted in conformity with the World Health Organization's Good Clinical Practice Guidelines (LBR-25) (refer to Section 8 for details).

Per the G-ACRE-IRB, for clinical research studies using the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB), the ACRE IRB must retain all relevant records (e.g., study documents specific to board activities and administrative documents related to ACRE IRB internal operations) per the following timelines (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the National Research Ethics Board of Liberia (NREB) and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.):

• All records regarding a research application (regardless of whether it is approved) must be retained for at least three (3) years
• All records regarding all applications that are approved, and the research initiated must be retained for at least three (3) years after completion of the research
• Denied applications will be treated as terminated files and records must be retained for three (3) years after the denial of the research

The G-ACRE-IRB further explains the research records from a study must be retained by the investigator(s) for a period of no more than five (5) years following the closure date. If other regulations and policies apply to a particular protocol, then the duration of protocol retention is in accordance with the applicable regulations/policies. For detailed ACRE IRB recordkeeping requirements, refer to the G-ACRE-IRB.

The G-ACRE-IRB also specifies that although a research protocol has been closed, the investigator(s) should keep the data they have collected, including identifiable private data, in a manner consistent with the board-approved protocol and participant consent requirements. The investigator(s) must continue to honor any confidentiality protections of the data. Refer to the Informed Consent topic for additional information on documentation requirements and research participant rights during the informed consent process.

Responsible Parties

For the purposes of data protection regulation in India, the ITAct, the ITActAmend, and the IT-SPDIRules delineate responsibilities of the “body corporate.” The body corporate as defined by the ITAct, the ITActAmend, and the IT-SPDIRules refers to any company including a firm, sole proprietorship, or other association of individuals engaged in commercial or professional activities. The IT-SPDIRules further explains that the body corporate or any person on its behalf is the entity responsible for collecting, receiving, possessing, storing, dealing with, or handling personal information, including sensitive personal data and information. (Note: In ClinRegs, the “body corporate” is referred to as “sponsor,” but the requirements may apply to other parties as well).

Data Protection

Data protection in India is currently regulated by the ITAct, the ITActAmend, and the IT-SPDIRules. Per the IT-SPDIRules, the sponsor (or the “body corporate”) must provide a privacy policy for the handling of or dealing with this personal information including sensitive personal data or information. The IT-SPDIRules defines sensitive personal data or information as information relating to password(s); financial information; physical, physiological, and mental health condition(s); sexual orientation; medical records and history; and biometric information. The sponsor must ensure that this policy is available for view by the information providers under a lawful contract. The policy must be published on the sponsor’s or its representative’s website and provide the following:

• Clear and easily accessible statements of its practices and policies
• The type of personal information including sensitive personal data or information collected
• The purpose of collection and usage of such information
• Disclosure of information including sensitive personal data or information
• Reasonable security practices and procedures

Please refer to the IT-SPDIRules for detailed requirements on implementing security practices and procedures and collecting, disclosing, and transferring sensitive personal data or information.

See also IND-65 for more detailed information on India’s data protection requirements.

Pursuant to the G-LabValidTest, laboratory validation testing is used to ensure that laboratory test data and results are accurate, consistent, and precise, and may include tests that are conducted using residual, archived, unlinked, and anonymous biological samples such as blood, urine, tissue, cells, saliva, DNA, etc. The G-LabValidTest indicates that if the biological samples are linked to different types of personal identifiers (name, address, etc.) or with health-related data (chronic illnesses, prior hospital stays), and other types of potentially sensitive data (travel history, family history), there is a risk for breach of confidentiality and such samples are not recommended for laboratory validation testing without ethics committee (EC) approval. The investigator undertaking laboratory validation testing must also keep the EC informed regarding use of leftover, archived, or anonymous samples. The laboratories involved in the validation of tests/methods, may be exempted from ethical approval when using leftover archived and anonymized samples.

See also the G-AI-BiomedRes for data privacy and confidentiality guidelines in biomedical and health research involving artificial intelligence-based tools and technologies.

Additionally, the Digital Personal Data Protection Act, 2023 was enacted on August 11, 2023, with an effective date to be determined by the Indian Government. The ClinRegs team will update the Personal Data Protection section when more information becomes available.

Consent for Processing Personal Data

As set forth in the IT-SPDIRules, the body corporate or its representative must obtain consent in writing through letter, fax, or email from the provider of the sensitive personal data or information regarding the purpose of usage before collection of such information. The IT-SPDIRules further states that while collecting information directly from the information provider, reasonable steps must be taken to ensure that the information provider receives details regarding the following:

• The fact that the information is being collected
• The purpose for which the information is being collected
• The intended recipients of the information; and
• The name and address of the agency that is collecting the information, and the agency that will retain the information

Per the IT-SPDIRules, the body corporate or its representative, must provide an option to the information provider to withhold the requested data or information prior to the collection of information including sensitive personal data or information. The information provider must, at any time, also have the option to withdraw consent given earlier to the sponsor or the sponsor’s representative. This withdrawal of consent must be sent in writing.

Responsible Parties

No information is available related to responsible parties for personal data protection.

Data Protection

No information is available related to data protection.

Consent for Processing Personal Data

As stated in the LibCTReg, the clinical trial participant must be informed of the purpose and scope of the collection and use of personal data, especially medical data. The trial participant must be informed especially of the fact that where necessary, the collected data should be:

• Kept available for inspection by the Liberia Medicines and Health Products Regulatory Authority (LMHRA) or for monitoring or auditing by the sponsor in order to verify the proper conduct of the clinical trial
• Be passed on to the sponsor and the LMHRA without disclosing the identity of the trial participant

Obtaining Consent

In all Indian clinical trials, a freely given, written informed consent is required to be obtained from each participant to comply with the requirements set forth in the 2019-CTRules, the G-ICMR, and the G-Children.

As per the 2019-CTRules and the G-ICMR, prior to beginning a clinical trial, the investigator is required to obtain ethics committee (EC) approval for the informed consent form (ICF) and the patient information sheet. This documentation must also be supplied to the Drugs Controller General of India (DCGI), prior to the trial’s initiation. The ICF and patient information sheet are ultimately integrated into one (1) document referred to as the ICF. (See the Required Elements section for details on what should be included in the form.) (Note: The DCGI is head of the Central Drugs Standard Control Organization (CDSCO) and is commonly referred to as the Central Licensing Authority in the Indian regulations.)

