The absence of adventitious agents must be demonstrated to release biotherapeutics. Yet, the traditional compendial methods that have been used for decades for this purpose are laborious, difficult to automate, time-consuming, have a long analytical lead time, and can cause significant delays before results are obtained.
Alternative adventitious agent detection methods, or adventitious agent tests (AATs), have been available for many years and have been advocated by global regulatory authorities. However, their widespread adoption in the biotherapeutic industry has been slow.
To address some of the roadblocks when implementing alternative AATs, BioPhorum has published A structured approach for the evaluation, validation, and implementation of NAT-based mycoplasma detection methods.
The paper provides case studies and best practice guidance for validating an alternative mycoplasma detection assay using nucleic acid testing (NAT). It includes an example of how to complete a user requirement specification for evaluating an alternative mycoplasma detection assay and its validation and implementation. Strategies are also included to help identify suitable technologies for defined applications.
Finally, it gives a framework for how a validation protocol for an alternative mycoplasma detection assay can be executed. This will meet regulator expectations that the alternative method is equivalent to, or better than, the current compendial methods (culture method and indicator cell culture method).
A nine-step framework
Biopharmaceutical manufacturers take various approaches when implementing alternative, NAT-based mycoplasma detection methods. The process can be broken down into nine steps, from initial evaluation to final implementation of the method. These nine steps have been described in a separate BioPhorum publication and provide a framework for alternative adventitious agent detection methods in biopharmaceuticals.
The paper applies this general framework to NAT-based mycoplasma detection and an organization may take all or some of these steps to meet internal requirements and fulfill regulatory expectations. The nine steps are:
Step 1 — Identify the operational/business need
Step 2 — Define the application
Step 3 — Assess the requirements
Step 4 — Compare options and technologies (landscaping and candidate(s) selection)
Step 5 — Develop the business case (technical, quality and business evaluation and justification)
Step 6 — Perform proof-of-concept studies/feasibility studies/pre-validation studies
Step 7 — Validate at pilot or primary site
Step 8 — Deploy global/company-wide qualification of additional laboratories
Step 9 — Review considerations for regulatory filings and implementation strategy.
Kevin McCarthy, QC Scientist, Global ASAT ‘Adventitious Agent Testing & Alternative Microbiological Methods’ at Roche-Genentech and one of the paper’s lead authors, said: “Adventitious agent testing is a critical and required aspect of ensuring drug safety. This paper is the culmination of an extensive collaborative effort by several biomanufacturers and vendors to help improve these safety measures. Through this well thought out, step-by-step process for implementing new adventitious agent testing technologies, industry gains the opportunity to harmonize its new technology implementation processes. This harmonization can streamline the evaluation and approval of new technologies by appropriate health authorities with the end effect of promoting more safe, responsive and timely drug release for enhancing patient care.”
BioPhorum’s Biomanufacturing Technology Roadmap outlined the aspiration for a <2-day AAT for product release by 2026. However, as the biomanufacturing landscape evolves to include advanced therapy medicinal products, industry must embrace new technologies that assure safety from adventitious agents in a much shorter timeframe. The COVID-19 pandemic has also emphasized an urgent need for changing paradigms to enable faster lot release and access to life-saving therapeutics.
This paper will help biomanufacturers meet this increasing need for rapid solutions.