South Africa
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

NOTE: As of June 1, 2017, the South African Health Products Regulatory Authority (SAHPRA) has replaced the Medicines Control Council (MCC) as the Regulatory Authority overseeing medicines and clinical research. The ClinRegs team will study the impact of this change and update the South Africa page where appropriate. 

For more information, see the following:

  • Proclamation No. 20 of 2017 (Proc20of2017), which proclaims June 1, 2017 as the commencement date for Act No. 72 of 2008
  • Act No. 72 of 2008: Medicines and Related Substances Act, 2008 (MRSA, 2008), which establishes the SAHPRA
  • Act No. 14 of 2015: Medicines and Related Substances Act, 2015 (MRSA, 2015), which establishes the SAHPRA Board
QUICK FACTS
Clinical trial application language English
Parallel regulatory and ethical review permitted Yes
Clinical trial registration required Yes
In-country sponsor presence/representation required No
Age of minors 21 & Under
Specimens export allowed Yes
Regulatory Authority > Regulatory Authority
Last content review/update: December 22, 2017
Summary

Overview

As stated in MRSA, 2008, MRSA, 2015, and Proc20of2017, as of June 1, 2017, the South African Health Products Regulatory Authority (SAHPRA) was established as the regulatory authority overseeing medicines and clinical research, replacing the Medicines Control Council (MCC). However, per MRSA, 2015, the MCC will continue to perform the SAHPRA’s functions until SAHPRA’s first Board meeting. The full scope of SAHPRA’s activities will be implemented over the next few years. As stated in the MRSA and the GRMRSA, SAHPRA is responsible for clinical trial oversight, approval, and inspections in South Africa. It grants permission for clinical trials to be conducted in South Africa in accordance with the provisions of the GRMRSA.

Per MRSA, 2008 and MRSA, 2015, the SAHPRA is an independent, state-owned entity that was established to oversee the regulation of medicines in South Africa. According to Additional Resource (A), this agency 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.

Per MRSA, 2008 and MRSA, 2015, and as described in Additional Resource (C), SAHPRA is a state-owned entity within the public administration but outside the public service. It acts through a Board that is appointed by South Africa’s Minister of the National Department of Health (NDOH). For details on the Board appointments, see Additional Resource (D). The Board, after consultation with the Minister, will appoint a Chief Executive Officer (CEO) to administer SAHPRA. The CEO will be appointed for a term of five (5) years and may be reappointed for one (1) additional term. Reporting to the Board, the CEO will appoint and supervise staff and determine the structure and policies for SAHPRA. When fully established, SAHPRA will provide for the monitoring, evaluation, regulation, investigation, inspection, registration, and control of clinical trials. Among other functions, SAHPRA will ensure that clinical trial protocols are being assessed according to prescribed ethical and professional criteria and standards.

As indicated in Additional Resource (B), the MCC is housed within South Africa’s NDOH, 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 (MRA), also known as Registrar of Medicines, serves as executive secretariat to the MCC. There are four (4) Directorates within the 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 December 21, 2017)
South African National Clinical Trials Register, National Department of Health
(B) (Website) Medicines Control Council – About the MCC (Current as of December 21, 2017)
Medicines Control Council, National Department of Health
TimesLIVE
Requirements
(1) (Legislation) No. 72 of 2008: Medicines and Related Substances Act, 2008 (MRSA, 2008) (April 21, 2009)
Parliament, Republic of South Africa
Relevant Sections: 1, 2, and 20
(2) (Legislation) Act No. 14 of 2015: Medicines and Related Substances Amendment Act, 2015 (MRSA, 2015) (January 8, 2016)
Parliament
Relevant Sections: 2, 3, and 26
(3) (Proclamation) Proclamation No. 20 of 2017 (Proc20of2017) (May 22, 2017)
President
(4) (Legislation) Medicines and Related Substances Act 101 of 1965 (MRSA) (May 2, 2003)
Parliament, Republic of South Africa
Relevant Sections: Parts 2 and 35
(5) (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) (September 15, 2014)
National Department of Health
Relevant Sections: Part 34 (1)
Regulatory Authority > Scope of Assessment
Last content review/update: December 22, 2017
Summary

Overview

As stated in MRSA, 2008, MRSA, 2015, and Proc20of2017, as of June 1, 2017, the South African Health Products Regulatory Authority (SAHPRA) was established as the regulatory authority overseeing medicines and clinical research, replacing the Medicines Control Council (MCC). However, per MRSA, 2015, the MCC will continue to perform the SAHPRA’s functions until SAHPRA’s first Board meeting. The full scope of SAHPRA’s activities will be implemented over the next few years. Because the MCC is performing the regulatory functions of the SAHPRA, this ClinRegs profile will at times still refer to the MCC where it is still applicable.