The 2019-CTRules, the G-ICMR, and the G-Children specify that investigator(s) should provide detailed study information to the research participant or the legal representative/guardian. The ICF content should be briefly and clearly presented orally, and in writing, and in a manner that is easy to understand, commensurate with the comprehension level of the participants, and without coercion or unduly influencing a potential participant to enroll in the trial. Per the G-ICMR, the ICF language should not only be scientifically accurate and simple, but should also be sensitive to the participant’s social and cultural background. In addition, the participant or the legal representative/guardian, should be given adequate time to consider whether to participate. The consent should also be given voluntarily and not be obtained under duress or coercion of any sort or by offering any inducements.

The G-ICMR also states that, in the case of differently abled participants, such as those with physical, neurological, or mental disabilities, appropriate methods should be used to enhance the participants’ understanding (e.g., Braille for the visually impaired).

As delineated in the 2019-CTRules, investigator(s) must obtain an audio-video (AV) recording of the informed consent process for vulnerable participants in clinical trials for a new chemical or molecular entity, including the procedure of providing information to the participant and their understanding of the consent. This AV recording should be retained in the investigator’s files. In cases where clinical trials are conducted on anti-human immunodeficiency virus (HIV) and anti-leprosy drugs, the investigator(s) must only obtain an audio recording of the informed consent process. The investigator(s) is also required to retain the audio recording for their records.

For specific guidelines regarding gene therapy and stem cell therapy clinical trials, see G-GeneThrpy and G-StemCellRes.

Re-Consent

According to the G-ICMR and the G-Children, investigator(s) are required to renew the informed consent of each participant if there are any changes in the ICF related to the study conditions or research procedures, or if new information becomes available during the trial.

Per the G-ICMR and the G-Children, re-consent is applicable in cases in which a participant regains consciousness from an unconscious state and/or recovers mental capacity to understand the research study. If such an event is expected, then procedures to address this circumstance should be explained clearly in the ICF.

The G-ICMR and the G-Children explain that re-consent is required in the following situations:

• New information pertaining to the study becomes available that has implications for the participant(s) or that changes the benefit and risk ratio
• A research participant who is unconscious regains consciousness or suffered loss of mental competence and regains the ability to understand the research implications
• A child becomes an adult during the study, or the parent/legal guardian have changed
• Research requires a long-term follow up or an extension
• There is a change in treatment modality, procedures, site visits, data collection methods, or tenure of participation which may impact a participant’s decision to continue in the research
• There is possibility of identity disclosure through data presentation or photographs (this should be camouflaged adequately) in an upcoming publication
• Future research may be carried out on stored biological samples if not anonymized

The partner/spouse may also be required to give additional re-consent in some of the above cases.

Language Requirements

As stated in the 2019-CTRules and the G-ICMR, the ICF should be written in English and/or in a vernacular language that the participant is able to understand.

Documenting Consent

The G-ICMR and the G-Children specify that the participant or the participant’s legal representative/guardian must sign and date the ICF. If the participant is incapable of giving an informed consent, the legal representative/guardian should sign and date the ICF. Where the participant or the legal representative/guardian is illiterate, verbal consent should be obtained in the presence of and countersigned by an impartial witness.

Per the G-ICMR, if the participant or the legal representative/guardian cannot sign, a thumb impression must be obtained. In addition, the investigator(s) who administers the consent should also sign and date the ICF. As stated in the G-ICMR and the G-Children, when written consent as a signature or thumb impression is not possible, verbal consent may be taken with the EC’s approval, in the presence of an impartial witness who should sign and date the consent document, or through an AV recording. Per the G-ICMR, the ICF may also be administered and documented electronically, as long as the EC approves the process first.

As described in the G-ICMR, the following special situations may also arise in administering consent:

• The gatekeeper’s (a group’s head/leader or the culturally appropriate authorities), may provide permission on the group’s behalf in writing or audio/video recording and be witnessed
• Community consent is required for certain populations in order for participants to be permitted to participate in the research

According to the G-ICMR and the G-Children, a copy of the signed ICF and the patient information sheet should be given to the participant or the legal representative/guardian. Per the G-Children, the investigator should also keep a signed copy of the ICF.

Waiver of Consent

As specified in the G-ICMR and the G-Children, the investigator(s) can apply to the EC for a waiver of consent if the research involves less than minimal risk to participants and the waiver will not adversely affect the rights and welfare of the participants. In addition, per the G-ICMR, the EC may grant a waiver of consent in the following situations:

• Research cannot practically be carried out without the waiver and the waiver is scientifically justified
• Retrospective studies, where the participants are de-identified or cannot be contacted
• Research on anonymized biological samples/data
• Certain types of public health studies/surveillance programs/program evaluation studies
• Research on data available in the public domain, or
• Research during humanitarian emergencies and disasters, when the participant may not be in a position to give consent. An attempt should be made to obtain the participant’s consent as soon as possible

Refer to the Children/Minors section for information on waivers involving children.

See the G-ICMR, IND-5, and IND-27 for additional information on informed consent requirements.

Obtaining Consent

In accordance with the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines. Per LBR-8, a freely given informed consent must be obtained from every study participant prior to clinical trial participation. According to the G-ACRE-IRB, the G-NREB, and LBR-8, the informed consent form (ICF) is viewed as an essential document that must be reviewed and approved by an ethics committee (EC).

As delineated in the LibCTReg, the trial participant should be informed of the nature, significance, and implications of the clinical trial and have given a voluntary written informed consent. The trial participant or witness, if applicable, must be informed by an investigator, who is a healthcare professional or a person designated by the investigator, and who is knowledgeable about the nature, significance, risks, and implications of the clinical trial as well as about the participant’s right to withdraw from the clinical trial at any time. A generally comprehensible information sheet is to be handed out to the participant. The trial participant is also to be given the opportunity to have a counseling session with an investigator or a person designated by the investigator about the other conditions surrounding the conduct of the clinical trial.

The LibCTReg further notes that a declaration of consent to participate in a clinical trial can be revoked at any time in the presence of the investigator or a member of the investigating team, orally or in writing, without disadvantage to the trial participant. In the case of a revocation of consent, the study participant must decide whether their stored data may continue to be used.

