Biosafety Open Forum

Contamination of a biological product with viruses, potentially harmful for humans, is of concern for therapeutics derived from human and animal sources, i.e. plasma, and for protein therapeutics and vaccines produced in mammalian cells.  More recent “Advanced Therapeutic Medicinal Products (ATMPs)”, such as gene and cell therapies, share the same concern.  Tests for viral contaminants are performed at several stages of manufacturing.  Current tests for detection of viruses are lengthy; cell culture based assays and animal experiments are required.  Alternative molecular tests, such as “next generation sequencing (NGS)”, provide faster results, and can eventually replace in vivo animal studies.  It is noteworthy that identification of a viral contaminant that evaded detection in classical tests, by NGS, has been demonstrated.  Since NGS based virus tests yield results significantly faster than current assays, additional applications for in-process testing and viral contamination control can be envisioned.  In this presentation applications for unbiased and targeted NGS in testing of biologics will be discussed.

Over the past few decades, technological advancements in NGS have enabled biopharmaceutical companies to adopt NGS for biosafety testing. During a typical manufacturing process, NGS-based biosafety is implemented at several stages to accelerate production and prevent large-scale contamination. Although some pharmaceutical companies benefit from faster results and reduced costs, widespread implementation of this technique has been slow due to challenges and complexities related to sample preparation, data analysis, bioinformatics, and evolving instruments. To overcome these limitations, we need to bring about harmonization by introducing standards to the terms, methods, and technologies used in this process. Now is the time to facilitate conversation between key players in healthcare to harmonize and improve the use of NGS-based biosafety in the pharmaceutical industry.

As the efforts to harness NGS for adventitious agent detection gather pace, a greater understanding is emerging of how this technology can best be applied in different situations. Experimental protocols and bioinformatics pipelines are, for example, tailored to the type of therapeutic agent being produced, or the stage of production at which testing is taking place. Computational biologists face many choices when crafting NGS read processing and analysis pipelines, and may create several pipelines depending on different needs. Ideally, this expertise and knowledge should be encapsulated in a way that virologists can run the pipeline easily themselves, with results presented clearly so they can bring their expertise to bear. Where appropriate, the process should be automated to the extent possible: this is the next hurdle.