In accordance with the GRMRSA, the SA-GCPs, and the G-Clin, the 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 December 21, 2017)
Medicines Control Council, National Department of Health
Requirements
(1) (Legislation) No. 72 of 2008: Medicines and Related Substances Act, 2008 (MRSA, 2008) (April 21, 2009)
Parliament, Republic of South Africa
Relevant Sections: 1, 2, and 20
(2) (Legislation) Act No. 14 of 2015: Medicines and Related Substances Amendment Act, 2015 (MRSA, 2015) (January 8, 2016)
Parliament
Relevant Sections: 2, 3, and 26
(3) (Proclamation) Proclamation No. 20 of 2017 (Proc20of2017) (May 22, 2017)
President
(4) (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) (September 15, 2014)
National Department of Health
Relevant Sections: Part 34 (1)
(5) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
National Department of Health
Relevant Sections: 1.5.1, Appendices D and F
(6) (Guidance) Clinical (Version 1) (G-Clin) (December 2003)
Registrar of Medicines, Medicines Control Council, National Department of Health
Relevant Sections: 3
(7) (Guidance) General Information (Version 8) (G-GenInfo) (August 2012)
Registrar of Medicines, Medicines Control Council, National Department of Health
Relevant Sections: 13.5
(8) (Guidance) Guideline on Completing Clinical Trial Applications (G-CTA) (May 2003) (Updated August 2010)
Registrar of Medicines, Medicines Control Council, National Department of Health
Relevant Sections: A
Regulatory Authority > Regulatory Fees
Last content review/update: December 22, 2017
Summary

Overview

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

  • Authorization of the use of an unregistered medicine requires an application fee payable with the full submission of the application: company sponsored trial fee (9,000 South African 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 a manufacturing license (3,000 ZAR)
  • Clinical trial amendments - (i) technical amendments (2,100 ZAR per amendment); (ii) administrative amendment (600 ZAR per amendment)
  • Manufacturing site inspection(s) - local manufacturing site (650 ZAR per hour); international manufacturing site (4,000 ZAR per hour)
  • Manufacturing New license (21,800 ZAR)
  • Manufacturing Renewal license (19,000 ZAR)

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 South African Health Products Regulatory Authority (SAHPRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting) 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: Cheque 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 cheque 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, National Department of Health
Requirements
(1) (Guidance) General Information (Version 8) (G-GenInfo) (August 2012)
Registrar of Medicines, Medicines Control Council, National Department of Health
Relevant Sections: 2.9 and 4.8
(2) (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)
National Department of Health
Relevant Sections: 5. Use of Unregistered Medicines, 6. In respect of licenses, and 7. Inspections to assess the quality of medicines
(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, National Department of Health
Ethics Committee > Ethics Committee
Last content review/update: December 22, 2017
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 National Department of Health (NDOH) 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. (Note: ECs are referred to as health research ethics committees (HRECs) in South Africa).

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. 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; if there are more than 15 members, the quorum may be 33%
  • Have a chairperson
  • Include members of both genders; not more than 70% of its members should be one gender
  • Include at least one (1) lay person; however, the SA-GCPs, an older guideline, requires 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
National Health Research Ethics Council, National Department of Health
Requirements
(1) (Legislation) National Health Act 61 of 2003 (NHA) (July 23, 2004)
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)
National Department of Health
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)
National Department of Health
Relevant Sections: 4.2, 4.4, 5.1, 5.2, and 5.3
Ethics Committee > Scope of Review
Last content review/update: December 22, 2017
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 South African Health Products Regulatory Authority (SAHPRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting) and a registered EC for review and approval before a study may commence. Because the MCC is performing the regulatory functions of the SAHPRA, this ClinRegs profile will at times still refer to the MCC where it is still applicable. 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 National Department of Health (NDOH) 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 other relevant clearances, such as provincial and hospital approvals. 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 December 21, 2017)
National Department of Health
(B) (Website) South African Human Research Electronic Application System (Current as of December 21, 2017)
National Health Research Ethics Council, National Department of Health
Requirements
(1) (Legislation) National Health Act 61 of 2003 (NHA) (July 23, 2004)
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)
National Department of Health
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)
National Department of Health
Relevant Sections: 2, 4, 5, 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 Sections: 3
Ethics Committee > Ethics Committee Fees
Last content review/update: December 22, 2017
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)
National Department of Health
Relevant Sections: 4.2 and 4.3.1
(2) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
National Department of Health
Relevant Sections: 8.5
Ethics Committee > Authorizing Body
Last content review/update: December 22, 2017
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 National Department of Health (NDOH)’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 Council for Harmonisation's 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
National Health Research Ethics Council, National Department of Health
(B) (ICH Guidance) Guideline for Good Clinical Practice E6(R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(C) (WMA Guidance) Declaration of Helsinki (October 19, 2013)
World Medical Association
Requirements
(1) (Legislation) National Health Act 61 of 2003 (NHA) (July 23, 2004)
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)
National Department of Health
Relevant Sections: 1.2.7, 1.5.3, 1.5.4, 2.2, 8.2, and Appendix F
(3) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
National Department of Health
Relevant Sections: 4.6, 5.2, and 5.4
Clinical Trial Lifecycle > Submission Process
Last content review/update: December 22, 2017
Summary

Overview

According to the G-CTA and Additional Resource (A), the review and approval of clinical trial applications by the South African Health Products Regulatory Authority (SAHPRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting) and an accredited ethics committee (EC) may be conducted in parallel. Because the MCC is performing the regulatory functions of the SAHPRA, this ClinRegs profile will at times still refer to the MCC where it is still applicable. 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. Refer to each EC’s website for specific submission procedures. (Note: ECs are referred to as health research ethics committees (HRECs) in South Africa).