Per the G-ACRE-IRB, the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB) must assess the study to ensure the voluntary, non-coercive recruitment of research participants. The board must ensure that they have adequately considered the following in the protocol (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the National Research Ethics Board of Liberia (NREB) and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.):

• Procedures for obtaining informed consent
• Content of the participant information sheet
• Content and language of the informed consent document
• Translation of the informed consent document into the local language
• The language used in the documents should be simple relative to the general public’s level of understanding
• Contact persons with their addresses and telephone numbers (for both the study team and the EC)
• Privacy and confidentiality
• Risks (physical, mental, social)
• Benefits to participants and to others
• Compensation (reasonable/unreasonable)
• Involvement of vulnerable participants
• Provision for medical/psychosocial support
• Treatment for study-related injuries
• Use of biological materials

Per the G-ACRE-IRB, if the informed consent procedures and consent document(s) are reviewed by the ACRE IRB Secretariat and found to be complete, the documentation is then submitted to the board for review. If the documentation qualifies for expedited review, the chairperson or a designated expedited reviewer will evaluate the materials. After the investigator makes the required changes suggested by the ACRE IRB, the application may be approved by the chair.

(See the Required Elements section for details on what should be included in the ACRE IRB and NREB forms. Refer to LBR-33 for the NREB Exempt Human Research Consent Script Form and LBR-34 for the NREB Short Consent Form.)

LBR-8 states that the investigator or the designated representative must provide detailed research study information to the participant or legal representative/guardian. LBR-8 further specifies that the oral and written information concerning the trial, including the ICF, should be easy to understand and presented without coercion or unduly influencing a potential participant to enroll in the clinical trial. The participant or legal representative/guardian, should also be given adequate time to consider whether to participate.

Further, per LBR-8, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant or the legal representative/guardian to waive or to appear to waive the legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or their representatives from their liabilities for any negligence.

Re-Consent

According to LBR-8, the LMHRA and an EC should approve any change in the ICF due to a protocol modification before such changes are implemented. The participant or legal representative/guardian should be informed in a timely manner if new information becomes available that might be relevant to the participant’s willingness to continue participation in the trial. The participant or legal representative/guardian will also be required to re-sign the revised ICF and receive a copy of any amended documentation.

In addition, per the G-ACRE-IRB, in the case that ACRE IRB approval is reinstated, the ACRE IRB may require previously enrolled participants to re-consent.

Language Requirements

As stated in the G-LibClinTrial, all clinical trial application documentation must be submitted in English. If documents are written in another language, a certified translation is required.

Documenting Consent

The LibCTReg states that if the trial participant is unable to read or write English, the informed consent should be obtained in the language the participant understands and in the presence of at least one (1) witness. The witness, who should be able to read and write English and understand the local language in which the trial participant is informed, should not be a member of the investigating team. The consent given by the trial participant must be documented in writing, dated, and signed by the witness and thumb printed by the trial participant.

Per LBR-8, before participating in the study, the participant or legal representative/guardian should receive a copy of the signed and dated ICF. The participant or legal representative/guardian should also receive a copy of the signed and dated consent form updates and a copy of any amendments to the written information provided to the participants.

LBR-34 also provides a sample NREB ICF for adults capable of consent. A witness must also be present during the consent process and the witness must sign and date the ICF. The number of copies to be signed and distributed is not specified.

Per LBR-8, if a participant is unable to read or if a legally acceptable representative is unable to read, an impartial witness should be present during the entire informed consent discussion. The witness should sign and date the ICF after the following steps have occurred:

• The written ICF and any other written information provided to the participant is read and explained to the participant and legal representative/guardian
• The participant and legal representative/guardian, have orally consented to the participant’s involvement in the trial, and has personally signed and dated the ICF, if capable of doing so

Waiver of Consent

As specified in the G-ACRE-IRB, to obtain a waiver or alteration of informed consent, the investigator must include the request (and provide justification for the waiver or alteration) in the protocol submission to the ACRE IRB. The request for waiver or alteration will be reviewed by the convened board, the ACRE IRB Chair, or the designated expedited reviewer. The ACRE IRB reviewer (Chair or designee) may approve the waiver or alteration of informed consent, if the board reviewer can establish that the research is to be conducted by or subject to the approval of state or local government officials and is designed to study, evaluate, or otherwise examine:

• Public benefit or service programs
• Procedures for obtaining benefits or services under those programs
• Possible changes in or alternatives to those programs or procedures, or
• Possible changes in methods or levels of payment for benefits or services under those programs

The ACRE IRB reviewer should also be able to ascertain that the research could not practicably be carried out without the waiver or alteration.

Additionally, per the G-ACRE-IRB, the ACRE IRB reviewer may approve the waiver or alteration of informed consent, if the reviewer determines the following:

• The research involves no more than minimal risk to the participants
• The research could not practicably be conducted without the requested waiver or alteration
• If the research involves using identifiable private information or identifiable biospecimens, the research could not practicably be carried out without using such information or biospecimens in an identifiable format
• The waiver or alteration will not adversely affect the rights and welfare of the participants, and
• Whenever appropriate, the participants or legal representative/guardian will be provided with additional pertinent information after participation. The ACRE IRB reviewer will document the findings for waiver or alteration of informed consent. An alteration to informed consent may apply when conducting a study where there is deception or an incomplete disclosure (for example, studies that require deception because the study would be compromised if participants were told the true purpose)

In addition, the G-ACRE-IRB explains that a waiver of a signed ICF may be appropriate for some research studies such as survey or interview studies containing highly sensitive questions (e.g., health status, sexual practices, criminal behavior, etc.), or surveys containing non-sensitive information. To obtain a waiver of documented (signed) informed consent, the investigator must include the request (and provide justification for the waiver or alteration) in the protocol submission process. The request for waiver or alteration will be reviewed by the convened ACRE IRB, the Chair, or the designated expedited reviewer. The ACRE IRB reviewer will consider the investigator’s request and review the request to determine if:

• The only record linking the participant and the research would be the consent document, and the principal risk would be potential harm resulting from a breach of confidentiality
• The research presents no more than minimal risk of harm to participants and involves no procedures for which written consent is normally required outside of the research context
• The participants or legal representative/guardian are members of a distinct cultural group or community in which signing forms is not the norm, that the research presents no more than minimal risk of harm to participants, and provided that there is an appropriate alternative mechanism for documenting that informed consent was obtained. In cases where the documentation requirement is waived, the ACRE IRB may require the investigator to provide participants with a written statement regarding the research, such as an information sheet, instead of an informed consent document

