The SAHPRA, like many other developing country regulatory authorities with capacity constraints, has implemented in 2019, a reliance approach for the registration of medicines, to reduce registration timelines and speed up access to new medicines, including biologicals such as biosimilars. This pathway depends on prior registration of medicines by recognised regulatory authorities (RRA), which have stringent regulatory systems in place and with which the SAHPRA is aligned. The reliance mechanism also extends to products that have been prequalified by the WHO Prequalification Programme. A special guideline1, which has recently been updated (March 2022), has been published by the SAHPRA and lists the documentation requirements as well as the general principles that are applied when companies submit dossiers for registration via this pathway.
The reliance mechanism has, unfortunately, not been very successful in expediting registration. The regulator ascribes this failure primarily to two factors:
- the difficulty in obtaining unredacted reports from recognised regulatory agencies, which had registered the product, and
- a lack of understanding on the part of applicants about the difference between redacted and unredacted reports.
The SAHPRA is aware that local applicants may not have access to the unredacted or complete evaluation reports and consequently has developed a Letter of Access (LOA) that must be co-signed by the marketing authorisation holder (MAH) in the country or jurisdiction in which the RRA that issued the MA certificate is located. Unfortunately, the SAHPRA has experienced great difficulty in obtaining the unredacted reports as the RRA often claims that there are legal issues involved, such as that the local applicant is not listed as the MAH for the application and, hence, that they cannot release the full report to SAHPRA on the authorisation of an applicant not registered with them. In addition, the MAH for the product in the jurisdiction of the RRA often does not want to collaborate with the local applicant. When an unredacted report is eventually released by the RRA, more than 6 months may have passed, and in this time the submission dossier could have gone through the SAHPRA’s full evaluation process. As a consequence, the SAHPRA may amend the guideline by requiring applicants to submit the unredacted reports themselves. Another factor that may contribute to the reluctance of the RRA to release unredacted reports is the administrative burden of providing such reports to the many regulatory agencies that have implemented reliance.
The other issue that complicates the reliance pathway is the confusion among applicants about the difference between unredacted and redacted reports. This may be because they do not understand the purpose for which the SAHPRA requires the assessment reports. Contrary to what many applicants may think, the reports are not used to determine whether the evaluation by the RRA has been performed to a required standard that is acceptable to the SAHPRA. They are instead used to verify that the information in the submitted dossier corresponds to that in the application that was received and assessed by the RRA. Examples of such information include the names and addresses of suppliers of raw materials and providers of services such quality control testing, labelling information, limits of specifications, the specific manufacturing process for commercial manufacture, the product control strategy, reference standards, and so forth. This information is often removed from assessment reports of the FDA, which only makes available redacted reports. The complete or unredacted report is, therefore, required by the SAHPRA to carry out the verification exercise.
I hope that this short post will help to remove some of the confusion that currently exists around the reliance mechanism for registration. What would be ideal is if the SAHPRA could organise a workshop to further clarify misunderstandings about the reliance approach. Such a workshop with industry could also serve as a brainstorming session where an alternative to the unredacted report could be developed that will serve the same purpose.
- South African Health Products Regulatory Authority. Reliance Guideline version 3 (5.08). March 2022. https://www.sahpra.org.za/document/reliance-guideline/