WHO Drug Information Vol. 15, No. 3 & 4, 2001
(2001; 76 pages) View the PDF document
Table of Contents
View the documentWHO Drug Information
Open this folder and view contentsPersonal Perspectives
Open this folder and view contentsReports on Individual Drugs
Close this folderQuality Assurance Issues
View the documentWHO pilot pre-qualification project for pharmaceutical products
Open this folder and view contentsCurrent Topics
Open this folder and view contentsGeneral Information
Open this folder and view contentsRegulatory and Safety Matters*
Open this folder and view contentsATC/DDD Classification
Open this folder and view contentsRegulatory Information
View the documentRecommended International Nonproprietary Names (rec. Inn): List 46
View the documentSelected WHO Publications of Related Interest

WHO pilot pre-qualification project for pharmaceutical products

It is recognized that low-cost drugs of assured quality have the greatest potential for maximizing efforts to combat major communicable diseases. As an integral part of their health care programmes and services, WHO and many other international agencies have traditionally been involved in the procurement and supply of drugs. More recently, a focus on access to drugs for HIV, malaria, and TB has become a priority at both international and country level and recent funding commitments by major industrialized countries articulate current efforts to address major public health concerns with determination and urgency.

In addition to the immediate problems of manufacture, provision and distribution, efforts to accelerate access to HIV-related drugs through generic competition have highlighted the complexities of assuring quality products in large-scale procurement programmes. Within such programmes, drugs are sourced from various manufacturers. However, at national level these drugs are not always subject to registration by a drug regulatory authority and subsequent assessment of quality is often lacking. Without quality assurance mechanisms, programmes risk supplying substandard, counterfeit and/or contaminated medicines, leading to product complaints and recalls, waste of precious funding and, more seriously, creating a potential health disadvantage to patients through administration of ineffective medicines.

Some organizations involved in procurement, including UN agencies, have devised their own quality systems but these have been developed independently. Additionally, although some agencies contract inspections at the site of manufacture, the extent and quality of these inspections varies according to the resources available. The establishment of harmonized procedures would render such inspections consistent, making mutual recognition and coordination possible. In short, uniform pre-qualification and quality assurance systems are essential for procurement agencies to function effectively.

Pilot project on procurement, quality and sourcing

As a matter of urgency, WHO and other UN agencies have begun to address these problems by setting up a plan to provide systems for the pre-qualification of manufacturers wishing to supply pharmaceutical products to international procurement agencies. Given the magnitude and ambitiousness of the task, the project is being implemented in a step-wise fashion covering:

• Pre-qualification of a certain number of manufacturers by WHO.

• Creation of unified procedures for performing inspections of suppliers prior to sourcing of pharmaceuticals.

• Evaluation of information on quality specifications of products submitted by suppliers.

• Creation of a model quality assurance system and pre-qualification procedures for use by procurement agencies.

Because of the overwhelming need to increase access to HIV drugs in those countries where the disease is now the leading cause of mortality, a pilot project will target manufacturers of pharmaceuticals for HIV/AIDS for WHO pre-qualification.

Important secondary outcomes are expected as a result of the pilot project. These include:

• pre-qualification by WHO for the procurement of drugs for other public health threats such as TB and Malaria.

• agreement among interested agencies on coordination of inspections, evaluation of product quality, training of inspectors, and mutual recognition of inspection reports, enabling resources to be saved and duplication avoided.

• strengthening of confidence in public health and enhanced patient compliance of treatments by assuring the quality of pharmaceuticals.

• strengthening of collaboration between WHO regional and country offices and drug regulatory authorities. Ongoing monitoring, review and modification of existing quality-related systems and programmes.

• establishing more effective networking and information exchange on drug regulatory and quality assurance issues.

Establishment of a quality assurance system for pre-qualification by WHO

A quality assurance system has been established by WHO for use in the pre-qualification of HIV drugs. Detailed procedures are set out in the Operational Quality Manual, covering product evaluation, site inspections, and related activities. The system covers good manufacturing practices, a code of conduct for inspectors, an inspection procedure, inspection report formats, standard operating procedures for inspectors, compilation of a product dossier, and guidance for evaluation of supporting documentation. These documents are published on the WHO HIV/AIDS Drugs Pre-qualification website (www.who.int/medicines) and are available from Quality and Safety: Medicines, Essential Drugs and Medicines, World Health Organization, 1211 Geneva 27, Switzerland.

Procedure for pre-qualification

Pre-qualification will involve evaluation of:

• Information provided by the supplier, manufacturer, and drug regulatory authorities.

• Production and quality control activities of the manufacturer.

• Product information submitted by manufacturers including formulation, manufacture, test data and results.

• Assessment of consistency in production and quality control through inspection of compliance with GMP.

• Random sampling and testing of drugs supplied.

• Storage and distribution of products.

• Handling of complaints and recalls.

• Complaints from agencies and countries.

Essential requirements

• The product must be manufactured in compliance with WHO GMP.

• Product certificates should be obtained in accordance with the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce.

• Products must be of assured quality compliant with WHO guidelines.

• Specific ethical conditions determined by UN agencies should be complied with.

• Product data and information dossiers as set out on the following page.

