Regulatory Authority
Regulatory Authority
Scope of Assessment
Regulatory Fees
Ethics Committee
Ethics Committee
Scope of Review
Ethics Committee Fees
Authorizing Body
Clinical Trial Lifecycle
Submission Process
Submission Content
Timeline of Review
Trial Initiation
Safety Reporting
Progress Reporting
Sponsorship
Definition of Sponsor
Trial Authorization
Insurance
Compensation
Quality, Data & Records Management
Site/Investigator Selection
Informed Consent
Documentation Requirements
Required Elements
Compensation Disclosure
Participant Rights
Special Circumstances/Emergencies
Vulnerable Populations
Children/Minors
Pregnant Women, Fetuses & Neonates
Prisoners
Mentally Impaired
Investigational Products
Definition of Investigational Product
Manufacturing & Import
IMP/IND Quality Requirements
Labeling & Packaging
Product Management
Specimens
Definition of Specimen
Import & Export
Consent for Specimens
South Africa
QUICK FACTS
Clinical trial application languageEnglish
Parallel regulatory and ethical review permittedYes
Clinical trial registration requiredYes
In-country sponsor presence/representation requiredNo
Age of minors21 & Under
Specimens export allowedYes
Regulatory Authority > Regulatory Authority
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SUMMARY

Overview
As stated in the MRSA and the GRMRSA, the Medicines Control Council (MCC) is the regulatory authority responsible for clinical trial oversight, approval, and inspections in South Africa. The MCC grants permission for clinical trials to be conducted in South Africa in accordance with the provisions of the GRMRSA.

The MCC is a statutory body appointed by the Minister of Health that was established by the MRSA to oversee the regulation of medicines in South Africa. According to Additional Resource (A), the MCC is responsible for ensuring that all clinical trials of both non-registered medicines and new indications of registered medicines comply with the essential requirements for safety, quality, and efficacy.

As indicated in Additional Resource (B), the MCC is housed within South Africa’s Department of Health (DOH), and operates through nine (9) Council Committees. These technical committees are represented by 146 external experts from various academic institutions in the country. A Clinical Committee and a Clinical Trials Committee are included among these committees.

In addition, per Additional Resource (B), the MCC’s Registrar office provides administrative and technical support to the Council and its activities. The Medicines Regulatory Authority, also known as Registrar of Medicines, serves as executive secretariat to the MCC., There are four (4) Directorates within the Medicines Regulatory Authority (MRA) responsible for coordinating and carrying out various activities. Further information on the MCC and its technical committees is available at Additional Resource (B).

Contact Information
Medicines Control Council

Postal Address:
Registrar of Medicines
Private Bag X 828
Pretoria
0001
South Africa

Physical Address:
Civitas Building
42 Thabo Sehume  Street
Pretoria
0001
South Africa

Clinical Evaluations and Trials Contact:
Phone: 012.395.8126

For General Inquiries:
Main Switchboard: 012.395.8000 (International: +27.12.395.8000)

Cluster Manager and Registrar's Office:
Phone: 012.395.8003
Fax: 012.395.9201

ADDITIONAL RESOURCES

(A) (Website) The Medicines Control Council (Current as of June 1, 2016)
South African National Clinical Trials Register, Department of Health, Republic of South Africa

(B) (Website) Medicines Control Council – About the MCC (Current as of June 1, 2016)
Medicines Control Council, Department of Health, Republic of South Africa

REQUIREMENTS

(1) (Legislation) Medicines and Related Substances Act 101 of 1965 (MRSA) (May 2, 2003)
Parliament, Republic of South Africa

Relevant Sections: Parts 2 and 35

(2) (Regulation) Medicines and Related Substances Act 101 of 1965 - General Regulations Made in Terms of the Medicines and Related Substances Act 101 of 1965, as Amended (GRMRSA) (February 15, 2014)
Department of Health, Republic of South Africa

Relevant Section: Part 34 (1)

(3) (Guidance) General Information (Version 8) (G-GenInfo) (August 2012)
Registrar of Medicines, Medicines Control Council, Department of Health, Republic of South Africa

Relevant Section: 2.3

Regulatory Authority > Scope of Assessment
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SUMMARY

Overview
In accordance with the GRMRSA, the SA-GCPs, and G-Clin, the Medicines Control Council (MCC) is responsible for reviewing and approving all clinical trial applications for an unregistered medicine, and for any new indication or dosage regimen of a registered medicine. The scope of the MCC’s assessment includes all clinical trials (Phases I-IV) and bioequivalence/bioavailability studies.

Clinical Trial Review Process
As indicated in the SA-GCPs, the Medicines Regulatory Authority (MRA) is secretariat to the MCC and coordinates the clinical trial application process. The MRA forwards all submitted clinical trial applications to the MCC’s Clinical Trials Committee (CTC). The CTC committee, in turn, considers the scientific, medical, and ethical issues of the applications, and also ensures that the submissions provide proof of safety, quality, and efficacy of the investigational product for both unregistered and registered medicines. (See the Clinical Trial Lifecycle topic, Submission Process subtopic for detailed submission requirements.)

As per G-GenInfo, the MCC’s CTC is specifically charged with evaluating the following:

  • Clinical trial applications and clinical trial amendments
  • Adverse event reports arising from a clinical trial
  • Applications for named patient use (compassionate use) of unregistered medicines
  • Applications for the use of unregistered medicines for clinical trial purposes

The SA-GCPs’ MCC clinical trial evaluation checklist states that the CTC application review should evaluate previous research relating to the safety and potential benefit of intervention, assess trial methods, and consider ethical issues. The G-CTA also provides the following list of questions to guide the committee in its review process:

  • Does the proposed trial contribute to new knowledge in a scientific way?
  • Are all aspects of the proposed trial ethical?
  • Can patient safety be assured?
  • Should the trial be conducted in South Africa?
ADDITIONAL RESOURCES

(A) (Website) Medicines Control Council – About the MCC (Current as of June 1, 2016)
Medicines Control Council, Department of Health, Republic of South Africa

REQUIREMENTS

(1) (Regulation) Medicines and Related Substances Act 101 of 1965 - General Regulations Made in Terms of the Medicines and Related Substances Act 101 of 1965, as Amended (GRMRSA) (February 15, 2014)
Department of Health, Republic of South Africa

Relevant Section: Part 34 (1)

(2) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 1.5.1, Appendices D and F

(3) (Guidance) Clinical (Version 1) (G-Clin) (December 2003)
Registrar of Medicines, Medicines Control Council, Department of Health, Republic of South Africa

Relevant Section: 3

(4) (Guidance) General Information (Version 8) (G-GenInfo) (August 2012)
Registrar of Medicines, Medicines Control Council, Department of Health, Republic of South Africa

Relevant Section: 13.5

(5) (Legislation) No. 72 of 2008: Medicines and Related Substances Act, 2008 (MRSA, 2008) (April 21, 2009)
Parliament, Republic of South Africa

Relevant Section: 20

(6) (Guidance) Guideline on Completing Clinical Trial Applications (G-CTA) (May 2003) (Updated August 2010)
Registrar of Medicines, Medicines Control Council, Department of Health, Republic of South Africa

Relevant Section: A

Regulatory Authority > Regulatory Fees
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SUMMARY

Overview

Official Fees
Applicants are responsible for paying several non-refundable fees to submit a clinical trial application. As delineated in the G-GenInfo and the MRSA-Fees, the various fee types include the following:

  • Application fee payable with the full submission of the application: company sponsored trial fee: 9,000 South Africa Rand (ZAR); institution sponsored trial fee: 4,500 ZAR; any other clinical trial fee: 2,200 ZAR
  • Registration fee, payable when the application complies with all the registration requirements, and which is payable prior to a registration certificate being issued
  • Annual retention fee to maintain registration
  • Clinical trial amendments - (i) technical amendments: 2,100 ZAR per amendment; (ii) administrative amendment: 600 ZAR per amendment
  • Manufacturing site inspection(s) fee
  • Authorization of the use of an unregistered medicine fee

Instructions for Payment of Clinical Trial Application Fees
The G-MCCFees, the G-GenInfo, and Additional Resource (A) state that all payments made to the Medicines Control Council's (MCC) Registrar of Medicines should be made by check or electronic payment. Checks should be made payable to: “Medicines Control Council.” To ensure evaluation of the relevant submission, a copy of the check/proof of payment must also be attached in a separate envelope to the original cover letter of the relevant submission; no other documents should be attached.

Payments should be sent to:
Account name: Medicines Control Council
Account type: Checking Account
Account number: 40-5939-2080
Bank: ABSA
Bank Branch Code: 632005
Bank physical address: 240 Vermeulen Street, Pretoria 0001, South Africa
Swift Code: ABSAZAJJ

Applicants may transfer fees directly into the MCC bank account by electronic or manual deposit process. As soon as the deposit has been made, confirmation of such deposit should be faxed to the MCC at the following fax number: +27 12 395 8468 (international dialing).

Further details regarding procedures for check and electronic payment are available in the G-MCCFees and the G-GenInfo.

ADDITIONAL RESOURCES

(A) (Information Sheet) Payments Made to the Registrar of Medicines (Version 1) (December 2010)
Medicines Control Council, Department of Health, Republic of South Africa

 

REQUIREMENTS

(1) (Regulation) Medicines and Related Substances Act, 1965 (Act No. 101 of 1965) –
Schedules – Fees Payable in terms of the Provisions of the Act (MRSA-Fees) (March 19, 2015)
Department of Health, Republic of South Africa

Relevant Section: 3. Category D Medicines (Human Medicines)

(2) (Guidance) General Information (Version 8) (G-GenInfo) (August 2012)
Registrar of Medicines, Medicines Control Council, Department of Health, Republic of South Africa

Relevant Sections: 2.9 and 4.8

(3) (Guidance) Guideline for the Direct Transmission of Fees Payable to the Registrar of Medicines (Version 2.1) (G-MCCFees) (October 2012)
Medicines Control Council, Department of Health, Republic of South Africa

Ethics Committee > Ethics Committee
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SUMMARY

Overview
South Africa has a centralized registration process for ethics committees (ECs). The National Health Research Ethics Council (NHREC) serves as the central body that advises the Department of Health (DOH) on health research ethics management in South Africa and sets ethical norms and standards. The NHREC was established as a statutory body in 2006 by the Minister of Health as specified in Section 72 of the NHA.

Section 73 of the NHA requires that every institution, health agency, and health establishment at which research is conducted, establish an EC or have access to an independent EC. In South Africa, ECs are more commonly referred to as research ethics committees. The EC must be registered with the NHREC. The NHREC website provides a list of registered ECs which is also available through Additional Resource (A). Please refer to Authorizing Body subtopic for additional information.

EC Composition
As delineated in the SA-GCPs and the G-EthicsHR, an EC must consist of members who collectively encompass the qualifications and experience required to review and evaluate the scientific, medical, and ethical aspects of all proposed research studies.

Specifically, the EC composition should:

  • Represent the communities served and reflect its demographic profile
  • Have at least nine (9) members, with 60% representing a quorum
  • Have a chairperson
  • Include members of both genders; not more than 70% of its members should be one gender
  • Include at least two (2) lay persons who have no affiliation with the institution, are not currently involved in medical, scientific, or legal work, and are preferably from the community in which the research is to take place
  • Include at least one (1) member with knowledge of, and current experience in areas of research likely to be regularly considered by the EC
  • Include at least one (1) member with knowledge of and current experience in the medical profession, counseling and/or treatment of people
  • Include at least one (1) member who has professional training in both qualitative and quantitative research methodologies
  • Include at least one (1) member who is legally trained
  • Ensure that the membership is equipped to address all relevant considerations arising from the research areas likely to be submitted
  • Be adequately informed on all aspects of a research protocol, including its scientific and statistical validity, that are relevant to deciding whether the protocol is ethically acceptable

Terms of Reference and Review Procedures
In addition to complying with composition requirements, an institution or organization must select EC members according to prescribed recruitment and appointment procedures. As stated in the SA-GCPs and the G-EthicsHR, members must receive a formal notice of appointment and assurance that they will be legally protected with respect to any liabilities that may arise during their term.

An EC must also establish and record written procedures to address several administrative issues including: meetings, agenda/minutes preparation, research protocol presentations, application registration, protocol submission requirements, review and decision notification process, adverse event reporting, protocol amendment reporting, and end-of-trials review. For detailed EC procedures and information on other administrative processes, see Sections 4 and 5 of the G-EthicsHR and Section 8 of the SA-GCPs.

ADDITIONAL RESOURCES

(A) (Website) Database of Research Ethics Committees (Current as of June 1, 2016)
National Health Research Ethics Council, Department of Health, Republic of South Africa

REQUIREMENTS

(1) (Legislation) National Health Act 61 of 2003 (NHA) (September 2, 2013)
Parliament, Republic of South Africa

Relevant Sections: Chapter 9, Sections 72 and 73

(2) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 1.2.7, 1.5.3, 1.5.4, 1.6, 2.2, 2.3,8.3, 8.4, and 8.5

(3) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Sections: 4.2, 4.4, 5.1, 5.2, and 5.3

Ethics Committee > Scope of Review
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SUMMARY

Overview
In accordance with the NHA, the SA-GCPs, and the G-EthicsHR, ethics committees (ECs) must evaluate the ethical and scientific rigor of all research studies to be conducted in the country. An EC’s primary responsibilities are to:

  • Review protocols to ensure that research involving human participants will promote health, and prevent or cure disability and disease
  • Ensure that human participants’ rights are protected, that they are treated with dignity, that their safety and well-being is not compromised, and that informed consent is obtained
  • Grant approval for research where the protocols meet the ethical standards of the institution, agency, or establishment

An EC must also pay special attention to protecting the welfare of certain classes of participants deemed to be vulnerable (See Informed Consent topic, and the subtopics of Vulnerable Populations; Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners, and Mentally Impaired for additional information about these populations).

Role in Clinical Trial Approval Process
As per the G-EthicsHR, the SA-GCPs, and the NHAParticipants, the principal investigator (PI) or the sponsor must submit a clinical trial application to both the Medicines Control Council (MCC) and a registered EC for review and approval before a study may commence. The National Health Research Ethics Council (NHREC) is responsible for establishing a research tracking system for the ECs. According to Additional Resources (A) and (B), the PI or the sponsor must register his/her clinical trial information on the South African Human Research Electronic Application System (Ethicsapp) website, and then the system will generate an NHREC application/registration number. Once the ethics or MCC approval is obtained, the PI or the sponsor should enter these regulatory approval numbers using the NHREC number on the South African National Clinical Trials Register (SANCTR) website. The Department of Health (DOH) then issues the SANCTR National Register Number. The SANCTR number will be generated within two (2) working days. This will be done either by email or fax and will be sent to both the relevant EC(s) and the PI or the sponsor. Receipt of the SANCTR number provides the research team with the authority to commence the study pending the approval of all other relevant regulatory clearances. See Additional Resources (A) and (B) for detailed registration instructions.

