Whole genome sequencing and analysis of live biotherapeutic products

The US Food and Drug Administration (FDA) created live biotherapeutic products (LBP) as a new category in the 2012 guidelines.¹ It defined LBPs as drug products containing live microorganism(s) to be used to prevent, treat or cure a disease or condition in human beings.¹ The European Directorate for the Quality of Medicines & Healthcare (EDQM) also accepted LBP as a new category of medicinal products for the European market in 2019.²

Similar to other drug products, strict good manufacturing practices (GMPs) should apply to the production of live biotherapeutic products. Under normal circumstances, GMPs govern that the end product should be devoid or contain a very limited number of microorganism(s). However, for LBPs, the GMP requirements ensure the viability of the desired microorganism(s), both in the final product and at the end of the claimed shelf life of the product. 

Despite these guidelines, there are many knowledge gaps of drug regulatory requirements for LBPs, partly because microbial growth and viability are challenging to control at the production level and the product lifecycle. Therefore, characterisation of the microorganism(s) is of utmost importance to LBP quality documentation. Among an array of tests suggested for LBP testing, the EMA and FDA have given prime importance to the whole genome sequence characterisation of the strain in the final product dossier. However, neither agency provides specific guidelines defining the quality parameters for next-generation sequencing (NGS) platforms, whole genome sequencing (WGS) and bioinformatics analysis.

This article proposes a tentative approach for a minimum standard requirement for the WGS and bioinformatics analysis of LBPs.  Download and read more now…