Pharmacy Board of Sierra Leone

As per the G-SLAppClinTrial and the SL-GCPs, the Pharmacy Board of Sierra Leone (PBSL) is the regulatory authority responsible for clinical trial approvals, oversight, and inspections in the country. SLE-22 and SLE-13 state that the PBSL was originally established through an Act of Parliament in 1988, and re-established in 2001 by the PDA2001, to regulate pharmaceutical products, medical devices, cosmetic chemical substances, food and dietary supplement and herbal products, the practice of pharmacy, and any other related matters. The PBSL operates within the Ministry of Health and Sanitation (MoHS). Per SLE-13, the PBSL is responsible for the safety, efficacy, and quality of all locally manufactured, imported, exported, distributed, sold or used drugs, medical devices, cosmetics, and nutritional agents.

Per the G-SLAppClinTrial, the PBSL monitors a clinical trial from beginning to end in order to ensure adequate protection of the general public against the risk of adverse events from authorized clinical trials. The PBSL also conducts on-site inspections of the clinical trial site, sponsor, or manufacturing facilities to ensure the safety of clinical trial participants, the quality and reliability of data obtained in a trial, and that the facilities used continue to be acceptable throughout the clinical investigation.

The G-SLAppClinTrial requires that the PBSL establish an Expert Committee on Pharmacovigilance and Clinical Trials to provide support in reviewing and authorizing clinical trial applications, and to give medical and scientific opinions on issues related to clinical trials and medicines safety. The PBSL acts as the Secretariat for the committee. For more information, see the G-SLAppClinTrial.

SLE-15 indicates that the PBSL’s Pharmacovigilance and Clinical Trials department is responsible for ensuring that the PBSL’s legal obligations in relation to drug safety are fulfilled in accordance with PDA2001.

Please note: Sierra Leone is party to the Nagoya Protocol on Access and Benefit-sharing (SLE-2), 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 SLE-18.

Contact Information

According to the PBSL website, the contact information for the PBSL is as follows:

Pharmacy Board of Sierra Leone
Central Medical Stores Compound
New England Ville, Freetown
P.M.B. 322
Sierra Leone
Phone: +232 73994830 and +232 99117117
Email: info@pharmacyboard.gov.sl; registrar@pharmacyboard.gov.sl

SLE-4 provides the following details for the Pharmacovigilance and Clinical Trials Department:

Head of Department: Pharm. Onome Abiri Thomas
Phone: +232 78534757

Overview

In accordance with the G-SLAppClinTrial and the SL-GCPs, the Pharmacy Board of Sierra Leone (PBSL) is the regulatory authority responsible for reviewing, evaluating, and approving applications for clinical trials using registered and unregistered investigational products (IPs). The scope of the PBSL’s assessment includes all clinical trials (Phases I-IV). As delineated in the G-SLAppClinTrial, clinical trial application submissions to the PBSL and the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), may be made in parallel in the case of a public health emergency or as deemed fit by the PBSL.

Clinical Trial Review Process

As set forth in the G-SLAppClinTrial and the SL-GCPs, the PBSL coordinates the clinical trial application process. The SL-GCPs states that the sponsor/principal investigator (PI) must apply to the PBSL for approval to conduct a trial for a non-registered drug or a registered drug for new indications. The PBSL is responsible for reviewing the study design, which involves reviewing all significant ethical questions. The PBSL does a thorough scientific review of all applications for clinical trials to be conducted in Sierra Leone. According to the G-SLAppClinTrial, the PBSL must issue a Clinical Trial Certificate to authorize the initiation and conduct of the clinical trial.

As delineated in the G-SLAppClinTrial, the PBSL will inform the applicant in writing about the receipt of a valid clinical trial application or the formal grounds for non-acceptance, and the applicant must address formal grounds for non-acceptance. If changes are required and the applicant fails to modify the application correspondingly within a maximum of 30 working days, following the reasoned objections, the application will be deemed rejected. During evaluation, additional documents or changes may be requested through a query letter. Once a query has been raised and issued to the applicant, the process stops until the PBSL receives a written response to the query. If the PBSL requires changes to the application and the applicant fails to modify the application correspondingly within a maximum of 90 days following the reasoned objections, the application will be deemed rejected. See Figure 1 in Section 5.17 of the G-SLAppClinTrial for more details on the PBSL’s clinical trial authorization process.

The G-SLAppClinTrial indicates that any proposed amendment to the trial application, trial arrangements, and IP must be submitted to the SLESRC and the PBSL for approval before such amendments are carried out. If the amendments are substantial and are likely to have an impact on the safety of the trial participants, or are likely to change the interpretation of the scientific documents in support of the conduct of the trial, the sponsor must notify PBSL of the reasons for, and the content of, the amendments. For more details, see the G-SLAppClinTrial and the amendment form in Appendix V. See also SLE-8 for the amendment checklist.

According to the G-SLAppClinTrial, the Clinical Trial Certificate must be renewed annually with an application for renewal to the PBSL. A Clinical Trial Certificate will be revoked if conditions for which the certificate was issued are violated.

The G-SLAppClinTrial further states that if a clinical trial application is rejected by the PBSL, any person or institution may appeal the decision in writing within 60 days after receipt of the decision, to request PBSL review or reconsideration of the initial decision. The applicant must give grounds for review for each reason given in the clinical trial rejection. The grounds for the request must be based on the information that was submitted in the application. Upon review of the appeal application, the PBSL must provide the appeal application decision in writing, including a statement of reasons (e.g., findings, references to evidence, and reasons for the decision). For more information on appeal contents and timelines, see the G-SLAppClinTrial.

The G-SLInspect indicates that clinical trial inspections through on-site visits form part of the PBSL’s monitoring activities. Periodic good clinical practice (GCP) inspections of trial sites are conducted to ensure that the facilities used continue to be acceptable throughout the clinical investigation. The inspections may be carried out randomly and/or for specific reasons and are either announced or unannounced. An inspection would consist of a comparison of the procedures and practices of the PI with the commitments set out in the protocol and reports submitted to the PBSL by the investigator or the sponsor. See the G-SLInspect for more information.

Expedited Review During a Public Health Emergency

According to the G-SLAppClinTrial, if expedited review of a clinical trial during a public health emergency is anticipated, the applicant should inform the PBSL in writing. This will allow for a review team to be assembled and plans to be made to manage the workload as well as interactions with other oversight bodies such as the SLESRC. To ensure a rapid start of the clinical study, the PBSL will conduct simultaneous review, rather than sequential review, of the application with the SLESRC. For more information, see the G-SLAppClinTrial.

Other Considerations

The G-SLAppClinTrial indicates that the PBSL may accept the decisions or scientific opinions of other national regulatory authorities, regional bodies, and international bodies if the IP or trial has been authorized by:

• International Council for Harmonisation (ICH) founding regulatory members
• ICH standing regulatory members
• ICH regulatory members
• ICH legislative and administrative authorities
• The African Vaccine Regulatory Forum (AVAREF) at a joint review meeting facilitated by the World Health Organization (WHO) with the provision of a favorable scientific opinion
• Any other regulatory decision deemed appropriate by the PBSL

According to the G-SLAppClinTrial, the PBSL may also consider an application for joint or assisted review by multiple national regulatory authorities and ECs for certain medical products of high public health value to countries on the African continent. For more information, see the G-SLAppClinTrial.

For information on applications involving biosimilar products, see the G-SLBiosimilar.

Pharmacy Board of Sierra Leone

As per the G-SLAppClinTrial, the applicant is responsible for paying a non-refundable fee to the Pharmacy Board of Sierra Leone (PBSL) to submit a clinical trial application for authorization. As delineated below, the authorization fees for foreign sponsored clinical trials of therapeutics, vaccines, and other biological products are as follows:

• Industry Funded (Phase I): $6,500 USD
• Industry Funded (Phase II): $6,500 USD
• Industry Funded (Phase III): $7,000 USD
• Research Institution Funded: $5,000 USD
• Protocol Amendment: $1,000 USD
• Expedited Protocol Review: $1,200 USD
• Renewal of Clinical Trial Certificate (yearly): $100 USD

For locally sponsored clinical trials of therapeutics, vaccines, and other biological products the fees are as follows:

• Investigator/Local Phases: $2,000 USD
• Protocol Amendment: $750 USD
• Expedited Protocol Review: $900 USD
• Renewal of Clinical Trial Certificate (yearly): $50 USD

Payment Instructions

No information is currently available regarding payment instructions for the clinical trial application fee to the PBSL.