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 two (2) 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
Medicines Control Council, National Department of Health
(B) (Website) Medicines Control Council – Contact the MCC (Current as of December 21, 2017)
Medicines Control Council, National Department of Health
Requirements
(1) (Legislation) Medicines and Related Substances Act 101 of 1965 (MRSA) (May 2, 2003)
Parliament, Republic of South Africa
(2) (Guidance) Guideline on Completing Clinical Trial Applications (G-CTA) (May 2003) (Updated August 2010)
Registrar of Medicines, Medicines Control Council, National Department of Health
(3) (Guidance) General Information (Version 8) (G-GenInfo) (August 2012)
Registrar of Medicines, Medicines Control Council, National Department of Health
Relevant Sections: 2.4, 2.5, and 13.5
(4) (Legislation) No. 72 of 2008: Medicines and Related Substances Act, 2008 (MRSA, 2008) (April 21, 2009)
Parliament, Republic of South Africa
Relevant Sections: 20
(5) (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) (September 15, 2014)
National Department of Health
Relevant Sections: Application for the Registration of a Medicine – Part 22 (4)
Clinical Trial Lifecycle > Submission Content
Last content review/update: December 22, 2017
Summary

Overview

In accordance with the NHA, the SA-GCPs, the G-EthicsHR, and the NHA Participants, a sponsor (or the principal investigator when there is no sponsor) must apply to the South African Health Products Regulatory Authority (SAPHRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting) and an accredited ethics committee (EC) to conduct a clinical trial for a non-registered drug or a registered drug for new indications. Because the MCC is performing the regulatory functions of the SAHPRA, this ClinRegs profile will at times still refer to the MCC where it is still applicable.

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))
  • Two (2) additional completed signed copies of the clinical trial application
  • 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 (Annex 1)
  • Investigator’s brochure (IB) and /or all professional information (i.e., package insert(s))
  • Signed Investigator’s curriculum vitae(s)(CVs) in MCC format (Annex 2)
  • Signed declaration(s) by investigators and site staff (Annexes 3 and 5)
  • Good clinical practice (GCP) certificates (not more than 3 years old)
  • Workload forms for investigators (Annex 7)
  • Proof of Registration with a professional statutory body (e.g., Health Professions Council of South Africa, South African Pharmacy Council, or South African Nursing Council)
  • Regional monitor’s MCC CV and declaration (Annexes 2 and 6)
  • Signed joint financial declaration by sponsor and national principal investigator (PI) (Annex 4)
  • Signed Declaration by Applicant and National Principal Investigator
  • CVs and Signed Declaration by Regional Monitor(s)
  • Certificate(s) of analysis (may be submitted with ethics approval letter)
  • Indemnity/insurance certificate and/or proof of malpractice insurance of trialist(s)
  • Active insurance certificate for clinical trial
  • Proof of sponsor indemnification for investigators and trial site
  • Proof of application to register the trial on the South African National Clinical Trials Register
  • Ethics approval or copy of letter submitted to EC
  • Copy or copies of recruitment advertisement(s) ) and Questionnaires (if applicable)
  • Financial declaration (sponsor/national PI)
  • Citations
  • Labelled CD-ROM (list of files submitted on CD-ROM)

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), (D), (E), and (F) to exemplify the common elements shared by the various application forms:

  • Cover letter
  • Completed EC-specific 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 (if applicable)
  • 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
  • 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
Medicines Control Council, National Department of Health
Relevant Sections: Application Form, Checklist, Declarations, Annexes 1-7, and Appendix
Biomedical Research Ethics Committee, University of Kwazulu-Natal
(C) (Form) Research Ethics Committee Application Form (Version 1) (May 28, 2010)
Human Sciences Research Council (HSRC), South Africa
(E) (Website) Human Research Ethics Committee - Forms and Instructions (Current as of December 21, 2017)
Faculty of Health Science, University of Cape Town
(F) (Website) Ethics Resources (Current as of December 21, 2017)
Pharma-Ethics Independent Research Ethics Committee
Requirements
(1) (Legislation) National Health Act 61 of 2003 (NHA) (July 23, 2004)
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)
National Department of Health
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)
National Department of Health
Relevant Sections: 2.1, 2.3, 4, and 5.5
(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 Sections: 3
(5) (Guidance) Guideline on Completing Clinical Trial Applications (G-CTA) (May 2003) (Updated August 2010)
Registrar of Medicines, Medicines Control Council, National Department of Health
Clinical Trial Lifecycle > Timeline of Review
Last content review/update: December 22, 2017
Summary

Overview

Based on the G-CTA and Additional Resources (A), (B), and (C), the review and approval of clinical trial applications by the South African Health Products Regulatory Authority (SAPHRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting) 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. Because the MCC is performing the regulatory functions of the SAHPRA, this ClinRegs profile will at times still refer to the MCC where it is still applicable.

In addition, as described in the G-EthicsHR and Additional Resources (D) and (E), all clinical trials must obtain site-specific provincial and/or hospital approval to assess the impact the clinical trial will have on the resources of the establishment hosting the trial. While the submission requirements differ for each provincial health committee, generally, upon receipt of EC approval, the sponsor or investigator should register the study online at the National Health Research Database.

