Preclinical & Clinical Trial Requirements
All about preclinical & clinical trial requirements in South Africa. Prepared in association with Fasken, a leading global law firm, this is an extract from The Pharma Legal Handbook: South Africa, available to purchase here for USD 99.
1. Are clinical trials required to be conducted locally as a condition (stated or implicit) for marketing approval?
No. Clinical Trials do not have to be conducted locally in order for the Regulator to register the product and market approval to be provided.
As long as all the relevant required information (as set out in the Medicines Act, its regulations and the Guidelines and Rules of SAHPRA) is contained in the application for registration of the product – which information would include where the clinical trial was conducted and the authorisation by the relevant international Regulatory Authority for the country in which the clinical trial was approved.
There are separate processes available to applications for clinical trials which will be conducted within South Africa and for applications of registration of products where the clinical trials were conducted on other countries. Some requirements applicable to the standards of how the clinical trial was conducted will be reviewed by SAHPRA, as it will be documentation required in order for a full review to be completed prior to the application for registration of the product to be considered.
2. How are clinical trials funded?
Clinical Trials are funded by a Sponsor. In terms of the Guidelines for Good Practice in the Conduct of Clinical Trials with Human Participants in South Africa which is published by the Department of Health, a Sponsor is “the person or organisation responsible for the initiation, management or financing of a clinical trial.”
In the above context a Sponsor can be a Principle Investigator (PI) of the trial, a pharmaceutical company, a funding body or an individual or organisation designated by the funding body or principal investigator.
3. What are the requirements for preclinical and clinical trial protocols? Who must approve the protocols?
Clinical Trial protocols should include information on the following:
- General Information
- Background information
- Trial Objectives and Purposes
- Trial Design
- Selection and withdrawal of subjects
- Treatment of subjects Assessment of Efficacy
- Assessment of safety
- Direct Access to Source Data/Documents
- Quality control and Quality Assurance
- Data Handling and Record keeping
- Financing and Insurance
- Publication Policy
Protocols are reviewed and approved by Research Ethics Committees with the relevant authority as provided to them by the Regulator after a formal process. After the Research Ethics Committee has approved a Protocol, an application to conduct a clinical trial must be made to SAHPRA in terms of the Medicines Act.
4. What are the requirements for consent by participants in clinical trials?
In order for consent to be obtained in accordance with the legislative and regulatory compliance requirements, it must adhere to the following:
The Primary Investigator in a Clinical trial is responsible to ensure that adequate information is compiled in an information package, which must be in an acceptable format.
The importance within the South African context lies in the fact that the potential trial participant must provide informed consent. The onus is much higher to ensure the potential trial participant provides not only consent, but consent with all the information at their disposal and with an understanding of what they are actually consenting to.
This requires that the potential trial participant provides both verbally and in writing, consent to be a participant in the clinical trial, which include informed consent indicating their understanding of the following:
- That the trial involves research;
- The purpose of the trial;
- The trial treatment(s) and the probability for random assignment to each treatment (where appropriate);
- The trial procedures to be followed, including all invasive procedures;
- The participant’s responsibilities;
- The fact that participation in the trial is voluntary and refusal to participate or withdrawal from the trial will not prejudice the ongoing care of the person in any way;
- Those aspects of the trial that are experimental;
- The foreseeable risks of harm or inconveniences to the participant and, when applicable, to an embryo, foetus or nursing infant;
- The expected benefits. When there is no intended clinical benefit to the participant, the participant should be made aware of this (e.g. phase I Clinical Trial);
- The alternative procedure(s) or course(s) of treatment that may be available to the participant, and their important potential benefits and risks;
- The compensation and/or treatment available to the participant in the event of trial-related injury;
- The anticipated prorated payment, if any, to the participant for participating in the trial;
- The anticipated expenses, if any, to the participant for taking part in the trial;
- Allow access of sponsor, MCC National Health Research Ethics Council, relevant research ethics committee and/or other regulatory authority(ies) (pending that they have received permission to do so from the National Health Research Ethics Council) to participant records;
- Provide a contact name and number of the Primary Investigator and directly responsible investigator;
- The identity of a sponsor and any potential conflict of interests; and
- The requirement to preserve the confidentiality of the
- The expected duration of the subject’s participation;
- The Foreseeable circumstances and/or reasons under which the subject’s participation in the trial may be terminated;
- The approximate number of subjects involved in the trial.
Once the consent to participate in a clinical trial has been obtained, a copy of the signed informed consent forms and a source document identifying the study and recording the dates of participation should be placed in the participant’s medical record. The original signed informed consent form should be kept with the trial records and a copy of signed informed consent form should be offered to the participant.
5. May participants in clinical trials be compensated?
This is an aspect within the South African Clinical Research context which requires and receives careful consideration. The general rule is that an incentive should not be so excessive so as to unfairly influence a participant’s inclusion in a trial – basically they should not feel, with what they are being offered to take part in the study, that it is “an offer they cannot refuse”.
The sponsor of the trial must further ensure that information on incentives offered to participants involved in a specific trial, is included in the protocol. Where a trial is multi-centered (where a clinical trial is conducted according to a single protocol but at more than one site, and therefore, carried out by more than one investigator) information on the incentives given to participants at all the different trial sites, irrespective if these are multinational, must also be provided. If there is a difference in the type of incentive offered across the different sites, this discrepancy must be explained.
6. How are participants in clinical trials protected and indemnified against any harm that arises as a result of participation in the trial?
They are allowed to be checked and treated by the physician who is in charge of the trial, namely the Principal Investigator. The Trial participant remains the responsibility of the qualified physician (or dentist, when appropriate), who may be the Principal Investigator or a sub-investigator for the trial – this person should be responsible for all trial-related medical (or dental) decisions. There is a responsibility placed on the Principal Investigator which include that he should ensure that adequate medical care is provided to a participant for any adverse events, including clinically significant laboratory values, related to the trial. There is an additional onus on the Principal Investigator to inform a participant in the event that they do require medical care for intercurrent illness(es) of which the Principal Investigator/Investigator becomes aware.