Frequently Asked Questions (FAQ)

Answers to common questions can be found here. If you still have questions please submit them using the link in the right sidebar.

For active pharmaceutical ingredients (APIs) and finished pharmaceutical products (FPPs): 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.

The following is a simplified overview of the prequalification process for APIs and FPPs.

  1. 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.
  2. The manufacturer submits an application to WHO in accordance with the prequalification procedure for the product (either API or FPP).
  3. WHO reviews the information submitted for evaluation for prequalification. This review may include a request or requests for additional information. Inspection of the manufacturing site(s), and, if relevant, of the contract research organization that performed a related study, may also be necessary.
  4. 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.

(See detailed information)


For medicines quality control laboratories (QCL): Medicines quality control laboratories (QCLs) that undertake chemical and microbiological (including bacterial endotoxins) testing of medicines are also eligible to apply for prequalification.

The process for prequalification of QCLs is similar to that for APIs and FPPs, consisting of the following steps:

  1. The QCL consults the Invitation to Manufacturers to Quality Control Laboratories to Submit an Expression of Interest for Prequalification, to verify that it is eligible for prequalification.
  2. The QCL submits an application — which will include a laboratory information file — to WHO, in accordance with the prequalification procedure for QCLs.
  3. 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.

(See detailed information)

Once an API, FPP or QCL has met prequalification requirements it is added to the relevant WHO list.

The total time to prequalification of a finished pharmaceutical product (FPP) (if full assessment is carried out) depends on the quality of the submitted dossier, and the quality and promptness of the applicant’s subsequent replies to PQTm’s questions during the assessment process, and the results of any inspection carried out. The median WHO time to prequalification has consistently been around 200 days during the past few years. Prequalification of a stringently-approved FPP (i.e. a product already approved by a stringent regulatory authority) does not involve reassessment of the SRA-approved dossier. Instead, PQTm verifies that the product submitted is the same as the one that received SRA approval. The total WHO time to prequalification of an SRA-approved FPP is generally one to two months (median).

The total time to prequalification of an active pharmaceutical ingredient (API) will be reviewed later in 2016 when the benefit of additional resources is expected to become evident.

The total time to prequalification of a medicines quality control laboratory (QCL) is strongly dependent on the outcome of the inspection and, if needed, the speed and efficiency with which the QCL carries out corrective and preventive actions (CAPAs). A QCL may be prequalified immediately after initial inspection (usually conducted within six months of application for prequalification), if no CAPAs or reinspection were required. A shorter timeline of one to two months is possible if a the  QCL can provide a report of an inspection or audit performed  by a regulatory authority that applies standards that are at least equivalent to WHO-recommended quality standards for QCLs.

The standards against which WHO evaluates finished pharmaceutical products, active pharmaceutical ingredients and quality control laboratories are based on the principles and practices agreed by the world’s leading regulatory agencies and adopted by the WHO Expert Committee on Specification for Pharmaceutical Preparations.

(See Guidance: WHO Technical Report Series.)

 

 

The approval represented by inclusion of a finished pharmaceutical product (FPP) in the WHO List of Prequalified Medicinal Products, of an active pharmaceutical ingredient (API) in the WHO List of Prequalified Active Pharmaceutical Ingredients, or of a quality control laboratory (QCL) in the WHO List of Prequalified Quality Control Laboratories, is not valid indefinitely and must be actively maintained.

FPPs: As well as continuing to meet prequalification requirements on an ongoing basis, FPPs are subject to requalification. All FPPs are subject to requalification after five years. Additionally, in the event of notification of a product complaint, PQTm will generally carry out further product assessment and possibly also inspect the manufacturing site(s). And to verify that the quality of prequalified products is being maintained, WHO carries out random quality control testing of prequalified FPPs that have been supplied to countries.

APIs: Prequalified APIs are not subject to requalification but certain requirements must be met if prequalification status is to be retained. Holders of prequalified APIs must ensure the accuracy of the information contained in the API master file and:

  • provide all necessary documents to WHO to demonstrate that any change will not or has not had a negative effect on the API’s quality or safety
  • communicate information about any changes made to the API to FPP manufacturers who manufacture FPPs with that API.

QCLs: Although prequalified QCLs do not undergo requalification at any stage, ongoing monitoring of the activities of prequalified QCLs is carried out. This includes reinspection at regular intervals (at least once every three years), evaluation of results from participation in an appropriate proficiency testing scheme, and monitoring and investigation of complaints concerning the results of analysis or service provided by the listed laboratories. To facilitate the monitoring each prequalified laboratory is requested to submit a brief annual report on its activities related to quality control of medicines

The majority of quality control laboratories (QCLs) that WHO prequalifies are national laboratories or academic institutions, the financial resources of which are often limited. WHO therefore decided not to levy a fee for QCL prequalification.

Fees are levied for evaluation of applications for prequalification of active pharmaceutical ingredients (APIs) and finished pharmaceutical product (FPPs). In some instances, deferred fees may be applied.

In considering an application for prequalification evaluation, manufacturers should also consider the common expenses involved in preparing a product for WHO or other stringent evaluation.

 

guidance documents

 

PQTm staff responsible for assessments and inspections are generally recruited from regulatory agencies. They work with regulators from stringent regulatory authorities (SRA) (for example, SRA assessors attend the assessment sessions held in Copenhagen, adn SRA inspectors join WHO inspections as co-inspector) or to ensure that their levels of knowledge and expertise in medicines regulation and pharmaceutical science are maintained. They also work with regulators from low-income countries where the medicines will be used, to ensure that the process and results are understood and trusted by those countries.

Additionally, the assessment and inspection groups include rotational staff from low-income regulatory agencies. The rotational staff work with PQTm for several months and then return to their agency. Upon their return home they share the knowledge and experience they have acquired with colleagues and also serve as an ambassador for WHO prequalification.

The WHO List of Prequalified Medicines Products was originally intended to provide UN agencies, such as UNICEF, with a range of quality medicines to select from. With time, the growing list of products has become as a useful tool for any agency or organization undertaking bulk purchasing medicines.

The WHO List of Prequalified Active Pharmaceutical Ingredients (APIs) is used by manufacturers seeking quality-assured APIs for manufacture of finished pharmaceutical products (FPP). It is also used by national medicines regulatory authorities to validate the quality of FPPs when reviewing applications for marketing authorization. Procures also use the list when considering procurement of FPPs manufactured by the same applicant, or at a site at which a prequalified API is manufactured.

The WHO List of Prequalified Quality Control Laboratories is used, among others, by procurers, ministries of health, health care organizations and donors who need to organize testing of medicines at a laboratory and wish to be assured that the laboratory selected meets international standards and can provide the type of testing required.

All members of staff working on medicines prequalification are bound by confidentiality agreements. Likewise, in accordance with the terms contained in an agreement which they are requested to sign, appointed experts (assessors, inspectors and technical assistance providers) commit to treating all information to which they have access during product dossier assessment, or site inspection, or provision of technical assistance, as strictly confidential, and proprietary to WHO, or to parties collaborating with WHO.