Every year, millions of patients in resource-limited countries receive life-saving medicines that are purchased by or through international procurement agencies such as UNICEF, UNFPA, UNITAID and the Global Fund to Fight AIDS, TB and Malaria. The WHO Prequalification of Medicines Programme ensures that selected medicines supplied by these agencies meet international standards of quality, safety and efficacy.
The Programme has prequalified more than 280 products since it was established in 2001. Its original focus was medicines for treating HIV/AIDS, TB and malaria; but this expanded in 2006 to cover medicines for reproductive health, in 2007 to cover medicines for influenza and then again in 2008 to cover zinc for the management of acute diarrhoea in children. More recently, the Programme started to evaluate the quality of medicines for treating neglected tropical diseases
“Ensuring that patients have access to quality-assured medicines to treat AIDS, tuberculosis and malaria has been a priority for the Global Fund since its inception in 2002,” said Debrework Zewdie, Deputy Executive Director of the Global Fund to Fight AIDS, Tuberculosis and Malaria. “The WHO Prequalification Programme played a critically important role in supporting the Global Fund Board in its efforts to establish and strengthen its Quality Assurance Policy for Pharmaceutical Products. Today, WHO prequalification status gives Global Fund grant implementers the confidence they need that they are procuring medicines that meet internationally recognized standards.”
How prequalification works
Manufacturers apply to WHO to have a product evaluated. They must provide comprehensive information about the product’s quality, safety, and efficacy. This is evaluated by a team of assessors – including staff from WHO and experts from national regulatory authorities worldwide.
In addition, a WHO inspection team visits the manufacturing site(s) of both the finished pharmaceutical product and its active pharmaceutical ingredient(s) to verify that these comply with WHO good manufacturing practice (GMP). The team, which includes an inspector from a “stringent regulatory authority” may also verify that any contract research organization that conducted any studies relating to the product complied with good clinical and laboratory practices. When the comprehensive scientific assessment and necessary inspections indicate that the product meets international standards for quality, safety and efficacy the product is added to the WHO list of prequalified medicinal products. But if the manufacturer fails to provide sufficient data, or if its manufacturing site is found to not comply with GMP, it is requested to provide additional data, to carry out additional studies, and/or to carry out corrective action at its manufacturing site(s).
Ongoing monitoring and intervention to assure quality
To ensure prequalified products continue to meet the WHO specifications, the Programme regularly tests samples of prequalified medicines and re-inspects manufacturing sites. It also assesses changes made by manufacturers to their prequalified products quality specifications and/or to the manufacturing processes of those products to ensure that these variations do not affect quality and safety.
Moreover, after 5 years, a prequalified product must undergo “requalification”.
If quality issues are identified in relation to a prequalified product, WHO intervenes swiftly, applying a complaint procedure that stipulates thorough investigation, including on-site investigation and quality control analysis. In one example last year in Kenya, WHO’s prequalification programme was notified by an NGO of a quality complaint. As a consequence of a swift inspection of the suspected manufacturer the programme found evidence of unauthorized relabeling of prequalified lamivudine, zidovudine and nevirapine tablets (antiretrovirals) with the fraudulent aim to extend its expiry date. The Kenyan regulatory authority was able to confirm these findings and ordered a recall of tablets by batch number.
“However, neither assessment nor monitoring alone can guarantee the safety of a country’s medicines supply”, says Dr Kees de Joncheere, Director of WHO’s Department of Essential Medicines and Health Products. “There are multiple threats to medicines supply systems, especially in regions where regulatory and enforcement systems are the weakest. That is why this Programme also works with countries to develop their capacity to regulate medicines entering their markets.”
In 2011, the Programme organized or co-organized training in medicines quality and safety issues for more than 1600 participants, including regulators, manufacturers, laboratory staff and partner organizations. The hands-on training includes a rotational fellowship, and invitations to developing country assessors and inspectors to participate in Programme activities under the supervision of experienced senior experts.
Added benefits of prequalified medicines
One consequence of the prequalification programme is that it has helped bring down drugs prices in low- and middle-income countries.
“The resultant price decreases mean that many more patients can be treated,” says His Excellency Maurice Peter Kagimu Kiwanuka, Uganda’s Ambassador to Switzerland. “Ten years ago, one month of first line antiretroviral drugs treatment for HIV cost US$ 1000. Today it costs less than US$ 50. So in 2003, only 17 000 patients received antiretroviral in Uganda, whereas by September 2010, this number had increased to just under a quarter of a million.”
Experts in the field credit prequalification as one of the critical success factors in getting vital medicines to large numbers of people with no compromise of quality.
“The creation of prequalification was a radical and courageous move on WHO’s part and it showed the international community that ambitious treatment targets could be achieved,” said Ellen’t Hoen, international pharmaceutical policy expert from the University of Amsterdam, The Netherlands.
Perhaps most importantly, the Programme has helped create a level playing field by ensuring that medicines are evaluated according to internationally-agreed, transparent standards, no matter where or by whom they are produced.