Expression of interest

In the context of increasing access and affordability of HIV/AIDS-related care and treatment, WHO, in collaboration with UNICEF, UNAIDS, and UNFPA has invited expressions of interest (EOI) from manufacturers of pharmaceutical products used in the management of HIV-related diseases. This activity is also supported by the World Bank.

Manufacturers have been requested to submit EOIs and product dossiers for various dosage forms and strengths of products in the following categories:

Non-nucleoside reverse transcriptase inhibitors





Nucleoside reverse transcriptase inhibitors







lamivudine + zidovudine


Protease inhibitors






lopinavir + ritonavir


Anti-infective drugs:

Antibacterial and antimycobacterial agents













folic acid



Antiviral agents






Antifungal agents

amphotericin B





Anticancer drugs






Drugs for palliative care



HIV diagnostic tests

HIV-associated laboratory equipment

WHO has twice invited expressions of interest (EOI) in the international press and through the Internet (http://www.who.int/medicines) and will continue to do this as and when specific groups of products are identified for pre-qualification. Manufacturers should be committed to provide such products at preferential prices to developing countries.

Submission of product data and information dossiers

In addition to the essential requirements, information should be submitted either as described below or in the format of a standard dossier such as that prepared when requesting product approval by a drug regulatory authority.

1. For innovator products.

• A summary of product characteristics (SPC).
• Assessment report (s) issued by the respective drug regulatory authority.
• A WHO-type batch certificate from the manufacturer. In the event that packaging of the product is different from that approved by ICH drug regulatory authorities, stability testing data should also be submitted. If the formulation, strength, specifications, etc. are different from the product for which the WHO-type product certificate(s) was issued, arguments and/or data to support the applicability of the certificate(s) despite the differences should be submitted.

2. For other multisource (generic) products, the data and information to be submitted should be in conformity with that described in “Marketing Authorization of Pharmaceutical Products with Special Reference to Multisource (Generic) Products” (WHO/DMP/RGS/98.5) published by WHO, and should include information on:

(a) Details of the product.
(b) Regulatory status in different countries.
(c) Active pharmaceutical ingredient(s) (API) data including:

Properties of the API
Route(s) of synthesis
Pharmacopoeial description or in-house specifications
Stability testing results
Sites of manufacture

d) Finished product data including:


Manufacturing procedure

Specifications for excipients

Specifications for the finished product

Container/closure system(s) and other packaging

Stability testing results

Container labelling

Product information

Patient information and package inserts

Justification for any differences to the product in the country or countries issuing the WHO- type certificate(s)


Summary of pharmacology, toxicology and efficacy of the product

Sites of manufacture

Screening of dossiers

Each dossier is screened for completeness prior to evaluation. If incomplete, the manufacturer is requested to rectify this within a specified time period. In the event this is not complied with, the dossier will not be retained. Dossiers that are in compliance with the requirements of the WHO are retained for evaluation and the manufacturing site listed for an inspection.

Dossier evaluation

Dossiers are evaluated by a team of experts appointed by WHO with experience in pharmaceutical development, pharmaceutics, bioequivalence and related areas. Evaluators are drawn from drug regulatory authorities and appointed in accordance with established terms of reference and based on WHO guidelines to ensure uniformity of decisions. WHO is available to provide technical support to the evaluation when required. Evaluators are required to sign a confidentiality agreement and declaration that they have no conflict of interest.

Site Inspections

WHO is planning and coordinating inspections at the manufacturing sites to assess compliance with good manufacturing practices (GMP) as recommended by WHO. The inspection will be performed by inspectors appointed by WHO with regulatory experience in production, quality control, quality assurance and GMP. The inspectors will report their findings to WHO.

An inspector of the national drug regulatory authority will be invited to accompany the team to the manufacturing and testing facilities as part of the inspection team.

Report and outcome of the evaluation and inspection

The evaluators and inspection team(s) will finalize reports according to an established WHO format describing the findings and identifying any non-compliance with the WHO guidelines. This will be communicated to the manufacturers. If any additional information is required, or corrective action has to be taken, WHO will postpone its final recommendations until such information has been submitted and evaluated, or the corrective action verified.

Testing of samples

Random samples of pharmaceutical product(s) supplied by interested suppliers, will be taken for independent testing.

Pre-qualification results

Pre-qualification will cover only those product(s) indicated by the manufacturer in the EOI. Once WHO is satisfied that the product and manufacturing site meet the recommendations of WHO guidelines, the product and the manufacturer will be listed in the Pre-qualified Suppliers List.

The Pre-qualified Suppliers List will be published by WHO for use by procurement organizations, interested governments and related agencies for the purchase of pharmaceuticals. The List will be reviewed annually, published by WHO and made available on the WHO website. Activities related to WHO procurement and pre-qualification will be carried out by independent units.


1. WHO HIV/AIDS Drugs Pre-qualification website, http://www.who.int/medicines. Quality and Safety: Medicines, Essential Drugs and Medicines, World Health Organization, 1211 Geneva 27, Switzerland.

2. General procedures for the prequalification of manufacturers for the procurement and sourcing of pharmaceutical products. Endorsed by the Expert Committee on Specifications for Pharmaceutical Products (annex 8). 22-26 October 2001.


to previous section
to next section
The WHO Essential Medicines and Health Products Information Portal was designed and is maintained by Human Info NGO. Last updated: October 29, 2018