Accelerated Registration of Prequalified FPPs
Finished pharmaceutical products (FPPs) that are WHO-prequalified have been evaluated and inspected according to international standards. But they must still be approved for use by the national medicines regulatory authorities (NMRAs) of the countries for which market entry is sought. Repeating assessment and inspection of those FPPs not only consumes scarce regulatory resources but also extends the time needed to make them available to patients. WHO has therefore designed a collaborative procedure that both enables NMRAs to make use of work already carried out by WHO and to strengthen their own regulatory oversight processes, in line with international best practices. Of greatest interest to manufacturers is that application of the procedure enables faster registration.
The procedure (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) is open to NMRAs in all WHO Member States and holders of prequalified FPPs, on a voluntary basis, and its principles are a model for other regulatory collaborative initiatives.
How does it work?
An FPP that in all essential features is the same as the prequalified FPP is submitted for national registration in a country, the NMRA of which, is participating in the collaborative procedure. The countries of NMRAs that are currently participating in the procedure are listed in the Participating Countries side box. 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.
Applicants (generally companies) voluntarily express interest in applying the procedure for accelerated registration to their prequalified products. Applicants authorize WHO to share its assesment and inspection outcomes for the specific product(s), with the NMRA(s), of the country in which accelerated registration is sought. An applicant must submit the same dossier as the one approved by WHO for prequalification, although individual NMRAs may agree to submission of simplified dossiers and minor administrative differences are permitted, to reflect local labelling and other regulatory requirements. The technical part of the dossier should be updated to reflect the data as approved by WHO during prequalification, any WHO-approved variations and requalification (where applicable). If, at the time of submission, any variations await WHO prequalification approval, the applicant should inform the NMRA accordingly. (National rules for submission of applications and regulatory fees will apply.)
WHO then shares information regarding its evaluation of the FPP for prequalification (i.e. assessment and inspection outcomes) with the NMRA. The information is shared via a secure internet-based platform, subject to confidentiality undertakings and agreed restrictions on use. Within the NMRA, only the designated focal person(s) can access the information.
The NMRA can, of course, decline to apply the collaborative procedure to the FPP. If so, it will be requested to indicate to WHO its reasons for not doing so. Similarly, if it declines to register the FPP on the basis of the information it received about the prequalified FPP, or if the terms of its decision deviate from those of prequalification, it will be requested to give its reasons for reaching a conclusion that differs from that of WHO.
How long does it take?
If the NMRA of the country in which registration of the prequalified 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 whether it will register the FPP, and to communicate its decision to WHO and the applicant within a further 30 days.
What happens following collaborative registration of a product?
After granting of national registration, WHO will add the relevant product to its list of prequalified products that have been registered under the collaborative procedure. This list is available on this website. Thereafter the NMRA must inform WHO of any post-approval changes (variations) made to the nationally-registered product. These changes must follow those approved by WHO to ensure that consistency between the prequalified product and the nationally-registered product is maintained. Some changes (deviations) are acceptable e.g. in labelling or product information. However, changes relating to quality aspects, and as defined in the guideline for sameness, will mean that the nationally-registered product is no longer considered to be the same as the prequalified product.
What are the benefits of the procedure?
- Shorter time to registration, thereby products can enter the market and and be made available to health care providers and patients more quickly.
- Less duplication of work for applicants in terms of preparation of dossiers: participating NMRAs largely accept submissions already approved by WHO, that is, in the same CTD format as requested by WHO.
- NMRAs save resources since they do not need to carry out a full assessment of the prequalified product or to inspect its manufacturing sites.
- Opportunities for work sharing between WHO and NMRAs when assessing variations, carrying out follow-up inspections, or organizing sample testing by prequalified quality control laboratories.
- Capacity building at the participating NMRAs: prequalification reports (dossier evaluation, inspection reports and test results) are available to staff, providing excellent examples of assessment and inspection carried out to international standards.
- Transparency for buyers: products registered through the collaborative procedure are in all essential features the same as the related WHO-prequalified products and are, in effect, regulated by both WHO and the relevant NMRA(s).