ADDITIONAL RESOURCES

(A) (Website) South African National Clinical Trial Register – How to Register (Current as of June 1, 2016)
Department of Health, Republic of South Africa

(B) (Website) South African Human Research Electronic Application System (Current as of June 1, 2016)
National Health Research Ethics Council, Department of Health, Republic of South Africa

REQUIREMENTS

(1) (Legislation) National Health Act 61 of 2003 (NHA) (September 2, 2013)
Parliament, Republic of South Africa

Relevant Sections: Chapter 9, Sections 72 and 73

(2) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 1.2.7, 1.5.4, 1.6, 2.2, 2.3, 4.1, 4.2, 8, and Appendix F

(3) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Sections: 4.2, 4.3, 2.1, 2.3, 4, 5, 6, and Appendix 1

(4) (Legislation) National Health Act 61 of 2003: Regulations Relating to Research with Human Participants (NHAParticipants) (September 19, 2014)
Parliament, Republic of South Africa

Relevant Section: 3

Ethics Committee > Ethics Committee Fees
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SUMMARY

Overview
Based on the G-EthicsHR, and the SA-GCPs, ethics committees (ECs) may independently decide whether to charge fees for a protocol review. The EC procedures section of both the G-EthicsHR, and the SA-GCPs state that an EC should establish and record working procedures concerning fees charged, if any.

Although South African ECs may decide on their own whether to charge a research review fee, ECs typically only charge to review research funded outside of the institution or industry-sponsored research. No charge is assessed to review investigator-driven research conducted for academic purposes within the institution.

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Section: 4.5

(2) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Section: 8.5

Ethics Committee > Authorizing Body
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SUMMARY

Overview
The National Health Research Ethics Council (NHREC) is the central statutory body responsible for the registration and auditing of ethics committees (ECs) in South Africa. As per the terms of Section 72 in the NHA, the NHREC was created by the Minister of Health to provide ethical oversight of clinical research and to safeguard the rights and welfare of human participants involved in clinical studies.

As delineated in the NHA, the SA-GCPs, and the G-EthicsHR, the NHREC’s core responsibilities center on promoting, ensuring, and monitoring compliance by ECs. This includes conducting the following activities:

  • Determining guidelines for EC operations
  • Registering and auditing ECs
  • Setting norms and standards for conducting research on humans and animals, including norms and standards for conducting clinical trials
  • Adjudicating complaints about the functioning of ECs and handling researcher discrimination complaints

NHREC Composition
According to the NHA and the G-EthicsHR, the Minister of Health is authorized to appoint 15 members to the NHREC and the NHREC elects its own chairperson. The Council meets four (4) times per year, and submits an annual report to advise the Minister about policy. The Council is also provided with secretariat support from the Department of Health (DOH)’s Research Directorate. For additional information on the NHREC, see the NHA and the NHREC website.

Registration and Auditing
As delineated in the NHA, the G-EthicsHR, and the SA-GCPs, all ECs are required to register with the NHREC in order to undertake the ethical review of a clinical study. The EC registration is then recorded and publicly listed by the NHREC. The NHREC then performs an audit of the application, and depending on the EC’s structure and function, will categorize the committee as either a Level 1 or Level 2 EC. Level 1 ECs include those that have the capacity to assess straightforward research designs involving minimal risk to human participants. These include research proposals that do not involve drug research, biomedical research involving human tissues, high-budget research, or high-technology research. Level 2 ECs comprise those that may review all types of research proposals.

The NHREC’s categorization of ECs is based on the principles set forth in the SA-GCPs, the Declaration of Helsinki, and the International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs). The NHREC audits occur as part of an annual review process. EC categorization may change based on these annual reviews to reflect new ethical concerns or standards that have arisen in South Africa or internationally. The Council will publish any additional requirements that emerge on its website. See G-EthicsHR for detailed information on the NHREC registration, auditing, and categorization process.

ADDITIONAL RESOURCES

(A) (Website) National Health Research Ethics Council – Database of Research Ethics Committees (Current as of June 1, 2016)
National Health Research Ethics Council, Department of Health, Republic of South Africa

(B) (ICH Guidance) International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Conference on Harmonisation, Geneva, Switzerland

REQUIREMENTS

(1) (Legislation) National Health Act 61 of 2003 (NHA) (September 2, 2013)
Parliament, Republic of South Africa

Relevant Section: Chapter 9, Sections 72 and 73

(2) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Sections: 4.6, 5.2, and 5.4

(3) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 1.2.7, 1.5.3, 1.5.4, 2.2, 8.2, and Appendix F

Clinical Trial Lifecycle > Submission Process
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SUMMARY

Overview
According to the G-CTA and Additional Resource (A), the review and approval of clinical trial applications by the Medicines Control Council (MCC) and an accredited ethics committee (EC) may be conducted in parallel. The applicant must notify each regulatory body of the other’s approval once it has been received. In addition, each EC has its own required submission procedures, which can differ significantly regarding the number of copies to be supplied and application format requirements.

Delivery Address for Clinical Trial Application
As indicated by the MCC and the G-GenInfo, clinical trial applications and correspondence should be mailed to:

Medicines Control Council
Registrar of Medicines
Private Bag X 828
Pretoria, 0001
South Africa

If the application is being delivered in person, it should be delivered to:

Medicines Control Council
Civitas Building
42 Thabo Sehume Street
Room NG090
Pretoria
South Africa

All applications and correspondence should be clearly coded as specified in the following list:

  • TGC – General correspondence
  • TCA – Application to conduct a clinical trial
  • TCV – Amendment of an existing clinical trial
  • TCR – Response to Clinical Trial Committee resolution
  • TAE – Report of adverse drug events arising from a clinical trial
  • TUM – Applications related to unregistered medicines as per MRSA, 2008

Assembly and Number of Copies
Additional Resource (A) states that all applications must be submitted in duplicate with two (2) electronic copies (including, but not limited to: application form (sections 1-3), the protocol, the investigator’s brochure, and/or other relevant documents). An additional 25 copies of the application form itself must also be submitted and labeled diskette(s)/CD-ROM(s) (MS-Word or rich text format) with a list of files included on the diskette/CD-ROM(s).

Clinical Trial Application Language Requirements
As per the G-GenInfo and the GRMRSA, all applications and supporting data submitted to the MCC should be presented in English. Original documents that are not in English must be accompanied by an English translation.

All documents provided to ECs are to be submitted and approved in English.

ADDITIONAL RESOURCES

(A) (Form) Application to Conduct Clinical Trials (Version 1) (CTF1) (May 2003)
Medicines Control Council, Department of Health, Republic of South Africa

(B) (Website) Medicines Control Council – Contact the MCC (Current as of June 1, 2016)
Medicines Control Council, Department of Health, Republic of South Africa

REQUIREMENTS

(1) (Guidance) General Information (G-GenInfo) (August 2012) (Version 8)
Registrar of Medicines, Medicines Control Council, Department of Health, Republic of South Africa

Relevant Sections: 2.4 and2.5

(2) (Legislation) No. 72 of 2008: Medicines and Related Substances Act, 2008 (MRSA, 2008) (April 21, 2009)
Parliament, Republic of South Africa

Relevant Section: 20

(3) (Regulation) Medicines and Related Substances Act 101 of 1965 - General Regulations Made in Terms of the Medicines and Related Substances Act 101 of 1965, as Amended (GRMRSA) (February 15, 2014)
Department of Health, Republic of South Africa

Relevant Section: Application for the Registration of a Medicine – Part 22 (4)

(4) (Guidance) Guideline on Completing Clinical Trial Applications (G-CTA) (May 2003)
Registrar of Medicines, Medicines Control Council, Department of Health, Republic of South Africa

Relevant Section: A

Clinical Trial Lifecycle > Submission Content
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SUMMARY

Overview
In accordance with the NHA, the SA-GCPs, the G-EthicsHR, and the NHAParticipants, a sponsor (or the principal investigator when there is no sponsor) must apply to the Medicines Control Council (MCC) and an accredited ethics committee (EC) to conduct a clinical trial for a non-registered drug or a registered drug for new indications.

MCC Requirements
As per Additional Resource (A), the following documentation must be submitted to the MCC:

  • Cover letter
  • Cover sheet
  • Completed Form CTF1 – Application to Conduct Clinical Trials (See Additional Resource (A))
  • Protocol (Refer to Clinical Protocol section of this subtopic)
  • Patient Information Leaflet(s) (PILs) and informed consent form(s) (ICFs) (See Informed Consent topic, Required Elements subtopic for additional information)
  • Standardized MCC contact details to be added to PILs
  • Investigator’s brochure (IB) and all package insert(s)
  • Investigator’s curriculum vitae(s)(CVs) in MCC format
  • Signed declaration(s) by investigators
  • Regional monitor’s CV and declaration
  • Signed joint declaration by sponsor and national principal investigator (PI)
  • Certificate(s) of analysis (may be submitted with ethics approval letter)
  • Indemnity/insurance certificate and/or proof of malpractice insurance of trialist(s)
  • Letter endorsing generic insurance certificate
  • Ethics approval or copy of letter submitted to EC
  • Copy or copies of recruitment advertisement(s) (if applicable)
  • Financial declaration (sponsor/national PI)

In addition, as outlined in Additional Resource (A), a sponsor is required to include the following investigational product (IP) information in the clinical trial application:

  • Name(s) and details of IP(s)
  • Name(s) and details of comparator product(s)
  • Name(s) and details of concomitant medication(s) including rescue medications required in the protocol
  • Estimated quantity of trial material (each drug detailed separately) for which exemption will be required
  • If any of the above drugs are available in South Africa, an explanation for not using what is available in South Africa
  • Details of drug delivery from supplier, and storage, dispensing, and packaging of drugs
  • Date MCC registration applied for – or envisioned date of application for trial medication. Explain if registration is not envisioned
  • IP registration status for the indication to be tested in this trial, in other countries

See the G-CTA for detailed IP clinical trial application submission requirements.

EC Requirements
Each 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, the requirements list provided below is basically consistent across all South African ECs.

The following list was compiled from Additional Resources (B), (C), and (D), to exemplify the common elements shared by the various application forms:

  • Cover letter
  • Completed EC application form
  • Protocol
  • Protocol synopsis
  • PIL(s) and ICF(s) and process for obtaining informed consent
  • Separate assent form is required for adolescents/children under the age of 18 (See Informed Consent topic, Children/Minors subtopic for additional information)
  • IB and package insert(s) (if applicable)
  • MCC approval letter or letter of application and notification
  • Approval letter from institution’s scientific committee
  • Copy of completed clinical trial application signed by all participating investigators
  • All questionnaires and diaries to be used in the study
  • Advertisement(s) (if applicable)
  • Trial site information (address, telephone numbers, PI names, etc.)
  • Trial payment schedule and budget schedule per site/draft financial contract and additional funding details
  • Proof of submission fees payment
  • Current investigator(s) CVs
  • Good clinical practice (GCP) training certificates for PIs and subinvestigators
  • National Health Research Ethics Committee (NHREC) trial registration form
  • Declaration of trialists (PI and subinvestigators) in MCC format
  • Insurance certificate

Clinical Protocol
As delineated in Appendix B of the SA-GCPs, the clinical protocol should contain the following information:

  • General information
  • Background information
  • Trial objectives and purpose
  • Trial design
  • Participant selection/withdrawal
  • Participant treatment
  • Efficacy assessment
  • Safety assessment
  • Statistics
  • Direct access to source data/documents
  • Quality control/quality assurance
  • Ethics
  • Data handling/recordkeeping
  • Financing/insurance
  • Publication policy

For detailed information on these elements, please refer to the SA-GCPs.

ADDITIONAL RESOURCES

(A) (Form) Application to Conduct Clinical Trials (Version 1) (CTF1) (May 2003)
Medicines Control Council, Department of Health, Republic of South Africa

(B) (Form) Application for Ethics Approval for Research on Human Participants (Biomedical) (September 2012)
Biomedical Research Ethics Committee, University of Kwazulu-Natal

(C) (Form) Research Ethics Committee Application Form (May 28, 2010)
Human Sciences Research Council (HSRC), South Africa

(D) (Form) Application to the Human Research Ethics Committee: (Medical) – For Clearance of Research – For Pharmaceutical/Grant/Donor Sponsored Clinical Trials Involving Drugs/Devices (Version 3) (2013)
Human Research Ethics Committee, University of the Witwatersrand, Johannesburg

REQUIREMENTS

(1) (Legislation) National Health Act 61 of 2003 (NHA) (September 2, 2013)
Parliament, Republic of South Africa

Relevant Sections: Chapter 9, Sections 72 and 73

(2) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections 1.5.3, 1.5.4, 1.6, 2.2, 3.1, 4.1, and Appendix B

(3) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Sections: 2.1, 2.3, 4, and 5.5

(4) (Guidance) Guideline on Completing Clinical Trial Applications (G-CTA) (May 2003) (Updated August 2010)
Registrar of Medicines, Medicines Control Council, Department of Health, Republic of South Africa

(5) (Legislation) National Health of Act 61 of 2003: Regulations Relating to Research with Human Participants (NHAParticipants) (September 19, 2014)
Parliament, Republic of South Africa

Relevant Section: 3

Clinical Trial Lifecycle > Timeline of Review
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SUMMARY

Overview
Based on the G-CTA and Additional Resources (A), (B), and (C), the review and approval of clinical trial applications by the Medicines Control Council (MCC) and an accredited ethics committee (EC) may be conducted in parallel. The applicant must notify each regulatory body of the other’s approval once it has been received.

MCC Approval
According to Additional Resources (B), (C), (D), and (E), the typical timeline for the MCC review and approval averages 12 to 16 weeks. This timeframe is based on a two-tiered review process within the MCC. When an applicant submits a clinical trial application to the MCC, the first review tier is essentially administrative, and occurs within two (2) weeks of submission. The second review tier is scientific and ethical, and is composed of two (2) separate cycles in which the external reviewer initially reviews the application followed by the Clinical Trial Committee (CTC) review.

The scientific and ethical review phase is initially conducted by an external reviewer who then takes his/her comments to the CTC meeting. At the CTC meeting, the reviewer and the CTC committee members discuss shared concerns and comments, and applicant queries are compiled. The Secretariat faxes the queries to the applicant, who has seven (7) calendar days to respond via hard and electronic copies (on a CD). The applicant’s responses are then forwarded to the original reviewer for his/her evaluation and approval.

