Recovering from an FDA inspection.
Your inspection is over, but that’s not the end if unacceptable conditions have been observed. It’s the beginning of a final phase that must be properly managed to bring your company and your device into compliance.
Inspection observations and citations
Observations are listed on U.S. Food and Drug Administration (FDA) Form 483 in order of severity, as determined by the inspector. Each observation includes a citation of the law, regulation or Act that applies to each particular finding, along with a statement of the specific conditions noted during the inspection.
Data from the FDA shows that 422 Form 483s were issued to device manufacturers between October 1, 2019 and September 30, 2020 (FY 2020). Reasons for receiving a 483 are varied, but frequently include:
- Failure to investigate device, packaging or labeling flaws
- Failure to provide access to management or SMEs
- Failure to provide adequate supplier data
- Failure to submit timely Medical Device Reporting (MDR)
- Failure to validate automation software for its intended use
- Lack of design history files or design validation
- Lack of documentation, reports, records, or files
- Lack of maintenance schedules
- Lack of training, quality, process control, or environmental procedures
Form 483 responses
Form 483s are provided to company management at the end of the inspection. The inspector recites the observations and discusses their significance to ensure that each citation is fully understood.
Companies are expected to respond to the 483s in writing, with a comprehensive outline of corrective actions for each citation. You should list citations in the order of severity, beginning with the most severe.
Responses should be submitted within 15 days after receiving a 483. You may wish to engage legal counsel to review your responses if time allows.
Corrective actions should be put in place as soon as possible. It is also wise to review processes and procedures that were not cited, in order to take proactive measures prior to the next inspection.
FDA warning letters are far more serious than a Form 483 in that they address critical violations with the potential to disrupt or halt business. A warning letter provides directions for a thorough response, along with a firm deadline for receipt of said response.
Reasons for receiving a warning letter are varied. The FDA warning letter database lists several recurring subjects including, but not limited, to:
- False or misleading claims
- Incomplete quality system regulation (QSR)
- Investigational device exemptions
- Lack of premarket approval (PMA) inspection
- Nonconformance with current good manufacturing practice (cGMP) guidelines
- Unapproved, adulterated or misbranded products
Failure to expedite corrective actions, as outlined in your response, can result in fines, criminal complaints, or orders to stop production.
A consent decree comes down after recurrent nonconformance with cGMP guidelines, as noted in Form 483 observations and subsequent warning letters. It is a legal agreement enforced by the U.S. Department of Justice (DOJ). This action impacts all areas of the business with heavy financial penalties, remediation costs, dropped sales, lower stock value, and a tarnished reputation.
The Food and Drug Law Institute outlines the components of a consent decree as ordered under the Federal Food, Drug, and Cosmetic Act (FDCA). While the specifics will vary, consent decrees typically involve:
- Naming of individual defendants
- Injunctive provisions regarding the resumption of operations
- Engagement of an independent auditor at the company’s cost
- Agreed upon schedule of periodic audits “Letter shutdown” provision which allows the government to close business operations
- Liquidated damages paid to the government by day, by violation, and by retail value
- Notification of any change in ownership or named defendants
- Length of the decree and its dissolution under court order
The government may also seek disgorgement and restitution. However, this is a controversial action that has been challenged before the Supreme Court.