Good Manufacturing Practice (GMP) Compliance for Phage Therapy Medicinal Products.

Facing the emergence of difficult-to-treat bacterial infections, the perspective of using bacteriophages has re-gained interest in many countries. In terms of pharmaceutical classification in EU and United States, phages are considered as anti-infectious medicinal products and biological products, given the intended use and their live nature. During the production steps, the compliance with the Good Manufacturing Practice (GMP) represents the gold-standard to ensure the quality, safety and efficacy of medicinal products, either investigational or approved. In practice, the implementation of GMP rules for phage therapy medicinal products benefits from the long history of vaccine development. Accordingly, a well-structured strategy can be defined for each medicinal product, taking into account the specified indication (i.e., the target bacteria species, the infected site, the route of administration, the product composition). Based on the experience of different phage therapy medicinal products from the recent years, the most important requirements to achieve and claim GMP grade are reviewed here, including for genetically modified phages. Like all new medicinal products, the manufacturing of investigational phages incorporates significant challenges. However, the use of GMP-certified phages provides the best guarantee for the rigorous assessment of quality, safety and efficacy during the clinical development of phage medicinal products, thus appears as a key component for the successful development of phage therapy approaches.

Cell substrates for the production of viral vaccines.

Vaccines have been used for centuries to protect people and animals against infectious diseases. For vaccine production, it has become evident that cell culture technology can be considered as a key milestone and has been the result of decades of progress. The development and implementation of cell substrates have permitted massive and safe production of viral vaccines. The demand in new vaccines against emerging viral diseases, the increasing vaccine production volumes, and the stringent safety rules for manufacturing have made cell substrates mandatory viral vaccine producer factories. In this review, we focus on cell substrates for the production of vaccines against human viral diseases. Depending on the nature of the vaccine, choice of the cell substrate is critical. Each manufacturer intending to develop a new vaccine candidate should assess several cell substrates during the early development phase in order to select the most convenient for the application. First, as vaccine safety is quite naturally a central concern of Regulatory Agencies, the cell substrate has to answer the regulatory rules stringency. In addition, the cell substrate has to be competitive in terms of viral-specific production yields and manufacturing costs. No cell substrate, even the so-called "designer" cell lines, is able to fulfil all the requested criteria for all viral vaccines. Therefore, the availability of a variety of cell substrates for vaccine production is essential because it improves the chance to successfully respond to the current and future needs of vaccines linked to new emerging or re-emerging infectious diseases (e.g. pandemic flu, Ebola, and Chikungunya outbreaks).