Overview

The G-SLAppClinTrial states that in Sierra Leone, the Sierra Leone Ethics and Scientific Review Committee (SLESRC) fulfills the functions of the ethics committee (EC) (known as an Independent Ethics Committee (IEC) in Sierra Leone). Ethical clearance for all phases of clinical trials involving humans must be sought from the SLESRC. The SLESRC is responsible for ensuring the protection of the rights, safety, and well-being of trial participants, and providing assurance of that protection by reviewing, approving, and providing comments on trial protocols and the suitability of the investigator(s), facilities, and the methods and materials to be used in obtaining and documenting informed consent of the trial participants.

Ethics Committee Composition

As per the SL-GCPs, the EC (i.e., the SLESRC) should consist of members who collectively have the qualifications and experience required to review and evaluate the scientific, medical, and ethical aspects of a proposed clinical trial. Specifically, it is recommended that the EC should include:

• At least five (5) members

• At least one (1) member whose primary area of interest is nonscientific

• At least one (1) member who is independent of the institution/trial site

Terms of Reference, Review Procedures, and Meeting Schedule

As set forth in the SL-GCPs, the EC (i.e., the SLESRC) must perform its functions according to written standard operating procedures (SOPs), maintain written records of its activities and meeting minutes, and comply with good clinical practices (GCPs) and other applicable regulatory requirements. An EC must make its decisions at announced meetings where a quorum, as stipulated in the SOPs, is present. Only those EC members who are independent of the trial’s principal investigator (PI) and sponsor should vote or provide an opinion on any trial-related matters. In addition, only members who participate in the EC review process and discussion should vote and provide their opinion.

The SL-GCPs also states that the EC must retain all relevant records (e.g., written procedures, membership lists, lists of occupations/affiliations of members, submitted documents, minutes of meetings, and correspondence) for at least three (3) years after the study’s conclusion, and make them available to the Pharmacy Board of Sierra Leone (PBSL) upon request. The EC may be asked by investigators, sponsors, or the PBSL to provide its written procedures and membership lists.

Overview

According to the G-SLAppClinTrial and the SL-GCPs, the primary scope of information assessed by the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), relates to protecting the well-being and rights of research participants and ensuring their safety throughout their participation in a clinical trial.

As per the SL-GCPs, the EC (i.e., the SLESRC) must also pay special attention to trials that may include vulnerable subjects.

Role in Clinical Trial Approval Process

As indicated in the G-SLAppClinTrial, clinical trial application submissions to the Pharmacy Board of Sierra Leone (PBSL) and the SLESRC may be made in parallel in the case of a public health emergency or as deemed fit by the PBSL. For parallel submissions, the PBSL requires proof of the application’s submission to the SLESRC, as well as any updated versions of documents or information as requested by the SLESRC.

The G-SLEthics further specifies that the principal investigator (PI) must obtain approval for a clinical trial from the SLESRC. The PI should submit a proposal along with other required documentation to the SLESRC Chair at least two (2) calendar months prior to the anticipated commencement of the proposed study.

The SL-GCPs requires that the EC review a proposed clinical trial within a reasonable time and document its views in writing, clearly identifying the trial, the documents reviewed, and the dates for the following: approval/favorable opinion; modifications required prior to its approval/favorable opinion; disapproval/negative opinion; and termination/suspension of any prior approval/favorable opinion. The EC must conduct continuing review of each ongoing trial at intervals appropriate to the degree of risk to human participants, but at least once per year.

There is no stated expiration date for EC approval in the G-SLAppClinTrial, the SL-GCPs, or the G-SLEthics.

(See the Submission Process and Timeline of Review sections for detailed submission process requirements.)

Sierra Leone Ethics and Scientific Review Committee

The G-SLEthics indicates that the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), requires the principal investigator (PI) to pay a nonrefundable administrative fee to submit a protocol for ethical review and approval. The fees are as follows:

• For self-funded, individual Sierra Leonean researchers based in Sierra Leone: 300,000 Leones
• For graduate students studying in Sierra Leone: 200,000 Leones
• For Sierra Leonean students studying abroad: $100 United States Dollars (USD)
• For Sierra Leonean academics abroad: $150 USD
• For all foreign students studying abroad: $200 USD
• For self-funded, international researchers: $400 USD
• For national/local non-governmental organizations (NGOs)/community-based organizations (CBOs): 2,000,000 Leones
• For international NGOs based in Sierra Leone and international universities conducting non-clinical research: 4,000,000 Leones
• For multinational institutions, donor agencies, and institutions not ordinarily based in Sierra Leone: $1,500 USD
• For exclusively government funded studies: 500,000 Leones (must be submitted with a cover letter from the Permanent Secretary of the relevant Ministry or the Chief Medical Officer in the case of the Ministry of Health and Sanitation (MoHS))
• For any amendment made to a previously approved application: 25% of the current fee for the first request, 50% for the second, and 100% for subsequent ones. Sierra Leonean students are exempt from this charge.
• For an application extension: 25% of the original fee
• For exclusively electronic applications: additional $50 USD

Payment Instructions

No information is currently available regarding payment instructions for the SLESRC.

Overview

SLE-3 indicates that the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), does not have a supervisory or oversight mandate over institutional ECs for health research. Few institutions have their own institutional ECs.

Registration, Auditing, and Accreditation

No applicable requirements.

Overview

In accordance with the G-SLAppClinTrial and the SL-GCPs, Sierra Leone requires the sponsor and principal investigator (PI) to obtain clinical trial authorization from the Pharmacy Board of Sierra Leone (PBSL) before commencement of the clinical trial. Furthermore, per the G-SLEthics, the PI is required to obtain ethics approval from the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC).

As indicated in the G-SLAppClinTrial, a favorable opinion from the SLESRC is a required element of a clinical trial application to the PBSL. However, submissions to the PBSL and the SLESRC may be made in parallel in the case of a public health emergency or as deemed fit by the PBSL.

Regulatory Submission

The G-SLAppClinTrial indicates that applicants must submit 15 hard copies of all clinical trial application documents to the PBSL, as well as one (1) soft copy in Microsoft Word format (Acrobat PDF files are also acceptable).

As per the G-SLAppClinTrial, the delivery address for a clinical trial application is as follows:

The Registrar
Pharmacy Board of Sierra Leone
Central Medical Stores
New England Ville, Freetown
P.M.B. 322
Sierra Leone

As per SLE-23, the clinical trial application and accompanying material must be provided in English.

Ethics Review Submission

The G-SLEthics states that the PI should submit to the SLESRC five (5) hard copies of the full research proposal (and all supporting documents) detailing the ethical issues in the study and how they will be addressed (only three (3) copies for extensions), each in a separate envelope. In addition, an electronic copy of the application should be emailed to efoday@health.gov.sl. The G-SLEthics also indicates that the PI may submit an exclusively electronic application for an additional fee. See the Ethics Committee Fees section for more information.

The G-SLEthics states that PIs should submit their applications with a cover letter addressed to the Chair of the SLESRC at least two (2) calendar months before the anticipated commencement of the proposed study.

Per the G-SLEthics, the delivery information for the SLESRC is as follows:

Office of the Sierra Leone Ethics and Scientific Review Committee
Ministry of Health and Sanitation
Directorate of Policy, Planning & Information (DPPI)
Youyi Building, Fifth Floor, East Wing
Freetown
Sierra Leone
Phone: +23278 366493

Regulatory Authority Requirements

As per the G-SLAppClinTrial, the following documentation must be submitted to the Pharmacy Board of Sierra Leone (PBSL):