MCC Approval

According to Additional Resources (B), (C), (G), and (H), 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 (G) 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 Resource (G) indicates that the EC review process on average is typically completed in four (4) to eight (8) 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
Medicines Control Council, National Department of Health
(B) (Article) Clinical Trials in South Africa 101 (April 7, 2011)
The Official Blog of Cato Research
(C) (Article) Discovering South Africa (June 1, 2005)
Scholtz, Herman and Pretorius, Sybrand, Applied Clinical Trials
The Clinical Research Centre at the University of Cape Town
Relevant Sections: Chapter 4 – South Africa (MCC, HREC, Provincial/Hospital (full ebook only available for purchase)
(F) (Website) National Health Research Database (Current as of December 21, 2017)
National Department of Health, Republic of South Africa
Arianne Corporation
Katsoulis, Lynn, Journal for Clinical Studies
Relevant Sections: 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, National Department of Health
Relevant Sections: A
(2) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
National Department of Health
Relevant Sections: 5.5
Clinical Trial Lifecycle > Trial Initiation
Last content review/update: December 22, 2017
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 South African Health Products Regulatory Authority (SAPHRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting) and from an accredited local ethics committee (EC). There is no waiting period required following the applicant’s receipt of these approvals. Because the MCC is performing the regulatory functions of the SAHPRA, this ClinRegs profile will at times still refer to the MCC where it is still applicable.

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.

Per the SA-GPPs, pharmacists must be involved in clinical trials, including for example, assisting in the development of protocols, overseeing medicine supplies, monitoring administration protocols, and maintaining registries.

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 National Department of Health (NDOH) 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 (e.g., institutions) 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 December 21, 2017)
National Department of Health
(C) (Website) South African Human Research Electronic Application System (Current as of December 21, 2017)
National Health Research Ethics Council, National Department of Health
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) (September 15, 2014)
National Department of Health
Relevant Sections: 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)
National Department of Health
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)
National Department of Health
Relevant Sections: 4 and 5
(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 Sections: 3
(5) (Guidance) Good Pharmacy Practice in South Africa (4th Edition) (SA-GPPs) (2010)
South African Pharmacy Council
Relevant Sections: General Objectives and Requirements of Pharmaceutical Services
Clinical Trial Lifecycle > Safety Reporting
Last content review/update: December 22, 2017
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)

Per the G-EmergencyProc, all clinical trial sites must have an emergency standard operating procedure that should be available for inspection by the South African Health Products Regulatory Authority (SAPHRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting). In addition, each clinical trial site should have adequately trained investigators to manage medical emergencies. Further, there must be an emergency 24-hour contact number for trial participants who experience an unexpected AE. Because the MCC is performing the regulatory functions of the SAHPRA, this ClinRegs profile will at times still refer to the MCC where it is still applicable.

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 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 (8) 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 Reactions Reporting Form may be used to complete SAE/SADR reports. For marketed medicine, the form must be submitted to the MCC’s adverse drug reaction monitoring program (see Additional Resource (A) to access the form). Per an in-country subject matter expert, applicants may use their in-house reporting 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
Medicines Control Council, National Department of Health
Chin, Richard and Bairu, Menghis, eds., Academic Press
Relevant Sections: Chapter 13, Section 13.12
Requirements
(1) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
National Department of Health
Relevant Sections: 3.12, 4.19, and Appendix F
(2) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
National Department of Health
Relevant Sections: 4.5.1 and Appendix 1
(3) (Guidance) Reporting Adverse Drug Reactions in South Africa (Version 1_2) (G-ADR) (December 2012)
Medicines Control Council, National Department of Health
Relevant Sections: 2.1, 2.2, 2.3, 2.4, 2., 2.6, 5.1, and 7.1
(4) (Guidance) Emergency Procedures for Clinical Trial Sites (G-EmergencyProc) (October 2016)
Medicines Control Council, National Department of Health, Republic of South Africa
Relevant Sections: 1, 2, and 6
(5) (Legislation) No. 72 of 2008: Medicines and Related Substances Act, 2008 (MRSA, 2008) (April 21, 2009)
Parliament, Republic of South Africa
Relevant Sections: 20
(6) (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) (September 15, 2014)
National Department of Health
Relevant Sections: Parts 1, 34, and 37
Clinical Trial Lifecycle > Progress Reporting
Last content review/update: December 22, 2017
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 South African Health Products Regulatory Authority (SAHPRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting), 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 National 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 December 21, 2017)
Clinical Research Centre, University of Cape Town, Republic of South Africa
Relevant Sections: 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) (September 15, 2014)
National Department of Health
Relevant Sections: 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)
National Department of Health
Relevant Sections: 3.14 and 6.4
Sponsorship > Definition of Sponsor
Last content review/update: December 22, 2017
Summary

Overview

As defined in the SA-GCPs, a sponsor is the person or organization responsible for the initiation, management and 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. Further, per the G-Monitor, the sponsor is solely responsible for adequate oversight of the conduct of a clinical trial, including the justification for and selection of monitoring methods. Any trial-related responsibilities transferred to and assumed by a CRO should be specified in writing. The sponsor retains those responsibilities not specifically transferred to and assumed by a CRO.

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)
National Department of Health
Relevant Sections: 1.5.6, 4, and 4.5
(2) (Guidance) Oversight and Monitoring in Clinical Trials (Version 1) (G-Monitor) (November 2016)
Medicine Control Council, National Department of Health, Republic of South Africa
Relevant Sections: 1
Sponsorship > Trial Authorization
Last content review/update: December 22, 2017
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 South African Health Products Regulatory Authority (SAHPRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting) 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
Medicines Control Council, National Department of Health
Requirements
(1) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
National Department of Health
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, National Department of Health
Sponsorship > Insurance
Last content review/update: December 22, 2017
Summary

Overview

The South African Health Products Regulatory Authority (SAHPRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting) 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
Medicines Control Council, National Department of Health
Association of the British Pharmaceutical Industry, United Kingdom
Association of the British Pharmaceutical Industry, BioIndustry Association, and Clinical Contract Research Association, United Kingdom
Relevant Sections: 3 and 4
National Health Research Ethics Council, National Department of Health
Requirements
(1) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
National Department of Health
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, National Department of Health
Relevant Sections: A (1)
Sponsorship > Compensation
Last content review/update: December 22, 2017
Summary

