Created in 1999, WHO prequalification ensures that essential medicines comply with WHO standards of quality, safety and efficacy. In so doing, this prequalification facilitates the work of National Regulatory Authorities, which lack the resources, for example in Africa, to qualify medicines.

Historically, WHO prequalification initially focused on antimicrobials, but was subsequently extended. It has given an impetus to the prequalification of medicines by major international agencies and has inspired the Belgian NGO QUAMED, which recently developed a much-appreciated Quality Certification Programme.

In the absence of sufficient funding, WHO prequalification remains a fragile, vulnerable and limited structure, since the majority of medicines and other essential health products are still waiting to be prequalified. 

What does ‘Prequalification’ mean?

Normally, the qualification of a medicine, i.e. its compliance with acceptable standards of quality, safety and efficacy, falls within the remit of the Stringent Regulation Authorities (SRAs). In Belgium, this role is played by the FAMHP, an acronym for the Federal Agency for Medicines and Health Products. Once compliance has been ensured by the SRA, a marketing authorisation (MA) can be issued and the product placed on the market.

In practice, many SRAs in low- and middle-income African countries do not have sufficient expertise and financial resources to carry out compliance analyses despite their efforts to do so; they rarely exceed maturity level 2 on a scale of 4.

WHO prequalification carries out this analysis ‘upstream’ for a certain number of essential generic medicines (see my previous article on the WHO List of Essential Medicines); this can considerably facilitate the work of SRAs classified in a category lower than 4.

In addition, international drug purchasing organisations such as UNICEF, the Global Fund to Fight AIDS, Tuberculosis and Malaria and UNITAID, which purchase medicines worth billions of US dollars, rely on the conformity decisions issued by WHO prequalification.

A Brief History

Prequalification of medicines is a WHO global service created in 1999 to assess the quality, safety and efficacy of medical products. Initially, in 2001, the focus was on medicines to treat HIV/AIDS, tuberculosis and malaria. In 2006, WHO prequalification broadened its product range to include medicines and products for reproductive health. In 2008, the prequalification of zinc – for the management of severe acute diarrhoea in children – was added; it was also extended to diagnostic tests and medical devices. At the end of 2013, the WHO list of medical products included more than 316 prequalified medicines, and this list continues to grow and diversify.

How does the WHO Medicines Prequalification System Work?

Prequalification is a voluntary process that consists of five stages:

  1. Invitation

The WHO Prequalification of Medicines Programme invites manufacturers to express their interest in the evaluation of an essential medicine they produce.

  1. Submission of the dossier

The manufacturer provides a complete set of data relating to the quality, safety and efficacy of the product under evaluation. This package includes in particular:

– data on the purity of all ingredients used in manufacture;

– data on the finished pharmaceutical product (such as stability information);

– the results of bioequivalence tests (clinical trials on healthy volunteers), unless a     derogation has been granted.

  1. Assessment

A team of assessors evaluates all the data submitted. The evaluation team includes WHO staff and experts from national regulatory authorities around the world.

  1. Inspection

A team of inspectors verifies that the manufacturing sites of the finished pharmaceutical product and the active pharmaceutical ingredient(s) comply with WHO Good Manufacturing Practice.

  1. The decision

If the experts conclude that the product meets the specified requirements, and that the associated manufacturing site(s) comply with WHO standards, the product is added to the WHO list of prequalified medical products.

To ensure that prequalified products continue to meet WHO specifications, WHO Prequalification regularly inspects the manufacturing sites of prequalified products. It also assesses any changes (called “variations”) made to the specifications, manufacturing processes and quality control of prequalified products, and conducts randomized quality control tests on samples of prequalified products.

The WHO prequalification service also provides targeted technical assistance to quality control laboratories. To date, 41 laboratories are WHO-accredited worldwide, including 9 in Africa.

In addition, UNICEF, UNDP, UNFPA (United Nations Population Fund), MSF and UNDP (United Nations Development Programme) have developed their own qualification mechanisms for a wider range of products, but not always to the same exacting standards as WHO prequalification.