• Cover letter, including the list of documents submitted and their version number and date
• Non-refundable application fee as specified in the PBSL’s Fee Schedule (see Appendix I of the G-SLAppClinTrial)
• Protocol (see below for detailed protocol requirements)
• Two (2) copies of the completed clinical trial application forms signed by authorized persons (see Appendix II of the G-SLAppClinTrial)
• Proof of registration with the Pan African Clinical Trial Registry (PACTR) (SLE-19) or an internationally recognized PBSL-approved online registry
• Investigator’s Brochure (IB)
• Synopsis of previous trial(s) with the investigational product(s) (IP(s)), if applicable
• Summary of product characteristics or other professional information for all registered medicines used in the trial, or the international equivalent if the medicines are not registered in Sierra Leone
• A list of the planned clinical trial sites and the planned number of trial participants at the sites
• The name and position of the principal investigator(s) (PI(s)) who will be responsible for the sites where the trial is to be conducted, who must be registered with the relevant statutory health council, where applicable, and a resident in Sierra Leone
• Investigator(s) and pharmacist(s) curriculum vitae(s) (CVs) and other relevant documents (see Annex 8 of SLE-6 for the recommended CV format for staff conducting clinical trials)
• Proof of current training in Good Clinical Practice (GCP) for investigator(s), pharmacist(s), and monitor(s)
• Any previous training in the principles of GCP or experience obtained from work with clinical trials and patient care
• Any conditions, such as economic interests and institutional affiliations, that might influence the impartiality of the investigator(s)
• Proof of current, relevant, and appropriate study insurance for all participants undertaken by the sponsor
• Proof of sponsor indemnification for investigator(s) and trial site(s) (see Annex 7 of SLE-6 for suggested wording of the sponsor indemnification)
• Professional indemnity insurance for investigator(s) and other trial staff
• 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 IP. This should include a description of the suitability of facilities, equipment, and human resources, and a description of expertise, issued by the head of the clinic/institution at the clinical trial site or other responsible party
• A favorable opinion from the Sierra Leone Ethics and Scientific Review Committee (SLESRC)
• Recruitment arrangements
• Signed joint financial declaration between the sponsor and the PI (see Appendix IIIc of the G-SLAppClinTrial and Annex 4 of SLE-6)
• Data Safety Monitoring Board (DSMB) membership, CVs, and signed charter
• IP dossier and label
• Current Good Manufacturing Practice (GMP) certificate issued from the national regulatory authority of the country where the IP(s) is manufactured
• Certificate(s) of Analysis
• Certificate(s) of accreditation for the central laboratories
• Participant information sheet, informed consent form (ICF), and informed consent procedure
• Signed declaration by the applicant (see Annex 2 of SLE-6)
• Sponsor/PI contractual agreement, including the study budget
• Signed declaration by the PI and the sponsor of the trial that they are familiar with and understand the protocol, and will comply with GCP as determined by the PBSL in the conduct of the trial (see Appendix IIIa of the G-SLAppClinTrial and Annex 4 on page 12 of SLE-6)
• Workload forms for investigator(s)
• Signed declaration(s) by each investigator and key staff participating in the clinical trial (see Appendix IIIb of the G-SLAppClinTrial and Annex 5 of SLE-6)

• CVs and signed declaration by local monitor(s) (see Annex 6 of SLE-6)

• Copies of recruitment advertisement(s) and questionnaires, if applicable
• Electronic copies of key peer reviewed publications following International Committee of Medical Journal Editors (ICMJE) recommendations to support the application, if applicable
• Labelled CD-ROM (list of files submitted on CD-ROM)

See the G-SLAppClinTrial for more details, including the application submission checklist (Appendix IIa) and the application form (Appendix IIb). The application form is also available at SLE-6.

Ethics Committee Requirements

As per the G-SLEthics, the SLESRC requires the PI to submit the following documentation for ethics approval:

• Cover letter to the Chair of the Committee
• ICF attached to each proposal (Committee does not accept verbal consent, except where it is supported by an independent witness)
• Completed checklist for the Essential Elements in the Application for Approval (see the G-SLEthics)
• Brief CV for the PI and associates clearly stating their roles (not more than four (4) pages each)
• Study proposals submitted for award of a degree must be accompanied by a letter of confirmation from the supervisor and approval by the institution’s review board
• Requests for amendment or extension of study should include a copy of the previous approval letter
• A non-refundable administrative fee for each proposal submitted (see the Ethics Committee Fees section for detailed fee information)

Clinical Protocol

The G-SLAppClinTrial indicates that the clinical trial protocol must comply with the International Council for Harmonisation's (ICH) Guideline for Good Clinical Practice E6(R2) (SLE-24) and the SL-GCPs. Accordingly, the protocol must include:

• 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
• Financing and insurance
• Publication policy

Overview

The G-SLAppClinTrial indicates that the Pharmacy Board of Sierra Leone (PBSL) and the Sierra Leone Ethics and Scientific Review Committee (SLESRC) reviews may be conducted in parallel in the case of a public health emergency or as deemed fit by the PBSL. For parallel submissions, the PBSL requires proof of the application’s submission to the SLESRC, as well as any updated versions of documents or information as requested by the SLESRC.

Regulatory Authority Approval

Per the G-SLAppClinTrial, the PBSL’s processing times of clinical trial applications for different investigational products (IPs) are as follows, unless otherwise specified by the PBSL on a case-by-case basis:

• Medical devices - 40 working days
• Pharmaceuticals - 50 working days
• Biological and biotechnology medical products - 60 working days
• Genetically modified organisms - 120 working days

As delineated in the G-SLAppClinTrial, the PBSL will inform the applicant in writing about the receipt of a valid clinical trial application or the formal grounds for non-acceptance within 10 working days from the receipt of the application. The applicant must address formal grounds for non-acceptance within 10 working days. If changes are required and the applicant fails to modify the application correspondingly within a maximum of 30 working days, following the reasoned objections, the application will be deemed rejected. If the PBSL requires changes to the application and the applicant fails to modify the application correspondingly within a maximum of 90 days following the reasoned objections, the application will be deemed rejected. See Figure 1 in Section 5.17 of the G-SLAppClinTrial for more details on the PBSL’s clinical trial authorization process.

According to the G-SLAppClinTrial, if expedited review of a clinical trial during a public health emergency is anticipated, the applicant should inform the PBSL in writing. The timeline for processing such applications is 10-20 working days. For more information, see the G-SLAppClinTrial.

The G-SLAppClinTrial further indicates that any proposed amendment to the trial application, trial arrangements, and IP must be submitted to the SLESRC and the PBSL for approval before such amendments are carried out. The PBSL’s processing time for protocol amendment applications is 30 working days. For more details, see the G-SLAppClinTrial and the amendment form in Appendix V. See also SLE-8 for the amendment checklist.

The G-SLAppClinTrial states that the PBSL must issue a Clinical Trial Certificate to authorize the trial to be conducted, which must be renewed annually. The PBSL’s processing time for a Clinical Trial Certificate renewal application is 15 working days.

The G-SLAppClinTrial further states that if a clinical trial application is rejected by the PBSL, any person or institution may appeal the decision in writing within 60 days after receipt of the decision, to request PBSL review or reconsideration of the initial decision. The PBSL’s response to the appeal application must be addressed to the affected person or institution within 90 days of the appeal’s submission. For more information on appeal contents and timelines, see the G-SLAppClinTrial.

Ethics Committee Approval

No information is currently available on the SLESRC’s timeline of review.

Overview

In accordance with the G-SLAppClinTrial, a clinical trial can only commence after the sponsor and the principal investigator (PI) receive authorization from Sierra Leone’s Pharmacy Board of Sierra Leone (PBSL) via a Clinical Trial Certificate. Additionally, per the G-SLAppClinTrial, the Sierra Leone Ethics and Scientific Review Committee (SLESRC) fulfills the functions of the ethics committee (EC) (known as an Independent Ethics Committee (IEC) in Sierra Leone) in the country. Ethics approval must be obtained from the SLESRC prior to initiating a study. The G-SLEthics indicates that the PI must obtain the SLESRC approval.

In addition, as per SLE-23, no waiting period is required following the applicant’s receipt of PBSL and SLESRC approval.

As per the G-SLAppClinTrial, a permit from the PBSL is required for the import of an investigational product (IP) to be used in a trial. (See the Manufacturing & Import section for additional information.)

According to the G-SLAppClinTrial, the PBSL must be informed of the trial’s initiation in writing on the exact date the study commences. If the trial does not begin or is delayed, then the PBSL must be informed of the new commencement date within 90 days of the Clinical Trial Certificate’s issuance. SLE-23 further indicates that investigators are required to notify their local institution prior to initiating a trial.

Clinical Trial Agreement

The G-SLAppClinTrial and the SL-GCPs state that the clinical protocol submitted to the PBSL must include a signed contractual agreement between the sponsor and the PI.

As required by the G-SLAppClinTrial, the sponsor/PI contractual agreement must have sections indicating:

• Study title
• Protocol version and date
• Trial site
• IP information
• Definitions of all terms
• Effective date of agreement
• Outline of the sponsor’s responsibilities, which must include general management of the trial; provision of adequate funding, resources/logistics and IPs for the study; and insurance for the study participants
• Outline of the PI’s responsibilities, which must include retaining all trial related essential documents until the sponsor informs the PI these documents are no longer needed
• Term (period of study duration) and termination of agreement (conditions for this)
• Confidentiality

Per the SL-GCPs, the sponsor should obtain the investigator’s/institution’s agreement to:

• Conduct the trial in compliance with good clinical practices (GCPs), with the applicable regulatory requirement(s), and with the PBSL-approved protocol
• Comply with procedures for data recording/reporting
• Permit monitoring, auditing, and inspection

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

Clinical Trial Registration

The G-SLAppClinTrial states that proof of trial registration with the Pan African Clinical Trial Registry (PACTR) (SLE-19), or an internationally recognized PBSL-approved online registry, must be submitted as part of a clinical trial application to the PBSL.