Additional Resource (E) states that the reviewer and CTC also assign an approval category as follows:

  • 1a – Approval
  • 1b – Ethics Committee Approval Outstanding
  • 2a – Outstanding issues can be dealt with “in-house”
  • 2b – Outstanding Issues must be checked by Original Reviewer
  • 3 – Original Reviewer reports back to full Committee
  • 4 – Referral for Specialist Opinion
  • 5 – Rejection of Application and requires Full Resubmission if to be reconsidered
  • 6 – Rejection because of missing component(s)

Those applications which receive up to a 2b rating are deemed to have minor queries, and pending the reviewer’s approval to his/her responses, the trial will be approved and ratified in the MCC meeting.

Applications that receive a rating of Category 3 or above have serious deficiencies in the protocol design or in the study’s scientific rationale, and resubmission and review over the next submission cycle may be required.

Once the reviewer approves the application, the CTC presents the committee’s/reviewer’s recommendations to the MCC, which usually meets about six (6) weeks following the CTC meeting. An approval letter from the MCC allows the study to begin and also serves as an importation permit for the investigational product.

EC Approval
As earlier stated, an applicant must also submit the clinical trial application for review and approval by an accredited local EC. Additional Resources (C) and (D) indicate that the EC review process on average is typically completed in four (4) to six (6) weeks. An applicant can request conditional approval from the MCC until the EC has completed its approval of the study. This may be necessary in clinical studies in which multiple EC approvals are required.

ADDITIONAL RESOURCES

(A) (Form) Application to Conduct Clinical Trials (Version 1) (CTF1) (May 2003)
Medicines Control Council, Department of Health, Republic of South Africa

(B) (Article) Clinical Trials in South Africa 101 (March 2011)
The Official Blog of Cato Research

(C) (Article) Discovering South Africa (June 1, 2005)
Scholtz, Herman and Pretorius, Sybrand
Applied Clinical Trials

(D) (Brochure) Why Conduct Clinical Trials in South Africa? (September 2012)
Arianne Corp, San Diego, California

(E) (Article) Regulatory Timelines and Enrolment Potential in South Africa Starting to Improve (January 2010)
Katsoulis, Lynn
Journal for Clinical Studies

Relevant Section: pages 10-11

REQUIREMENTS

(1) (Guidance) Guideline on Completing Clinical Trial Applications (G-CTA) (May 2003) (Updated August 2010)
Registrar of Medicines, Medicines Control Council, Department of Health, Republic of South Africa

Relevant Section: A

 

Clinical Trial Lifecycle > Trial Initiation
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SUMMARY

Overview
In accordance with the GRMRSA, the SA-GCPs, the G-EthicsHR, and the NHAParticipants, a clinical trial can only commence in South Africa once an applicant receives approval from the Medicines Control Council (MCC) and from an accredited local ethics committee (EC). There is no waiting period required following the applicant’s receipt of these approvals.

In addition, the principal investigator (PI) for each study site must be a South African-based scientist (resident of South Africa), and should have the appropriate qualifications, training, and experience to assume responsibility for the proper conduct of a trial. The trial must be conducted in compliance with the SA-GCPs, the G-EthicsHR, and the GRMRSA. Also, per the SA-GCPs, all clinical trials must be conducted in a laboratory complying with Good Laboratory Practices.

South African National Clinical Trial Register (SANCTR) Recording Requirements
According to the SA-GCPs, NHAParticipants, and Additional Resources (A) and (C), once the trial has obtained approval from the MCC and the EC, the sponsor or the PI must register his/her clinical trial information on the South African Human Research Electronic Application System (Ethicsapp) website, and then the system will generate a National Health Research Ethics Council (NHREC) application/registration number. Once the ethics or MCC approval is obtained, the PI or the sponsor should enter these regulatory approval numbers using the NHREC number on the South African National Clinical Trials Register (SANCTR) website. The Department of Health (DOH) then issues a unique SANCTR National Register Number. The SANCTR number will be generated within two (2) working days. This will be done either by email or fax and will be sent to both the relevant EC(s) and the PI or the sponsor. Receipt of the SANCTR number provides the research team with the authority to commence the study pending the approval of all other relevant regulatory clearances. See Additional Resources (A) and (C) for detailed registration instructions.

In addition, because multi-center trials and multi-sponsor trials are susceptible to duplicate registration, sponsors must be attentive when registering the trials. For multi-sponsored trials, the lead sponsor should take responsibility for registration. It is critical that investigators and sponsors work together to ensure that a trial is registered only once with SANCTR.

In addition, per an in-country subject matter expert, because SANCTR is not an International Committee of Medical Journal Editors (ICMJE) recognized register, applicants will also need to register on one of the World Health Organization (WHO) affiliated registries (e.g., Pan African Clinical Trials Registry).

Clinical Trial Agreement
According to the SA-GCPs, before the trial begins, a sponsor must prepare a written agreement which includes any information not covered in the protocol. The agreement must be signed by the sponsor and the PI, and any other parties involved with the trial to confirm the contract terms.

The sponsor should also obtain the investigator's agreement to:

  • Conduct the trial in compliance with the SA-GCPs, the MCC requirements, and with the EC approved protocol
  • Comply with data recording/reporting procedures
  • Permit monitoring, auditing, and inspection
  • Retain the trial-related essential documents until the sponsor informs the investigator(s) and institution(s) that these documents are no longer needed

In addition, the financial aspects of the trial should be documented in the agreement. A declaration must be signed by the sponsor and PI stating that sufficient funds are available to complete the study.

EC Confirmation of Review
The SA-GCPs mandate that the sponsor receive confirmation of EC review from the investigator(s) or institution(s). The sponsor must receive the following information prior to the trial’s commencement:

  • EC member profiles (names and addresses)
  • Documented approval of EC’s favorable opinion
  • Copy of EC recommendations in case it has based its approval on change(s) in any aspect of the study (e.g., protocol modifications, written informed consent form, or any other written information or other procedures)

The sponsor should also obtain from the PI documentation and dates relating to any EC re-evaluations, re-approvals, withdrawals, or suspensions of approval. (See Ethics Committee, Scope of Review subtopic and Clinical Trial Lifecycle topic, Submission Content subtopic for additional details on EC review process).

ADDITIONAL RESOURCES

(A) (Website) South African National Clinical Trial Register - How to Register (Current as of June 1, 2016)
Department of Health, Republic of South Africa

(B) (Handbook) Handbook – Good Laboratory Practices (GLP): Quality Practices for Regulated Non-clinical Research and Development (2nd Edition) (2009)
World Health Organization

(C) (Website) South African Human Research Electronic Application System (Current as June 1, 2016)
National Health Research Ethics Council, Department of Health, Republic of South Africa

REQUIREMENTS

(1) (Regulation) Medicines and Related Substances Act 101 of 1965 - General Regulations Made in Terms of the Medicines and Related Substances Act 101 of 1965, as Amended (GRMRSA) (February 15, 2014)
Department of Health, Republic of South Africa

Relevant Section: Part 34 (1 and 5)

(2) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 1.2.5, 1.5.5, 1.5.7, 1.6, 3.2, and 4.3

(3) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Sections: 4 and 5

(4) (Legislation) National Health of Act 61 of 2003: Regulations Relating to Research with Human Participants (NHAParticipants) (September 19, 2014)
Parliament, Republic of South Africa

Relevant Section: 3

Clinical Trial Lifecycle > Safety Reporting
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SUMMARY

Overview
In accordance with the SA-GCPs, the G-EthicsHR, and the G-ADR, the following definitions provide a basis for a common understanding of South Africa’s safety reporting requirements:

  • Adverse Event/Experience (AE) – Any untoward medical occurrence that may present during treatment with a medicine, but which does not necessarily have a causal relationship with this treatment
  • Adverse Drug Reaction or Adverse Reaction (ADR) – A noxious and unintended response to a medicine in humans or animals, including lack of efficacy, and which occurs at any dosage and can also result from overdose, misuse, or abuse of a medicine
  • 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 patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, or is a congenital anomaly or birth defect
  • Unexpected Adverse Drug Reaction – One in which the nature, specificity, severity, and outcome is inconsistent with the applicable product information (i.e., with the approved package inserts for registered medicines, the investigator’s brochure, or other product information for unregistered medicines being used)

Reporting Requirements for AEs/ADRs
Investigator Responsibilities
As specified in the SA-GCPs and the G-EthicsHR, the principal investigator (PI) must inform the sponsor, within the time specified in the protocol, of any unexpected SADRs/SAEs occurring during the study. The initial SAE/SADR report form and any relevant follow-up information should be sent to the sponsor. According to an in-country subject matter expert, investigators may forward reports directly to the ethics committee (EC) as relevant.

The following must be reported by the PI as part of the six-month progress reports:

  • All suspected, unexpected SAEs/SADRs originating from clinical trials conducted with unregistered medicines at worldwide sites outside South Africa and as authorized under MRSA, 2008 should be reported as part of the six-month progress reports in a line listing format
  • All SAEs/SADRs must be included as part of the six-month progress reports in a line listing format only
  • All non-serious unexpected suspected AEs/ADRs must be included as part of the six-month progress reports in a line listing format only

Sponsor Responsibilities
As delineated in the GRMRSA, the SA-GCPs, and the G-EthicsHR, the sponsor is required to report all expected or unexpected SAEs/SADRs on an expedited basis to all concerned parties, including investigator(s) and institution(s), the Medicines Control Council (MCC), and the ECs. As per the G-ADR, if the sponsor does not agree with the causal association assigned by the initial reporter/investigator, the reaction should still be reported.

Depending on the severity of an AE/ADR during a clinical trial, the following reporting requirements apply under the G-ADR:

  • Unexpected SAEs/SADRs that are not fatal or life-threatening must be reported as soon as possible, and not later than 15 calendar days after first knowledge by the sponsor
  • All fatal and life-threatening, unexpected SAEs/SADRs should be reported within seven (7) calendar days after first knowledge by the applicant. The initial notification must be followed by as complete a report as possible, within an additional eight calendar days.
  • Suggested change(s) in the nature, severity, or frequency of expected AEs/ADRs, or when new risk factors are identified should be communicated to the MCC within 15 calendar days after first knowledge by the sponsor. The basis on which these assessments are made should also be included.
  • Any information, which may in any way influence the benefit-risk assessment of a medicine, or which would be sufficient to consider changes in the administration of the medicine, or in the overall conduct of a clinical trial, must be reported to the MCC within three (3) calendar days of first knowledge.
  • If the study is multi-centered, the SA-GCPs states that the sponsor should ensure that all SAEs/SADRs occurring at any study site are reported without delay to the investigator(s)/institution(s), the MCC, and the ECs.

See the G-ADR for additional details on SAEs/SADRs.

The sponsor must also submit to the MCC and the EC(s) all required safety updates and periodic reports. Review of reported serious and unexpected ADRs/AEs should include analysis, evaluation, and a complete account of the entire body of safety information of the drug, as such data may have emerged during the course of the trial.

Form Completion & Delivery Requirements
The MCC's Adverse Drug Reaction and Product Quality Problem Report Form may be used to complete SAE/SADR reports. For marketed medicine, the form must be submitted to the MCC’s National Adverse Drug Event Monitoring Centre (see Additional Resource (A) to access the form). Per an in-country subject matter expert, applicants may use their in-house report forms, provided all the necessary data elements are included in a readable format.

For unregistered medicines as authorized under MRSA, 2008 and in clinical trials involving unregistered medicines, send the form to:

Office of the Registrar of Medicines
Pharmacovigilance Unit
Private Bag X828
Pretoria
0001
South Africa
Tel: (012) 395 8176/7/8
Fax: (012) 395 8775

ADDITIONAL RESOURCES

(A) (Form) Adverse Drug Reaction and Product Quality Problem Report Form (Version 3) (April 2011) 
Medicines Control Council, Department of Health, Republic of South Africa

(B) (ebook) Global Clinical Trials: Effective Implementation and Management (June 6, 2011)
Chin, Richard and Bairu, Menghis, eds., Academic Press

Relevant Section: Chapter 13, Section 13.12

REQUIREMENTS

(1) (Regulation) Medicines and Related Substances Act 101 of 1965 - General Regulations Made in Terms of the Medicines and Related Substances Act 101 of 1965, as Amended (GRMRSA) (February 15, 2014)
Department of Health, Republic of South Africa

Relevant Sections: Parts 1, 34, and 37

(2) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 3.12, 4.19, and Appendix F

(3) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Sections: 4.5.1 and Appendix 1

(4) (Guidance) Reporting Adverse Drug Reactions in South Africa (Version 1_2) (G-ADR) (December 2012)
Medicines Control Council, Department of Health, Republic of South Africa

Relevant Sections: 2.1, 2.2, 2.3, 2.4, 2., 2.6, 5.1, and 7.1

(5) (Legislation) No. 72 of 2008: Medicines and Related Substances Act, 2008 (MRSA, 2008) (April 21, 2009)
Parliament, Republic of South Africa

Relevant Section: 20

Clinical Trial Lifecycle > Progress Reporting
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SUMMARY

Overview
In accordance with the GRMRSA and the SA-GCPs, the principal investigator (PI) is responsible for submitting progress reports on the status of a clinical trial.

Progress Reports
As per the SA-GCPs, the PI is obligated to submit progress reports to the sponsor, the Medicines Control Council (MCC), and the relevant ethics committee(s) (ECs). These reports should contain the following information:

  • Study status
  • Number of participants included in relation to the number expected
  • Number of dropouts and withdrawals
  • Adverse events/Adverse drug reactions
  • If the planned time schedule is still appropriate

The GRMRSA requires the PI to submit these reports to the MCC every six (6) months from the date at which the trial commenced. Additional Resource (A) contains MCC’s progress report template to be used by the investigators.

Final Study Reports
The PI is also required to submit a final report to the MCC 30 days following the trial’s completion as stated in the GRMRSA. In addition, upon the trial’s end, the PI, where applicable, should provide the EC, the MCC, and other relevant regulatory authorities with a summary of the trial’s outcomes, and a statement that the trial has been conducted in accordance with the GRMRSA and the SA-GCPs.

The SA-GCPs also specifies that the protocol, statistical, and clinical aspects of the trial be integrated to obtain a final study report that is consistent with the study data generated. Essential elements to include are:

  • Baseline comparisons between the treatment groups
  • Number of participants actually randomized into the study by treatment group, and the number of participants excluded from any of the analyses, by reason, and by treatment group
  • Major efficacy and safety results by treatment group using tables, graphs, test variables, and statistical parameters as appropriate

An assessment of between-group differences with confidence intervals

In multicenter studies, an evaluation of the center effect may also be included, and should always be conducted where significant center variation is suspected.

