WHO assesses information submitted in support of finished pharmaceutical products (FPPs) or active pharmaceutical ingredients (APIs) to determine whether they meet the requirements and standards for WHO prequalification. The master file (MF) of an API may be assessed either because it is linked to an FPP, or because the API itself has been submitted for prequalification.

Full FPP assessment ensures that a product is:

• supported with information that demonstrates that it meets international standards of quality, safety and efficacy
• manufactured and controlled to consistently meet acceptable standards
• of an acceptable quality, safety and efficacy when stored and used in accordance with appropriate instructions for use.

Full API assessment ensures that the API is:

• supported with information that demonstrates that it meets international standards of quality
• manufactured and controlled to consistently meet acceptable standards.

How assessment is organized

Assessment of an FPP dossier or an APIMF is conducted at WHO headquarters in Geneva, Switzerland and during assessment sessions held every two months at UN City in Copenhagen, Denmark. The initial step includes screening to verify that the FPP or API is invited for prequalification, and that the FPP dossier or APIMF contains the required information. Applications for FPPs or APIs that are not eligible for evaluation for prequalification (i.e. not included in an Invitation to Manufacturers to Submit an Expression of Interest for Product Evaluation), that lack the required information, or that have other critical deficiencies that cannot be addressed by the applicant within a reasonable time frame, are rejected at initial screening.

Once an FPP dossier or APIMF has been accepted for assessment, a full assessment based on the relevant WHO guidelines is undertaken.  This is also the signal for Inspection Services to plan for an on-site inspection, as necessary.

The details of the assessment are described in written assessment reports. For any given FPP dossier of a generic product for which assessment is performed, at least two assessment reports — on safety/efficacy (S/E), and on quality — are prepared. Usually, questions and/or comments are generated during an assessment, which must be sent to the applicant. In turn the applicant will respond to these comments with additional information, which is included in the next step of the assessment process. Therefore, as an assessment report is generated for each step of this back-and-forth communication, more than one S/E report and one quality report are typically written before the dossier is finally accepted. S/E reports generally incorporate bioequivalence or biowaiver assessments, but may also include clinical assessment.

Two assessors are assigned to assess the quality part of each FPP dossier or APIMF: the role of the first assessor is that of the primary assessor. The role of the second assessor is that of a peer reviewer, who reviews the first assessor's report. In addition, two efficacy assessors are assigned to each FPP dossier, who carry out functions similar to those of the aforementioned quality assessors. Each FPP dossier is assessed independently, but an assessor is expected to seek advice or consult with other assessors on cross-cutting issues. Such consultation is summarized in the assessment report.

The assessment of an APIMF in support of API prequalification consists of an independent review of the API information, whereas, the APIMF assessment conclusions for an APIMF submitted in support of an FPP seeking prequalification contribute to the overall FPP quality assessment.

When each assessment stream (quality, and, in the case of an FPP dossier, safety/efficacy) has completed its assessment and concluded that the data and information provided is sufficient and acceptable, the FPP dossier or APIMF enters the final quality assurance stage of the assessment process. This final assessment stage is undertaken to confirm that the required data is available and ensure that consistency between assessments is maintained. During this stage further questions may or may not be forwarded to the applicant. Once any issues arising from this process have been addressed, the assessment of the FPP dossier or APIMF is considered to be complete. During assessment, issues or areas of concern may be identified that should be investigated specifically during a future inspection. These are indicated to Inspection Services.

Once the dossier or APIMF assessment is considered to be acceptable, and Inspection Services has verified compliance with WHO Good Manufacturing Practices, and, in the case of an FPP, also WHO Good Clinical Practice and Good Laboratory Practice, as appropriate, the FPP or API can be prequalified.

Ensuring that the quality of prequalified FPPs or APIs is maintained

The value and relevance of WHO prequalification is highly dependent on the ongoing quality, safety and efficacy of prequalified FPPs and APIs. This necessitates:

• monitoring and/or review of variations to FPPs, and amendments to APIMFs submitted to WHO for notification or approval
• requalifying FPPs: every five years from the date of prequalification, or when requested to do so by WHO, the holder of a prequalified FPP is requested to submit data and information about that FPP, to WHO for assessment.

FPPs that have already undergone stringent assessment

FPPs and APIs that have already undergone assessment by and received approval from a stringent regulatory authority (SRA) do not undergo full assessment by WHO. Rather, assessment is carried out mainly to ensure that the product submitted for prequalification is identical to the product that was approved by the SRA. Time to prequalification is correspondingly shorter.

WHO Public Assessment Reports

The key publicly available outputs of WHO medicines assessment include the WHO Public Assessment Reports (WHOPARs). A WHOPAR is posted on this website following prequalification of an FPP.

The WHOPAR of an FPP for which full assessment was carried out summarizes the assessment of the product data and information that was submitted in the product dossier and provides relevant information on the product's quality, safety and efficacy. Similarly, WHOPAR for an SRA-approved product provides the relevant product information as approved by the reference SRA and as applicable, discusses supplemental data and information reviewed by WHO.  WHOPARs are therefore useful documents for both regulators and procurers.