Internal Auditing: A Sound Business Practice to Ensure Successful Project Outcomes in cGMP Manufacturing

From annual inspections by the FDA to regular auditing from sponsoring companies, Contract Manufacturing Organizations (CMOs) are under close scrutiny to ensure that their procedures and quality control processes keep them in good standing with Current Good Manufacturing Practice regulations (cGMP), Federal Drug Administration (FDA) and International Standards Organization (ISO) guidelines.

But quality CMOs should never stop there. Implementing regular internal audits can help ensure that there are no issues that could impact the APIs and pharmaceuticals they produce, their safety and efficacy and the safety of the lab and its staff.

Revisiting SOPs

All CMOs have their own Standard Operating Procedures (SOPs) in place that on occasion need to be revisited to make sure they are not only effective, but that they are being adhered to across the organization. An internal audit gives CMOs the opportunity to identify their strengths and weaknesses and possible risks and find ways to improve their organizational effectiveness to benefit current sponsors and those to come.

In the most extreme case, conducting internal audits help improve the odds that the FDA won’t beat you to the punch, and can help ensure that any future FDA inspection doesn’t end with a notation on form 483, which could impact drug approval.

So to make sure the odds for successful product commercialization come to pass, and to comply with cGMP regulations, CMOs need to conduct regular and frequent internal audits – at least several times a year – which can reveal issues that need attention.

Making Frequent Audits a Key SOP

In many cases, many of the problems that are revealed during an internal audit can be easily addressed if there are short timespans between audits. Yet when problems are uncovered with huge gaps between audits, they can impact multiple batches of chemicals, going back many months and sometimes you don’t know about them until it’s too late.

For example, an internal audit could reveal that there may be something wrong with your cleaning protocol, which can make every batch that came out of the equipment suspect. If you catch it early on, perhaps it only impacts a few recent batches that need to be analyzed.

So how can a CMO go about implementing a sound internal auditing program? Below are four key considerations.

1. Follow the FDA Quality Systems Approach. A convenient way to ensure you are covering all the bases is to use this proven approach, which involves evaluating six key operations: your Quality Systems, Production System, Facilities and Equipment System, Laboratory Controls System, Materials System and Packaging and Labeling System.
2. Appoint a Point Person. There should be one person whose central role is to manage internal audits – a project manager of sorts, who should be managing an internal team of auditors, as well as external auditors.
3. Implement an Audit Plan. A good internal audit requires an audit plan, as well as timely audit reporting that communicates the audit’s findings to the organization. This report should include an assessment of compliance risk and a comparison to current industry standards, regulations and guidelines to ensure compliance.
4. Don’t End with the Audit. All the internal audits in the world are meaningless without proper action. CMOs must assign and complete all the follow-up corrective and preventative steps related to the audit observations, which may include retraining staff or amending the SOP. These also should be included in a trend analysis that should be communicated to senior management.

Internal audits provide a good snapshot of the health of a CMO’s critical systems. By following consistent processes that focus on proper planning, analysis and reporting they provide one more assurance of the safety and quality of essential operations, and help ensure FDA and other external audits result in no negative findings – all necessary steps to help you get one step closer to product commercialization.

About the Author

Ed is the President and CEO of PCI Synthesis (PCI), he serves as a co-chair of the New England CRO/CMO Council and sits on the Industrial Advisory Board for the Department of Chemical Engineering at UMass, Amherst. Ed is also a long standing member of the American Chemical Society and advises the Bulk Pharmaceutical Task Force of the Society of Chemical Manufacturer’s and Affiliates (SOCMA).

Do you have questions? Talk to Ed.