Safety Reporting Definitions

According to the G-SLAppClinTrial and the SL-GCPs, the following definitions provide a basis for a common understanding of Sierra Leone’s safety reporting requirements:

• Adverse Event (or Adverse Experience) (AE) – Any untoward medical occurrence in a participant to whom an investigational medicinal product has been administered, including occurrences which are not necessarily caused by or related to that product

• Adverse Drug Reaction (ADR) – Any noxious and unintended response to an investigational medicinal product which is related to any dose administered to that participant

• 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, or is a congenital anomaly/birth defect

• Unexpected Adverse Event/Adverse Drug Reaction – An adverse reaction where the nature or severity is inconsistent with the applicable product information

Safety Reporting Requirements

As stated in the G-SLAppClinTrial, the sponsor and the principal investigator(s) (PIs) are responsible for proper reporting of AEs and SAEs. The sponsor should expedite the reporting of all AEs that are both serious and unexpected. Any SAEs/SADRs must be reported to the Pharmacy Board of Sierra Leone (PBSL) immediately where possible. In any event, the SAEs/SADRs must be reported to the PBSL within 48 hours of site awareness, but no later than 15 calendar days.

The SL-GCPs indicates that all SAEs/SADRs should be reported immediately except for those incidents documented by the protocol or the investigator’s brochure that do not require immediate reporting. The immediate reports should be followed promptly by detailed, written reports. The reports should identify participants by unique code numbers. AEs and/or laboratory abnormalities identified in the protocol as critical to safety evaluations should be reported to the PBSL. Furthermore, per the G-SLAppClinTrial, any SAE/SADR related to the investigational product (IP) should receive immediate medical attention.

According to the G-SLAppClinTrial, follow-up reports must be submitted immediately when there is a change in the severity of the SAE/SADR initially reported, whenever there is any new development on an initially reported SAE/SADR, and/or when the SAE/SADR is resolved. Follow-up reports must include an assessment of the importance and implication of any findings. All fatal cases must be accompanied by a formal autopsy report. In exceptional circumstances where a formal autopsy is not practicable, provision of a verbal autopsy report must be prior approved by the PBSL and be given with ample reasons.

In addition, per the G-SLAppClinTrial, any frequent AEs/ADRs should be reported to the PBSL immediately where possible, and in any event, within seven (7) days of site awareness. Non-serious AEs must be reported to the PBSL on request and, where applicable, submitted as part of an application for registration.

The G-SLAppClinTrial indicates that non-serious AEs must be reported on request and where applicable, submitted as part of an application for registration.

Investigator Responsibilities

The G-SLAppClinTrial states that in the event of an SAE/SADR, the PI is required to submit follow-up information (e.g., copies of diagnostic test results, laboratory reports, medical record progress notes) as soon as it becomes available. This information should be clearly marked as updated information and include the protocol and participant numbers.

As per the SL-GCPs, the investigator should also comply with applicable regulatory requirements related to reporting unexpected SAEs/SADRs to the PBSL. For a reported death, the investigator should supply the PBSL with any additional requested information (e.g., autopsy reports and terminal medical reports).

Sponsor Responsibilities

According to the G-SLAppClinTrial and the SL-GCPs, the sponsor is required to expedite the reporting of all AEs/ADRs that are both serious and unexpected to the PBSL. The SL-GCPs further indicates that the sponsor must also expedite the reporting of all AEs/ADRs that are both serious and unexpected to all concerned investigator(s)/institutions(s) and the ethics committee(s).

Per the SL-GCPs, the sponsor is responsible for the ongoing safety evaluation of IPs, and should promptly notify the investigator(s)/institution(s) and the PBSL of findings that could adversely affect participant safety, impact the conduct of the trial, or alter the PBSL’s approval of the trial.

Other Safety Reports

The G-SLAppClinTrial indicates that notifications of changes in nature, severity, or frequency of risk factors must be submitted to the PBSL within 28 days, and new information that impacts the risk benefit profile of the product or conduct of the trial must be reported within seven (7) days.

Per the G-SLSftyMntrng and the G-SLAppClinTrial, a Development Safety Update Report (DSUR) must be submitted annually to the PBSL.

According to the G-SLSftyMntrng, the main objective of a DSUR is to present a comprehensive, thoughtful annual review and evaluation of pertinent safety information collected during the reporting period related to a drug under investigation, whether or not it is marketed, by:

• Examining whether the information obtained by the sponsor during the reporting period is in accord with previous knowledge of the IP’s safety
• Describing new safety issues that could have an impact on the protection of clinical trial participants
• Summarizing the current understanding and management of identified and potential risks, and
• Providing an update on the status of the clinical investigation/development program and study results

For more information on DSURs, see Section 12 of the G-SLSftyMntrng.

For safety reporting from foreign sites and other reporting requirements, see Appendicies VIa – VIc of the G-SLAppClinTrial.

Form Completion & Delivery Requirements

According to the G-SLAppClinTrial, the SAE/SADR report form must include detailed information to enable a causality assessment report to be prepared by the PBSL’s Expert Committee on Drug Safety. The SAE/SADR form must conform to the format of the Council for International Organizations of Medical Sciences’ (CIOMS) Form I (SLE-7), or must be previously approved by the PBSL. Furthermore, all SAEs/suspected unexpected serious adverse reactions (SUSARs) and AEs/ADRs must be reported using the SLE-7 form format and also electronically through the PBSL’s online reporting platform (SLE-14). Frequent AEs/ADRs should be reported to the PBSL in a line listing and through the PBSL’s online reporting platform. Electronic submissions must be E2B compliant. See SLE-12 for the International Council for Harmonisation (ICH)’s E2B Guidelines.

For non-serious AEs, the G-SLAppClinTrial indicates that individual reporting must be formatted in accordance with the data elements specified in the ICH Harmonised Tripartite Efficacy Guideline on Clinical Safety Data Management: Definitions and Standards for Expedited Reporting (E2A) (see SLE-12).

Interim and Annual Progress Reports

Per the SL-GCPs, the investigator should submit written summaries of the trial status to the Pharmacy Board of Sierra Leone (PBSL) as required in the G-SLAppClinTrial, or more frequently, if requested by the PBSL. The investigator should also promptly provide written reports to the PBSL on any changes that significantly affect the conduct of the trial and/or increase the risk to participants.

As set forth in the G-SLAppClinTrial, quarterly reports must be submitted starting from the date the Clinical Trial Certificate is issued using the Quarterly Progress Report Form provided in Appendix VIIb. The reports must be submitted to the PBSL within 21 days following the end of the previous quarter, and an interim report must be submitted within 21 days after the end of the first half of the trial period, and as stipulated in the protocol. If the trial is interrupted, the reason must be communicated in writing to the PBSL within 10 working days. See the G-SLAppClinTrial for additional details on preparing progress reports.

Final Report

According to the G-SLAppClinTrial, the principal investigator (PI) or the sponsor must notify the PBSL no later than 30 days following the trial’s completion and submit a preliminary report on the trial. This report, referred to as a close-out report in the G-SLAppClinTrial, must be submitted to PBSL after study completion in the recommended format as per Appendix VIII.

The G-SLAppClinTrial delineates that in addition to the close-out report, the PI or the sponsor must compile and submit a comprehensive formal report to the PBSL no later than 90 days following the trial’s completion. The report should conform to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Harmonised Tripartite Guideline - Structure and Content of Clinical Study Reports (E3) (SLE-11). The report must include a short but comprehensive summary of the essential findings of the trial, as well as its methodology and course, and be submitted in hard and soft copies. Publication(s) of the study in a scientific journal or other medium for the purpose of disseminating the information obtained to stakeholders may be done only after notification of the PBSL.

The SL-GCPs indicates that the investigator is responsible for submitting the final report summarizing the trial’s outcome to the PBSL.

As per the G-SLAppClinTrial and the SL-GCPs, a sponsor is defined as an individual, company, institution, or organization that takes ultimate responsibility for the initiation, management, and financing of a trial.

In accordance with the G-SLAppClinTrial and the SL-GCPs, the sponsor may authorize a contract research organization (CRO) to perform one (1) or more of its trial-related duties and functions. However, the ultimate responsibility for the trial’s data quality and integrity always resides with the sponsor.

