Prequalification Procedures and Fees: FPPs, APIs & QCLs
The Prequalification Procedures and Fees section of this website is dedicated to enabling potential applicants to determine how, whether and what information they must compile in order to submit an application for WHO prequalification.
Who can participate in WHO prequalification of medicines?
Any manufacturer of active pharmaceutical ingredients (APIs) and/or finished pharmaceutical products (FPPs) can express an interest in having its API or FPP products evaluated by WHO, provided those products are eligible for assessment. FPPs eligible for evaluation include both generic and innovator FPPs, and FPPs that contain just one active ingredient or that combine several.
Medicines quality control laboratories (QCLs) that undertake chemical and microbiological (including bacterial endotoxins) testing of medicines are also eligible to apply for prequalification.
What are the steps of the prequalification process?
The following is a simplified overview of the prequalification process for APIs and FPPs.
- The manufacturer verifies that the API or FPP that it wants to submit for evaluation for prequalification is included in the relevant Invitation to Manufacturers to Submit an Expression of Interest for Evaluation.
- The manufacturer submits an application to WHO in accordance with the prequalification procedure for the product (either API or FPP).
- WHO screens the information submitted for evaluation for prequalification, using a screening checklist. This is an in-house list of dossier characteristics that need to be confirmed to be acceptable before a dossier is assigned a WHO reference number and accepted for full assessment. The checklist provides insight into what aspects are considered to be the key elements of an assessment of a generic FPP. The screening may lead to a request or requests for additional information.
- If the API or FPP has already been approved by a stringent regulatory authority, the applicant may choose to make a submission for abbreviated assessment.
- Assessment of dossier and verification of compliance of the manufacturing (API and FPP) and clinical testing sites (i.e. contract research organizations) with relevant WHO good practices.
The process for prequalification of QCLs is similar to that for APIs and FPPs, consisting of the following steps:
- The QCL consults the Invitation to Quality Control Laboratories to Submit an Expression of Interest for Prequalification, to verify that it is eligible for prequalification.
- The QCL submits an application — which will include a laboratory information file — to WHO, in accordance with the prequalification procedure for QCLs.
- WHO reviews the laboratory information file (or quality manual). It may request submission of additional information and it may also stipulate inspection of the QCL.
- If the QCL meets prequalification requirements it is added to the WHO List of Prequalified Quality Control Laboratories.
What happens when an API, FPP or QCL is prequalified?
APIs for which the API master file and manufacturing site(s) meet prequalification requirements, are included on the WHO List of Prequalified Active Pharmaceutical Ingredients, together with the applicant’s name, and corresponding product and manufacturing site details. Also, the manufacturer of each prequalified API is issued with a document known as a WHO Confirmation of Active Pharmaceutical Ingredient Prequalification. This document contains the accepted active ingredient specifications, and copies of the assay and related substances test methodology. It can be provided to interested parties, at the manufacturer’s discretion.
FPPs that are considered to have met prequalification requirements are included on the WHO List of Prequalified Medicinal Products, together with the applicant’s name, and corresponding product and manufacturing site details. In addition, for any FPP that underwent full (as opposed to abbreviated) assessment, a WHO Public Assessment Report (WHOPAR) and a WHO Public Inspection Report (WHOPAR), for any inspection that was conducted and concluded successfully, are posted on this website. The WHOPAR will summarize the assessment of the product information that was submitted in the product dossier. The WHOPIR(s) will provide the date, duration and scope of the inspection, and a summary of the observations and findings of the inspection(s).
Posting of the WHOPAR and WHOPIR(s) generally occurs some time after inclusion of the relevant product in the WHO List of Prequalified Medicinal Products. This is because their contents must be agreed with the manufacturer. This includes ensuring that proprietary information regarding the product, and any individual observations that were communicated in the full inspection report(s), have been excluded.
Prequalified QCLs are included in the WHO List of Prequalified Quality Control Laboratories, together with details of the type of analysis each carries out with respect to FPPs and/or APIs.
Applicable fees for medicines prequalification depend on:
- whether the product is an API or FPP
- the type of assessment to be undertaken: full or abridged assessment of a new application, or assessment of a major variation.
The annual fee is determined by the type of initial assessment carried out, i.e. full or abridged.
For an FPP a single product is defined as:
- a medicine of a unique strength and single dose form, but that may include multiple presentations, or
- a combination of medicines co-packed together.
For an API, a single product is defined as an API that is supported by a single active pharmaceutical ingredient master file (APIMF).
An invoice for the application fee will be issued after the application has been screened and accepted for assessment. Similarly, an invoice for the fee associated with a major variation will be issued following screening and acceptance of the variation application. Payment should be made within 15 days of receipt of the invoice from WHO. An invoice for the annual fee will be issued on or before 1 October each year. The annual fee will be applied to all FPPs or APIs that, by 1 September of that year, have been prequalified for 12 months or more. Payment of the annual fee should be made before 30 November of the calendar year in which the invoice was issued.
Applicants whose product(s) generate only a low level of profit may apply for a waiver of the annual fee, with a justification indicating, for each product, the sales and net profit in the last year. In order to apply for such a waiver the manufacturer must provide sufficient justification, including information about the sales and net profit for the preceding year for the product(s) concerned. Products listed in the box below are among those for which a waiver can be considered.
Verifying that the quality of prequalified APIs, FPPs, or of testing services provided by prequalified QCLs are being maintained, is essential to the continuing value and relevance of WHO prequalification. WHO ensures ongoing quality of prequalified APIs, FPPs and QCLs through:
- monitoring and/or review of amendments to API master files and variations to FPPs
- FPP requalification
- reinspection of API and FPP manufacturing sites, and of QCLs
- quality monitoring surveys, field sampling and testing projects
- monitoring of the quality of services provided by prequalified QCLs.