Alternative and rapid microbiological methods (ARMMs) for detecting microorganisms and adventitious agents during testing are now available to the biopharmaceutical industry, and regulatory authorities are encouraging their adoption. These innovative technologies will help improve the monitoring and assurance of control processes and manufacturing environments and shorten cycle times in the supply chain.
Yet despite the benefits, implementation of alternative adventitious agent testing (AAT) remains slower than desired to meet industry targets. Also, the path for drug sponsors to progress from a specific operational, business, or quality need to a filed and fully implemented method is sometimes unclear.
What is needed is a systematic and best practice approach to support your adoption of AAT methods.
This is why BioPhorum has published Alternative adventitious agents detection methods in biopharmaceuticals: A proposal for a structured best practice approach for their evaluation, validation, and implementation
This describes the strategies and best practices you need to overcome current barriers to the efficient identification, evaluation, validation, implementation, and lifecycle management of alternative AATs. It does this through a nine-step framework and common language that can be applied if you want to take advantage of the numerous benefits of ARMMs and alternative AATs.
The framework builds on a previous BioPhorum paper A framework for the evaluation, validation and implementation of alternative and rapid microbiological testing methods and provides an alternative AAT focus.
The steps are:
- Identify the operational/business need
- Define the application
- Assess the requirements
- Compare options and technologies – landscaping and candidate(s) selection
- Develop a business case: technical, quality and business evaluation and justification
- Perform proof-of-concept studies/feasibility studies/pre-validation studies
- Validate at pilot or primary site
- Deploy global/company-wide qualification of additional laboratories
- Define regulatory filings and implementation strategy.
Each step has clear inputs and outputs to several other steps; therefore, a purely linear approach may not fit all cases. In practice, the steps are sometimes knitted together in the order listed; in other cases, feedback loops may change the order. To help facilitate Step 3, a generic user requirement specification for alternative AATs is included as an appendix.
“The new framework document for the evaluation, validation, and implementation of alternative adventitious agents test methods is based on the already published document for alternative microbiological methods,” said Sven Deutschmann, Head of Global ASAT “Adventitious Agent Testing & Alternative Microbiological Methods” at Roche and the paper’s lead author. “Several companies have already used the procedure described in the latter document very successfully in practice. Based on these positive experiences, I am confident that the framework document for alternative adventitious agent tests will be just as helpful for colleagues.”
Looking ahead, a case study is planned to apply this framework to alternative mycoplasma detection methods. This will also include a user requirements specification to facilitate the rapid release of mammalian cell-based products. Subsequent papers will provide case studies on applying this framework to AAT detection methods.
The original framework has been used for a paper on Automated Colony Counting Systems published by the Parenteral Drug Association. It is also being used in a best practice paper on Alternative Sterility Test Systems scheduled to be published later in 2022.