Overview

Additional Resource (A) states that the South African Health Products Regulatory Authority (SAHPRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting) Clinical Trial Committee recommends a minimum compensation of 150 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
Medicines Control Council, National Department of Health
Association of the British Pharmaceutical Industry, United Kingdom
Association of the British Pharmaceutical Industry, BioIndustry Association, and Clinical Contract Research Association, United Kingdom
Relevant Sections: 3
National Health Research Ethics Council, National Department of Health
Requirements
(1) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
National Department of Health
Relevant Sections: 3.1.7
(2) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
National Department of Health
Relevant Sections: 2.2 and 4.11
Sponsorship > Quality, Data & Records Management
Last content review/update: December 22, 2017
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. Per the G-Monitor, the responsibility for adequate oversight of the conduct of a clinical trial, including the justification for and selection of monitoring methods, remains that of the sponsor solely.

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. Per the G-Monitor, when developing a study’s monitoring plan, the sponsor should consider how it uses electronic data capture (EDC) systems. EDC systems that are capable of assessing quality metrics in real time will help identify high-risk sites that need more intensive monitoring.

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 South African Health Products Regulatory Authority (SAHPRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting) and ethics committee (EC) review. Because the MCC is performing the regulatory functions of the SAHPRA, this ClinRegs profile will at times still refer to the MCC where it is still applicable. The person responsible for auditing must submit a report to the MCC when evidence of Good Clinical Practice non-compliance exists.

In addition, per the G-Monitor, the sponsor’s monitoring plan should include planned audits to ensure that monitoring activities are in accordance with the monitoring plan, applicable regulations, guidance, and sponsor’s plans and policies.

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
  • 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)
National Department of Health
Relevant Sections: 4.4, 4.8, 5.2, 6.5, 6.7, and 7
(2) (Guidance) Oversight and Monitoring in Clinical Trials (Version 1) (G-Monitor) (November 2016)
Medicine Control Council, National Department of Health, Republic of South Africa
Relevant Sections: 1 and 4
Sponsorship > Site/Investigator Selection
Last content review/update: December 22, 2017
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. Further, per the G-Monitor, the sponsor should consider previous experience with the investigator or site, workload of the investigator, and resource availability at the study site during investigator and site selection. 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).

Per the G-CTInvestigators, the South African Health Products Regulatory Authority (SAHPRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting) will recognize and approve categories of investigators for trial leadership. The Principal Investigator (PI) must be a South Africa-based scientist, who has sole or joint responsibility for the design, conduct, delegation of trial responsibilities, analysis and reporting of the trial. The PI is accountable to the sponsor and regulatory authorities. The PI can designate and supervise Sub-Principal Investigator(s) (Sub-PI) of which at least one (1) must be a clinician and registered with the appropriate statutory entity to provide clinical oversight within his/her scope of practice. Further, the MCC recognizes a category of Co-Principal Investigator (Co-PI), which allows for a team consisting of two (2) Co-PIs to lead a study at a site. At least one (1) of the Co-PIs must be a clinician registered with the appropriate statutory body and qualified to provide clinical oversight within his/her scope of practice. For multi-center studies, there must be a National PI appointed, who may or may not be a site PI. The National PI must have appropriate experience and expertise in that field and must be responsible for the application to the MCC to conduct the study. The National PI must meet all other requirements to be a PI and sign a declaration accepting the responsibility as National and sign off on the clinical trial application. For more information on PI requirements, roles, and responsibilities, see the G-CTInvestigators.

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)
National Department of Health
Relevant Sections: 4.2, 4.6, 4.7, 4.9, and 4.10
(2) (Guidance) Oversight and Monitoring in Clinical Trials (Version 1) (G-Monitor) (November 2016)
Medicine Control Council, National Department of Health, Republic of South Africa
Relevant Sections: 5
(3) (Guidance) Clinical Trial Investigators (Version 2) (G-CTInvestigators) (May 2017)
Medicines Control Council, National Department of Health, Republic of South Africa
Relevant Sections: 1 and 2
Informed Consent > Documentation Requirements
Last content review/update: December 22, 2017
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 Council for Harmonisation's 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 South African Health Products Regulatory Authority (SAHPRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting) 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, the G-GPHlthCare, and the G-GPHlthCare-IC, in all cases, both written informed consent must be obtained. The SA-GCPs also states that verbal 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-IC 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.

The G-GPHlthCare states that the researchers should provide information to the participants in a language that the participant understands and in a manner that takes into account the participant’s level of literacy, understanding, values, and personal belief systems.

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 requires an additional copy of the signed informed consent form and a source document identifying the study and recording the participation dates should be placed in the participant’s medical records. The SA-GCPs also requires contact information for the EC and for the MCC be provided in the ICF.