The SL-GCPs further requires that any trial-related duty and function that is transferred to and assumed by a CRO should be specified in writing. The sponsor should 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 contracted CRO(s). Any trial-related duties and functions not specifically transferred to and assumed by a CRO are retained by the sponsor.

Additionally, as delineated in the SL-GCPs, a sponsor-investigator is defined as an individual who both initiates and conducts, alone or with others, a clinical trial, and under whose immediate direction the investigational product is administered to, dispensed to, or used by a participant. The term does not include any person other than an individual (e.g., it does not include a corporation or an agency). The obligations of a sponsor-investigator include both those of a sponsor and those of an investigator.

Overview

The SL-GCPs states that the sponsor is responsible for selecting the investigator(s) and the institution(s) for the clinical trial and for ensuring that the investigator(s) are qualified by training and experience. Additionally, the sponsor must define and allocate all trial-related duties and responsibilities to the relevant parties. Prior to entering into an agreement with the investigator(s) and the institution(s) to conduct a study, the sponsor should provide the investigator(s) with the protocol and an investigator’s brochure.

As stated in the G-SLAppClinTrial, the principal investigator (PI) directly in charge of a trial, and at each site in a multi-center trial, must possess appropriate qualifications, training, and experience. The PI must be a scientist and domicile in Sierra Leone.

The G-SLAppClinTrial and the SL-GCPs further indicate that the PI must be responsible for the proper conduct of the trial(s), have previous experience as a co-investigator in at least two (2) trials in the relevant professional area, and have proof of formal training in good clinical practice (GCP) for at least two (2) years. See the G-SLAppClinTrial and the SL-GCPs for additional requirements.

Foreign Sponsor Responsibilities

No information is currently available on foreign sponsor responsibilities.

Data and Safety Monitoring Board

As indicated in the G-SLAppClinTrial, the sponsor must establish an independent data-monitoring committee, such as a Data and Safety Monitoring Board (DSMB), to regularly assess the trial’s progress and analyze safety data. The applicant must provide a copy of the DSMB’s membership, curriculum vitaes, and signed charter in the clinical trial application package submitted to the Pharmacy Board of Sierra Leone (PBSL). However, the SL-GCPs indicates that establishing a DSMB is optional.

The G-SLAppClinTrial further indicates that a duly signed and authenticated DSMB report(s) and/or minutes must be forwarded to the PBSL upon request. For more information on DSMB requirements, see the G-SLAppClinTrial.

Multicenter Studies

As delineated in the SL-GCPs, 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 the approvals of the PBSL and the ethics committee
• 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 between investigators is facilitated

In addition, the sponsor may organize a coordinating committee or select coordinating investigators.

Insurance

The G-SLAppClinTrial states that for all sponsor-initiated trials, a valid insurance certificate for the duration of the study must be provided before initiating the study, and a copy of this coverage must be included in the clinical trial application submission to the Pharmacy Board of Sierra Leone (PBSL). Sponsors and principal investigators (PIs) must ensure insurance cover for clinical trial participants and must submit a certificate of insurance cover for participants as evidence. The certificate must at least contain:

• Insurance company
• Policy number
• Initial date
• Expiry date
• Insured (Policy Holder/Sponsor)
• Description of activity (purpose of the policy)

The G-SLAppClinTrial and the SL-GCPs also state that the sponsor must provide insurance or indemnify the investigator(s)/institution(s) against claims arising from the trial, except for those claims arising from malpractice and/or negligence as stipulated in the G-SLAppClinTrial. See Annex 7 of SLE-6 for suggested wording of the sponsor indemnification.

Compensation

Injury or Death

The SL-GCPs indicate that the sponsor's policies and procedures should address the costs of treatment of trial subjects in the event of trial-related injuries in accordance with the applicable requirement(s). In addition, when trial participants receive compensation, the method and manner of compensation should comply with the PBSL's requirements.

Trial Participation

According to the SL-GCPs, the ethics committee (EC) (i.e., the Sierra Leone Ethics and Scientific Review Committee (SLESRC)) should review both the amount and method of payment to participants to assure that neither presents problems of coercion or undue influence. Payments to a participant should be prorated and not wholly contingent on the participant’s completion of the trial. The EC should also ensure that information regarding payment to participants, including the methods, amounts, and schedule of payment, is set forth in the written informed consent form and any other written information to be provided to participants. The way payment will be prorated should be specified.

Quality Assurance/Quality Control

As stated in the SL-GCPs, the sponsor 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 are generated, recorded, and reported in compliance with the protocol, good clinical practice (GCP), and the Pharmacy Board of Sierra Leone (PBSL)’s regulatory requirement(s). The sponsor is responsible for obtaining agreement from all involved parties to ensure direct access to all trial related sites, source data/documents, reports for monitoring and auditing purposes, and inspection by domestic and foreign regulatory authorities. QC should be applied to each stage of data handling to ensure that all data are reliable and have been correctly processed.

Monitoring Requirements

As part of its QA system, the SL-GCPs notes that the sponsor may choose to perform a clinical trial audit. The purpose of the audit should be to evaluate trial conduct and compliance with the protocol, SOPs, the PBSL, and other applicable regulatory requirements. The sponsor should ensure that the auditors are qualified by training and experience, and that their qualifications are documented. The sponsor must also ensure that the audit is conducted in accordance with the sponsor’s own written procedures on what to audit, how to audit, the frequency of audits, and the form and content of audit reports. The observations and findings of the auditor(s) should be documented. No specific timeframe is provided for the audit process. See the SL-GCPs for detailed audit requirements.

Premature Study Termination/Suspension

As per the SL-GCPs, if a trial is terminated or suspended prematurely, the sponsor should promptly inform the investigator(s)/institution(s) and the PBSL of the termination or suspension, and explain the reason(s) for the termination or suspension. The ethics committee (EC) (i.e., the Sierra Leone Ethics and Scientific Review Committee (SLESRC)) should also be informed promptly and provided the reason(s) for the termination or suspension by the sponsor or by the investigator/institution.

Electronic Data Processing System

As delineated in the SL-GCPs, when using electronic trial data handling and/or remote electronic data systems, the sponsor must ensure and document that the electronic data processing system(s) conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance, and that the sponsor maintains standard operating procedures (SOPs) for using these systems. The responsibilities of the sponsor, investigator, and other parties with respect to the use of these computerized systems should be clear, and the users should be provided with training in their use. Refer to the SL-GCPs for detailed information on electronic trial data systems.

Records Management

As set forth in the SL-GCPs, the sponsor, or other data owners, should retain all sponsor-specific essential documents pertaining to the trial for at least two (2) years after formal discontinuation of the trial or in conformance with the applicable regulatory requirement(s) of the country(ies) where the product is approved, and/or where the sponsor intends to apply for approval(s). In addition, all clinical and experimental data (electronic or paper) must be kept in a secure place for a period of five (5) years, or 20 years for a new drug application, after a trial’s completion. The data must also be readily available for review upon request by the Pharmacy Board of Sierra Leone (PBSL).

See the SL-GCPs for a list of essential documents for the conduct of a clinical trial.

No information is currently available regarding personal data protection requirements.

Obtaining Consent

In all Sierra Leone clinical trials, a freely given informed consent must be obtained from each participant in accordance with the requirements set forth in the SL-GCPs. In obtaining and documenting informed consent, the investigator should comply with Pharmacy Board of Sierra Leone (PBSL) requirements and should adhere to good clinical practice (GCP) and to the ethical principles that have their origin in the Declaration of Helsinki (SLE-5), which is available in Appendix 3 of the SL-GCPs.

As per the SL-GCPs and the G-SLAppClinTrial, the informed consent form (ICF) is viewed as an essential document. The sponsor and principal investigator (PI) must submit the ICF to the PBSL with the clinical trial application. The G-SLEthics further indicates that the PI must also submit the ICF to the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), for review. (See the Required Elements section for details on what should be included in the form.)

The SL-GCPs states that the investigator, or the investigator’s designated representative, must provide detailed research study information to the participant and/or the legal representative(s) or guardian(s). In addition, 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, and the legal representative(s) or guardian(s), should also be given adequate time to consider whether to participate.

As per the SL-GCPs, none of the oral and written information concerning the research study, including the written ICF, should contain any language that causes the participant and/or the legal representative(s) or guardian(s) to waive or appear to waive their 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 the SL-GCPs, the participant and/or the legal representative(s) or guardian(s) should be informed in a timely manner if new information becomes available that may be relevant to the participant’s willingness to continue participation in the trial. The communication of this information should be documented, and the participant and/or the legal representative(s) or guardian(s) should receive a copy of the signed and dated ICF updates, including a copy of any amendments to the written information provided to the participants.