Per the 2019-CTRules, the G-ICMR, and the G-Children, the informed consent form (ICF) should include the following statements or descriptions, as applicable (Note: Each of the items listed below will not necessarily be found in all sources, which provide overlapping and unique elements):

• The study involves research and an explanation of its nature and purpose
• The expected duration of the participant’s participation
• Any benefits reasonably expected from the research to the participant or others; if no benefit is expected, the participant should be made aware of this
• The disclosure of specific appropriate alternative procedures or therapies available to the participant
• The mechanism by which confidentiality of records identifying the participant will be maintained and who will have access to the participant’s medical records
• An explanation about whom to contact for trial-related queries, participant rights, and in the event of any injury
• The policy on compensation and/or medical treatment(s) available to the participant in the event of a trial-related injury, disability, or death
• Participation is voluntary, the participant can withdraw from the study at any time, and refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled
• Any reasonably foreseeable risks or discomforts to the participant resulting from participation
• Approximate number of participants enrolled in the study

Additional requirements listed in the G-ICMR and the G-Children include:

• Foreseeable extent of information on possible current and future uses of the biological material and of the data to be generated from the research (e.g., storage period of sample/data; probability of material being used for secondary purposes; whether material is to be shared with others; participant’s right to prevent use of their biological sample(s) at any time during or after the study; risk of discovery of biologically sensitive information and provisions to safeguard confidentiality)
• Publication, if any, including photographs and pedigree charts
• Payment/reimbursement for participation and incidental expenses depending on the type of study
• Insurance coverage, if any, for research-related or other adverse events
• If there is a possibility that the research could lead to any stigmatizing condition (e.g., HIV and genetic disorders, provision for pre-test and post-test counseling)
• Post-research plan/benefit sharing for biological material research and/or if data leads to commercialization

Additional requirements listed in the 2019-CTRules include:

• The procedures to be followed, including all invasive procedures
• The investigational product (IP) may fail to achieve the intended therapeutic effect
• In the case of a placebo-controlled trial, the placebo administered to the participant(s) must not have any therapeutic effect
• The anticipated prorated payment, if any, to the participant for participating in the trial
• The participant’s responsibilities in participating in the trial
• Foreseeable circumstances under which the investigator(s) may remove the participant without consent
• The consequences of a participant’s decision to withdraw from the research, and procedures for orderly withdrawal by the participant
• The participant or the legal representative/guardian will be notified in a timely manner if significant new findings develop during the study which may affect the participant’s willingness to continue
• The particular treatment or procedure may involve risks to the participant (or to the embryo or fetus, if the participant is or may become pregnant), which are currently unforeseeable
• Additional costs to the participant that may result from participating in the study
• Any other pertinent information
• Clinical trial treatment schedule(s) and the probability for random assignment to each treatment

See the Vulnerable Populations and Consent for Specimen sections for further information.

For specific guidelines regarding gene therapy and stem cell therapy clinical trials, see G-GeneThrpy and G-StemCellRes.

Liberia Medicines and Health Products Regulatory Authority

As specified in the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) to comply with informed consent requirements for use along with the LMHRA guidelines.

LBR-8 states that the informed consent form (ICF) should include the following statements or descriptions, as applicable:

• The study involves research and an explanation of its purpose
• Trial treatment(s) and the probability for random assignment to each treatment
• Trial procedures to be followed, including all invasive procedures
• The participant’s responsibilities in participating in the trial
• Experimental aspects of the study
• Any foreseeable risks or discomforts to the participant, and when applicable, to an embryo, fetus, or nursing infant
• Alternative procedures or treatment that may be available to the participant, and if any, which might be advantageous to the participant
• Compensation and/or medical treatment available to the participant or the participant’s family or dependents in the event of a trial-related injury
• Any expected benefits or prorated payment to the participant for participating in the trial
• Any additional costs to the participant that may result from participation in the research
• Participation is voluntary, the participant may withdraw at any time, and refusal to participate will not involve any penalty or loss of benefits, or reduction in the level of care to which the participant is otherwise entitled
• The LMHRA, the monitor(s), the auditor(s), and the ethics committee (EC) will be granted direct access to the participant’s original medical records to verify clinical trial procedures and/or data without violating the participant’s confidentiality
• A statement describing the extent to which, if any, confidentiality of records identifying the participant will be maintained, and if the results of the trial are published, the participant’s identity will remain confidential
• The participant or legal representative/guardian will be notified in a timely manner if significant new findings develop during the course of the study which may affect the participant's willingness to continue
• The person(s) to contact for further information regarding the trial and the rights of trial participants, and whom to contact in the event of trial-related injury
• Foreseeable circumstances under which the investigator(s) may remove the participant without the participant’s consent
• The expected duration of the participant's participation
• Approximate number of participants involved in the trial

National Research Ethics Board of Liberia

The following elements are to be included in the National Research Ethics Board of Liberia (NREB)’s Exempt Human Research Consent Script Form (LBR-33) and the NREB Short Consent Form (LBR-34) respectively (Note: Each of the items listed below will not necessarily be found in both sources, which provide overlapping and unique elements):

• Indication that the person is being asked to take part in a research study
• Research study purpose and reason for participant’s eligibility to participate in study
• Duration of research study
• Participation is voluntary and participant may withdraw at any time
• Explanation of study-specific procedures and sample questions provided to participants
• Possible risks associated with participating in study
• Benefits to participant or to others from participating in study
• Appropriate alternative procedures, or courses of treatment, if any
• Explanation of what is experimental vs. routine standard of care
• Statement regarding who will have access to the participant’s personal information
• Participant’s right to decline participating in any part of study for any reason and right to end participation at any time, and refusal to participate will not be held against the participant
• Researcher’s contact information for any questions the participant may have prior to deciding to participate and throughout the participant’s involvement in the study

See LBR-33 and LBR-34 for additional details.

