WHO publishes Variations Guideline for Prequalified APIs and Medicinal Products

In May 2013, the WHO released its new Technical Report (TRS 981) including 4 Annexes entitled:

• Release procedure for International Chemical Reference Substances (Annex 1)
• WHO guidelines on quality risk management (Annex 2)
• WHO guidelines on variations to a prequalified product (Annex 3)
• Collaborative procedure between the World Health Organization Prequalification of Medicines Programme and national medicines regulatory authorities in the assessment and accelerated national registration of WHO-prequalified pharmaceutical products (Annex 4)

We reported about the content of Annex 2 in our GMP News from 19 June 2013.

Annex 3 is composed of a Variations Guideline which has been updated to take into consideration the provisions laid down in the new WHO Generic Guideline (see our GMP News from 3 April 2013). The complete title of this Variations Guideline is "WHO guidelines on variations to a prequalified product" and applies to prequalified APIs and medicinal products. This guideline thus belongs to the range of documents which form the regulatory framework to the prequalification programme of the WHO.

The new Variations Guideline intends to provide guidance with respect to the classification of administrative and quality-related changes as well as to changes in a Certificate of Suitability (CEP) or in the prequalification documentation of an API.

The guideline addresses 2 variation categories:

• Minor Variation (Vmin). A minor variation is a change that may have minor effects on the safety, efficacy and quality of the medicinal product. Such variations have to be reported and can be implemented if no objection letter has been issued within a time period indicated on the WHO/PQP website. If questions arise during the specified period, the change can only be implemented on receipt of a letter of acceptance from WHO.
• Major Variation (Vmaj). A major variation is a change that could have major effects on the safety, efficacy and quality of the medicinal product and must be reported. Such variation can only be implemented on receipt of a letter of acceptance from WHO.

For changes which could have minimal or no adverse effects on the overall safety, efficacy and quality of the medicinal product, the Guideline categorizes:

• Annual notification (AN). An AN has to be submitted to WHO/PQP within 12 months of implementation of the changes.
• Immediate notification (IN). An IN can be implemented immediately at the time of submission and they can be considered accepted if an objection is not issued by WHO/PQP within 30 calendar days of the date of acknowledgement of receipt of the application.

The list of each change is -  analogous to the new Variations Guideline of the EU Commission (please see the following GMP News in this Newsletter on the final Variations Guideline), is presented in tabular form too.

The WHO prequalification programme includes the prequalification of APIs, finished medicinal products, QC labs and is limited to medicinal products used for HIV/AIDS, malaria, tuberculosis and for reproductive health. To obtain prequalification for an API or a medicinal product, the applicant has to submit a dossier in the CTD format which - comparable to an authorisation in Europe - proves the quality, efficacy and  safety of the medicinal product. Further information about the prequalification programme can be found on the WHO website.