An account must also be made of missing, unused, or spurious data during statistical analyses. All omissions of this type must be documented to enable review to be performed. The sponsor or the PI is responsible for recording the final study results in the Department of Health’s South African National Clinical Trial Register (SANCTR) within one (1) year of the study’s completion.

ADDITIONAL RESOURCES

(A) (Website) Regulatory and Other Approvals (Current as of June 1, 2016)
Clinical Research Centre, University of Cape Town, Republic of South Africa

Relevant Section: MCC Clinical Progress Report

REQUIREMENTS

(1) (Regulation) Medicines and Related Substances Act 101 of 1965 - General Regulations Made in Terms of the Medicines and Related Substances Act 101 of 1965, as Amended (GRMRSA) (February 15, 2014)
Department of Health, Republic of South Africa

Relevant Section: Part 34 (6)

(2) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 3.14 and 6.4

Sponsorship > Definition of Sponsor
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SUMMARY

Overview
As defined in the SA-GCPs, a sponsor is the person or organization responsible for the initiation, management, or financing of a clinical trial. A sponsor can be a pharmaceutical company, the principal investigator (PI), a funding body, or an individual or organization designated by the funding body or PI.

A sponsor may be domestic or foreign. A sponsor may transfer any or all of his/her trial-related duties and functions to a contract research organization (CRO). However, he/she is always ultimately responsible for the study data quality and integrity. Any trial-related responsibilities transferred to and assumed by a CRO should be specified in writing. Those responsibilities not specifically transferred to and assumed by a CRO are retained by the sponsor.

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 1.5.6, 4, and 4.5

Sponsorship > Trial Authorization
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SUMMARY

Overview
In accordance with the SA-GCPs, a sponsor or his/her designated contract research organization (CRO) is responsible for submitting a clinical trial application to the Medicines Control Council (MCC) to obtain approval to conduct a study. As indicated in Additional Resource (A), if there is no sponsoring organization, the principal investigator (PI) must clearly state in the protocol who will be assuming the sponsor’s role of initiating, managing, or funding the clinical trial.

To complete the clinical trial application package, a sponsor must use the MCC’s Application to Conduct Clinical Trials form (CTF1) listed in Additional Resource (A). In addition to the completed application, a sponsor must also provide three (3) copies of the protocol, the patient information leaflet and informed consent form, a signed joint declaration by the sponsor and PI, a financial declaration signed by the sponsor, and other documentation covered in the Clinical Trial Lifecycle topic, Submission Content subtopic. It is both the sponsor’s and the PI’s responsibility to ensure that the protocol satisfies the requirements of the protocol checklist in Additional Resource (A) and complies with the G-CTA.

ADDITIONAL RESOURCES

(A) (Form) Application to Conduct Clinical Trials (Version 1) (CTF1) (May 2003) 
Medicines Control Council, Department of Health, Republic of South Africa

REQUIREMENTS

(1) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 1.6 and 4.1

(2) (Guidance) Guideline on Completing Clinical Trial Applications (G-CTA) (May 2003) (Updated August 2010)
Registrar of Medicines, Medicines Control Council, Department of Health, Republic of South Africa

Sponsorship > Insurance
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SUMMARY

Overview
The Medicines Control Council (MCC) and the ethics committee(s) (ECs) require a sponsor to provide comprehensive insurance for injury and damage to all trial participants as described in the SA-GCPs, and Additional Resources (B) and (C). As delineated in the SA-GCPs, a sponsor must follow the principles set forth in the Association of the British Pharmaceutical Industry’s guidelines (Additional Resources (B) and (C)) to comply with South Africa’s clinical trial insurance requirements. A sponsor must ensure that he/she has obtained insurance and indemnity to cover his/her liability in a clinical trial.

As delineated in Additional Resource (A), an insurance certificate and indemnity must be included in the clinical trial application submitted to the MCC. The insurance certificate must include the following:

  • References to the applicable regulatory and legal provisions
  • Insurer company name
  • Insurance policy number
  • Name and address of the policy holder
  • Study name, identification number, and protocol dates covered by the policy

The policy must also indicate the minimum coverage amount for a biomedical research study. In addition, the G-CTA states that if the insurance certificate is not specific to the protocol being submitted in a clinical trial application, the applicant must ensure that a letter accompanies the generic insurance certificate for verification purposes.

ADDITIONAL RESOURCES

(A) (Form) Application to Conduct Clinical Trials (Version 1) (CTF1) (May 2003)
Medicines Control Council, Department of Health, Republic of South Africa

(B) (Guidance) Clinical Trial Compensation Guidelines (G-CTComp) (December 11, 2014)
Association of the British Pharmaceutical Industry, United Kingdom

(C) (Guidance) Insurance and Compensation in the Event of Injury in Phase I Clinical Trials (2nd Edition) (G-InsComp) (June 2013)
Association of the British Pharmaceutical Industry, BioIndustry Association, and Clinical Contract Research
Association, United Kingdom

Relevant Sections: 3 and 4

REQUIREMENTS

(1) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 2.2 and 4.11

(2) (Guidance) Guideline on Completing Clinical Trial Applications (G-CTA) (May 2003) (Updated August 2010)
Registrar of Medicines, Medicines Control Council, Department of Health, Republic of South Africa

Relevant Section: A (1)

Sponsorship > Compensation
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SUMMARY

Overview
Additional Resource (A) states that the Medicines Control Council’s (MCC) Clinical Trial Committee recommends a minimum compensation of 50 South African Rand per study visit to cover participant travel and incidental expenses. In addition, the G-EthicsHR also addresses researcher requirements to budget for participant travel and other expenses. (See the G-EthicsHR for detailed information).

As per the SA-GCPs, the sponsor must follow the principles set forth in the Association of the British Pharmaceutical Industry’s guidelines (Additional Resources (B) and (C)) to comply with South Africa’s participant compensation and treatment requirements due to trial-related injuries.

The guidelines state that the sponsor should furnish written assurance to the investigator that he/she will agree to pay compensation to participants and/or his/her legal heirs in the event of trial-related injuries or death. The investigator, in turn, communicates this information to the relevant ethics committee(s).

Compensation Principles
The SA-GCPs and the Additional Resource (B) provide several basic principles to guide sponsors in fulfilling their compensation obligations. Compensation should be paid as follows:

  • When it can be demonstrated that a causal relationship exists between a participant’s injury and his/her participation in a trial
  • When a child is injured in utero through his/her mother’s participation in a clinical trial
  • When the injury results in permanent injury or disability to the participant
  • When there is an adverse reaction to a medicinal product under trial, and injury is caused by a procedure adopted to deal with that adverse reaction

The likelihood of an adverse reaction, or the fact that the participant has freely consented (whether in writing or otherwise) to participate in the trial should not exclude him/her from being eligible for compensation. (See the aforementioned guidelines and the Informed Consent topic, Compensation Disclosure subtopic for additional information on a participant’s right to compensation).

Payment Procedures and Requirements
According to the SA-GCPs and the Additional Resource (B), the amount of compensation to be paid to the participant should be appropriate to the nature, severity, and persistence of the injury. The compensation should also be generally consistent with the amount of damages commonly awarded for similar injuries.

The amount paid in compensation should be abated, or in certain circumstances excluded, in light of the following factors (which will depend on the risk level the participant can reasonably be expected to accept):

  • The seriousness of the disease being treated
  • The degree of probability that adverse reactions will occur and any warning given
  • The risks and benefits of the established treatments relative to those known or suspected of the trial medicines

In any case where the sponsor agrees to pay the participant, but the two parties differ on what is the appropriate level of compensation, it is recommended that the sponsor agree to seek at his/her own cost, the opinion of a mutually acceptable independent expert. This opinion should then be made available to the participant(s), and the expert’s opinion should be given substantial weight by the sponsor in reaching a decision on the payment amount.

Additionally, any participant claims pursuant to the SA-GCPs and Additional Resource (B), should be made to the sponsor, preferably via the investigator. The participant should include details on the nature and background of the claim which the sponsor should review expeditiously. The review process may be delayed if the participant requests an authority to examine any medical records relevant to the claim.

ADDITIONAL RESOURCES

(A) (Form) Application to Conduct Clinical Trials (Version 1) (CTF1) (May 2003)
Medicines Control Council, Department of Health, Republic of South Africa

(B) (Guidance) Clinical Trial Compensation Guidelines (2014)
Association of the British Pharmaceutical Industry, United Kingdom

(C) (Guidance) Insurance and Compensation in the Event of Injury in Phase I Clinical Trials (2nd Edition) (June 2012)
Association of the British Pharmaceutical Industry, BioIndustry Association, and Clinical Contract Research
Association, United Kingdom

Relevant Section: 3

(D) (Article) Payment of trial participants in South Africa: Ethical considerations for Research Ethics Committees (2012)
National Health Research Ethics Council, Department of Health, Republic of South Africa

REQUIREMENTS

(1) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 2.2 and 4.11

(2) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Sections: 3.1.7

Sponsorship > Quality, Data & Records Management
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SUMMARY

Overview
As clinical trial oversight manager, the sponsor must implement and maintain 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 and the SA-GCPs. The sponsor is responsible for obtaining agreement from all involved parties to ensure direct access to all trial related sites, source data/documents, and reports for monitoring and auditing purposes, and inspection by domestic and foreign regulatory authorities. Agreements made by the sponsor with the principal investigator and any other involved parties should be in writing either as part of the protocol or in a separate agreement.

Electronic Data Processing System
The sponsor must ensure that the electronic data processing system conforms to the specific documented requirements for completeness, accuracy, reliability, and consistency of intended performance, and that he/she maintains SOPs for using these systems. Refer to the SA-GCPs for detailed information on electronic trial data systems.

Independent Data Monitoring Committee
The sponsor is permitted to establish an Independent Data Monitoring Committee (IDMC) to assess the trial’s progress. The IDMC would review the safety and data and critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify, or stop a trial. The IDMC should also have written SOPs and maintain written records of all its meetings.

Record Management
As set forth in the SA-GCPs, the sponsor should inform the investigator(s) and institution(s) in writing of the need for record retention, and should notify these parties in writing when the trial related records are no longer needed.

Following the trial’s completion, a sponsor should retain copies of all study-related documentation which does not contain participant identifying information. The files should also include information on study site personnel responsible for maintaining the participant lists, and those responsible for archiving investigator documents. These documents should be saved for 15 years after the trial’s termination, and preferably for the product’s commercial lifetime. Refer to the SA-GCPs for additional record retention requirements.

Audit Requirements
As part of its QA system, the sponsor should perform a clinical trial audit. No specific timeframe is provided for the audit process. The audit should be conducted separately and independently from other routine monitoring or QC functions. It should evaluate study conduct and compliance with the protocol, the SOPs, and the SA-GCPs. The sponsor may appoint qualified external auditors who have appropriate documentation. The sponsor must also ensure that the audit is conducted in accordance with his/her own SOPs, that the auditor observations are archived, and that data is available as needed for the Medicines Control Council (MCC) and ethics committee (EC) review. The person responsible for auditing must submit a report to the MCC when evidence of Good Clinical Practice non-compliance exists.

Premature Study Termination/Suspension
If a trial is prematurely terminated or suspended, a sponsor must promptly notify the investigator(s), the institution(s), the EC, and the MCC accordingly. The notification should document the reason(s) for the termination/suspension. The sponsor is also responsible for ensuring that the South African National Clinical Trial Register (SANCTR) is updated as well.

Multicenter Studies
In the event of a multicenter clinical trial, the sponsor must make administrative arrangements to ensure the protocol is followed by investigators at different institutions. Some of the tasks requiring special consideration include:

  • Ensuring strict adherence to the protocol
  • Confirming case report forms (CRFs) are designed to capture the required data at all multi-center trial sites
  • Documenting the responsibilities of coordinating investigator(s) and the other participating investigators
  • Supplying investigators with instructions on following the protocol, on complying with a uniform set of standards to assess clinical and laboratory findings, and on completing the CRFs, and
  • Facilitating communication between investigators
ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 4.4, 4.8, 5.2, 6.7, and 7

Sponsorship > Site/Investigator Selection
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Last content review/update: June 01, 2016. Submit updates or comments.
SUMMARY

Overview
As set forth in the SA-GCPs, the sponsor is responsible for selecting the investigator(s) and institution(s) for the clinical trial, taking into account the appropriateness and availability of the study site and facilities. The sponsor must ensure that the investigator(s) are qualified by training and experience, and that they have adequate resources to properly conduct the trial. Prior to entering into an agreement with the investigator(s) and the institution(s) to conduct a study, the sponsor 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, if a multi-center trial is going to be conducted, the sponsor must organize a coordinating committee or select coordinating investigator(s).

In the case of a multi-country study, the sponsor must ensure that any differences in trial designs between the South African site and other sites must be clearly documented and explained in the study protocol and related documents.

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 4.2, 4.6, 4.7, 4.9, and 4.10

Informed Consent > Documentation Requirements
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SUMMARY

Overview
In all South African clinical trials, a freely given, written informed consent is required to be obtained from each participant in accordance with the principles set forth in the NHA, the Declaration of Helsinki, the SA-GCPs, and the International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs).

As per the SA-GCPs, the G-EthicsHR, and the G-GPHlthCare, the informed consent form (ICF) and patient information sheet(s) are essential documents that must be reviewed and approved by an accredited ethics committee (EC) based in South Africa and provided to the Medicines Control Council (MCC) with the clinical trial application. (See the Informed Consent topic, Required Elements subtopic for details on what should be included in the form.)

The principal investigator (PI), or a person designated by the PI, should provide research study information to the participant and/or his/her legal representative(s), or guardian(s). When drafting and presenting the ICF, special consideration must be taken with regard to the participant’s culture, traditional values, intelligence, and education. The ICF content should be briefly and clearly presented, without coercion or unduly influencing a potential participant to enroll in the clinical trial.

According to the SA-GCPs, the G-EthicsHR, and the G-GPHlthCare, in all cases, both written and verbal informed consent must be obtained. Where the participant is illiterate and/or his/her legal representative(s) or guardian(s) is illiterate, verbal consent should be obtained in the presence of and countersigned by a literate witness. The participant and/or the participant’s legal representative(s) or guardian(s), the PI or person designated by the PI, and if applicable, a literate witness must personally sign the ICF.

Re-Consent
The G-GPHlthCare states that the participant must be informed of any relevant new findings over the course of the study, and be given the choice to continue to participate or withdraw from the study.

Language Requirements
According to the SA-GCPs, the G-EthicsHR, and the G-GenInfo, the ICF and any patient information sheet(s) should be written in English and in the vernacular language that the participant is able to understand.

Documentation Copies
As stated in the SA-GCPs, the G-EthicsHR, and the G-GPHlthCare, the ICF should be signed by the participant and the PI, or the person designated by the PI. If the participant is incapable of giving an informed consent, his/her legal representative(s) or guardian(s) should sign the ICF.