Per LBR-34, if applicable, the following information is also included in the NREB Short Consent Form:

• Whether the participant will get treated or paid if injured
• The possibility of unknown risks
• When the participant may be taken off the research study without the participant’s agreement
• Added costs from taking part in the study
• What will happen if the participant stops taking part
• Steps to safely stop taking part
• What new information will be shared with the participant
• The number of participants expected to take part in the study
• What happens to the participant’s collected data if the participant withdraws from the trial
• An explanation of the ClinicalTrials.gov (LBR-40) website

Atlantic Center for Research and Evaluation Institutional Review Board

The G-ACRE-IRB indicates that the principal investigator (PI) is responsible for preparing the ICF and that the ICF should include the following statements or descriptions (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.):

• The study involves research and an explanation of its purpose
• The expected duration of a participant’s involvement in the research
• A description of the procedures to be followed
• Identification of any experimental study procedures
• Any foreseeable risks or discomforts to the participant
• Any benefits to the subject or to others that may reasonably be expected from the research
• Alternative procedures or treatment that may be available to the participant, and if any, which might be advantageous to the participant
• A statement describing the extent to which, if any, confidentiality of records identifying the participant will be maintained
• A statement noting the possibility that the EC (or its designees) and the study sponsor may inspect the study records, if the research is sponsored by a funding source
• For research involving more than minimal risk, an explanation of compensation and/or medical treatment available to the participant or the family or dependents in the event of a trial-related injury, and if injury occurs, what the medical treatments consist of, or where further information may be obtained
• The person(s) to contact for further information regarding the trial and the rights of research participants, and whom to contact in the event of research-related injury
• Participation is voluntary, the participant may withdraw at any time, and refusal to participate will not involve any penalty or loss of benefits, or reduction in the level of care to which the participant is otherwise entitled

In addition to the required elements listed above, per the G-ACRE-IRB, for research involving the collection of identifiable private information or identifiable biospecimens, one (1) of the following must be included in the informed consent:

• A statement that identifiers will be removed from the identifiable private information or identifiable biospecimens and that, after such removal, the information or biospecimens could be used for future research studies without additional informed consent from the participant or legal representative/guardian
• A statement that the participant's information or biospecimens collected as part of the research, even if identifiers are removed, will not be used or distributed for future research studies

See also the Consent for Specimen section for additional information on informed consent relating to specimens.

Overview

In accordance with the 2019-CTRules and the G-ICMR, India’s ethical standards promote respect for all human beings and safeguard the rights of research participants. The G-ICMR upholds the Declaration of Helsinki (IND-63). The 2019-CTRules, the G-ICMR, and the G-Children state that a participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process.

The Right to Participate, Abstain, or Withdraw

As stated in the 2019-CTRules, the G-ICMR, and the G-Children, the participant or the legal representative/guardian should be informed that participation is voluntary, the participant may withdraw from the research study at any time, and refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As per the 2019-CTRules, the G-ICMR, and the G-Children, a potential research participant or the legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation or treatment in the case of injury, and any significant new information regarding the research study.

The Right to Privacy and Confidentiality

As described in the 2019-CTRules, the G-ICMR, and the G-Children, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right. The 2019-CTRules also states that it is the responsibility of the investigator(s) to safeguard the confidentiality of research data to protect the identity and records of research participants.

The Right of Inquiry/Appeal

The 2019-CTRules, the G-ICMR, and the G-Children state that the research participant or the legal representative/guardian should be provided with contact information for the investigator(s) and the ethics committee (EC) to address trial-related inquiries and/or to appeal against a violation of the participant’s rights.

The Right to Safety and Welfare

The G-ICMR clearly states that a research participant’s right to safety and protection of health and welfare must take precedence over the interests of science and society.

See the G-ICMR and IND-27 for additional information on informed consent requirements. Refer to the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.

See also the G-AI-BiomedRes for guidelines on safeguarding participants rights in biomedical and health research involving artificial intelligence-based tools and technologies.

Overview

As specified in the LibCTReg and the G-LibClinTrial, the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines. The G-ACRE-IRB also complies with the Council for International Organizations of Medical Sciences (CIOMS)’ International Ethical Guidelines for Health-related Research Involving Humans (LBR-2) and the national ethical guidelines for research on human participants. (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the National Research Ethics Board of Liberia (NREB) and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.)

As per LBR-8, Liberia’s ethical standards promote respect for all human beings and safeguard the rights of research participants. LBR-8 and the G-ACRE-IRB state that a participant’s rights must also be clearly addressed in the informed consent form (ICF) and during the informed consent process.

The Right to Participate, Abstain, or Withdraw

As set forth in the G-ACRE-IRB, LBR-8, LBR-33, and LBR-34, the participant or legal representative/guardian should be informed that participation is voluntary, that the participant may withdraw from the research study at any time, and that refusal to participate will not involve any penalty or loss of benefits to which the participant is otherwise entitled.

The Right to Information

As per the G-ACRE-IRB, LBR-8, LBR-33, and LBR-34, a potential research participant or legal representative/guardian has the right to be informed about the nature and purpose of the research study, its anticipated duration, study procedures, any potential benefits or risks, any compensation for participation or injury/treatment, and any significant new information regarding the research study. (See the Required Elements section for a more detailed list.)

The Right to Privacy and Confidentiality

As per LBR-8 and the G-ACRE-IRB, all participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement that recognizes this right.

The Right of Inquiry/Appeal

The G-ACRE-IRB, LBR-8, LBR-33, and LBR-34, state that the research participant or legal representative/guardian should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries.

The Right to Safety and Welfare

LBR-8 states that the research participant’s rights, safety, and well-being must take precedence over the interests of science and society.

(See the Required Elements and Vulnerable Populations sections for additional information regarding requirements for participant rights.)

Children in Emergency Situations

Per the G-Children, research involving children in emergency situations should only be carried out when it is scientifically justified and cannot be conducted outside this setting. The ethics committee(s) (EC) should review and approve these studies as well as the proposed timeframe in which formal consent will be obtained. If consent cannot be obtained in an emergency, deferred consent is suggested. Deferred consent involves giving minimum information verbally, followed by full details and formal consent later. If the parent/legal guardian is unavailable or unable to give consent, another individual, such as the participant’s doctor or a person nominated by the healthcare provider, can give consent. However, the doctor or a person nominated by the healthcare provider may not be involved in the research. It is recommended that a Data Safety Monitoring Board (DSMB) be strongly considered for these types of studies. See the Children/Minors section for additional pediatric informed consent requirements.

