Audits in the time of COVID-19 – Implications for a CMO

Travel restrictions imposed by the pandemic have limited the ability of pharmaceutical companies and health authority personnel to travel and conduct in-person inspections of contract manufacturing organizations (CMOs). 

Due to these limitations, both health authorities and CMOs must adapt and move to new processes for conducting audits. This can be done by leveraging innovation and technology solutions.

Over the past two years, health authorities, globally, have adapted their inspection processes to respond to quality concerns, new product approvals and post-approval changes.  In the US, the Food and Drug Administration (FDA) is currently only conducting an in-person facility inspection if it is mission-critical. Mission-critical inspections include products that are in drug shortage, breakthrough therapies and products that treat serious diseases for which there is no substitute.

Pharmaceutical companies with products that do not meet mission-critical criteria may experience delays in the approval of new products or post-approval changes. These delays can be avoided if the manufacturing site is eligible to participate in alternative evaluation tools (such as Remote Interactive Evaluations (RIE), Mutual Recognition Agreements, and Records Requests). The FDA does not consider these tools as a replacement for inspections, rather they provide a means for the FDA to evaluate risks and data integrity remotely in order to make a regulatory decision.

A manufacturing facility is eligible to participate in alternative evaluation tools based upon FDA’s facility risk assessment of the site and review of its compliance history. 

Considerations for evaluating a site’s risk include: 

• Compliance history
• Recall history 
• Manufacturing processing steps 
• Frequency of inspection (including foreign inspections)
• Product risk (dosage form, route of administration, etc.)

Whether the manufacturing facility is supporting a remote evaluation by FDA or virtual inspection by another health authority, the following best practices should be considered:

• Verify that there is adequate internet bandwidth in all production areas in scope of the remote audit. The quality of live-streaming video during remote evaluations is critical for health authorities to effectively evaluate the equipment, personnel, and operations.
• Secure enough portable tablets for hosts and site tour guides, specifically in areas where cameras may not be installed, such as testing laboratories and warehousing.
• Test audio quality of devices to ensure it is clear and crisp and not muffled.
• For documentation requests provided electronically, ensure that the file naming conventions are standardized and can be easily interpreted. All files should be well-organized by topic or request.
• Effective use of downtime when a large time difference exists between the manufacturing site and the health authority and being flexible when following up to open requests.

Looking Ahead – Technology solutions and digitalization plays an important role in pharmaceutical manufacturing.  The future of product quality, including the surveillance framework developed by health authorities regulating pharmaceutical manufacturing facilities, will continue to be influenced by digitalization advancements.

Article References:

- FDA Mapp 5014

- RIE FDA Guidance

- PQRI Presentation: Remote Interactive Evaluations (RIEs) to Support FDA’s Facility Oversight during the COVID-19 Pandemic and Beyond • Stelios Tsinontides, Ph.D., FDA

- FDA Guidance, “Manufacturing, Supply Chain, and Drug and Biological Product Inspections During COVID-19 Public Health Emergency Questions and Answers Guidance for Industry” (updated May 2021)