RAPID DETECTION OF BACTERIA AND VIRUSES IN BIOPROCESS SAMPLES: JUSTIFICATION, REGULATION, REQUIREMENTS AND TECHNOLOGIES — HOW CAN INDUSTRY ACHIEVE BROAD ADOPTION? CONNECT COLLABORATE ACCELERATE TM 1 Contents 1.0 Executive summary .......................................................................................................................................................................... 6 2.0 Introduction ....................................................................................................................................................................................... 8 3.0 Current practices ............................................................................................................................................................................10 3.1 Sterility testing ............................................................................................................................................................................. 10 3.2 Mycoplasma testing .................................................................................................................................................................... 11 3.3 Virus testing .................................................................................................................................................................................. 13 4.0 Drivers for change ...........................................................................................................................................................................15 5.0 Overcoming barriers to change ..................................................................................................................................................17 5.1 Technical/operational attributes and impediments .......................................................................................................... 20 5.2 Cost–benefit ratio ........................................................................................................................................................................ 21 5.3 Regulatory acceptance ............................................................................................................................................................... 21 5.4 Behavioral ...................................................................................................................................................................................... 22 5.5 Summary ........................................................................................................................................................................................ 23 6.0 Advocacy for improvement and change ....................................................................................................................................24 7.0 Conclusions and path forwards ...................................................................................................................................................25 References ......................................................................................................................................................................................................27 Definitions/glossary .....................................................................................................................................................................................30 Acronyms/abbreviations ............................................................................................................................................................................35 Appendix: Different types of PCR .............................................................................................................................................................36 ©BioPhorum Operations Group Ltd | October 2019 Rapid detection of bacteria and viruses 2 List of tables Table 1: Use and limitation of adventitious virus testing (adapted from ICH Q5A) .............................................................................................................................................................................. 14 Table2: Analysis of potential behavioral barriers to the adoption of new technologies ..................................................................................................................................................................... 23 List of figures Figure 1: Areas of dissatisfaction with current GMP lot release tests ........................................................................................................................................................................................................ 17 Figure 2: Impediments to implementing alternative rapid microbiology methods for GMP release testing ............................................................................................................................. 18 Figure 3: Activities to drive regulatory acceptance of alternative rapid microbiology methods ..................................................................................................................................................... 19 ©BioPhorum Operations Group Ltd | October 2019 Rapid detection of bacteria and viruses 3 Authors The following member company participants are acknowledged for their efforts and contributions in the production of this document: AstraZeneca Merck & Co., Inc., Kenilworth, NJ, USA Jennifer Anderson Scott Hooper Rick Lu Novo Nordisk Biogen Corinna Cavan Pedersen Cassandra Braxton Maria Rathmann Sørensen Chugai Pharma Manufacturing Co., Ltd Pall Biotech Kunihiro Kamata Morven McAlister Fujifilm Diosynth Biotechnologies Roche Williams Nkrumah Sven Deutschmann Kevin McCarthy Lonza Eva Tur Garcia Thermo Fisher Scientific Rita Tommasi Michael Brewer Merck BioPhorum Cristina Barbirato Bela Green Audrey Chang Contributor The team would like to thank the following non-member contributor: Bioprocessing Technology Institute, Agency for Science, Technology and Research Andre Choo ©BioPhorum Operations Group Ltd | October 2019 Rapid detection of bacteria and viruses 4 About BioPhorum The BioPhorum Operations Group’s (BioPhorum’s) mission is to create environments where the global biopharmaceutical industry can collaborate and accelerate its rate of progress, for the benefit of all. Since its inception in 2004, BioPhorum has become the open and trusted environment where senior leaders of the biopharmaceutical industry come together to openly share and discuss the emerging trends and challenges facing their industry. Growing from an end-user group in 2008, BioPhorum now comprises 53 manufacturers and suppliers deploying their top 2,800 leaders and subject matter experts to work in seven focused Phorums, articulating the industry’s technology roadmap, defining the supply partner practices of the future, and developing and adopting best practices in drug substance, fill finish, process development and manufacturing IT. In each of these Phorums, BioPhorum facilitators bring leaders together to create future visions, mobilize teams of experts on the opportunities, create partnerships that enable change and provide the quickest route to implementation, so that the industry shares, learns and builds the best solutions together. BioPhorum Technology Roadmapping BioPhorum Technology Roadmapping establishes a dynamic and evolving collaborative technology management process to accelerate innovation by engaging and aligning industry stakeholders to define future needs, difficult challenges and potential solutions. The Phorum involves biomanufacturers, supply partners, academia, regional innovation hubs and agencies, serving to communicate the roadmap broadly while monitoring industry progress. The project through which this paper has been developed is part of a broad portfolio of collaborative technology implementation projects, mobilized to impact the most critical challenges identified by the first edition of BioPhorum’s BioManufacturing Technology Roadmap https://www.biophorum.com/ phorum/technology-roadmapping/trm-projects-2. This paper is an example of how the Phorum is continuing to deliver tangible results on its mission to accelerate industry innovation. For more information on the Technology Roadmapping mission and membership, please see https://www.biophorum.com/phorum/technology-roadmapping/overview/ ©BioPhorum Operations Group Ltd | October 2019 Rapid detection of bacteria and viruses 5 1.0 Executive summary The need for absence of adventitious agents (fungi, viruses, bacteria, including mycoplasma) is inherent to every pharmaceutical manufacturing process, but is of critical concern to the biopharmaceutical industry, where a contamination event can arise from a contaminated cell line, raw materials, cell substrates, equipment, facilities or operators. Biological therapeutics must be demonstrated to be devoid of adventitious agents. This is enforced through extensive selection and testing of cell lines and raw materials, incorporation of dedicated manufacturing steps to remove or inactivate any adventitious agents, and in-process and final product testing. The expectations for assurance of microbial safety are clearly stated by global or regional regulatory guidelines and the United States, European and Japanese Pharmacopeias. However, many of these mandatory methods have remained unchanged for decades and most, if not all, are performed off-line. In the first edition