Alignment in post-approval changes (PAC) guidelines in emerging countries may increase timely access to vaccines: An illustrative assessment by manufacturers.

A comparison of the regulations and guidelines from 33 countries, across different regions, on the requirements and procedures for the management of chemical, manufacturing and control (CMC) changes for vaccines, also known as post- approval changes (PACs), reveals significant variability and lack of predictability of timelines for regulatory review and approval. These shortcomings imply that multiple data packages have to be prepared for submission to different authorities, generating a complex regulatory environment. Moreover, the timelines for approval by individual national regulatory authorities are variable, which results in manufacturers keeping various stocks of vaccines produced in accordance with the various approved specifications and procedures, in the different countries. This can seriously affect timely availability of vaccine in those countries. The World Health Organization (WHO) guidelines on procedures and data requirements for changes to approved vaccines provide a consensual framework for alignment, but are still underused. Reliance on both the review and approval by the regulatory authority in the country of manufacturing, or on the review performed by other national regulatory authorities, recognized by WHO as stringent, or on WHO prequalification dossier, offer alternative ways forward. These and other options to improve the management of post-approval changes during the product lifecycle of vaccines are discussed in this report, and aimed at improving guidelines alignment and regulatory convergence to advance immunization equity and coverage.

Establishment of pandemic influenza vaccine production capacity at Bio Farma, Indonesia.

In Indonesia, avian influenza A(H5N1) virus started to spread in humans in June 2005, with an alarming case-fatality rate of more than 80%. Considering that global influenza vaccine production capacity would barely have covered 10% of the world's pandemic vaccine needs, and that countries with no production facilities or prearranged contracts would be without access to a vaccine, the Government of Indonesia embarked on a programme to increase its readiness for a future influenza pandemic. This included the domestic production of influenza vaccine, which was entrusted to Bio Farma. This health security strategy consists of developing trivalent influenza vaccine production capacity in order to be able to convert immediately to monovalent production of up to 20 million pandemic doses for the Indonesian market upon receipt of the seed strain from the World Health Organization (WHO). For this purpose, a dedicated production facility is being constructed within the Bio Farma premises in Bandung. As an initial stage of influenza vaccine development, imported seasonal influenza bulk has been formulated and filled in the Bio Farma facility. Following three consecutive batches and successful clinical trials, the product was licensed by the Indonesian National Regulatory Authority and distributed commercially for the Hajj programme in 2009. With continued support from its technology transfer partners, Bio Farma is now advancing with the development of upstream processes to produce its own bulk for seasonal and pandemic use.