The original signed ICF and patient information sheet(s) should be retained by the investigator and a copy should be given to the participant for his/her record. The SA-GCPs also requires contact information for the EC and for the MCC be provided in the ICF.

ADDITIONAL RESOURCES

(A) (ICH Guidance) International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Conference on Harmonisation, Geneva, Switzerland

REQUIREMENTS

(1) (Legislation) National Health Act 61 of 2003 (NHA) (September 2, 2013)
Parliament, Republic of South Africa

Relevant Section: Chapter 9 (71)

(2) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 1.2.8, 2.1, 2.2, 3.5, and 8.6.2

(3) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Sections: 1.3, 1.4, 1.5, 1.6, 2.3, 3.1, 3.2, 4.3, and 5.2

(4) (Guidance) Guidelines for Good Practice in the Health Care Professions; General Ethical Guidelines for Biotechnology Research, Booklet 7 (G-GPHlthCare) (May 2008)
Health Professions Council of South Africa, Department of Health, Republic of South Africa

Relevant Sections: 2.6.4, 2.6.4.1, 2.6.4.2, 2.6.4.3, and 2.6.4.4

(5) (Guidance) General Information (G-GenInfo) (August 2012) (Version 8)
Registrar of Medicines, Medicines Control Council, Department of Health, Republic of South Africa

Relevant Sections: 2.4 and 2.5

Informed Consent > Required Elements
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SUMMARY

Overview
As delineated in the SA-GCPs, the G-EthicsHR, and the G-GPHlthCare, prior to beginning a research study, the principal investigator (PI) is required to obtain ethics committee (EC) approval for the written informed consent form (ICF), and for all information being provided to the research participant and his/her legal representative(s) or guardian(s).

Information should be presented in an easily understandable and unambiguous language in both written and oral form. Adequate time should be given to the participant and/or his/her legal representative(s) or guardian(s) to inquire about the details of the study, and have all questions answered to his/her satisfaction.

No Coercion
None of the oral or written information concerning the study, including the written ICF, should contain any language that causes the participant and/or his/her legal representative(s) or guardian(s) to waive or to appear to waive his/her legal rights, or that releases or appears to release the investigator(s), the institution, the sponsor, or his/her representatives from his/her liabilities for any negligence.

ICF Required Elements
Based on the informed consent essential elements checklists in the SA-GCPs, the G-EthicsHR, the G-GPHlthCare, and the NHAParticipants, the ICF should include the following statements or descriptions, as applicable:

  • The study involves research and an explanation of its nature and purpose
  • The procedures to be followed
  • The participant’s responsibilities
  • Any foreseeable risks or discomforts to the participant, and when applicable, to an embryo, fetus, or nursing infant
  • Any benefits to the participant or to others that may reasonably be expected from the research; if no benefit is expected, the participant should also be made aware of this
  • A disclosure of appropriate alternative procedures or treatments, and their potential benefits and risks
  • The probability for random assignment to each treatment
  • 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
  • Compensation and/or medical treatment available to the participant in the event of a trial-related injury
  • The anticipated prorated payment, if any, to the participant for participating in the trial
  • The extent to which confidentiality of records identifying the participant will be maintained, the possibility of record access by the sponsor, the EC, or the Medicines Control Council (MCC)
  • PI and co-investigator(s) contact information
  • The sponsor’s identity, and any potential conflicts of interest
  • The consequences of a participant's decision to withdraw from the study
  • Alternative procedures or treatment that may be available to the participant
  • The study has been approved by an accredited South African-based EC, and EC contact information
  • The approximate number of participants in the research study
  • The expected duration of the participant's participation
  • Information regarding a multicentered study, if applicable
  • An explanation of whom to contact in the event of research-related injury
  • Additional costs to the participant that may result from participation in the study
  • Foreseeable circumstances under which the investigator(s) may remove the participant without his/her consent
  • The participant and/or his/her legal representative(s) or guardian(s) will be notified if significant new findings developed during the study which may affect the participant's willingness to continue
  • If the research involves collecting biological materials, participants must be provided with an explanation on how the specimens will be managed at the end of the study. If samples will be stored for future use, separate consent should be obtained

See the Informed Consent topic, Compensation Disclosure subtopic and Vulnerable Population subtopic as well as the Specimens topic, Consent for Specimens subtopic for further information.

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd Edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 1.2.8, 1.5.4, 2.2, 3.1, 3.5, 3.11, 8.2, Appendix A, and Appendix F

(2) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Sections: 2.3.6 and 3.3.6

(3) (Guidance) Guidelines for Good Practice in the Health Care Professions; General Ethical Guidelines for Biotechnology Research, Booklet 7 (G-GPHlthCare) (May 2008)
Health Professions Council of South Africa, Department of Health, Republic of South Africa

Relevant Sections: 2.6.4, 2.6.4.1, 2.6.4.2, and 2.6.4.3

(4) (Legislation) National Health Act 61 of 2003: Regulations Relating to Research with Human Participants (NHAParticipants) (September 19, 2014)
Parliament, Republic of South Africa

Relevant Section: 5

Informed Consent > Compensation Disclosure
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SUMMARY

Overview
In accordance with the SA-GCPs, the G-EthicsHR, and the G-GPHlthCare, the informed consent form (ICF) should contain a statement describing the compensation or benefits a participant may receive for participating in a clinical trial. In addition, as specified in the SA-GCPs, sponsors and investigators must also comply with the Association of the British Pharmaceutical Industry’s (ABPI) guidelines relating to participant compensation and treatment requirements due to trial-related injuries (See Additional Resources (A) and (B)).

Compensation for Participation in Research
As per the SA-GCPs, the ICF should contain a statement with a description of the anticipated prorated payment to the participant(s) that is reasonably expected for participation in the trial. The ICF should also contain a statement indicating whether any compensation and medical treatment will be made available if injury occurs.

The sponsor must ensure that participants are reimbursed for all reasonable costs incurred by their participation in the trial. However, any compensation or incentive to participants must not be so excessive that it may unfairly influence participants, or cause them to overlook important facts and risks.

If the studies are multicentered, information regarding incentives to be given to participants at the different sites must be provided, and the differences across sites must be explained.

Compensation for Injury
As per the SA-GCPs, the G-EthicsHR, the G-GPHlthCare, and Additional Resources (A) and (B), a statement must be included in the ICF regarding compensation or treatment for research-related injuries available to the participant(s). If applicable, this should include a statement regarding compensation for any potential injury received by a child in utero or a nursing child, through the mother’s participation in a research study.

The Medicines Control Council (MCC) and the ethics committee(s) (ECs) require a sponsor to provide comprehensive insurance for injury and damage to all trial participants as described in the SA-GCPs, and Additional Resources (A) and (B). A sponsor must furnish written assurance to the investigator that he/she will agree to pay compensation to participants who incur research-related injuries or death. The investigator, in turn, communicates this information to the relevant EC(s).

The SA-GCPs and Additional Resource (A) also provide the following basic principles to guide compensation payment to participants:

  • A causal relationship exists between a participant’s injury and his/her participation in a trial
  • A child is injured in utero through his/her mother’s participation in a trial, and should be treated as if he/she were a participant
  • For more serious injuries of an enduring and disabling nature, and not for temporary pain or discomfort, or less serious or curable complaints
  • An adverse drug reaction (ADR) occurs to a participant using a medicinal product under trial, and injury is caused by a procedure adopted to deal with that ADR. The injury should be treated as if it were caused directly by the medicinal product under trial
  • Any trial-related injuries, regardless of the participant’s ability to prove that the sponsor has been negligent in relation to the research or development of the medicinal product under trial, or, that the product is defective

The participant should be eligible for compensation even if he/she freely consented (in writing or otherwise) to participate in the trial, or he/she was aware that there was a likelihood of an ADR. (See the aforementioned guidelines and the Sponsorship topic, Compensation subtopic for additional information on sponsor compensation responsibilities; the Informed Consent topic, Required Elements subtopic for additional details on what should be included in the ICF.)

ADDITIONAL RESOURCES

(A) (Guidance) Clinical Trial Compensation Guidelines (2014)
Association of the British Pharmaceutical Industry, United Kingdom

(B) (Guidance) Insurance and Compensation in the Event of Injury in Phase I Clinical Trials (2nd Edition) (June 2012)
Association of the British Pharmaceutical Industry, BioIndustry Association, and Clinical Contract Research Association, United Kingdom

Relevant Sections: 3 and 4

REQUIREMENTS

(1) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd Edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 2.2, 3.5, 4.11, and 4.12

(2) (Guidance) Ethics in Health Research: Principles Processes, and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Sections: 3.1.7 and 3.5.3

(3) (Guidance) Guidelines for Good Practice in the Health Care Professions; General Ethical Guidelines for Biotechnology Research, Booklet 7 (G-GPHlthCare) (May 2008)
Health Professions Council of South Africa, Department of Health, Republic of South Africa

Relevant Section: 2.6.4.1

Informed Consent > Participant Rights
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SUMMARY

Overview
South Africa’s ethical standards promote respect for all human beings and safeguard the rights of research study participants. In accordance with the principles held forth in the Declaration of Helsinki, the SA-GCPs, the G-EthicsHR, the G-GPHlthCare, the NHAParticipants, and the International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs), a participant’s rights must be clearly addressed in the informed consent form (ICF) and during the informed consent process. Below are the basic rights for participants in clinical research studies. (See the Informed Consent topic, Required Elements subtopic and the Informed Consent topic, Vulnerable Populations subtopic for additional information regarding requirements for participant rights.)

The Right to Participate, Abstain, or Withdraw
According to the NHA and the NHAParticipants, everyone has the right to participate in any decision affecting their health or treatment, including research. The participant and/or his/her legal representative(s) or guardian(s) should be informed that participation is voluntary, that he/she 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
A potential research study participant has the right to be fully informed on the nature and purpose of the research study, its anticipated duration, the sponsor and investigator(s), any potential benefits or risks, study procedures, any compensation for participation, injury and/or treatment, and any significant new information regarding the research study. (See the Informed Consent topic, Required Elements subtopic for a more detailed list.)

The Right to Privacy and Confidentiality
Participants have the right to privacy and confidentiality. All participants must be afforded the right to privacy and confidentiality, and the ICF must provide a statement identifying this right. It is the responsibility of the investigator to safeguard the confidentiality of research data to protect the identity and records of research participants.

The Right of Inquiry/Appeal
The research participant and/or his/her legal representative(s) or guardian(s) should be provided with contact information for the investigator(s), and the ethics committee to address clinical trial-related queries, in the event of any injury and/or to appeal against a violation of his/her rights. It is also required that the Medicines Control Council (MCC) address and contact information be provided. (See the Informed Consent topic, Required Elements subtopic for more detailed information regarding participant rights.)

The Right to Safety and Welfare
The SA-GCPs and the Declaration of Helsinki clearly state that research participants have the right to safety and well-being which must take precedence over the interest of science and society. The NHA and the NHAParticipants safeguard the rights of all South Africans including vulnerable populations.

ADDITIONAL RESOURCES

(A) (Draft Guidance) Ethical-Legal Protection for Vulnerable Research Participants in South Africa; An Audit of Relevant Laws and Ethical Guidelines (July 2011 draft for comment)
National Health Research Ethics Council (NHREC), Republic of South Africa

(B) (ICH Guidance) International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Conference on Harmonisation, Geneva, Switzerland

REQUIREMENTS

(1) (Legislation) National Health Act 61 of 2003 (NHA) (September 2, 2013)
Parliament, Republic of South Africa

Relevant Sections: Chapter 1 (2), Chapter 2 (8 and 11), and Chapter 9 (71)

(2) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 1.2.8, 2.3, 3.5, and Appendix A

(3) (Guidance) Ethics in Health Research: Principles, Processes and Structures(2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Sections: 1.1, 2.3 and 3.1

(4) (Guidance) Guidelines for Good Practice in the Health Care Professions; General Ethical Guidelines for Biotechnology Research, Booklet 7 (G-GPHlthCare) (May 2008)
Health Professions Council of South Africa, Department of Health, Republic of South Africa

Relevant Sections: 1.1, 1.4, 2, 2.6.4, 2.6.4.1, 2.6.4.2, 2.6.4.3, 2.6.4.4, and 2.6.5

(5) (Legislation) National Health of Act 61 of 2003: Regulations Relating to Research with Human Participants (NHAParticipants) (September 19, 2014)
Parliament, Republic of South Africa

Relevant Sections: 2 and 5

Informed Consent > Special Circumstances/Emergencies
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SUMMARY

Overview
The NHA, the SA-GCPs, and the G-EthicsHR make provisions to protect the rights of a research participant during the informed consent process when the procedure is complicated by special circumstances. Special circumstances can be medical emergencies, or when a research participant is mentally incapacitated, or has physical impairments requiring special considerations.

Medical Emergencies
As per the SA-GCPs and the G-EthicsHR, the ethics committee (EC) may approve emergency medical research when informed consent cannot be obtained from the participant or his/her legal representative(s) or guardian(s) if the investigator(s) ensures the protocol meets the following requirements:

  • Reasonable steps are being taken to ascertain the participant’s religious and cultural sensitivities
  • The participant’s condition precludes giving consent
  • Inclusion in the trial is not contrary to the interests of the patient
  • 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 treatments
  • The participant, his/her next of kin, and/or legal representative(s) or guardian(s) will be informed as soon as is reasonably possible of the participant’s inclusion in the study, and have the option to withdraw from the study at any time
  • The participant will be informed, and consent obtained, once he/she has undergone the necessary emergency procedures and regained consciousness
  • The research is based on valid scientific hypotheses, and offers a realistic possibility of benefit over standard care

Research Involving Unconscious Persons
The SA-GCPs and the G-EthicsHR state that research involving unconscious persons requires consent to be provided by the participant’s legal representative(s) or guardian(s), include 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.

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Legislation) National Health Act 61 of 2003 (NHA) (September 2, 2013)
Parliament, Republic of South Africa

Relevant Sections: Chapter 2 (7, 8, and 9)

(2) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 2.3.3, 2.3.6.5, 2.3.9, 5, 5.9, and 5.14

(3) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Sections: 3.1, 3.2, and 3.4

(4) (Guidance) Guidelines for Good Practice in the Health Care Professions; General Ethical Guidelines for Biotechnology Research, Booklet 7 (G-GPHlthCare) (May 2008)
Health Professions Council of South Africa, Department of Health, Republic of South Africa

Relevant Sections: 2.6.4.4, 2.6.4.4.1, and 2.6.4.4.2

Informed Consent > Vulnerable Populations
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SUMMARY

Overview
In all South African clinical trials, research participants from vulnerable populations must be provided additional protections to safeguard their health and welfare during the informed consent process.