Problems related to the WHO Prequalification

  1. The slowness of the process:

The WHO prequalification process for medicines can be completed within three months, if all the data submitted is complete and demonstrates that the product meets all the required standards. It often takes much longer. Why is this?

– because of incomplete data supplied by the manufacturer.

– because of the high standards required for WHO prequalification. Its mandate requires it to adhere strictly to the standards in force (good manufacturing and distribution practices).

This slowness sometimes clashes with the urgency of the decision-making process for public health reasons. Given this urgency, should we be less demanding in terms of quality (cf. the EU’s flexibility in putting the new Covid vaccine on the European market)? This is a question of ethics: the assessment of the benefit-risk in terms of public health will weigh up the advantage of putting a particular drug on the market as a matter of urgency against the human and financial cost of inadequate quality of that drug (resistance, serious side effects, failure to cure, the cost of recalling a batch of drugs withdrawn from the market, etc.).

  1. The limited number of prequalified products:

Ideally, WHO prequalification should cover all essential medicines, but unfortunately this is not the case due to the limited resources available to the WHO prequalification service.

  1. The economic weight of those involved in WHO prequalification:

– That of the pharmaceutical industry: this is enormous and the stakes are high. The market, with the stock market, is by its very nature lucrative and not virtuous. This has an impact on WHO prequalification that is difficult to measure.

– The economic weight of donors: The Bill Gates Foundation is the biggest provider of funds to the WHO prequalification budget. It is particularly interested in paediatric and reproductive health medicines. The other donors are the major international drug purchasing organisations, WHO member states and private sponsors. This undermines the independence of the WHO prequalification service and its long-term survival.

The Role of the EU:  the ‘EU Medicines for All’ Procedure (previously known as the ‘Article 58 procedure’).

Since 2004, the European Medicines Agency (EMA), in cooperation with the WHO, has issued scientific opinions on high-priority human medicines, including vaccines, intended to be marketed outside the EU.

The aim is to facilitate patient access to essential medicines in low- and middle-income countries, particularly in Africa, including new or improved therapies that meet unmet medical needs and are intended to prevent or treat diseases of major public health importance.

The procedure combines the EMA’s scientific review capabilities with the local epidemiology and disease expertise of the WHO and SRAs in the target countries, to provide a unique development and evaluation pathway.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) evaluates medicines and vaccines under this procedure to the same rigorous standards as medicines intended for use in Europe.

At the end of the evaluation, the EMA publishes its scientific opinion on the product’s risk-benefit ratio, which is intended to facilitate the WHO’s prequalification of the medicinal product and its registration in the target countries.

Apart from this ‘EU medicines for all’ procedure, the budget made available by the EU to the WHO prequalification service is limited.


QUAMED is an independent Belgian non-profit association whose mission is to improve access to quality medicines for all. The association was created in 2010 and became an independent non-profit association under Belgian law in 2017.

QUAMED brings together international NGOs, pharmaceutical supply centres and experts from countries, particularly in Africa, who are committed to ensuring the quality of medicines.

QUAMED has developed a Quality Certification Programme called QCP QUAMED, which uses the criteria and technical standards defined by the WHO to assess the pharmaceutical quality systems of wholesalers and manufacturers.

Thanks to this innovative programme, QUAMED offers wholesalers and manufacturers the possibility of applying for QCP QUAMED certification.

QUAMED thus responds to the limitations of WHO prequalification, which only concerns certain categories of medicines.

In Conclusion:

The adventure of WHO prequalification is remarkable. The WHO has succeeded in making its mark on the delicate and enormous issue of the quality of medicines placed on the world market.

It has done so in a professional manner, thanks to motivated and persevering experts.

Nevertheless, this initiative remains limited and fragile, and needs to be not only consolidated but considerably developed.

QUAMED is contributing to the major prequalification effort being made worldwide, not only by the WHO but also by the major purchasing groups.

The QUAMED initiative deserves broad support.

AEFJN asks the EU and the Belgian Government:

– With regard to the WHO prequalification service: to increase their budget for its benefit.

– Concerning QUAMED: to financially support the QCP QUAMED initiative.

Thanks to: Mr Jean-Michel Caudron, pharmacist, medicines quality expert


Br. Christian Roberti, CSSp