Moreover, per the G-Children, if a child’s parent/legal guardian refuses to give consent once their child is stabilized, the child should not be included in the research, and no further research related procedures/data collection should be done. Additionally, the previously collected data obtained prior to the consent process should not be used without the parent's/legal guardian's permission.

Humanitarian Emergencies

As explained in the G-ICMR, during a humanitarian emergency or disaster, close attention should be paid to the effect of the emergency on perceptions of ethical questions, altered or increased vulnerabilities, provider-patient and researcher-participant relationships, and issues related to integrity of studies and ethical review processes. Obtaining valid informed consent in humanitarian emergencies is a challenge as the decisional capacity of the participants would be so low that they may not be able to differentiate between reliefs offered and research components. This should be very clearly distinguished during the informed consent process. Additional safeguards are required for participants due to their vulnerability, for example, counseling, psychological help, medical advice, and process of stakeholder consultation.

In addition, the G-ICMR indicates that the potential research participants might be under duress and traumatized. Researchers should be sensitive to this situation and are obligated to ensure that the informed consent process is conducted in a respectful manner. Researchers should strive to identify and address barriers to voluntary informed consent and not resort to inducements for research participation. The different roles of researchers, caregivers and volunteer workers must always be clarified, and potential conflict of interest declared. If research involves vulnerable individuals (such as minors), then the legal representative/guardian should give consent. Additional protections might be required in special cases, for example, children with untraceable or deceased relatives. In these situations, consent should be obtained from an individual who is not part of the research team who should be designated by the institution/agency conducting research.

For seeking a waiver of consent, the researchers should give the rationale justifying the waiver. The EC should approve such a waiver after careful discussion on the issue. Refer to the Documentation Requirements section for additional information on waivers of consent. When consent of the participant or the legal representative/guardian is not possible due to the situation, informed consent must be administered to the participant or the legal representative/guardian at a later stage, when the situation allows. However, this should be done only with the prior approval of the EC. See IND-5 for additional information on consent requirements during medical emergencies.

As set forth in the LibCTReg, in an emergency situation where consent cannot be obtained, treatment which is necessary without delay to save the life of the trial participant can be started immediately. Such situations must be defined by the Liberia Medicines and Health Products Regulatory Authority (LMHRA) and consent for continued participation must be obtained as soon as possible and not later than as defined by the National Research Ethics Board of Liberia (NREB) for a given clinical trial.

The LibCTReg and the G-LibClinTrial further explain that the LMHRA has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines. LBR-8 makes provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by medical emergencies in which prior consent from the participant is not possible.

As delineated in LBR-8, in an emergency, if the signed informed consent form (ICF) cannot be obtained from the research participant, the consent of the legal representative/guardian should be obtained. If the prior consent of the participant or legal representative/guardian cannot be obtained, the participant’s enrollment should follow measures specified in the protocol, and/or elsewhere, with documented LMHRA approval to protect the rights, safety, and well-being of the participant, and to ensure compliance with ethics committee (EC) and LMHRA requirements. The participant or the participant’s legal representative/guardian should be informed about the trial and provide consent as soon as possible.

Per the G-LibClinTrial, examples of emergency situations are epidemics or other urgent public health interests that require fast utilization of new medicines or health products and/or fast gathering of information on products. Information provided to clinical trial participants about the process of obtaining consent must be included in the documents submitted to the LMHRA. Refer to 2.3 of the G-LibClinTrial for additional information on how to submit an expedited clinical trial application package.

Overview

As set forth in the 2019-CTRules and the G-ICMR, in all clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process. The G-ICMR further describes vulnerable groups and individuals as those who may have an increased likelihood of incurring additional harm, as they may be relatively (or absolutely) incapable of protecting their own interests. According to the G-ICMR, vulnerable populations are characterized as individuals/communities with hierarchical relationships (e.g., prisoners, armed forces personnel, or staff and students at medical, nursing, or pharmacy academic institutions); economically and socially disadvantaged individuals (e.g., persons who are unemployed, abandoned, orphans, have language barriers, or cultural differences); persons below the poverty line; ethnic, religious, or sexual minority groups; tribal and marginalized communities; terminally ill patients or those suffering from stigmatizing or rare diseases; patients in emergency situations; institutionalized persons; homeless persons, nomads, or refugees; minors; women in special situations (e.g., pregnant or lactating women, those with poor decision-making powers, or poor access to healthcare); those with mental illness and cognitively impaired, differently abled, or mentally or physically disabled; or others incapable of personally giving consent.

See the G-ICMR for detailed safeguards that must be complied with when trials involving vulnerable populations are conducted. The G-ICMR also describes research principles that must be upheld during these trials and upholds the Declaration of Helsinki (IND-63). See also the G-AI-BiomedRes for guidelines on safeguarding participants rights in biomedical and health research involving artificial intelligence-based tools and technologies, especially those participants from underrepresented and vulnerable populations.

See the Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired sections for additional information about these vulnerable populations. See also IND-5 for additional information on consent requirements for vulnerable populations.

For specific guidelines regarding gene therapy and stem cell therapy clinical trials, see the G-GeneThrpy and the G-StemCellRes.

Terminally Ill Patients

Per the G-ICMR, terminally ill patients or patients seeking new treatments are vulnerable as they are ready to give consent for any intervention that could help them. The EC should carefully review protocols and recruitment procedures for these studies and comply with the following requirements:

• Additional monitoring should be done to detect any adverse event as soon as possible
• A benefit-risk assessment should be performed that considers the potential participant’s perception of benefits and risks
• Post-trial access to the medication

Indigenous Peoples

The G-ICMR states that research on tribal populations should only be conducted if it is of a specific therapeutic, diagnostic, and preventative nature with appropriate benefits to the tribal population. A competent administrative authority’s approval, such as the tribal welfare commissioner or the district collector, should be obtained prior to an investigator entering the area. Whenever possible, it is desirable to seek the help of government functionaries/local bodies or registered, non-governmental organizations who work closely with the tribal groups and have their confidence. The tribal leader, or other culturally appropriate authority may serve as the gatekeeper from whom permission to enter and interact should be obtained. A participant’s consent should be taken along as well as consulting with community elders and individuals who know the local language/dialect of the tribal population, and in the presence of appropriate witnesses. Additional precautions should be taken to avoid including children, pregnant women, and elderly people belonging to particularly vulnerable tribal groups. Benefit sharing with the tribal group should also be ensured for any research done using tribal knowledge that may have the potential for commercialization.