The NHA, the SA-GCPs, the G-EthicsHR, the G-GPHlthCare, and the NHAParticipants require special considerations for vulnerable populations, and characterize them by limited education, limited economic resources, inadequate protection of human rights, discrimination due to health status, limited ability to provide informed consent; limited availability of health care and treatment options, or an inadequate understanding of scientific research. Vulnerable populations include children/minors, mentally and physically disabled, pregnant women, substance abusers, prisoners, armed forces, the homeless, the elderly, and other vulnerable groups such as collectivities, and persons in dependent relationships.

The ethic committees (ECs) must pay special attention to protecting participants from vulnerable populations. The ECs may impose additional measures such as requiring post-research investigations to be conducted. As per the NHAParticipants, research with vulnerable participants must comply with the following requirements:

  • Involve vulnerable persons only when non-vulnerable persons are not appropriate for inclusion
  • Not systematically avoid inclusion of vulnerable participants because it is unfairly discriminatory, and would prevent this population from benefiting from relevant research
  • Be responsive to health needs and priorities of vulnerable persons, and
  • Provide special attention in the ethical review to ensure research-related risk are assessed and minimized, and appropriate consent procedures are followed

See Informed Consent topic, and the subtopics of Children/Minors; Pregnant Women, Fetuses & Neonates; Prisoners; and Mentally Impaired for additional information about these populations. Information on the other vulnerable populations specified in the SA-GCPs and the G-EthicsHR is provided below.

Persons in Dependent Relationships or Hierarchical Situations
Participants whose proposed involvement in research arises from dependent or hierarchical relationships need additional attention, and the EC must be satisfied that their consent is both adequately informed and voluntary. In addition, per the NHAParticipants, research is appropriate when research-related risks of harm are minimized. These types of relationships include, but are not limited to, those who are in junior or subordinate positions in hierarchically structured groups, such as prisoners and prison authorities, older persons and their caregivers, and patients and healthcare professionals.

Persons Highly Dependent on Medical Care
Participants who are highly dependent on medical care may have a limited capacity to provide informed consent due to the gravity of their medical condition. In addition, their medical condition may require invasive measures resulting in greater risk. There may also be a perception of coercion if a participant is reluctant to refuse consent for fear that it may compromise his/her medical treatment.

Terminally Ill Patients
Terminally ill patients require additional protection as they are more vulnerable to developing unrealistic expectations of benefits. Investigators must ensure that the prospective benefit from participation is neither exaggerated nor used to justify a higher risk than that involved in the patient’s current treatment. Investigators must also respect the participants’ wishes to spend time as they choose, particularly with family members.

The Elderly
As per the G-GPHlthCare, in the absence of any indication to the contrary, elderly persons are assumed to be competent to consent to participating in research. However, consideration must be given to the likelihood of possible mental deterioration, the inability to comprehend, and their dependence and vulnerability.

Research Involving Collectivities
A collectivity is a distinct group characterized by common beliefs, values, social structures, and other features identifying them as a separate group. Investigators are required to obtain EC approval for research involving a collectivity when any of the following conditions apply:

  • property or information private to the group as a whole is studied or used
  • research requires the permission of people occupying positions of authority, or involves members acknowledged as representatives to participate.
ADDITIONAL RESOURCES

(A) (Draft Guidance) Ethical-Legal Protection for Vulnerable Research Participants in South Africa; An Audit of Relevant Laws and Ethical Guidelines (July 2011 draft for comment)
National Health Research Ethics Council
Republic of South Africa

REQUIREMENTS

(1) (Legislation) National Health Act 61 of 2003 (NHA) (September 2, 2013)
Parliament, Republic of South Africa

Relevant Sections: Chapter 1 (2(c)(iv)), Chapter 2 (7, 8, and 11), and Chapter 9 (70(2)(d)) and 71)

(2) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 1.2.8, 2.3, 2.3.1, 2.3.2, 2.3.3, 2.3.4, 2.3.5, 2.3.6, 2.3.6.1, 2.3.6.2, 2.3.6.3, 2.3.6.4, 2.3.6.5, 2.3.7, 2.3.11, 2.3.12, and 3.5

(3) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Sections: 1.3, 2.3, 3.1, 3.2, 3.4, and 4.5

(4) (Guidance) Guidelines for Good Practice in the Health Care Professions; General Ethical Guidelines for Biotechnology Research, Booklet 7 (G-GPHlthCare) (May 2008)
Health Professions Council of South Africa, Department of Health, Republic of South Africa

Relevant Sections: 1.1, 2.6.4, 2.6.4.1, 2.6.4.2, 2.6.4.3, 2.6.4.4, 2.6.4.4.1, and 2.6.4.4.2

(5) (Legislation) National Health of Act 61 of 2003: Regulations Relating to Research with Human Participants (NHAParticipants) (September 19, 2014)
Parliament, Republic of South Africa

Relevant Sections: 1 and 4

Informed Consent > Children/Minors
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SUMMARY

Overview
The SA-GCPs state that a minor is a person 21 years of age or younger, and that every person younger than 18 is considered a child requiring a legal representative(s) or guardian(s) to assist with the decision to consent to research participation. ActNo5 also defines a child as a person under the age of 18 years.

According to the NHA, the G-EthicsHR, the SA-GCPs and the G-GPHlthCare, consent for minors/children to participate in research must be obtained from:

  • The legal representative(s) or guardian(s) in all but exceptional circumstances (such as emergencies)
  • The minor/child where he/she is competent to make the decision
  • Any organization or person required by law (defined in the NHA)
  • Where the minor/child is not competent, assent from the minor/child and consent from the legal representative(s) and/or guardian(s)

A minor's/child’s refusal to participate in research must be respected.

According to the NHA, where research or experimentation is to be conducted on a minor for therapeutic purposes, the study may only be conducted when:

  • It is in the best interests of the minor/child
  • It is carried out in such manner and on such conditions as may be prescribed
  • The consent of the minor’s parent or guardian is provided

Where research or experimentation is to be conducted on a minor for non-therapeutic purposes, the NHA and the NHAParticipants state that a study may only be conducted when:

  • It is carried out in such manner and on such conditions as may be prescribed
  • The consent of the Minister of Health is provided, or, where appropriate, consent from a delegated authority
  • The consent of the minor’s parent or guardian is provided
  • The consent of the minor is provided when he or she is capable of understanding

See the NHAParticipants for detailed application requirements.

In addition, the Minister of Health may not give consent if any of the following circumstances apply:

  • The study objective(s) can also be achieved if conducted on an adult
  • The research is unlikely to significantly improve scientific understanding of the minor’s/child's condition, disease or disorder to such an extent that it will result in significant benefit to the minor(s)/child(ren)
  • The reasons for the consent to the research by the parent or guardian and, if applicable, the minor/child are contrary to public policy
  • The research poses a significant risk to the health of the minor
  • The risk to the health or well-being of the minor is not significantly outweighed by the potential benefit

As delineated in, the SA-GCPs, the G-EthicsHR, and the NHAParticipants, the following additional criteria must be met to conduct clinical trials with minors/children:

  • The research study presents minimal risk
  • The research study presents more than minimal risk, but potentially direct or anticipated benefit for the participant outweighs the risk
  • The research presents more than minimal risk (minor increase), and may not have a direct benefit to the participant, but has a high probability of producing important and relevant information, and that benefit may outweigh the risk
  • Adults are not appropriate participants for the research

In all cases, there should be sufficient reasons to justify why minors/children should be included as participants.

Assent Requirements
The SA-GCPs and the G-EthicsHR require the ethics committee (EC) to ensure that adequate steps outlined in the clinical protocol are used to obtain a minor’s assent when, in the EC’s judgment, the minor is capable of providing such assent. When the EC determines that assent is required, it must also indicate whether and how such assent should be documented. A minor/child’s assent should not be assumed simply because he/she fails to object during the informed consent process. It is necessary for the minor/child and his/her legal representative(s) or guardian(s) to be in agreement on participation. The minor’s/child’s refusal to participate is final.

Conflict in Laws Regarding Minors/Children
As per the G-GPHlthCare, South African law has been inconsistent in its approach to addressing the capacity of minors/children to consent. Currently, there are no clear legal statutes specifying when children can independently consent to research.

ADDITIONAL RESOURCES

(A) (Draft Guidance) Ethical-Legal Protection for Vulnerable Research Participants in South Africa; An Audit of Relevant Laws and Ethical Guidelines (July 2011 draft for comment)
National Health Research Ethics Council, Republic of South Africa

REQUIREMENTS

(1) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 2.3, 2.3.1, 2.3.1.1, 2.3.1.2, and 2.3.1.3

(2) (Legislation) National Health Act 61 of 2003 (NHA) (September 2, 2013)
Parliament, Republic of South Africa

Relevant Section: Chapter 9 (71)

(3) (Legislation) Act No. 5 of 2015: Criminal Law (Sexual Offences and Related Matters) Amendment Act, 2015 (ActNo5 – English and Afrikaans)
Parliament, Republic of South Africa

Relevant Section: 1

(4) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Section: 3.2

(5) (Guidance) Guidelines for Good Practice in the Health Care Professions; General Ethical Guidelines for Biotechnology Research, Booklet 7 (G-GPHlthCare) (May 2008)
Health Professions Council of South Africa, Department of Health, Republic of South Africa

Relevant Section: 2.6.4.4.2

(6) (Legislation) Children’s Act 38 of 2005 (Children’s Act) (June 8, 2006) (Effective date: April 1, 2010)
Parliament, Republic of South Africa

Relevant Sections: Chapter 1, Chapter 2, Chapter 3, Chapter 5, and Chapter 7 (Part 3)

(7) (Legislation) National Health of Act 61 of 2003: Regulations Relating to Research with Human Participants (NHAParticipants) (September 19, 2014)
Parliament, Republic of South Africa

Relevant Sections: 4 and 7

Informed Consent > Pregnant Women, Fetuses & Neonates
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Last content review/update: June 02, 2016. Submit updates or comments.
SUMMARY

Overview
As per the NHA, the SA-GCPs, the G-EthicsHR, and the G-GPHlthCare, any research studies involving pregnant women, women who may become pregnant, or fetuses, required additional safeguards to ensure the research conforms to appropriate ethical standards and upholds societal values. The ethics committee (EC) must provide particular attention to these participants due to potential for additional health concerns that may arise during pregnancy, and the need to avoid unnecessary risk to the fetus.

The following conditions are required for research to be conducted involving pregnant women and fetuses:

  • Appropriate studies on animals and non-pregnant individuals have been completed
  • The risk to the fetus is minimal and is the least possible risk for achieving the study’s objectives, except where the purpose of the study is to meet the health needs of the mother and the fetus, and the foreseeable benefits outweigh the potential risks
  • Individuals engaged in the study have no part in deciding the timing, method, and procedures to be used to terminate the pregnancy, or in determining the viability of the fetus at the termination of the pregnancy

Pregnant women and fetuses may not be involved as research participants unless the mother and the fetus will be placed at risk to the minimum extent necessary to achieve the study’s health objectives, the purpose of the research is to meet the mother’s health needs, and the mother is legally competent, and has given informed consent after having been fully informed about the possible impact on the fetus.

In certain circumstances, recognition should be given to the interests of the father of the fetus to participate in decision making. However, the father's informed consent is not required if the purpose of the research is to meet the mother’s health needs, the father’s identity or whereabouts cannot reasonably be ascertained, the father is not reasonably available, or the pregnancy is a result of rape.

(See the Informed Consent topic, Required Elements subtopic for general ICF requirements).

ADDITIONAL RESOURCES

(A) (Draft Guidance) Ethical-Legal Protection for Vulnerable Research Participants in South Africa; An Audit of Relevant Laws and Ethical Guidelines (July 2011 draft for comment)
National Health Research Ethics Council, Republic of South Africa

REQUIREMENTS

(1) (Legislation) National Health Act 61 of 2003 (NHA) (September 2, 2013)
Parliament, Republic of South Africa

Relevant Sections: Chapter 1 (2(c)(iv)), Chapter 2 (7, 8, and 11), Chapter 9 (70(2)(d) and 71), and Chapter 11 (90(1)(s) and 90(2))

(2) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections:2.3.2.1 and 2.3.2.3

(3) (Guidance) Ethics in Health Research: Principles, Processes and Structure (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Section: 3.2

(4) (Guidance) Guidelines for Good Practice in the Health Care Professions; General Ethical Guidelines for Biotechnology Research, Booklet 7 (G-GPHlthCare) (May 2008)
Health Professions Council of South Africa, Department of Health, Republic of South Africa

Relevant Sections: 2.6.4.4.1

Informed Consent > Prisoners
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SUMMARY

Overview
According to the NHA, the CSA 1998, the SA-GCPs, the G-EthicsHR, and the NHAParticipants, a prisoner may not, even with his/her consent, participate in any scientific experimentation, research study, or clinical trial except with the Commissioner’s approval given on an application made by the prisoner. If the Commissioner approves, a research study may involve a prisoner as a participant only after the ethics committee (EC) has ensured that the clinical trial involves the following:

  • The study of the possible causes, effects, and processes of incarceration, and of criminal behavior
  • 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 (for example, 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 well-being of prisoners
  • The rights of prisoners, including but not limited to the rights to dignity, privacy, bodily integrity and equality, will be protected
  • The Department of Correctional Services’ procedures and guidelines will be followed

An EC reviewing the protocol involving prisoners must also ensure that:

  • A majority of the EC members have no association with the prisoner(s) involved
  • Where possible, a prisoner or an ex-prisoner should be an EC member
ADDITIONAL RESOURCES

(A) (Draft Guidance) Ethical-Legal Protection for Vulnerable Research Participants in South Africa; An Audit of Relevant Laws and Ethical Guidelines (July 2011 draft for comment)
National Health Research Ethics Council, Republic of South Africa

REQUIREMENTS

(1) (Legislation) National Health Act 61 of 2003 (NHA) (September 2, 2013)
Parliament, Republic of South Africa

Relevant Sections: Chapter 2 (7, 8, and 11) and Chapter 9 (71)

(2) (Legislation) Correctional Services Act, 1998 (Act No. 111 of 1998) (CSA 1998) (Effective date: July 31, 2004)
Parliament, Republic of South Africa

Relevant Sections: Chapter 1 (1) and Chapter 2 (7(7))

(3) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 2.3, 2.3.4, and 2.3.5

(4) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Section: 3.2

(5) (Legislation) National Health of Act 61 of 2003: Regulations Relating to Research with Human Participants (NHAParticipants) (September 19, 2014e)
Parliament, Republic of South Africa

Relevant Section: 4

Informed Consent > Mentally Impaired
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SUMMARY

Overview
According to the NHA, the MHA-18, the SA-GCPs, the G-EthicsHR, the G-GPHlthCare, and the NHAParticipants, sufficient justification must be provided for any research involving a participant who has a mental or intellectual impairment or substance abuse related disorder, and the research must be relevant to the mental disability or substance abuse disorder.

