In order to be prequalified, a multisource (generic) finished pharmaceutical product (FPP) must meet the requirements relating to the active pharmaceutical ingredient(s) (APIs) it contains, the finished pharmaceutical product (FPP), and the site(s) at which the FPP is manufactured. This will include:
- demonstrating the bioequivalence of the FPP
- demonstrating the quality of the API(s)
- demonstrating the quality of the FPP
- demonstrating adherence to WHO Good Manufacturing Practices.
Additionally, if a contract research organization (CRO) performed a related study, inspection of that CRO with respect to the particular study, may also be necessary.
The product dossier
The product dossier must contain information attesting to the quality, safety and efficacy of the product. The prequalification guidance documents and templates follow the modular format of the Common technical document (CTD) M4, as developed by the International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.
The product information must be presented following the guidance in the principle guidance documents listed below.
The dossier must also include summarized information using the templates below for the:
- quality information summary (QIS)
- quality overall summary – product dossier (QOS-PD)
- bioequivalence trial information form (BTIF).
The guidance documents that follow are the primary references for requirements on quality information to be included in the product dossier for both the API(s) and FPP.
Application form & templates
- Presentation of bioequivalence trial information - BTIF Appendix 1 - Template for Study AUC and Cmax Data (20 September 2018)
Demonstrating the quality of the API(s)
Data may be supported by any of the following options:
- a WHO-prequalified API
- a Certificate of Suitability to the monographs of the European Pharmacopoeia (CEP) issued by the European Directorate for the Quality of Medicines and HealthCare;
- an API master file (APIMF)
- a complete module 3.2.S for the API as part of the FPP dossier submitted for evaluation.
Complete details on the data required in the product dossier to support each of the above options are detailed in the main quality guidelines (2012).
Active Pharmaceutical Ingredient Master File (APIMF) procedure
Additional guidance is available when using the APIMF option, including requirements for amendments (changes).
Stability of the FPP
The FPP manufacturer must be able to demonstrate that the FPP is stable under climatic conditions prevailing in the country or countries in which the FPP is intended to be used. This means that the manufacturer must establish ― by using an appropriate stability-testing programme ― the shelf-life of the product in relation to recommended storage conditions. The stability testing programme and conditions must themselves have followed the recommendations included in the main WHO quality guideline (2012).
Reduced requirements apply (at the time of dossier submission only) to second-line anti-tuberculosis products and to products for reproductive health.
The manufacturer must also demonstrate that the FPP submitted is bioequivalent to the PQTm comparator product upon which it is based. This means being able to demonstrate that it satisfies the same standards as those applicable to the innovator product, and providing assurance that it is clinically interchangeable with, i.e. therapeutically equivalent to, the PQTm comparator product. This may necessitate that the manufacturer carries out a bioequivalence study and presents the bioequivalence study (trial) information: the data generated should provide a bridge between the comparator product for which safety and efficacy data are available and the generic products for which such data are not available. If a CRO carried out this study, the manufacturer must be able to demonstrate that the CRO adhered to WHO Good Clinical Practices and WHO Good Laboratory Practices when it carried out the study.
See also Bioequivalence section.
Magnesium sulfate injection
Reproductive health medicines
Medroxyprogesterone acetate depot (DMPA) injection products
Application forms & template
Criteria used to screen product dossiers
A screening checklist is an in-house list of dossier characteristics that need to be confirmed as being acceptable before a dossier is assigned a WHO reference number and accepted for full assessment. The screening requirements provide insight into what aspects are considered the key elements of assessment. To help applicants better understand the assessment process and to enhance their ability to meet screening requirements, the screening checklist is now published.
The manufacturing site(s)
Additionally, the manufacturing site of any FPP submitted for prequalification must comply with WHO Good Manufacturing Practices. An inspection or inspections may be necessary to verify compliance.
If a CRO carried out a study, on behalf of the manufacturer, to generate data that demonstrates the product's bioequivalence with the originator or innovator product, an inspection of the CRO may be required to verify adherence to WHO Good Clinical Practice and WHO Guidance for Organizations Performing In Vivo Bioequivalence Studies, as well as the date generated.