Additional Resources
(A) (ICH Guidance) Guideline for Good Clinical Practice E6(R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Relevant Sections: 3 and 6
(B) (WMA Guidance) Declaration of Helsinki (October 19, 2013)
World Medical Association
Requirements
(1) (Legislation) National Health Act 61 of 2003 (NHA) (July 23, 2004)
Parliament, Republic of South Africa
Relevant Sections: 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)
National Department of Health
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)
National Department of Health
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 Health Researchers, Booklet 13 (G-GPHlthCare) (September 2016)
Health Professions Council of South Africa, National Department of Health
Relevant Sections: 3.4 and 6.3
(5) (Guidance) Guidelines for Good Practice in the Health Care Professions: Seeking Patients’ Informed Consent: The Ethical Considerations, Booklet 4 (G-GPHlthCare-IC) (September 2016)
Health Professions Council of South Africa, Republic of South Africa
Relevant Sections: 11, 12.3, and 15.1.3
(6) (Guidance) General Information (Version 8) (G-GenInfo) (August 2012)
Registrar of Medicines, Medicines Control Council, National Department of Health
Relevant Sections: 2.4 and 2.5
Informed Consent > Required Elements
Last content review/update: December 22, 2017
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 South African Health Products Regulatory Authority (SAHPRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting)
  • 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)
National Department of Health
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)
National Department of Health
Relevant Sections: 2.3.6 and 3.3.6
(3) (Guidance) Guidelines for Good Practice in the Health Care Professions; General Ethical Guidelines for Health Researchers, Booklet 13 (G-GPHlthCare) (September 2016)
Health Professions Council of South Africa, National Department of Health
Relevant Sections: 6.3
(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 Sections: 5
Informed Consent > Compensation Disclosure
Last content review/update: December 22, 2017
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 (B) and (C)).

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.

Per the SA-GCPs and the G-GPHlthCare and as described in Additional Resource (A), 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 South African Health Products Regulatory Authority (SAHPRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting) 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). 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 (B) 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
National Health Research Ethics Council, National Department of Health
Relevant Sections: 4
Association of the British Pharmaceutical Industry, United Kingdom
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)
National Department of Health
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)
National Department of Health
Relevant Sections: 3.1.7 and 3.5.3
(3) (Guidance) Guidelines for Good Practice in the Health Care Professions; General Ethical Guidelines for Health Researchers, Booklet 13 (G-GPHlthCare) (September 2016)
Health Professions Council of South Africa, National Department of Health
Relevant Sections: 6.1
Informed Consent > Participant Rights
Last content review/update: December 22, 2017
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 G-GPHlthCare-IC, the NHAParticipants, and the International Council for Harmonisation’s 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

According to the G-GPHlthCare-IC, 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 South African Health Products Regulatory Authority (SAHPRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting) 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) (ICH Guidance) Guideline for Good Clinical Practice E6(R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(B) (WMA Guidance) Declaration of Helsinki (October 19, 2013)
World Medical 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)
National Department of Health
Relevant Sections: 1.2.8, 2.3, 3.5, and Appendix A
(2) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
National Department of Health
Relevant Sections: 1.1, 2.3 and 3.1
(3) (Guidance) Guidelines for Good Practice in the Health Care Professions; General Ethical Guidelines for Health Researchers, Booklet 13 (G-GPHlthCare) (September 2016)
Health Professions Council of South Africa, National Department of Health
Relevant Sections: 2, 3, 4, and 6
(4) (Guidance) Guidelines for Good Practice in the Health Care Professions: Seeking Patients’ Informed Consent: The Ethical Considerations, Booklet 4 (G-GPHlthCare-IC) (September 2016)
Health Professions Council of South Africa, Republic of South Africa
Relevant Sections: 1,2, and 3
(5) (Legislation) National Health 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
(6) (Legislation) National Health Act 61 of 2003 (NHA) (July 23, 2004)
Parliament, Republic of South Africa
Relevant Sections: Chapter 1 (2), Chapter 2 (8 and 11), and Chapter 9 (71)
Informed Consent > Special Circumstances/Emergencies
Last content review/update: December 22, 2017
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, the G-EthicsHR , and the G-GPHlthCare 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) (July 23, 2004)
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)
National Department of Health
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)
National Department of Health
Relevant Sections: 3.1, 3.2, and 3.4
(4) (Guidance) Guidelines for Good Practice in the Health Care Professions; General Ethical Guidelines for Health Researchers, Booklet 13 (G-GPHlthCare) (September 2016)
Health Professions Council of South Africa, National Department of Health
Relevant Sections: 6.3.8
Informed Consent > Vulnerable Populations
Last content review/update: December 22, 2017
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, research involving elderly persons requires consent to be provided by the participant’s legal representative(s) or guardian(s) on that person's behalf. Because of their vulnerability, the elderly should not be included in research unless the research is necessary to promote the health of this population and unless this research cannot instead be performed on legally competent persons.

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
No additional resources
Requirements
(1) (Legislation) National Health Act 61 of 2003 (NHA) (July 23, 2004)
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)
National Department of Health
Relevant Sections: 1.2.8, 2.3, and 3.5
(3) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
National Department of Health
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 Health Researchers, Booklet 13 (G-GPHlthCare) (September 2016)
Health Professions Council of South Africa, National Department of Health
Relevant Sections: 1, 2.4.6, 3.1, 4.1.2, 4.1.3, and 6.3
(5) (Legislation) National Health 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
Last content review/update: December 22, 2017
Summary

Overview

The SA-GCPs state that a minor is a person under 21 years of age and that assent from the minor should be obtained where he/she is capable of understanding.

On the other hand, the G-GPHlthCare-IC, states that a person over the age of 18 years is an adult and is legally competent to decide on all forms of treatment and medical procedures. However, a child who is 12 years of age and older is legally competent to consent to a proposed investigation if the child is of sufficient maturity and is able to understand the benefits, risks, social, and other implications of the research.