Elderly Persons

Permission to conduct clinical trials in geriatric patients must comply with the requirements listed in the Required Elements section. According to 2019-CTRules, geriatric patients should be included in Phase II and Phase III clinical trials at the sponsor’s (also known as the applicant’s) recommendation, in the following circumstances:

• The disease intended to be treated is typically a disease of aging
• The population to be treated is known to include substantial numbers of geriatric patients
• There is specific reason to expect that conditions common in the elderly are likely to be encountered
• The new drug is likely to alter the geriatric patient’s response (with regard to safety or efficacy) compared with that of the non-geriatric patient

Persons in Dependent Groups

As indicated in the G-ICMR, while reviewing protocols involving participants who are engaged in subordinate or dependent relationships, the ethics committee (EC) must ensure the following:

• Participant enrollment is specifically relevant to the research questions and is not merely a matter of convenience
• Extra efforts are required to ensure the autonomy of these individuals is respected, and that they are able to freely decide to participate or deny consent and/or later withdraw from the study without fear of any negative repercussions on their care
• Mechanisms to avoid coercion due to being part of an institution or hierarchy should be described in the protocol

Sexual Minorities and Sex Workers

Per the G-ICMR, sexual minorities and sex workers require additional protections as they are more vulnerable to privacy, confidentiality, stigma, discrimination, and exploitation issues during a research study. Research proposals should ensure the dignity of these participants is protected and that they have access to quality healthcare. Investigators should consult the community, if possible, prior to the proposal being finalized. It is also advised that a representative of the sexual minority group/lesbian/gay/bisexual and transgender (LGBT) community attend the EC meeting as a special invitee/member.

Overview

The LibCTReg and the G-LibClinTrial explain that the Liberia Medicines and Health Products Regulatory Authority (LMHRA) has adopted the International Council for Harmonisation's Guideline for Good Clinical Practice E6(R2) (LBR-8) for use along with the LMHRA guidelines. According to LBR-8, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process.

LBR-8 explains that vulnerable populations include those participants whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. Examples may include, but are not limited to, members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students; subordinate hospital and laboratory personnel; employees of the pharmaceutical industry; members of the armed forces; and persons kept in detention. Other vulnerable study participants include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.

Persons with Diseases

As indicated in the LibCTReg, in the case of a clinical trial on a person of legal age who is suffering from a disease for which the investigational product (IP) is to be used, one (1) of the following conditions should be applied along with the general clinical trial requirements delineated in the LibCTReg:

• The use of the IP is indicated according to the findings of medical science in order to save the person's life
• The IP must be of direct benefit to the group of patients who are suffering from the same disease as this person

Persons Under Legal Disability

As set forth in the LibCTReg, “persons under legal disability” are defined as being under the same category as a minor in terms of the individual’s ability to grant consent, except that the person under disability may be above the age of consent (18 years), but may be too ill to participate in decisions regarding their own health. In this case, priority is not given to parents or next of kin to petition the Probate Court for Guardianship, but priority is given to any natural person who demonstrates best interest in the welfare of the disabled.

The LibCTReg further explains that a person under legal disability may participate in a trial, if their parents/legal guardians have be informed of the nature, significance, and implications of the clinical trial and have given a written voluntary informed consent. If the informed implication is grave, it may be necessary for the guardian to secure the permission from the Probate Court before granting consent, due to the fact that the Decree of Guardianship has a clause that the Court appointed guardian should not release the disabled person to any other body in which case their welfare will be put at peril. Otherwise, it can be argued that the appointed guardian has breached their fiduciary duty to the Court by releasing the disabled person to peril.

See the Children/Minors and Mentally Impaired sections for additional information about these vulnerable populations.

As per the G-ICMR, children are individuals who have not obtained the legal age of consent, which is 18.

As stated in the G-ICMR, the 2019-CTRules, and the G-Children, in the case of pediatric clinical trials, participants are legally unable to provide written informed consent, and are dependent on their parents/legal guardians to assume responsibility for their participation in a research study.

However, as specified in the 2019-CTRules, all pediatric participants should be informed to the extent compatible with the child’s understanding, and if capable, the pediatric participant should sign and personally date the informed consent form (ICF). In these studies, the following requirements should be complied with:

• Written informed consent should be obtained from the parent/legal guardian; however, all pediatric participants should be informed to the fullest extent possible about the study in a language and in terms that they are able to understand
• Where appropriate, pediatric participants should additionally provide their assent to enroll in the study, and mature minors and adolescents should personally sign and date a separately designed written assent form
• Although a participant’s wish to withdraw from a study must be respected, there may be circumstances in therapeutic studies for serious or life-threatening diseases in which, in the investigator’s and parent’s/legal guardian’s opinion, a pediatric patient’s welfare would be jeopardized by failing to participate in the study. In this situation, continued parental/legal guardian consent should be sufficient to allow participation in the study

The 2019-CTRules further specifies requirements for pediatric studies involving new drugs. These studies must take into account the following issues:

• The timing of new drug pediatric studies will depend on the medicinal product, the type of disease being treated, safety considerations, and the efficacy and safety of available treatments
• If the new drug is for diseases predominantly or exclusively affecting pediatric patients, clinical trial data should be generated in the pediatric population except for initial safety and tolerability data, which will usually be obtained in adults, unless such initial safety studies in adults would yield little useful information or expose them to inappropriate risk
• If the new drug is intended to treat serious or life-threatening diseases, occurring in both adults and pediatric patients, for which there are currently no or limited therapeutic options, the pediatric population should be included in the clinical trials early, following assessment of initial safety data and reasonable evidence of potential benefit; in circumstances where this is not possible, lack of data should be justified in detail
• If the new drug has a potential for use in pediatric patients, pediatric studies should be conducted
• Pediatric studies should include clinical trials, relative bioequivalence comparisons between pediatric and adult formulations, and pharmacokinetic studies for dose selection across the age ranges of pediatric patients in whom the drug is likely to be used
• If the new drug is a major therapeutic advance for the pediatric population, studies should begin early in the drug development, and this data should be submitted with the new drug application

The reviewing ethics committee (EC) should also include members who are knowledgeable about pediatric, ethical, clinical, and psychosocial issues.

