NEW MEDICINE REGISTRATION APPLICATION PROCESS
1.1. Creating a new medicine registration application
All new medicine applications need to be of a high standard in order to be evaluated by SAHPRA. New registration applications need to comply with current guidelines and submitted in eCTD or eSubmission format. Applicants are expected to ensure that all required documents are included in the relevant sections. Appendix A contains a list of all relevant guidelines that should be used during the compilation of the application for registration of a new medicine. The remainder of this section provides further detail for the creation of new registration applications.
1.1.2. Application number
A request for application number/s should be sent to email@example.com before an application is submitted to SAHPRA. If the application has multiple strengths, these should be combined into one dossier. Please consult the Multiple Submissions guideline [2.40] for further information regarding duplicates and clones.
1.1.3. Electronic submissions
All applications for medicine registration submitted to SAHPRA must be electronic (eCTD or eSubmission). Both submission types should be structured in accordance with CTD specifications, the ICH granularity document, and the ICH file naming conventions. This extends to the submission of all responses to screening and evaluation queries. Please refer to the eCTD [2.23] or eSubmission [2.58] guidelines for more information. New medicines registration applications submitted to SAHPRA should always start with sequence 0000.
1.1.4. Reliance models
SAHPRA will be implementing reliance models for qualifying applications. The General Information Guideline [2.01] contains the latest information regarding SAHPRA’s evaluation pathways as well as SAHPRA’s Recognised Regulatory Authorities (RRAs) and collaborative /
work sharing procedures. The General Information Guideline is the primary reference for information on reliance, with additional information contained in the Clinical Guideline [2.09] and Quality and Bioequivalence Guideline [2.02].
All manufacturing and quality control sites affecting applications are required to be GMP compliant prior to the submission of the relevant application. A GMP certificate or equivalent manufacturing licence is required as evidence of GMP compliance. Please refer to 3.2 of the SA Guide to GMP [4.01] for additional information.
1.1.6. SCoRE document
The Summary of Critical Regulatory Elements (SCoRE) document is designed to enable a top- down summary-driven approach to reviews, reducing evaluation time of all applications. All new registration applications will require a completed SCoRE document [6.31] in 3.2.R.8.
1.1.7. Biostudy and biowaiver review forms
If a biostudy has been included in the application, please review and complete the Bioequivalence Trial Information Form (BTIF) template [6.32]. For circumstances where a biowaiver is submitted (no biostudy or biostudy done on a different product strength), please review and complete the following:
For the biowaiver templates, as well as additional information, please refer to the Quality and Bioequivalence Guideline [2.02]. The location of where these documents should be placed in the dossier is indicated in the validation templates [6.16] and [6.30].
1.1.8. Format change to PI and PIL
SAHPRA has adopted the EMA format for Professional Information and Patient Information Leaflets. This format is reflected in the updated SAHPRA guidelines [2.14] and [2.16].
1.1.9. Repository of PIs and PILs
SAHPRA has published a repository of PIs and PILs on its website for the benefit of health care providers and patients, as well as to enable streamlined Clinical evaluations of applications for generic medicines. Where available for a given molecule, applications for generic medicines are required to reference the latest published SAHPRA-approved innovator PI in the application. Clinical screening queries will be immediately flagged for applications referencing an outdated / illegible PI where the latest version has been published on SAHPRA’s website. Note that the published PIs on SAHPRA’s website may also be applicable to selected variation applications (e.g., safety update of a generic medicine where the same change has already been approved for the reference local innovator medicine).
SUBMITTING AN APPLICATION
Applications should be delivered on a CD, DVD or USB with the supporting paper documents to the following address:
The Chief Executive Officer
South African Health Products Regulatory Authority
Meiring Naude Road
Upon submission, the receipt of the application will be logged in Reception and physical proof of receipt will be provided. Applications should be clearly labelled with the code ANA-eCTD or ANA-eSub on the front page of the letter of application. For further information on submission, applicants should refer to the General Information Guideline [2.01] as well as the eCTD [2.23] and eSubmission [2.58] guidelines.
Before an application is evaluated, it will go through a screening process. The screening process will confirm that all SAHPRA’s requirements have been met, ensuring that only high-quality dossiers are allocated for evaluation. Applicants are required to complete and submit a validation template ([6.16] or [6.30]) with all new registration applications. Any omitted data or deviations from the validation template must be accompanied by a motivation for the application to be accepted. During screening, the following steps will be conducted (as detailed in the validation templates):
If an application fails a screening step, two outcomes are possible:
1. If the failure does not affect the next validation step, the application can proceed to the next
screening step. When the next updated sequence is submitted, all previous queries will be consolidated and will need to be updated in a single sequence.
2. If the failure prevents the application from proceeding to the next validation step, a query
round will be started and the applicant will need to submit an updated sequence.
In order to reduce the volume of query communications facilitated by the PC, the following screening queries will be consolidated and shared with the applicant together (where applicable):
1. A.3 and B
2. C, D and E
Applicants will be kept informed of their application’s status via an online tracker, which will be updated when an application passes screening.
After passing screening, the application will be allocated to an evaluator from each relevant SAHPRA unit (e.g., Clinical, ME&R (P&A), Inspectorate and N&S for a new registration application). The primary evaluation from each unit will then be peer reviewed by a senior evaluator. Should there not be consensus on the final outcome or outstanding queries, then the application will be allocated to an Advisory Committee for input. This re-engineered process is intended to streamline evaluations, reserving the Advisory Committee for the evaluation of relatively complex evaluations and responses. If an application passes evaluation, recommendations will be consolidated for final review and registration or rejection by SAHPRA.
If either the number of query rounds or the time to respond to queries is exceeded, the application will be at risk of rejection. Should a longer query response time be needed by an applicant, motivation should be provided. Extensions can be requested and they will be reviewed on a case by case basis.
It is recommended that applicants use the status updates on the online tracker to plan to have resources available to answer queries within the timelines (e.g. when an application enters the evaluation phase, a resource should be on standby to answer queries) All responses to evaluation queries / recommendations should be submitted to the SAHPRA reception via CD/DVD/USB with an incremental sequence number.
Once a new medicine application is recommended for registration, the Applicant will be contacted to pre- fill the new registration certificate template. Applicants will be contacted to collect new registration certificates.
APPENDIX A: RELEVANT DOCUMENTS
New / revised guidelines
[2.23] Jul 2019 Submission in eCTD format
[6.16] Jul 2019 New registration validation template for eCTD
[6.30] Jul 2019 New registration validation template for eSubmission
[6.31] Jul 2019 Summary of Critical Regulatory Elements
[6.32] Jul 2019 Bioequivalence Trial Information Form (BTIF) template
[6.33] Jul 2019 Abridged review template
[6.34] Jul 2019 Verified review template