According to the NHA, the G-EthicsHR, the SA-GCPs, the G-GPHlthCare, and the G-GPHlthCare-IC, 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, and the G-MinisterConsent 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

For more information on ministerial consent for non-therapeutic health research with minors, see the operational guidelines at the G-MinisterConsent.

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
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)
National Department of Health
Relevant Sections: 2.3, 2.3.1, 2.3.1.1, 2.3.1.2, and 2.3.1.3
(2) (Guidance) Guidelines for Good Practice in the Health Care Professions: Seeking Patients’ Informed Consent: The Ethical Considerations, Booklet 4 (G-GPHlthCare-IC) (September 2016)
Health Professions Council of South Africa, Republic of South Africa
Relevant Sections: 8.5
(3) (Legislation) National Health Act 61 of 2003 (NHA) (July 23, 2004)
Parliament, Republic of South Africa
Relevant Sections: Chapter 9 (71)
(4) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
National Department of Health
Relevant Sections: 3.2
(5) (Guidance) Guidelines for Good Practice in the Health Care Professions; General Ethical Guidelines for Health Researchers, Booklet 13 (G-GPHlthCare) (September 2016)
Health Professions Council of South Africa, National Department of Health
Relevant Sections: 5,6.3 and 8.5
(6) (Legislation) National Health 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
(7) (Guidance) Ministerial Consent for Non-therapeutic Health Research with Minors: Operational Guidelines (G-MinisterConsent) (2015)
National Health Research Ethics Council, National Department of Health, Republic of South Africa
Relevant Sections: 1-6 and Appendices 1-3
Informed Consent > Pregnant Women, Fetuses & Neonates
Last content review/update: December 22, 2017
Summary

Overview

As per the NHA, the SA-GCPs, and the G-EthicsHR, 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
No additional resources
Requirements
(1) (Legislation) National Health Act 61 of 2003 (NHA) (July 23, 2004)
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)
National Department of Health
Relevant Sections: 2.3.2.1 and 2.3.2.3
(3) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
National Department of Health
Relevant Sections: 3.2
Informed Consent > Prisoners
Last content review/update: December 22, 2017
Summary

Overview

According to the NHA, 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
No additional resources
Requirements
(1) (Legislation) National Health Act 61 of 2003 (NHA) (July 23, 2004)
Parliament, Republic of South Africa
Relevant Sections: Chapter 2 (7, 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)
National Department of Health
Relevant Sections: 2.3, 2.3.4, and 2.3.5
(3) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
National Department of Health
Relevant Sections: 3.2
(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 Sections: 4
Informed Consent > Mentally Impaired
Last content review/update: December 22, 2017
Summary

Overview

According to the NHA, the SA-GCPs, the G-EthicsHR, the G-GPHlthCare, and the NHAParticipants, sufficient justification must be provided for any research or treatment 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
No additional resources
Requirements
(1) (Legislation) National Health Act 61 of 2003 (NHA) (July 23, 2004)
Parliament, Republic of South Africa
Relevant Sections: Chapter 2 (7, 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)
National Department of Health
Relevant Sections: 2.3 and 2.3.3
(3) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
National Department of Health
Relevant Sections: 2.3 and 3.2
(4) (Guidance) Guidelines for Good Practice in the Health Care Professions; General Ethical Guidelines for Health Researchers, Booklet 13 (G-GPHlthCare) (September 2016)
Health Professions Council of South Africa, National Department of Health
Relevant Sections: 4 and 6.3
(5) (Legislation) National Health Act 61 of 2003: Regulations Relating to Research with Human Participants (NHAParticipants) (September 19, 2014)
Parliament, Republic of South Africa
Relevant Sections: 4
Investigational Products > Definition of Investigational Product
Last content review/update: December 22, 2017
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)
National Department of Health
Relevant Sections: Appendix F
(2) (Guidance) Guide to Good Manufacturing Practice for Medicines in South Africa (Version 5) (SA-GMPs) (November 2010)
Medicines Control Council, National Department of Health
Relevant Sections: Annex 13 – Glossary
Investigational Products > Manufacturing & Import
Last content review/update: December 22, 2017
Summary