Refer to the 2019-CTRules for detailed pediatric study requirements.

Per the G-ICMR, the EC should also perform a benefit-risk assessment to determine whether there is a need to implement additional safeguards/protections to conduct a study involving children. The EC should consider the circumstances of the children to be enrolled in the study including their age, health status, and other factors and potential benefits to other children with the same disease or condition, or to society as a whole. In addition, the G-Children should be consulted for detailed EC assessment criteria to be used to evaluate research studies involving children.

As per the G-Children, following EC approval of the protocol, the informed consent requirement for children may be waived in the following circumstances:

• When it is impractical to conduct research since confidentiality of personally identifiable information has to be maintained throughout the study (e.g., a study on the disease/burden of HIV/AIDS)
• Research is carried out on publicly available information, documents, records, works, performances, reviews, quality assurance studies, archival materials or third-party interviews, etc.
• Research on anonymized biological samples, leftover samples after clinical investigation/research, cell lines, or cell free derivatives (e.g., viral isolates, DNA or RNA from recognized institutions or qualified investigators, samples or data from repositories or registries, etc.) provided permission for future research on these samples has been taken in the previous ICF
• In emergency situations when no surrogate consent can be taken
• Retrospective studies, where the participants are de-identified or cannot be contacted

Assent Requirements

As delineated in the G-ICMR, the 2019-CTRules, and the G-Children, if the pediatric participant has the capacity for assent, the participant’s affirmative assent is required to participate in a study according to their developmental level and decision-making capacity. Per the 2019-CTRules, mature minors and adolescents should personally sign and date a separately designed written assent form. According to the G-ICMR, mature minors are those from age seven (7) up to age 18.

The G-Children also explains that in addition to the children’s developmental level and capability of understanding, the assent process and form should also take into account their age, maturity, reading level, independence, autonomy as well as cultural and social factors. For children between ages seven (7) and 11, oral assent must be obtained in the presence of their parent/legal guardian. For children between ages 12 and 18, written assent must be obtained.

A child’s dissent or refusal to participate must always be respected, and the child must be informed in an understandable manner that assent may be withdrawn at any time during the study. The EC may also issue a waiver of assent in the following circumstances:

• If the research has the potential to directly benefit the child, and this benefit is only available through this study
• If the research involves children with intellectual and other developmental disabilities, they may not have the developmental level and intellectual capability to give assent

For details and guidance on preparing and using an assent form, see the G-Children.

According to the LibCTReg and the G-NREB, Liberia defines children and minors as those persons under 18 years of age. The G-NREB also defines adolescents as those between the ages of 15 and 17.

The LibCTReg also states that the definition of legal guardian or the “legal representative of a minor” is based on the premise that a minor cannot grant consent or enter into an agreement. According to LibCTReg, the interest of a minor must be firstly protected by the parents (the father if the parents are married or the child is legitimized) or the mother of the child if the parents are not married. Where there is no parent alive, especially the mother if the child is not born out of wedlock or legitimized, any next of kin, preferably the grandparents first, the siblings second, or any person with interest in the welfare of the child, may petition the Probate Court for Decree of Guardianship. A guardian must be authorized to give consent for the minor child. No institution can serve as guardian and give consent for research on the child. A guardian must be a natural person, not an institution.

Additionally, per the LibCTReg, a minor may participate in a trial, if their parents/legal guardians have been informed of the nature, significance, and implications of the clinical trial and have given a written voluntary informed consent. If the informed implication is grave, it may be necessary for the guardian to secure the permission from the Probate Court before granting consent, due to the fact that the Decree of Guardianship has a clause that the Court appointed guardian should not release the minor to any other body in which case their welfare will be put at peril. Otherwise, it can be argued that the appointed guardian has breached their fiduciary duty to the Court by releasing the minor or disabled to peril.

Also, as indicated in LibCTReg, in the case of a clinical trial on a minor who suffers or may suffer from a disease for which the investigational product (IP) is to be used, the following conditions should be applied:

• The use of the IP must be indicated according to the findings of medical science in order to save the life of the trial participant, to restore the participant to health, to alleviate suffering, or to prevent a disease
• The clinical trial must be of direct benefit to the group of patients suffering from the same disease as the trial participant
• The research must be absolutely necessary in order to confirm data obtained in clinical trials on other persons or by means of other research methods
• The research must relate to a clinical condition from which the minor concerned is suffering or may suffer
• The research may cause only minimal risk and minimal burden to the trial participant

LBR-34 also provides a sample National Research Ethics Board of Liberia (NREB) informed consent form (ICF) for children that explains the parents’ or guardian’s signatures document their permission for the child to take part in a research study as well as their permission for the use and disclosure of the child’s protected health information. If a second parent’s signature is not obtained, the first parent or guardian needs to choose one (1) of the following options on the form to justify why this is not possible:

• The ethics committee (EC) has determined that the permission of one (1) parent is sufficient (this option is only listed on the form if it has been approved by the EC)
• Second parent is deceased
• Second parent is unknown
• Second parent is incompetent
• Second parent is not reasonably available
• Only one (1) parent has legal responsibility for the care and custody of the child

In addition, an individual may provide permission as a guardian for a child only if that individual can provide a written document indicating that the individual is legally authorized to consent to the child’s general medical care and this documentation must be attached to the signed ICF. LBR-34 indicates that the EC must approve the consent form, a witness must be present during the consent process, and the witness must sign and date the ICF.

LBR-8 further states that when a clinical trial includes minors, the minor should be informed about the trial to the extent compatible with his or her understanding and, if capable, the minor should sign and personally date the written informed consent.

As delineated in the G-ACRE-IRB, the Atlantic Center for Research and Evaluation Institutional Review Board (ACRE IRB) must classify research involving children into one (1) of four (4) categories and document its discussion of the risks and benefits of the research study in order to approve such research. The risk/benefit categories are as follows (Note: Per LBR-28, due to a Memorandum of Understanding (MOU) between the NREB and the ACRE IRB in 2022, the ACRE IRB does not review and approve clinical trial protocols. All clinical trial protocols submitted to the ACRE IRB are referred to the NREB.):