Language Requirements

As per SLE-23, the clinical trial application and accompanying material must be provided to the PBSL in English.

Documenting Consent

The SL-GCPs states that the participant and/or the participant’s legal representative(s) or guardian(s), as well as the investigator(s), must sign and date the ICF.

Where the participant is illiterate and/or the legal representative(s) or guardian(s) is illiterate, an impartial witness should be present during the entire informed consent discussion. The witness should sign and date the ICF after:

• The written ICF and any other written information is read and explained to the participant and the legal representative(s) or guardian(s);
• The participant and the legal representative(s) or guardian(s) have orally consented to the participant’s involvement in the trial; and
• The participant and the legal representative(s) or guardian(s) have signed and dated the ICF, if capable of doing so.

According to the G-SLEthics, the SLESRC does not accept verbal consent, except when supported by an independent witness.

Per the SL-GCPs, before participating in the study, the participant or the legal representative(s) or guardian(s) should receive a copy of the signed and dated ICF.

Waiver of Consent

The SL-GCPs delineates that where the protocol indicates that prior consent of the participant or the legal representative(s) or guardian(s) is not possible, the EC (i.e., the SLESRC) should determine whether the proposed protocol and/or other document(s) adequately addresses relevant ethical concerns and meets applicable regulatory requirements for such trials. See the Emergencies and Mentally Impaired sections for more information.

Based on the SL-GCPs, the informed consent form (ICF) should include the following statements or descriptions, as applicable:

• The study involves research and an explanation of its nature and purpose

• Trial procedures to be followed, including all invasive procedures

• Expected duration of participation

• Participant’s responsibilities in the trial

• Experimental aspects of the study

• Approximate number of participants involved in the trial

• The trial treatment(s) and the probability for random assignment to each treatment

• Any foreseeable risks or discomforts, and when applicable, to an embryo, fetus, or nursing infant

• Any expected benefits or prorated payment; if no benefit is expected, the participant should also be made aware of this

• Alternative procedures or treatment that may be available

• Compensation and/or medical treatment available to the participant in the event of a trial-related injury

• 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

• Any additional costs that may result from participation in the research

• That the monitor(s), the auditor(s), the ethics committee (EC) (i.e., the Sierra Leone Ethics and Scientific Review Committee (SLESRC)), and the Pharmacy Board of Sierra Leone (PBSL) 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

• That records identifying the participant will be kept confidential and, to the extent permitted by applicable laws and/or regulations, will not be made publicly available. If the results are published, the participant’s identity will remain confidential

• Foreseeable circumstances under which the investigator(s) may remove the participant without the participant’s consent

• That 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 participant and/or the legal representative(s) or guardian(s) 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

Additionally, see Annex 1 of SLE-6 for standardized wording for the ICF.

Overview

In accordance with the SL-GCPs, which is guided by the International Council for Harmonsation’s Guideline for Good Clinical Practice E6(R2) (SLE-24), the Declaration of Helsinki (SLE-5), and other international guidelines, Sierra Leone’s ethical standards promote respect for all human beings and safeguard the rights of research participants. The SL-GCPs and the G-SLAppClinTrial 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 SL-GCPs, the participant or the legal representative(s) or guardian(s) 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 SL-GCPs, a potential research participant and/or the legal representative(s) or guardian(s) 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

According to the SL-GCPs and the G-SLAppClinTrial, 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 SL-GCPs states that the research participant and/or the legal representative(s) or guardian(s) should be provided with contact information for the sponsor and the investigator(s) to address trial-related inquiries and/or the participant’s rights.

The Right to Safety and Welfare

As set forth in the SL-GCPs and the G-SLAppClinTrial, the research participant’s dignity, safety, and welfare 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.

The SL-GCPs make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by emergency situations.

As delineated in the SL-GCPs, if the signed informed consent form (ICF) cannot be obtained from the research participant in an emergency, then the consent of the legal representative(s) or guardian(s), if present, should be obtained. If prior consent of the participant and/or the legal representative(s) or guardian(s) cannot be obtained, then the participant’s enrollment should follow measures specified in the protocol, and/or elsewhere, with documented approval/favorable opinion by the ethics committee (EC) (i.e., the Sierra Leone Ethics and Scientific Review Committee (SLESRC)) and the Pharmacy Board of Sierra Leone (PBSL) to protect the rights, safety, and well-being of the participant and ensure compliance with EC and PBSL requirements. The participant and/or the participant’s legal representative(s) or guardian(s) should be informed about the trial and provide consent as soon as possible.

In addition, per the SL-GCPs, because the participants who are experiencing medical emergencies are usually extremely vulnerable, these individuals should be excluded from all but minimally invasive observational research. ECs must also take great care when assessing emergency care research. Once the researcher has presented clear reasons to justify the initiation of emergency care research without consent to the EC, the EC may approve the research provided it is satisfied that:

• Reasonable steps are being taken to ascertain the religious and cultural sensitivities of participants experiencing medical emergencies
• The condition of the participant precludes the giving of consent
• Inclusion in the trial is not contrary to the interests of the participant
• The research is intended to be therapeutic and poses no more risk than is inherent to the patient’s condition or would be caused by alternative methods of treatment
• The participant and the legal representative(s) or guardian(s) will be informed as soon as is reasonably possible of the patient’s inclusion in the study and of the option to withdraw from the research project at any time
• The participant will be informed, and consent obtained, once the participant who has undergone the necessary emergency procedures has regained consciousness
• The research is based on valid scientific hypotheses and offers a realistic possibility of benefit over standard care

Overview

As per the SL-GCPs, in all Sierra Leonean clinical trials, research participants selected from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process.

According to the SL-GCPs and the G-SLAppClinTrial, vulnerable populations include individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with the participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. The SL-GCPs states that other participants representing vulnerable populations 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. Additionally, types of research that need additional attention include research involving collectivities, indigenous medical systems, innovative therapy or interventions, HIV and AIDS clinical and epidemiological research, and emergency care research.

The SL-GCPs indicates that the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), must pay special attention to protecting the welfare of certain classes of participants, including minors, women, persons with mental disabilities or substance abuse related disorders, persons in dependent relationships or comparable situations, prisoners, and persons highly dependent on medical care.

Persons Highly Dependent on Medical Care

According to the SL-GCPs, participants who are highly dependent on medical care must be given special attention to protect the welfare of this vulnerable study population. Researchers need to acknowledge that the participant’s medical condition may compromise the participant’s informed consent and affect the participant’s ability to form an opinion or to communicate. There may also be a perception of coercion if a participant is reluctant to refuse consent for fear that it may compromise the participant’s medical treatment.

As delineated in the SL-GCPs, the following research areas require investigators to pay special attention to these participants to safeguard their welfare and ensure proper consent:

• Intensive care research – Characteristic features are the difficulties in communicating with participants receiving ventilatory assistance and the impairment of cognition in heavily sedated participants. Whenever possible, information should be obtained from potential participants prior to their admission to intensive care. These participants should be excluded from all but minimally invasive observational research due to their extreme vulnerability.
• Neonatal intensive care research – Research involving infants should be conducted in strict accordance with the principles discussed in the Children/Minors section. These principles do not permit research that is contrary to the child’s best interests.
• Terminal care research – Research in terminal care is distinguished by the short remaining life expectancy of participants and potential vulnerability to unrealistic expectations of benefits. Researchers must ensure that the prospect of benefit from research participation is neither exaggerated nor used to justify a higher risk than that involved in the participant’s current treatment.
• Research involving persons with impaired capacity to communicate or unconscious persons – Refer to the Mentally Impaired section.

Persons in Dependent Groups

As set forth in the SL-GCPs, for participants whose proposed involvement in research arises from dependent or comparable relationships, the EC must be satisfied that the participants’ consent is both adequately informed and voluntary.

The following list provides some examples of hierarchically structured groups and the junior or subordinate relationships that may exist in these groups:

• Older persons and their caregivers
• Persons with chronic conditions or disabilities and their caregivers
• Wards of the state and guardians
• Patients and healthcare professionals
• Students and teachers
• Prisoners and prison authorities
• Persons with life-threatening illnesses
• Employees and employers (e.g., farm workers and their employers, members of the uniformed services and hospital staff and their employers)

See the Children/Minors; Pregnant Women, Fetuses & Neonates; and Mentally Impaired sections for additional information about these vulnerable populations.

According to the SL-GCPs, a minor is someone under 18 years of age.

As set forth in the SL-GCPs, when the participant is a minor, informed consent must be obtained from the participant’s legal representative(s) or guardian(s). Assent from the minor must also be obtained where the minor is capable of understanding. A minor’s refusal to participate in research must be respected.

