Responsibility in Establishing and Maintaining FDA Audit Readiness

Continuing our plan to detail the regulatory and fundamental quality responsibilities that all brand manufacturers (especially online-only brands) need to embrace, this piece offers a short discussion about another responsibility/accountability gap that often exists in the industry regarding Internal Inspection.

Introduction: While the odds of a dietary supplement manufacturer or brand owner receiving an FDA audit are small, the learnings taken from a “mock” audit can be invaluable. An FDA audit may last a day or several days but the preparedness for the audit can impact the process and outcome of the inspection. Planning and training can make the difference between a positive and negative conclusion.

Issue: Most companies agonize over the idea of a surprise FDA audit. The ability to reduce that anxiety rests with preparation, planning and practice. The time to catch deficiencies is before an audit occurs. The practice exercise of conducting an annual internal audit provides the ability to build team confidence, identify potential problems and reduce the anxiety caused by an actual FDA.

Exercise: The internal audit should not be a surprise to the team and should be scheduled in advance. The goal of the mock inspection should not be to prove your company is perfect but to look for opportunities and issues that may not have been known previously. The key to a successful internal or external audit is the team’s ability to efficiently access and provide the auditor with the documentation that is required. Documentation is key because it is the only form of information an external auditor will easily accept. Even visual inspections are required to have SOP substantiation. All documentation should be controlled, up to date and easily accessible. In today’s digital files the practice of finding documents is critical.

The QA/QC trained personnel should work with management to develop a checklist to follow through the internal audit. The scope of the audit should focus on:

  • SOPs and organizational documents
  • Product production records
  • Records maintenance
  • Product inspection, storage and distribution records
  • Corrective action process and records
  • Building and equipment maintenance
  • Facility sanitation

Items such as employee training, personnel qualifications, management roles and other “people” SOPs should be easily accessed.

The quality systems are usually the first processes to be inspected. These systems should include cGMP monitoring, testing processes, specifications, retained samples, out of spec process, supplier qualification, and Adverse and Serious Adverse Event Reporting (AER/SAER) processes. The inspection should cover the facility including design, security, maintenance, sanitation, equipment placement and cleaning logs as well as maintenance records.

Other items for consideration should include material specification and control processes, material storage, inventory control.

Access to batch records, labels, inspection records, laboratory controls and cleaning records should be part of the internal audit checklist. Finished product testing and inspection processes to release for distribution are imperative.

Relevance: Brand owners who buy product from contract manufacturers often believe they are exempt from audits or cGMP requirements. This belief is incorrect as the FDA has repeatedly expressed through Warning Letters that the brand owner is obligated to know every aspect of production as if it were owned.         

Example:        From an actual FDA Warning Letter (Reishi D. International 02/17/18):

As a distributor that contracts with a manufacturer to manufacture, package, and label dietary supplements on your behalf that your firm releases for distribution under your firm’s name, your firm has an obligation to know what and how manufacturing, packaging, and/or labeling activities are performed so that you can make decisions related to whether your dietary supplement products conform to established specifications and whether to approve and release the products for distribution [72 Fed. Reg. 34752, 34790 (Jun. 25, 2007)]. Your firm introduces or delivers, or causes the introduction or delivery, of the dietary supplement into interstate commerce in its final form for distribution to consumers. As such, your firm has an overarching and ultimate responsibility to ensure that all phases of the production of that product are in compliance with dietary supplement CGMP requirements. Although a firm may contract out certain dietary supplement manufacturing, packaging, and/or labeling operations; however, it cannot contract out its ultimate responsibility to ensure that the dietary supplement it places into commerce (or causes to be placed into commerce) is not adulterated for failure to comply with dietary supplement cGMP requirements (see United States v. Dotterweich, 320 U.S. 277, 284 (1943) (explaining that an offense can be committed under the Act by anyone who has “a responsible share in the furtherance of the transaction which the statute outlaws”); United States v. Park, 421 U.S. 658, 672 (1975) (holding that criminal liability under the Act does not turn on awareness of wrongdoing, and that “agents vested with the responsibility, and power commensurate with that responsibility, to devise whatever measures are necessary to ensure compliance with the Act” can be held accountable for violations of the Act)). The Act prohibits a person from introducing or delivering for introduction, or causing the delivery or introduction, into interstate commerce a dietary supplement that is adulterated under section 402(g) for failure to comply with dietary supplement CGMP requirements (see 21 U.S.C. 342(g) and 331(a)). Thus, a firm that contracts with other firms to conduct certain dietary supplement manufacturing, packaging, and labeling operations for it is responsible for ensuring that the product is not adulterated for failure to comply with dietary supplement CGMP requirements, regardless of who actually performs the dietary supplement CGMP operations.

Conclusion: The internal audit, or mock inspection, is a valuable tool to not only practice for a real-life scenario but also serves to uncover issues previously unknown. Preparation, planning and practice can improve the company both before and at the time of an external audit.

For more information on mock audits and many other matters of regulatory assistance please contact Industry Transparency Center for additional assistance.