CAACB Projects

Virus Contaminations in Biomanufacturing

Virus contaminations are an industry-wide threat. The CAACB addresses these potentially devastating events through a project designed to uncover trends in the field. Detailed information was first collected from member companies through a comprehensive questionnaire and then the findings were analyzed in terms of risk to the industry. The results were compiled and distributed to provide companies with knowledge that might help them mitigate risks in the future.

Output:

  • Members only White Paper.

Evaluation of Media Treatment Options

Sterile media is a crucial component of preventing contaminations, and the CAACB has three sub-projects on methods of treating media to remove or inactivate potential viruses. The first centers around the ‘Harmonization of HTST Inactivation of MVM’ and was initiated because three published sets of data drew disparate conclusions about the efficacy of HTST inactivation of MVM. The project tackled whether the reported inactivation results diverged due to differences in experimental design or other causative factors. Additional data and analysis will allow for a consensus on the efficacy of HTST inactivation of MVM.

The second sub-project is on the ‘Economic Analysis of Media Treatment Technologies’ and surveyed technologies capable of inactivating or removing viral agents in cell-culture media. The development and implementation of these technologies has an impact on cost of goods. The CAACB reviewed cost estimates for barrier technologies, such as HTST treatment, UV-C, and nanofiltration, and designed a tool to aid companies in estimating the expense of implementing such technologies.

Lastly, the CAACB is conducting a project on the ‘Evaluation of Media Treatment Effectiveness’. Prior to this work, a database of virus inactivation or removal from media for HTST, UV-C and nanofiltration technologies did not exist. The CAACB addressed this absence by assembling and analyzing existing viral inactivation and removal data for media treatment from literature and confidential data from member companies. This data has been collected into a single source that can be leveraged by CAACB members.

Output:

  • Publication in preparation on ‘Harmonization of HTST Inactivation of MMV’
  • Members only White Paper and Cost Modeling Tool on ‘Economic Analysis of Media Treatment Technologies’
  • Members only White Paper on ‘A Survey of Industry and Literature Data on HTST, UVC and Nanofiltration for Media Treatment and Their Efficacy for Inactivation of Virus and Microbes’

Risk Assessment and Risk Control of Virus Contaminations

The goal of the ‘Risk Assessment and Risk Control of Virus Contaminations in Biomanufacturing’ project is to compile a Virus Contamination Risk Assessment and Risk Control handbook. This guide is intended to aid companies in their risk assessment and management process while also helping scientists, engineers, and quality risk control personnel to effectively assess the risk from viral contaminations. The completed white paper should also facilitate general communication around methods that can be used to handle such events.

Follow on efforts are using the CAACB Risk Assessment and Risk Control handbook to conduct a model case study of a virus contamination risk assessment of biomanufacturing in an open ballroom. There is growing industry interest in moving towards open ballrooms with functionally closed manufacturing systems, as seen in a parallel CAACB project defining “functionally closed”. However, there are not public examples on how to assess the risk of these new manufacturing modalities. Given this, the CAACB is conducting a risk assessment of a model process that uses functionally closed systems in a ballroom setting.

Output:

  • Members only White Paper on ‘Quality Risk Management in the Context of Viral Contamination’
  • BOOK CHAPTER: PW Barone, FJ Keumurian, J Leung, SL Springs, R Domike, GK Raju, S Monpoeho, K Murray, S Reich, M Ruffing, and M Wiebe. Quality Risk Management in the Context of Viral Contamination. In Microbial Control and Identification, edited by Donna Reber (PDA, Washington, 2018)

Facility Segregation for Viral Safety

It is critically important for manufacturers to design facilities to prevent contamination events and to contain one if such an incident were to occur. However, consistent practices or regulatory guidance on best approaches to facility segregation are currently lacking. The guidance that does exist is weakened by vague terminology. However, regulators expect appropriate segregation and justifications for that segregation, and the CAACB is attempting to help industry meet those requirements. The goals for this project are to: 1) reach a consensus on the definition of common terms, such as “functionally closed” and “pre/post viral clearance”; 2) identify an array of facility segregation approaches that are adequate and appropriate depending on the manufacturing facility and situation; and 3) communicate these items to the industry through presentations and peer-reviewed publications.

Output:

PUBLICATION: PW Barone, et. al. Biopharmaceutical Industry Approaches to Facility Segregation for Viral Safety: An Effort from the Consortium on Adventitious Agent Contamination in Biomanufacturing. 2019 PDA J. March/April, 73 (2), 191-203 link.