The SL-GCPs indicates that the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), must pay special attention to protecting the welfare of certain classes of participants, including minors. Research involving minors should be approved only if:

• The research interventions, including those in observational research, presents the participant with no greater than minimal risk; or
• The research interventions present more than minimal risk but hold out the prospect of direct benefit for the participant; or
• The research interventions, including those in observational research, present more than minimal risk and do not hold out the prospect of direct benefit to the participant, but have a high probability of yielding generalizable knowledge.

In all cases, the protocol must provide sufficient information to justify clearly why minors should be included as participants.

Assent Requirements

The G-SLAppClinTrial also states that in trials involving minors, legal representative(s) or guardian(s) of a minor are required to sign an informed consent form (ICF). In addition, an assent form similar to the ICF must also be signed and dated by a minor who is capable of understanding as a confirmation of the minor’s willingness to participate in a trial, after having been informed of all aspects of the trial that are relevant to the minor’s decision to participate.

As delineated in the SL-GCPs, assent refers to a minor’s affirmative agreement to participate in research. If a minor fails to object, this should not be construed as assent. The EC (i.e., the SLESRC) must ensure that adequate steps are specified in the protocol to obtain the minor’s assent when, in the EC’s judgment, the minor is capable of providing such assent. Additionally, when the EC determines that assent is required, it must also indicate whether and how such assent must be documented.

The SL-GCPs requires that the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), pay special attention to protecting the welfare of certain classes of participants, including women who are or may become pregnant.

The SL-GCPs states that the following conditions must be met for research conducted with pregnant women and fetuses:

• Applicable studies on animals and non-pregnant individuals have been completed
• The purpose of the study is to meet the health needs of the mother of the particular fetus, the risk to the fetus is minimal and, in all cases, presents the least possible risk for achieving the study’s objectives
• Individuals engaged in the study will have no part in any decision as to the timing, method, and procedures used to terminate the pregnancy, and determining the viability of the fetus at the termination of the pregnancy
• No procedural changes that could cause greater than minimal risk to the fetus or the pregnant woman will be introduced into the procedure for terminating the pregnancy solely in the interest of the activity

Per the SL-GCPs, for any study to be conducted that is associated with either the fetus in utero or ex utero, the parents should be legally competent and have given their informed consent.

The SL-GCPs also specifies that the father’s informed consent does not need to be obtained if any of the following applies:

• The study purpose is to meet the mother’s health needs
• The father’s identity or whereabouts cannot be reasonably established
• The father is not reasonably available
• The pregnancy is the result of rape

Further, per the SL-GCPs, no fetus in utero may be involved as a research participant unless:

• The purpose of the study is to meet the health needs of the particular fetus, and the fetus will be placed at risk only to the minimum extent necessary to meet these needs
• The risk to the fetus in the proposed study is minimal, and the study’s objective is to obtain biomedical knowledge that cannot be achieved by other means

According to the SL-GCPs, until it has been established whether a fetus ex utero is viable, a fetus ex utero may not be involved as a participant in any research study unless one (1) of the following conditions is met:

• The fetus faces no added risk from participation in the study, and the purpose of the study is to develop biomedical knowledge that cannot be obtained by other means
• The purpose of the study is to enhance the possibility of survival of the particular fetus to the point of viability

The SL-GCPs states that nonviable fetuses may not be involved as participants in any research activity unless both of these conditions are met:

• The vital functions of the fetus will not be artificially maintained; experimental activities that would terminate the heartbeat or respiration of the fetus will not be employed
• The purpose of the study is to acquire biomedical knowledge not otherwise obtainable

Participants engaged in the study will have no part in any decision as to timing, method, and procedures used to terminate the pregnancy, and/or determining the viability of the fetus at the pregnancy’s termination.

The SL-GCPs indicates that the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), must pay special attention to protecting the welfare of certain classes of participants, including prisoners. Prisoners are considered vulnerable because incarceration could affect their ability to make a voluntary decision regarding participation in research. A research study may only involve prisoners as participants when the EC (i.e., the SLESRC) has ensured that the clinical trial involves:

• The study of the possible causes, effects, and processes of incarceration and of criminal behavior with no more than minimal risk and inconvenience to the participants
• The study of prisons as institutional structures or of prisoners as incarcerated persons
• Research on conditions particularly affecting prisoners as a class (e.g., vaccine trials and other research on diseases that may be more prevalent in prisons, and research on social and psychological problems such as alcoholism, drug addiction, and sexual assaults) only after appropriate experts have been consulted
• Research on practices, both innovative and accepted, that have the intent and probability of improving the health or wellbeing of prisoners

In addition, per the SL-GCPs, in a study where some prisoners may be assigned to control groups that may not benefit from the research, the study may proceed only after appropriate experts have been consulted. Research that could be conducted on a population other than prisoners should not be permitted unless the EC is presented with a valid case and is convinced that the study does not represent exploitative research.

The SL-GCPs also states that when the EC reviews research involving prisoners, the following requirements must be met:

• The majority of the EC members, other than prison members, must have no association with the prison(s) involved
• At least one (1) member of the EC must be a prisoner, or a prisoners’ representative with appropriate background and experience to serve in that capacity. Where a research project is reviewed by more than one (1) EC, only one (1) EC need satisfy this requirement

According to the SL-GCPs, the national ethics committee (EC), the Sierra Leone Ethics and Scientific Review Committee (SLESRC), must pay special attention to research participants with mental disabilities, including those with psychiatric, cognitive, or developmental disorders, or participants with substance abuse related disorders. Individuals who have been institutionalized may be further compromised in terms of their capacity to make a truly voluntary decision to participate in a study.

Per the SL-GCPs, research involving people with mental disabilities or with substance abuse related disorders must therefore:

• Be relevant to mental disabilities or substance abuse related disorders so that it is necessary to involve people who have a mental disability and/or a substance abuse related disorder(s);
• Justify the involvement, as the study population, of institutionalized people with mental disabilities;
• Ensure appropriate evaluation procedures for ascertaining the participants’ ability to provide informed consent. If participants are deemed unable to understand and make a choice, then consent should be obtained from the participant’s legal representative(s) or guardian(s)
• Ensure that consent is free from coercion and risk to participants; and
• Ensure that only minimal risk is involved, and that the risk is outweighed by the anticipated benefits for the participants and by the importance of the knowledge that will be derived from the research.

In addition, the SL-GCPs notes that persons with intellectual or mental impairment should not participate in research that might equally well be conducted with individuals without those impairments. Consent cannot be given that is contrary to the interests of a participant with mental or intellectual impairment, and the person's refusal to participate in research must always be respected. Accordingly, consent must be obtained from one (1) of the following:

• The participant to the extent that the participant is competent to give informed consent
• The participant’s legal guardian(s) or representative(s) when the participant is deemed not competent to do so
• An authority, organization, or individual legally authorized to do so

The SL-GCPs further states that research involving participants with impaired capacity to communicate also requires special attention. The distinguishing features of research involving participants with impaired capacity to communicate include acute impairment states requiring medical care, as well as non-acute states. In acute impairment states, the condition and medical care may mask the participant’s degree of cognition and require different means of expression. In non-acute impairment states, the condition may prevent the participant from expressing wishes at all.

As indicated in the SL-GCPs, research involving unconscious persons requires consent to be provided by the participant’s legal representative(s) or guardian(s), including any relevant statutory authorities, on that person’s behalf. Because of their extreme vulnerability, unconscious persons should be excluded from all but minimally invasive observational research. When neither the prospective participant nor the legal representative(s) or guardian(s) is able to give consent in advance, the EC (i.e., the SLESRC) may approve a research project without prior consent if it is satisfied that:

• Inclusion in the trial is not contrary to the interests of the participant
• The research is intended to be therapeutic and poses no more risk than is inherent to the participant’s condition or would be caused by alternative methods of treatment
• The participant and the legal representative(s) or guardian(s) will be informed as soon as is reasonably possible of the participant’s inclusion in the study and of the option to withdraw from the research project at any time
• The research is based on valid scientific hypotheses and offers a realistic possibility of benefit over standard care

As delineated in the G-SLAppClinTrial and the SL-GCPs, an investigational product (IP) is defined as a pharmaceutical form of an active ingredient or placebo being tested or used as a reference in a clinical trial. This includes a product with a marketing authorization when it is used or assembled (formulated or packaged) in a different way from the approved form, when used for an unapproved indication, or when used to gain further information about an approved use.

