In countries with limited regulatory resources, management of diseases of major public health relevance is frequently jeopardized because of delayed access to needed therapies. Although a finished pharmaceutical product (FPP) may have undergone review by a globally-recognized regulatory body (such as the European Medicines Agency, the US Food and Drug Administration or another stringent regulatory authority (SRA)), local regulatory processes, that consume additional time and resources, must be completed, before it is approved for use and can be made available to patients.
Sharing of outcomes of SRA assessments and inspections, and cooperation among medicines regulatory authorities, could improve this situation. Just such an approach — as defined under the Collaborative Procedure between the World Health Organization Prequalification of Medicines Programme and National Medicines Regulatory Authorities in the Assessment and Accelerated National Registration of WHO-prequalified Pharmaceutical Products — has already been developed for application to FPPs prequalified by WHO. A new and similar procedure for application to SRA-approved FPPs has now been developed by WHO, with input from national medicines regulatory authorities (NMRAs), the International Federation of Pharmaceutical Manufacturers & Associations, and the European Generic and Biosimilar Medicines Association.
This new procedure aims to facilitate and accelerate national regulatory approvals by providing access to data that documents the relevant SRA decisions, and evidence that either the same FPP, as approved by the SRA, or an FPP whose differences from the SRA-approved product are well-defined and understood, is the FPP that is now being submitted for registration. As with the earlier procedure for prequalified products, the new procedure incorporates a mechanism for confidential sharing of the relevant information.
How does it work?
Participation will be open to any interested NMRA or pharmaceutical company, and the procedure is designed to be applicable to any SRA-approved FPP (innovator or generic) that is relevant to public health needs.
The pharmaceutical company (applicant) will submit an FPP for registration that is the “same” (as defined by the procedure) as the SRA-approved product, to participating NMRAs. In the case of deviations from the SRA-approved product, these must be specified by the applicant. The product dossier will be organized in the common technical document format (CTD) that was approved by the SRA and adapted for the purpose of the procedure.
In the case of innovator medicines, applicants will be advised to also provide a “bridging report” that contains additional discussion of data relevant to the countries to which the application is being submitted, if the SRA assessment report does not cover these elements sufficiently.
The applicant ― with the agreement of the relevant SRA ― will share the full assessment and inspection reports for the FPP with the participating NMRAs, as well as additional data documenting potential deviations from the FPP approved by the SRA. In organizing the sharing of the reports, the applicant will help to minimize any administrative burden on participating SRAs. The role of the SRA will be limited to data authentication, and, when specifically agreed with individual SRAs, provision of additional explanation of their decisions, should either or both be requested by the NMRAs.
Participating NMRAs will use the data submitted to support their decision-making regarding registration. They will seek to issue an “accelerated” decision on registration within 90 days of their acceptance of the submission. The procedure will not interfere with their national, regulatory decision-making processes, or with national legislation, or with levying of regulatory fees. Similarly, it will be the NMRAs’ responsibility to reach agreement with applicants regarding specific risk-management plans and pharmacovigilance follow-up.
To ensure that the FPP remains the same as the SRA-approved FPP, or that any deviations from the SRA-approved product are clearly indicated to the NMRAs, management of SRA-approved post-registration variations will follow principles similar to those applied under registration.
WHO’s role will be to facilitate cooperation among applicants, participating NMRAs and SRAs. It will be involved with application of the procedure to a specific FPP only if WHO considers the FPP to be of public health relevance.
How can pharmaceutical companies, NMRAs in resource-limited countries and SRAs participate?
Pharmaceutical companies may participate if they:
- hold a marketing authorization issued by an SRA for the FPP intended for submission
- agree with WHO on:
- the selection of the FPP for which the procedure is to be organized, and on the SRA that will be invited to share its full assessment and inspection reports for the FPP
- participating NMRAs to which they intend to apply for registration and proposed date(s) of submission(s) in the relevant countries,
- agree with the relevant SRA that the full updated assessment report and inspection report may be shared with the NMRAs to which they intend to apply for registration,
- agree with the conditions of the procedure and to submit data to NMRAs as defined by the procedure.
NMRAs in resource-limited countries may participate by confirming their interest in participation and committing to the principles of the procedure by signing the agreement defined by the procedure (Appendix 1). The countries of NMRAs that are currently participating in the procedure are listed in the Participating Countries table in this section. Additional NMRAs may be invited to participate by WHO if applicants express interest in registering their FPPs in countries the NMRAs of which are not yet participating in the procedure.
Any SRA that wishes to participate must:
- agree that the holder of the SRA marketing authorization can share with the relevant NMRAs the assessment and inspection reports for the FPP that it intends to submit for accelerated registration
- be willing to share additional information with the relevant NMRAs, in line with the principles of the procedure, if requested to do so (for example, information to be included in the list of participating SRAs, see Appendix 2).
Steps for applicants, SRAs and NMRAs
The steps to be followed during the procedure are as follows for the different participants:
- The interested holder (applicant) of the SRA marketing authorization:
- agrees with WHO that the procedure will be applied to the specific FPP(s) and that WHO will have access to the data shared with NMRAs (Appendix 8)
- grants the SRA permission to share information concerning the FPP(s) with the relevant NMRAs and WHO (Appendix 3B) and requests SRA permission to share the SRA’s assessment and inspection reports with NMRAs and WHO (Appendix 3A),
- submits an application for registration of the FPP(s), with the same set of technical data, electronically and/or in hard copy, to participating NMRAs, in line with the procedure and respecting specific national requirements (Appendices 4, 5, 6 and 7).
How long does it take?
If the NMRA of the country in which the registration of the SRA-approved FPP is sought, agrees to apply the procedure to the product concerned, it commits to reaching its decision within 90 days of receiving access to the assessment and inspection information, as to wether it will register the FPP, and to communicate its decision to WHO (Appendix 9) and the applicant within a further 90 days.
Contact for further information: firstname.lastname@example.org
All the signed original documents should be posted or sent by courier to:
World Health Organization
Mrs Dilber Gunlu, Room L256
20 Avenue Appia
1211 Geneva 27
- Full text of the procedure (WHO TRS 1010, 2018 - Annex 11)
- Appendix 1: Agreement of the national regulatory authority to participate in the collaborative procedure in assessment and accelerated national registration of pharmaceutical products and vaccines by stringent regulatory authorities
- Appendix 2: Example of information included in the list of participating reference stringent regulatory authority(ies)
- Appendix 3A: Manufacturer's consent for information sharing with participating national regulatory authority(ies) and the World Health Organization
- Appendix 3B: Manufacturer's request for SRA permission for sharing SRA-owned non-public information with participating NRAs and the World Health Organization
- Appendix 4: Quality information summary of the FPP or vaccine approved by the reference SRA (QIS-SRA (crp))
- Appendix 5: Proposed documentation for collaborative procedure for reference SRA-approved FPPs and vaccines
- Appendix 6: Requirements for provision of a bridging report for reference SRA-approved pharmaceutical product and vaccines for consideration of registration in participating countries
- Appendix 7: Expression of interest to national regualtory authority
- Appendix 8: Confidential disclosure agreement
- Appendix 9: Notification of an outcome of the national registration provided by the participating manufacturer to the World Health Organization