Overview

According to the SA-GCPs and the GRMRSA, the South African Health Products Regulatory Authority (SAHPRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting) is responsible for authorizing the manufacture of investigational products (IPs) in South Africa. Because the MCC is performing the regulatory functions of the SAHPRA, this ClinRegs profile will at times still refer to the MCC where it is still applicable. 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
WHO Technical Report Series, World Health Organization
(B) (Document) 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)
National Department of Health
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) (September 15, 2014)
National Department of Health
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 Sections: 20
Investigational Products > IMP/IND Quality Requirements
Last content review/update: December 22, 2017
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 Council for Harmonisation's 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)
  • 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 South African Health Products Regulatory Authority (SAHPRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting) also requires the application to provide a detailed review of the IPs to be used in the study. Because the MCC is performing the regulatory functions of the SAHPRA, this ClinRegs profile will at times still refer to the MCC where it is still applicable. 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 the 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
Medicines Control Council, National Department of Health
WHO Technical Report Series, World Health Organization
(C) (Document) Regulatory Requirements for the ZA CTD (September 15, 2010)
Southern African Pharmaceutical Regulatory Affairs Association
(D) (ICH Guidance) Guideline for Good Clinical Practice E6(R1) (ICH-GCPs) (Step 4 Version) (June 10, 1996)
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
Requirements
(1) (Guidance) Guidelines for Good Practice in the Conduct of Clinical Trials With Human Participants in South Africa (2nd edition) (SA-GCPs) (2006)
National Department of Health
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)
Medicines Control Council, National Department of Health
Relevant Sections: Annex 13
Investigational Products > Labeling & Packaging
Last content review/update: December 22, 2017
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 organization (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
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)
National Department of Health
Relevant Sections: 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) (September 15, 2014)
National Department of Health
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)
Medicines Control Council, National Department of Health
Relevant Sections: 13.6.7
Investigational Products > Product Management
Last content review/update: December 22, 2017
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 approvals from the South African Health Products Regulatory Authority (SAHPRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting) and EC. 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)
National Department of Health
Relevant Sections: 3.6, 4.14, 4.15, 4.16, 4.9, Appendix C (3.1), and Appendix F
(2) (Legislation) No. 72 of 2008: Medicines and Related Substances Act, 2008 (MRSA, 2008) (April 21, 2009)
Parliament, Republic of South Africa
Relevant Sections: 20
(3) (Guidance) Guide to Good Manufacturing Practice for Medicines in South Africa (Version 5) (SA-GMPs) (November 2010)
Medicines Control Council, National Department of Health
Relevant Sections: Annex 13
(4) (Guidance) Good Pharmacy Practice in South Africa (4th Edition) (SA-GPPs) (2010)
South African Pharmacy Council
Specimens > Definition of Specimen
Last content review/update: December 22, 2017
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 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)
Parliament, Republic of South Africa
Relevant Sections: 1
(2) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
National Department of Health
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 Sections: 1
(4) (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)
National Department of Health
Relevant Sections: 1
(5) (Legislation) National Health Act 61 of 2003 (NHA) (July 23, 2004)
Parliament, Republic of South Africa
Relevant Sections: 1
(6) (Regulation) National Health Act 61 of 2003 – Regulations Relating to Tissue Banks (R.182) (NHATissue) (March 2, 2012)
National Department of Health
Relevant Sections: 1
(7) (Regulation) National Health Act 61 of 2003 – Regulations Relating to Stem Cell Banks (R.183) (NHAStemCell) (March 2, 2012)
National Department of Health
Relevant Sections: 1
Specimens > Import & Export
Last content review/update: December 22, 2017
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 South African Health Products Regulatory Authority (SAHPRA) (currently functioning under its predecessor entity Medicines Control Council (MCC) until SAHPRA’s first Board meeting) and the local accredited ethics committee(s) (ECs). In addition, per the NHA, the NHABlood&Cells, the NHARegMicroLabs, the NHATissue, and the NHAStemCell, a permit must also be obtained from the National Department of Health (NDOH) Director General to import or export biological substances. Both the MCC approval letter and the NDOH 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.

NDOH Application Requirements

As set forth in the NHA, the NHABlood&Cells, the NHARegMicroLabs, the NHATissue, and the NHAStemCell, the NDOH Director-General as delegated by the NDOH 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, and the NHAStemCell, the NDOH 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 NDOH 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, and the NHAStemCell 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
Medicines Control Council, National Department of Health
(B) (Booklet) Biological Substances Export/Import Permits (Date Unavailable)
TNT and South African Clinical Research Association (SACRA)
(D) NIAID Communication with the National Department of Health Permit Programme (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) (September 15, 2014)
National Department of Health
Relevant Sections: 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)
National Department of Health
Relevant Sections: 1.6 and 4.3
(3) (Legislation) National Health Act 61 of 2003: Regulations Relating to Research with Human Participants (NHAParticipants) (September 19, 2014)
Parliament, Republic of South Africa
Relevant Sections: 3
(4) (Legislation) National Health Act 61 of 2003 (NHA) (July 23, 2004)
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)
National Department of Health
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)
Parliament, Republic of South Africa
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)
National Department of Health
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)
National Department of Health
Relevant Sections: 1 and 2
Specimens > Consent for Specimens
Last content review/update: December 22, 2017
Summary

Overview

In accordance with the NHA, the NHASpecAmend, and the NHABiol, prior to removing or withdrawing any biological material from the body of a living person for research purposes, consent must be obtained from that person in writing, 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 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 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 National Department of Health (NDOH) 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
MS Pepper, South African Journal of Bioethics and Law
Requirements
(1) (Legislation) National Health Act 61 of 2003 (NHA) (July 23, 2004)
Parliament, Republic of South Africa
Relevant Sections: Chapter 8 (55, 56, 57, 62, 67, and 68)
(2) (Regulation) National Health Act 61 of 2003 – Regulations Regarding the General Control of Human Bodies, Tissue, Blood Products, and Gametes: Amendment (NHASpecAmend) (April 26, 2017)
National Department of Health, Republic of South Africa
Relevant Sections: 1 and 2
(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 Sections: 3, 4, and 7
(4) (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)
(5) (Guidance) Ethics in Health Research: Principles, Processes and Structures (2nd Edition) (G-EthicsHR) (2015)
National Department of Health
Relevant Sections: 3.3
(6) (Regulation) National Health Act 61 of 2003 – Regulations Relating to Tissue Banks (R.182) (NHATissue) (March 2, 2012)
National Department of Health
Relevant Sections: 6
(7) (Regulation) National Health Act 61 of 2003 – Regulations Relating to Stem Cell Banks (R.183) (NHAStemCell) (March 2, 2012)
National Department of Health
Relevant Sections: 2 and 5
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