Manufacturing

As set forth in the PDA2001, the Pharmacy Board of Sierra Leone (PBSL) is responsible for authorizing the manufacture of all drug products in Sierra Leone. According to the SL-GCPs, the sponsor must ensure that the investigational product (IP) is manufactured in accordance with applicable Good Manufacturing Practice (GMP).

The G-SLAppClinTrial states that a GMP certificate from the national competent authority of the country of origin is required when the IP has no marketing authorization in Sierra Leone, or has marketing authorization but its original indication is modified for the purpose of the trial. The GMP certificate should conform to the World Health Organization (WHO) format.

Import

The G-SLAppClinTrial states that the PBSL is responsible for authorizing the import of IPs. A request to import an IP may be submitted after the PBSL has approved the clinical trial application.

The G-SLAppClinTrial indicates that the import application submission must include the following documentation:

• Letter stating the name/description and quantities of each IP, placebo, and trial related product to be imported as well as the details of the location where the product is coming from and details of the recipient in Sierra Leone
• Certificate of analysis of IP and placebo for all batches to be imported
• Lot release certificate (where applicable) for all batches to be imported
• Investigator, sponsor, and recognized clinical research entity’s name and address

According to the G-SLAppClinTrial, the PBSL’s processing time for IP import permits is 10 working days. Imported IPs may be inspected by PBSL officials at the port of entry before they are released to the recognized clinical research entity. The PBSL may order for destruction or re-exportation of the IPs if it has any reason to believe that there is a protocol violation resulting in the termination of the study. See the G-SLAppClinTrial for detailed IP import requirements.

As per the G-FastReg, if a product being registered in Sierra Leone is going to be used in a clinical trial, the registration application may be expedited. If the conditions for expedited registration are fulfilled, the PBSL will process the application and communicate its decision within 21 calendar days.

Please note: Sierra Leone is party to the Nagoya Protocol on Access and Benefit-sharing (SLE-2), 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 SLE-18.

Investigator’s Brochure

In accordance with the G-SLAppClinTrial and the SL-GCPs, the Investigator’s Brochure (IB) is a compilation of the clinical and nonclinical data on the investigational product(s) (IP(s)) which is relevant to the study of the IP(s) in human participants.

As per the SL-GCPs, the sponsor is responsible for providing the investigators with an IB, and the sponsor should update the IB as significant new information becomes available. The G-SLAppClinTrial further specifies that an updated IB should be submitted at least once a year, or whenever it is updated within this period. Additional information and any changes that have been incorporated in the updated IB should be highlighted for ease of review and evaluation.

According to the G-SLAppClinTrial, the content and structure of the IB must comply with the SL-GCPs and the International Council for Harmonisation’s (ICH) Guideline for Good Clinical Practice E6(R2) (SLE-24). Accordingly, the IB must provide coverage of the following areas:

• Physical, chemical, and pharmaceutical properties and formulation parameters
• Non-clinical studies (pharmacology, pharmacokinetics, toxicology, and metabolism profiles)
• Effects of IP in humans (pharmacology, pharmacokinetics, metabolism, and pharmacodynamics; safety and efficacy; and regulatory and post-marketing experiences)
• Summary of data and guidance for the investigator(s)
• Toxicological effects in any animal species tested under a single dose study, a repeated dose study, or a special study

See the SL-GCPs and SLE-24 for detailed content guidelines.

Quality Management

According to the G-SLAppClinTrial, a Good Manufacturing Practice (GMP) certificate from the national competent authority of the country of origin is required when the IP has no marketing authorization in Sierra Leone, or has marketing authorization but its original indication is modified for the purpose of the trial. The GMP certificate should conform to the World Health Organization (WHO) format.

Investigational product (IP) labeling in Sierra Leone must comply with the requirements set forth in the G-SLAppClinTrial and the SL-GCPs. As stated in the G-SLAppClinTrial, all label information should be in English and the print should be clear, legible, and indelible.

As set forth in the G-SLAppClinTrial, the Pharmacy Board of Sierra Leone (PBSL) requires the following information be included on the labels:

• Sponsor details
• Pharmaceutical dosage form, route of administration, quantity of dosage units, and in the case of open trials, the name/identifier and strength/potency
• Batch number
• Trial reference number
• Trial subject identification number
• Name and address of the clinical trial site and the principal investigator (PI)
• Directions for use and any warnings or precautions that may be necessary
• Statement indicating “For clinical trial/research use only”
• Storage conditions
• Period of use (use-by date, expiry date, or re-test date as applicable), in month/year format and in a manner that avoids any ambiguity as well as date of dispensing, if applicable
• Statement indicating “Keep out of reach of children” except when the product is for use in trials where the product is not taken home by participants

The SL-GCPs further states that in blinded trials, the coding system for the IP(s) should include a mechanism that permits rapid identification of the product(s) in case of a medical emergency, but does not permit undetectable breaks of the blinding.

Supply, Storage, and Handling Requirements

As delineated in the SL-GCPs, the sponsor must supply the investigator(s)/institution(s) with the investigational product(s) (IP(s)). The sponsor should not supply either party with the IP(s) until obtaining approval from the Pharmacy Board of Sierra Leone (PBSL).

The SL-GCPs specifies that the sponsor must:

• Ensure timely delivery of the IP(s) to the investigator(s)

• Maintain records that document shipment, receipt, disposition, return, and destruction of the IP(s)

• Maintain a system for retrieving IPs and documenting this retrieval
• Maintain a system for the disposition of unused IP(s) and documenting this disposition

• Take steps to ensure IP stability over the period of use
• Maintain sufficient quantities of the IP(s) to reconfirm specifications, if needed, and maintain records of batch sample analyses and characteristics

• Ensure the IP is manufactured according to any applicable Good Manufacturing Practices (GMPs)

• Ensure proper coding, packaging, and labeling of the IP(s)

Refer to the SL-GCPs for detailed sponsor-related IP requirements.

Per the SL-GCPs, the IP(s) should be packaged to prevent contamination and unacceptable deterioration during transport and storage. Additionally, per the G-SLAppClinTrial, the PBSL requires the IP packaging to comply with the following requirements:

• The container in which the product is contained should be of good quality
• The container and closure should be properly sealed in order to protect the product from the impact of outside environmental factors
• Each sample should contain an insert

According to the G-SLAppClinTrial, the principal investigator (PI) must notify the PBSL of each consignment of IP batches received on site. The notification must include the product name(s), quantities received, and batches received. The PBSL must approve destruction of IPs, which should be carried out in such a manner that all operations may be accounted for. These documents should clearly identify, or allow traceability to, the batches and/or participant numbers involved, and the actual quantities destroyed. A destruction certificate will be issued by the PBSL.

Record Requirements

The G-SLAppClinTrial indicates that for IPs purchased locally, the PI must document the source, proof of purchase, quantities purchased, and the Certificate of Analysis for each batch of IPs. Copies of all documents on the IP(s), whether purchased locally or imported, must be kept on site for verification and accountability during Good Clinical Practice (GCP) inspections.

As per the SL-GCPs, the sponsor should retain all sponsor-specific essential documents in conformance with the applicable regulatory requirement(s) of the country(ies) where the product is approved, and/or where the sponsor intends to apply for approval(s). All sponsor-specific essential documents should be retained for at least two (2) years after formal discontinuation of the trial or in conformance with applicable regulatory requirements. In addition, all clinical and experimental data (electronic or paper) should be kept in a secure place for a period of five (5) years, and 20 years for a new drug application after a trial’s completion, and be readily available for review upon request by the PBSL.

According to the G-SLAppClinTrial and SLE-23, the Pharmacy Board of Sierra Leone (PBSL) is responsible for authorizing the import and export of all biological specimens in Sierra Leone. However, the G-SLAppClinTrial does not have any additional information regarding specimens import.

Export

As set forth in the G-SLAppClinTrial and SLE-23, all institutions or individuals that wish to export any clinical information, medical records, and/or biological samples from Sierra Leone to an institution outside of the country, must complete PBSL’s requirement for material transfer authorization. The G-SLAppClinTrial further indicates that the sponsor must provide annual updates on the use of, and results obtained from, biological samples exported out of Sierra Leone.

Per the G-SLAppClinTrial and the G-MTA, the local principal investigator (PI) or study lead must submit an application for an export permit submitted through the Ministry of Health and Sanitation (MoHS) to the PBSL. All applications must be accompanied by the following documents:

• Evidence of informed consent for use of medical records, clinical information, and biological samples from living participants
• MoHS authorization for deceased patients
• Memorandum of understanding (MOU) between MoHS and the applicant
• Signed and dated Material Transfer Agreement (MTA)
• Payment of PBSL prescribed export permit fee

Please refer to SLE-1 for the materials transfer template.