What happens if an NMRA deregisters a collaboratively-registered product?
The NMRA will inform WHO of the deregistration within 30 days, or as soon as possible in cases where patient safety may be affected. WHO encourages NMRAs to consult with prequalification experts before de-registering a prequalified product. If WHO remains assured about product quality, de-registration does not affect the product’s prequalification status.
What happens if WHO suspends or de-lists a prequalified product?
Suspension or de-listing of a prequalified product may occur:
- at the request of the applicant
- or due to concerns about quality, safety or efficacy.
In the latter case WHO will post information about the suspension or de-listings on its website, and related additional information such as the latest inspection report on the secure internet-based platform used for the collaborative procedure. Additionally, it will alert NMRAs that have registered the product under the collaborative procedure.
How can NMRAs apply to participate?
Any NMRA that would like to participate in the collaborative procedure for accelerated registration should email:
- a signed and scanned participation agreement (Appendix 1, Part A)
- a signed confidentiality undertaking (Appendix 1, Part B) for each designated focal point who is to be granted permission to the restricted-access website for the purpose of downloading and uploading information and reports about FPPs that have been submitted for consideration for collaborative registration
to email@example.com. The signed originals of the documents should be posted or sent by courier to:
World Health Organization
Facilitated Product Introduction Team, Room L264
20 Avenue Appia
1211 Geneva 27
What is the procedure for submitting prequalified FPPs for accelerated registration?
In order to submit a prequalified FPP for registration in any country, the NMRA of which is participating in the procedure, the applicant (usually the manufacturer) should sign and email a consent form (Appendix 2) (one form per country) to firstname.lastname@example.org. This will serve to grant WHO permission to share its evaluation information with the NMRA. The signed originals of the consent form should be posted or sent by courier to:
World Health Organization
Facilitated Product Introduction Team, Room L264
20 Avenue Appia
1211 Geneva 27
Additionally, the applicant should submit an expression of interest in having the procedure applied to the FPP by completing Appendix 3, Part A and submitting it to the relevant NMRA. It should also email a completed Appendix 3, Part A to email@example.com.
The expression of interest (Appendix 3, Part A) should be submitted to the NMRA in addition to the national registration documents it requires (and irrespective of whether the application is new or pending).
Any differences between the prequalified dossier/data and the national submission should be stated as requested by Appendix 3, Part A. When a request is made for application of the procedure to a pending registration submission, the advice of the NMRA should be sought before submission.
What happens following the request for application of the procedure?
Following a request for application of the procedure:
- The NMRA agrees (or refuses, and gives a justification for its refusal) to apply the procedure to the FPP. It completes Appendix 3, Part B, provides it to WHO via the confidential restricted-access MedNet website — Collaborative Registrations Community — and informs the applicant that it has done so. Alternatively, the NMRA can convey the information to WHO by e-mail (firstname.lastname@example.org).
- WHO shares with the NMRA information relating to its evaluation of the FPP for prequalification and any variations (if applicable) via MedNet.
- The NMRA evaluates the product using the information provided by WHO, at its discretion, and makes its registration decision within 90 days of regulatory time; regulatory time starts after a valid application for the registration according to the procedure has been received and access to the confidential information has been granted (whichever is the later) and continues until the date of decision on registration. The regulatory time does not include the time granted to the applicant to complete missing parts of documentation, provide additional data or respond on queries raised by NMRAs.
- The NMRA, within a further 30 days, informs the applicant of its regulatory decision, and completes Appendix 3, Part C and provides it to WHO via MedNet or by e-mail (email@example.com).
- WHO adds the newly registered FPP to the list of products registered via the collaborative procedure.
- The NMRA, WHO and the prequalification holder collaborate to minimize post-approval differences between the prequalified and nationally-approved FPP and keep themselves informed throughout the post-registration phase regarding relevant variations made to the product, withdrawal, suspension, delisting from the WHO List of Prequalified Medicinal Products or national deregistration.NMRAs keep WHO informed by using Appendix 4 and forwarding it to WHO via MedNet or by e-mail.