Research involving these populations must conform to the following requirements:

  • Be relevant to mental disabilities or substance abuse related disorders so that it is necessary to involve people who have a mental disability or a substance abuse related disorder(s)
  • Justify the involvement, as the study population of institutionalized persons with mental disabilities
  • Ensure appropriate evaluation procedures for ascertaining the participants’ ability to give informed consent. If participants are deemed unable to understand or to make a choice, then an appropriate individual who is able to consent on their behalf must be identified
  • Ensure that consent is free from coercion and risk to participants
  • 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 gained from the research

In addition, persons with mental or intellectual impairment should not participate in research that might equally well be conducted with persons without those impairments. Consent to conduct research must be obtained from:

  • The participant, whenever he/she is competent to give informed consent
  • The participant’s legal representative(s) or guardian(s) where the participant is deemed not competent to do so
  • An authority, organization, or person having that responsibility by law

Consent cannot be given for participation in research that is contrary to the interests of the person with the mental or intellectual impairment. Finally, the mentally or intellectually impaired person's refusal to participate in research must always be respected.

ADDITIONAL RESOURCES

(A) (Draft Guidance) Ethical-Legal Protection for Vulnerable Research Participants in South Africa; An Audit of Relevant Laws and Ethical Guidelines (July 2011 draft for comment)
National Health Research Ethics Council, Republic of South Africa

REQUIREMENTS

(1) (Legislation) National Health Act 61 of 2003 (NHA) (September 2, 2013)
Parliament, Republic of South Africa

Relevant Sections: Chapter 2 (7, 8, and 11), and Chapter 9 (71)

(2) (Legislation) Mental Health Act No. 18 of 1973 (MHA-18) (March 26, 1973) (Effective date: March 27, 1975)
Parliament, Republic of South Africa

Relevant Sections: Chapter 4 and Chapter 9 (60A)

(3) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 2.3 and 2.3.3

(4) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Sections: 2.3 and 3.2

(5) (Guidance) Guidelines for Good Practice in the Health Care Professions; General Ethical Guidelines for Biotechnology Research, Booklet 7 (G-GPHlthCare) (May 2008)
Health Professions Council of South Africa, Department of Health, Republic of South Africa

Relevant Section: 2.6.4.1

(6) (Legislation) National Health of Act 61 of 2003: Regulations Relating to Research with Human Participants (NHAParticipants) (September 19, 2014)
Parliament, Republic of South Africa

Relevant Section: 4

Investigational Products > Definition of Investigational Product
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Last content review/update: June 01, 2016. Submit updates or comments.
SUMMARY

Overview
As delineated in the SA-GCPs and the SA-GMPs, an investigational product 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 used or assembled (formulated or packaged) in a different way from the approved form
  • When used for an unapproved indication
  • When used to gain further information about an approved use
ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Section: Appendix F

(2) (Guidance) Guide to Good Manufacturing Practice for Medicines in South Africa (Version 5) (SA-GMPs) (November 2010)

Relevant Section: Annex 13 – Glossary

Investigational Products > Manufacturing & Import
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SUMMARY

Overview
According to the SA-GCPs and the GRMRSA, the Medicines Control Council (MCC) is responsible for authorizing the manufacture of investigational products (IPs) in South Africa. In addition, IPs which are unregistered medicines may only be brought into the country after the clinical protocol has been approved by the MCC.

The SA-GCPs states that the clinical trial application approval document issued by the MCC also serves as the importation permit for the unregistered IP under MRSA, 2008. (See Clinical Trial Lifecycle topic, Submission Process, Submission Content, and Regulatory Authority topic, Regulatory Fees subtopics for detailed application requirements).

In addition, as per Additional Resources (A) and (B), the MCC requires a Certificate of Analysis to be issued by the manufacturer for all IPs to be used in a clinical trial.

ADDITIONAL RESOURCES

(A) (Model Form) Annex 10 – Model Certificate of Analysis (No. 902) (2002)
WHO Technical Report Series, World Health Organization

(B) (Presentation) Regulatory Requirements for the ZA CTD (September 15, 2010)
Southern African Pharmaceutical Regulatory Affairs Association

REQUIREMENTS

(1) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 3.6 and 4.15

(2) (Regulation) Medicines and Related Substances Act 101 of 1965 - General Regulations Made in Terms of the Medicines and Related Substances Act 101 of 1965, as Amended (GRMRSA) (February 15, 2014)
Department of Health, Republic of South Africa

Relevant Sections: Parts 12 and 34 (1)

(3) (Legislation) No. 72 of 2008: Medicines and Related Substances Act, 2008 (MRSA, 2008) (April 21, 2009)
Parliament, Republic of South Africa

Relevant Section: 20

(4) (Guidance) Guide to Good Manufacturing Practice for Medicines in South Africa (Version 5) (SA-GMPs) (November 2010)

Relevant Section: Annex 13

Investigational Products > IMP/IND Quality Requirements
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Last content review/update: August 22, 2016. Submit updates or comments.
SUMMARY

Overview
The SA-GCPs states that the information required to support the quality of the investigational product (IP) in South Africa is based upon the principles set forth in Section 7 (Investigator’s Brochure (IB)) of the International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs).

IB Content Requirements
The SA-GCPs and the ICH-GCPs require the IB to 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; regulatory and postmarketing experiences)
  • Summary of data and guidance for the investigator(s), and
  • Bibliography

See Section 7 of the ICH-GCPs for detailed content guidelines.

The sponsor is also accountable for supplying the IP, including the comparator(s) and placebo, if applicable. As defined in the SA-GCPs, he/she must ensure that the products are manufactured in accordance with the good manufacturing practices as laid down in Annex 13 of the SA-GMPs. (See Investigational Products topic, IMP/IND Quality Requirements subtopic for additional information on IP supply, storage, and handling requirements).

In addition to including the IB with the clinical trial application submission, the Medicines Control Council (MCC) also requires the application to provide a detailed review of the IPs to be used in the study. As indicated in Additional Resource (A), the following information must be furnished:

  • IP name(s) and details (e.g., formulation(s) and strength(s))
  • Comparator product(s) name(s) and details
  • Concomitant name(s) and details including rescue medications
  • Estimated quantity of trial material (each drug detailed separately) for which exemption will be required
  • Explanation for use of imported drugs when the same product is available in South Africa
  • Details of receiving of drugs from supplier including storage, dispensing, and packaging of drugs
  • Date MCC registration applied for – or envisioned date of application for trial medication; explain if registration is not envisioned
  • Registration status of entity, for the indication to be tested in this trial, in other countries

See Additional Resource (A) for detailed instructions on IP submission requirements.

Certificate of Analysis
As stated in the Manufacturing & Import subtopic, the MCC requires a Certificate of Analysis (CoA) to be issued by the manufacturer for all IPs to be used in a clinical trial. The CoA should identify the compound, dose, batch numbers, expiration dates, excipients, stability information (if available), and include a statement that the product is manufactured according to any applicable good manufacturing practices as described in the SA-GMPs. For the placebo group, the CoA must demonstrate that no active component exists in the formulation. If a comparator drug product is to be used in the trial, the CoA should confirm the appearance, dose, composition, expiration dates, stability (if available), and batch numbers for the product.

ADDITIONAL RESOURCES

(A) (Form) Application to Conduct Clinical Trials (Version 1) (CTF1) (May 2003)
Medicines Control Council, Department of Health, Republic of South Africa

(B) (Model Form) Annex 10 – Model Certificate of Analysis (No. 902) (2002)
WHO Technical Report Series, World Health Organization

(C) (Presentation) Regulatory Requirements for the ZA CTD (September 15, 2010)
Southern African Pharmaceutical Regulatory Affairs Association

(D) (ICH Guidance) International Conference on Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice E6 (R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Conference on Harmonisation, Geneva, Switzerland

REQUIREMENTS

(1) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 3.2, 4.14, 4.15, 4.16, and Appendix F

(2) (Guidance) Guide to Good Manufacturing Practice for Medicines in South Africa (Version 5) (SA-GMPs) (November 2010)

Relevant Section: Annex 13

Investigational Products > Labeling & Packaging
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SUMMARY

Overview
Investigational product labeling in South Africa must comply with the requirements set forth in the SA-GCPs, the GRMRSA, and the SA-GMPs. The GRMRSA states that for an investigational product (IP) to be used in a clinical trial, it must be properly labeled in English and at least one other official language, and should appear in clearly legible indelible letters. As set forth in the SA-GMPs, the following labeling information must be included on both the outer packaging and the immediate container:

  • The name, address and telephone number of the sponsor, contract research organisation (CRO), or investigator
  • The pharmaceutical dosage form, route of administration, quantity of dosage units, and in the case of open trials, the name/identifier and strength/potency
  • The batch and/or code number to identify the contents and packaging operation
  • A trial reference code allowing identification of the trial, site, investigator, and sponsor (if not given elsewhere)
  • The trial participant identification number/treatment number and where relevant, the visit number
  • The investigator name (if not already included above)
  • Directions for use (reference may be made to a leaflet or other explanatory document intended for the trial participant or person administering the product)
  • “For clinical trial use only” or similar wording
  • The storage conditions
  • The period of use (use-by date, expiration date or re-test date as applicable), in month/year format and in a manner that avoids any ambiguity
  • “Keep out of reach of children” except when the product is for use in trials where the product is not taken home by the participant

In addition, the SA-GCPs state that the IP be coded and labeled in a manner that protects the blinding, if applicable. The IPs must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage.

ADDITIONAL RESOURCES

(A) (Guideline) Good Pharmacy Practice in South Africa (Fourth Edition) (2010)
South African Pharmacy Council, Arcadia, SA

REQUIREMENTS

(1) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Section: 4.15

(2) (Regulation) Medicines and Related Substances Act 101 of 1965 - General Regulations Made in Terms of the Medicines and Related Substances Act 101 of 1965, as Amended (GRMRSA) (February 15, 2014)
Department of Health, Republic of South Africa

Relevant Sections: Parts 34 (8) and Part 8 (1)

(3) (Guidance) Guide to Good Manufacturing Practice for Medicines in South Africa (Version 5) (SA-GMPs) (November 2010)

Relevant Section: 13.6.7

Investigational Products > Product Management
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SUMMARY

Overview
In accordance with the SA-GCPs, the sponsor is responsible for providing the investigator(s) with an Investigator’s Brochure (IB). The IB must contain all of the relevant information on the investigational product(s) (IPs) including chemical, pharmaceutical, toxicological, pharmacokinetic, and pharmacodynamic data obtained from studies in animals as well as in humans, and the results of earlier clinical trials, if applicable. The information provided should be accurate and adequate enough to justify the nature, scale, and duration of the proposed trial, and to evaluate the potential safety and need for special precautions. Moreover, a sponsor must bring any new and relevant information arising during the study to the attention of the principal investigator(s) (PI(s)) and the ethics committee(s) (ECs), and update the IB, as required. The sponsor should also include all of the information contained in the IB in the clinical protocol. Refer to the Clinical Trial Lifecycle topic, Submission Content subtopic for additional IP requirements.

Investigational Product Supply, Storage, and Handling Requirements
As defined in the SA-GCPs, the sponsor must also supply the PIs/institution(s) with the IP(s), including the comparator(s) and placebo, if applicable. The sponsor should not supply the PI(s)/institution(s) with the IP(s) until the sponsor obtains Medicines Control Council (MCC) and EC approvals. The MCC approval is also a written authorization document to import unregistered drug products under MRSA, 2008.

The sponsor must provide the PI(s)/institution(s) with written procedures to follow for IP(s) handling and storage. The sponsor must ensure the following:

  • Timely delivery of IP(s) to the PI(s)/institution(s)
  • Maintenance of records documenting IP(s) shipment, receipt, disposition, return, and destruction
  • Maintenance of a system for retrieving IPs and documenting this retrieval
  • Maintenance of a system to dispose of unused IP(s) and corresponding documentation
  • Ensuring the IP(s) are stable over the period of use
  • Maintenance of sufficient quantities of the IP(s) used in the trial to reconfirm specifications, should this become necessary
  • Maintenance of records of batch samples analyses and characteristics

The sponsor must also ensure that the products are manufactured in accordance with any applicable Good Manufacturing Practices which are described in the SA-GMPs, and are coded and labeled in a manner that protects the blinding, if applicable. IP labeling should comply with the SA-GMPs labeling requirements. The sponsor should determine acceptable temperatures, conditions, times for IP storage, reconstitution fluids/procedures, and devices for product infusion, if any, that comply with the SA-GPPs.

In blinded trials, the IP(s) coding system should include a mechanism that permits rapid IP(s) identification in case of a medical emergency, but does not permit undetectable breaks of the blinding. If significant formulation changes are made in the IP(s) or comparator product(s) during the course of clinical development, the results of any studies of the newly formulated product(s) should be available prior to its use in the clinical trial. Refer to the SA-GCPs for detailed sponsor-related IP requirements.

Record Requirements
The sponsor is required to retain essential documents for at least 15 years, or, until at least two (2) years after the last approval of a marketing application and until there are no pending or contemplated marketing applications, or, at least 15 years have elapsed since the formal discontinuation of clinical development of the IP. These documents should be retained for a longer period however if required by the applicable regulatory requirement(s) or if needed by the sponsor.

The sponsor should inform the investigator(s) and institution(s) in writing of the need for record retention and should notify the investigator(s) and institution(s) in writing when the trial related records are no longer needed.

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 3.6, 4.14, 4.15, 4.16, 4.9, Appendix C (3.1), and Appendix F

(2) (Guidance) Guide to Good Manufacturing Practice for Medicines in South Africa (Version 5) (SA-GMPs) (November 2010)

Relevant Section: Annex 13

(3) (Legislation) No. 72 of 2008: Medicines and Related Substances Amendment Act, 2008 (MRSA, 2008) (April 21, 2009) Parliament, Republic of South Africa

Relevant Section: 20

(4) (Guidance) Good Pharmacy Practice in South Africa (4th Edition) (SA-GPPs) (2010)
South African Pharmacy Council, Arcadia, Republic of South Africa

Specimens > Definition of Specimen
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Last content review/update: June 01, 2016. Submit updates or comments.
SUMMARY

Overview
In South Africa, the NHARegMicroLabs refers to a specimen as a “diagnostic specimen,” and defines it as any human or animal material, including excreta, secreta, blood and its components, tissue or tissue fluids, that is to be used for the purpose of diagnosis, but does not include live infected animals. The G-EthicsHR, in turn, refers to a specimen as a “biological specimen,” and defines it as material from a person including blood and blood products, DNA, RNA, blastomeres, polar bodies, cultured cells, embryos, gametes, progenitor stem cells, small tissue biopsies, and growth factors.
 
The term “specimen” appears to be used interchangeably with “biological material” in South Africa. The NHABiol follows the G-EthicsHR definition of biological specimen, defining “biological material” as material from a human being including DNA, RNA, blastomeres, polar bodies, cultured cells, embryos, gametes, progenitor stem cells, small tissue biopsies, and growth factors from the same. The G-EthicsHR defines “human biological materials” with the same definition as is used for “biological specimen.”

In addition, the NHABlood&Cells generally refers to substances of human origin as biological substances.

Please refer to the G-EthicsHR, the NHABiol, the NHA, the HTA, the NHABlood&Cells the NHATissue, and the NHAStemCell for more specific definitions of selected terms including blood, cultured cells, embryonic tissue, human tissue, plasma, stem cell, and genetic material.

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Legislation) National Health Act 61 of 2003: Regulations Relating to the Registration of Microbiological Laboratories and the Acquisition, Importation, Handling, Maintenance and Supply of Human Pathogens (No.R.178) (NHARegMicroLabs) (March 2, 2012)

Relevant Section: 1

(2) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Sections: Chapter 3 (3.3) and Appendix 1

(3) (Regulation) National Health Act 61 of 2003 - Regulations Relating to the Use of Human Biological Materials (No.R.177) (NHABiol) (March 2, 2012)
Parliament, Republic of South Africa

Relevant Section: 1

(4) (Legislation) National Health Act 61 of 2003 (NHA) (September 2, 2013)
Parliament, Republic of South Africa

Relevant Section: 1

(5) (Legislation) Human Tissue Act 65 of 1983 (HTA) (May 20, 1983)
Parliament, Republic of South Africa

Relevant Section: 1

(6) (Regulation) National Health Act 61 of 2003 – Regulations Relating to the Import and Export of Human Tissue, Blood, Blood Products, Cultured Cells, Stem Cells, Embryos, Foetal Tissue, Zygotes and Gametes (No.R.181) (NHABlood&Cells) (March 2, 2012)
Department of Health, Republic of South Africa

Relevant Section: 1

(7) (Regulation) National Health Act 61 of 2003 – Regulations Relating to Tissue Banks (R.182) (NHATissue) (March 2, 2012)
Department of Health, Republic of South Africa

Relevant Section: 1

(8) (Regulation) National Health Act 61 of 2003 – Regulations Relating to Stem Cell Banks (R.183) (NHAStemCell) (March 2, 2012)
Department of Health, Republic of South Africa

Relevant Section: 1

Specimens > Import & Export
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Last content review/update: June 01, 2016. Submit updates or comments.
SUMMARY

Overview
As delineated in the GRMRSA, the SA-GCPs, and the NHAParticipants, to conduct a clinical trial using biological substances, a sponsor or his/her designated contract research organization (CRO) must submit a clinical trial application to receive approval from the Medicines Control Council (MCC) and the local accredited ethics committee(s) (ECs). In addition, per the NHA, the NHABlood&Cells, the NHARegMicroLabs, the NHATissue, the NHAStemCell, and the HTA, a permit must also be obtained from the Department of Health (DOH) Director General to import or export biological substances. Both the MCC approval letter and the DOH import/export permit must be included with each biological substance shipment. See also the Clinical Trial Lifecycle topic, Submission Content subtopic for information on completing a clinical trial application.

DOH Application Requirements
As set forth in the NHA, the NHABlood&Cells, the NHARegMicroLabs, the NHATissue, the NHAStemCell, and the HTA, the DOH Director General as delegated by the DOH Minister is responsible for establishing regulations related to the import and export of biological substances. In addition, only the Minister can authorize an institution or hospital to import or export biological substances for research purposes.

In accordance with the NHA, the NHABlood&Cells, the NHARegMicroLabs, the NHATissue, the NHAStemCell, and the HTA, the DOH Director-General reviews and approves all import or export requests by an institution or hospital. These requests must be submitted in writing using the application forms that may be obtained by contacting the National Department of Health Permit Programme:

Email: importexportpermit@health.gov.za

The forms also appear as Annexures 1 -6 in the NHABlood&Cells and Form 1 in the NHARegMicroLabs.

Upon review of the application, the Director-General will issue a permit or certificate authorizing the import or export request if he/she is satisfied that the submission meets the NHA, the NHABlood&Cells, the NHARegMicroLabs, the NHATissue, the NHAStemCell, and the HTA requirements, as applicable. The permit will contain an expiration date for the approved biological substance(s).

General Import/Export Requirements for Biological Substances
The NHABlood&Cells states that each biological substance to be imported into South Africa must be accompanied by a certificate from the supplier stating that the substance has been exported in terms of the originating country’s applicable laws and regulations.

As per the NHABlood&Cells and Additional Resource (B), export permits for biological substances may only be issued by the Director-General to a Southern African Development Community (SADC) member state or to a South African citizen, provided that the country’s market requirements have been met. An applicant must also be registered with the Health Professions Council of South Africa (HPCSA) and operating in South Africa in order to apply for a permit to import or export biological substances. The applicant must also provide the Director-General with written information on stock levels for this substance along with the export application. As stated in Additional Resource (C), it typically takes three (3) to seven (7) working days to complete the import/export application process.

Applicants to whom a permit has been issued must keep a record of the import or export and submit this information using the register forms listed in Annexures 4 , 5, and 6 of the NHABlood&Cells (Annexure 4 - Register of Imported Biological Substances of Human Origin and Register of Exported Biological Substances of Human Origin). The forms must be submitted to the Director-General before the end of February each year, for the preceding calendar year.

Import/Export Requirements for Specific Biological Substance Categories
The NHABlood&Cells provides details on unique application requirements for specific types of biological substances as outlined below:

  • Import of tissues being used for therapeutic purposes: application must be accompanied by donor health status
  • Export of tissues or gamete: application must include written proof that donated biological substance complies with the NHA requirements
  • Import or export of placenta tissue, embryonic or fetal tissue, embryonic, fetal or umbilical stem cells: applications will only be approved with the Minister’s written consent
  • Import or export of blood or blood products: applications must be accompanied by a national blood transfusion service certificate and test results. If no documentation is included, the applicant must submit a letter to the Director-General explaining the reason. The Director-General will decide whether tests must be conducted, and the Minister is authorized to determine whether the applicant’s institution can be exempted from these requirements
ADDITIONAL RESOURCES

(A) (Form) Application to Conduct Clinical Trials (Version 1) (CTF1) (May 2003)
Medicines Control Council, Department of Health, Republic of South Africa

(B) (Booklet) Biological Substances Export/Import Permits (Current as of March 2013)
TNT and South African Clinical Research Association (SACRA), Republic of South Africa

(C) (Document) South Africa Frequently Asked Questions (FAQs) Import/Export Permit Programme: (Human Tissue, Blood, Blood Products, Cultured Cells, Stem Cells, Embryos, Foetal Tissue, Zygotes & Gametes, Human Pathogens) (Date Unavailable)
Department of Health, Republic of South Africa

(D) NIAID Communication with the National Department of Health Permit Programme, Republic of South Africa (not available online) (May 2016)

REQUIREMENTS

(1) (Regulation) Medicines and Related Substances Act 101 of 1965 - General Regulations Made in Terms of the Medicines and Related Substances Act 101 of 1965, as Amended (GRMRSA) (February 15, 2014)
Department of Health, Republic of South Africa

Relevant Section: Part 34 (1)

(2) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
Department of Health, Republic of South Africa

Relevant Sections: 1.6 and 4.3

(3) (Legislation) National Health of Act 61 of 2003 - Regulations Relating to Research with Human Participants (NHAParticipants) (September 19, 2014)
Parliament, Republic of South Africa

Relevant Section: 3

(4) (Legislation) Act No. 61 of 2003: National Health Act, 2004 (NHA) (September 2, 2013)
Parliament, Republic of South Africa

Relevant Sections: Chapter 8 (54, 57, 60, and 68)

(5) (Regulation) National Health Act 61 of 2003 – Regulations Relating to the Import and Export of Human Tissue, Blood, Blood Products, Cultured Cells, Stem Cells, Embryos, Foetal Tissue, Zygotes and Gametes (No.R.181) (NHABlood&Cells) (March 2, 2012)
Department of Health, Republic of South Africa

Relevant Sections: 2, 3, 4, 5, and 7, and Annexures 1-6

(6) (Legislation) National Health Act 61 of 2003 – Regulations Relating to the Registration of Microbiological Laboratories and the Acquisition, Importation, Handling, Maintenance and Supply of Human Pathogens (No.R.178) (NHARegMicroLabs) (March 2, 2012)

Relevant Sections: 2-13 and Forms 1 and 2

(7) (Regulation) National Health Act 61 of 2003 – Regulations Relating to Tissue Banks (R.182) (NHATissue) (March 2, 2012)
Department of Health, Republic of South Africa

Relevant Sections: 1, 3, and 16

(8) (Regulation) National Health Act 61 of 2003 – Regulations Relating to Stem Cell Banks (R.183) (NHAStemCell) (March 2, 2012)
Department of Health, Republic of South Africa

Relevant Sections: 1 and 2

(9) (Legislation) Human Tissue Act 65 of 1983 (HTA) (May 20, 1983)
Parliament, Republic of South Africa

Relevant Sections: Chapter 3 (24 and 25)

(10) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Section: 3.3

Specimens > Consent for Specimens
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Last content review/update: June 01, 2016. Submit updates or comments.
SUMMARY

Overview
In accordance with the HTA, the NHA, and the NHABiol, prior to removing or withdrawing any biological substance from the body of a living person for research purposes, consent must be obtained from that person in writing or orally, before a competent witness. In the event that the person is a minor, the parents or guardians of that person must provide consent.

The NHABiol specifically states that when taking biological samples from a child, where the person is younger than 18 years, Part 3, Section 129 of the Children’s Act must be followed.

Additionally, the NHABiol requires the following consent for the removal or withdrawal of biological samples to treat a person with mental illness:

  • His/her consent, if he/she is capable;
  • A court appointed curator, spouse, next of kin, parent or guardian, major child, brother, or sister, or partner associate if mentally ill person is incapable of giving consent; and
  • The health institution’s head in the case of an emergency

Similarly, the HTA, the NHA, and the NHABiol include consent provisions for the donation of human bodies and the tissue of deceased persons. These documents state that any person who is competent to make a will may donate his/her body or any specified tissue to be used after his/her death for medical and dental purposes, as long as he/she signs the will in the presence of at least two (2) competent witnesses. The person may also give consent to a post-mortem examination of his/her body for research purposes, and may select an institution or person as the recipient. In the absence of a donation as described above, the individual’s spouse, child over 18 years, parent, guardian, or brother/sister over 18 years may donate his/her body or any specific tissue to an institution or person for research purposes. Please refer to the HTA, the NHA, and the NHABiol for detailed requirements. (See the Informed Consent topic, Required Elements and Participant Rights subtopics for additional information on informed consent).

Human Tissue Sample Consent Requirements
The G-EthicsHR presents separate consent provisions for the use of human tissue samples. With reference to human tissue samples, donor consent should be obtained where it is proposed to use tissue samples that have been held:

  • in storage following, or in association with, clinical investigations
  • in archives or banks, or removed during a clinical study, or used in research that may lead to harm, benefit, or injustice to a donor of such tissue

This guideline also requires that consent be voluntary and specific to the purpose for which the tissue is to be used. The participant must be given full information about the study, be advised on storage and future use of samples, and be assured of data related confidentiality and privacy.

In addition, per the NHATissue, tissue banks are required to develop donor record management systems in which the tissue donor register contains the full identity and relationship of the consenting person. The system will also document tissue banking processes, including the process of obtaining informed written consent.

Human Stem Cell Consent Requirements
The NHAStemCell similarly states that authorized stem cell banks must retain a record of the donor’s written informed consent. Further, no person shall use stem cells or its therapeutic research products for educational purposes unless he/she is authorized by the Department of Health (DOH) and complies with the following requirements:

  • Has obtained the donor’s informed written consent even in the case of residual tissue, blood or blood products; and
  • Is certain the donor has donated voluntarily and it is properly documented

The NHA also indicates that the Minister may permit research on stem cells and zygotes which are not more than 14 days old on a written application, and if the applicant documents the research for record purposes, and prior consent is obtained from the donor.

Human Genetic Research Consent Requirements
The G-EthicsHR states that the investigator or institution must obtain consent for human genetic research. Investigators and institutions must comply with numerous requirements to ensure participant consent, protection, and privacy rights are upheld with regard to the storage of genetic materials. See the G-EthicsHR for consent requirement details.

Consent Waivers
In reference to both human tissue sample and genetic research consent, the G-EthicsHR indicates that an ethics committee may sometimes waive the consent requirement in cases where there is minimal risk of commercial exploitation or privacy violations. For additional details, see section 3.3 of the G-EthicsHR.

ADDITIONAL RESOURCES

No additional resources

REQUIREMENTS

(1) (Legislation) Human Tissue Act 65 of 1983 (HTA) (May 20, 1983)
Parliament, Republic of South Africa

Relevant Sections: Chapter 1 (2) and Chapter 2 (18)

(2) (Legislation) Act No. 61 of 2003: National Health Act, 2004 (NHA) (September 2, 2013)
Parliament, Republic of South Africa

Relevant Sections: Chapter 8 (55, 56, 57, 62, 67, and 68)

(3) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
Department of Health, Republic of South Africa

Relevant Section: 3.3

(4) (Regulation) National Health Act 61 of 2003 – Regulations Relating to Tissue Banks (R.182) (NHATissue) (March 2, 2012)
Department of Health, Republic of South Africa

Relevant Section: 6

(5) (Regulation) National Health Act 61 of 2003 – Regulations Relating to Stem Cell Banks (R.183) (NHAStemCell) (March 2, 2012)
Department of Health, Republic of South Africa

Relevant Sections: 2 and 5

(6) (Regulation) National Health Act 61 of 2003 - Regulations Relating to the Use of Human Biological Materials (No.R.177) (NHABiol) (March 2, 2012)
Parliament, Republic of South Africa

Relevant Sections: 3, 4, and 7

(7) (Legislation) Children’s Act 38 of 2005 (Children’s Act) (June 8, 2006) (Effective date: April 1, 2010)
Parliament, Republic of South Africa

Relevant Sections: Chapter 7 (Part 3, Section 129)

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OMB #: 0925-0668
Expiration Date: 2/28/2019