The FDA conducts inspections of medical device manufacturers to assess compliance against regulatory requirements. These inspections can result in the issuance of “findings” in the form of a “483,” named for the form on which the investigator records their observations.
After an inspection, the FDA staff reviews the Form 483 Investigator findings, along with the response provided by the manufacturer, and decides whether further Agency action is needed to assure the cited violations are properly addressed. I once witnessed an FDA District Director state that the FDA will not issue a Warning Letter in association with Form 483 issues if the response provided by the manufacturer is adequate, assuring the FDA that the manufacturer can resolve the issues on their own. Who then is directly responsible, and what is expected of them?
FDA Regulatory Procedures Manual: 4-1-1 - Warning Letter Procedures: Responsible officials in positions of authority in regulated firms have a legal duty to implement whatever measures are necessary to ensure that their products, practices, processes, or other activities comply with the law. Under the law such individuals are presumed to be fully aware of their responsibilities.
The instructions provided by the Food and Drug Administration on both, a Form 483 and a Warning Letter, are stated as follows:
FDA 483 Instruction: “The observations noted in this Form FDA-483 are not an exhaustive listing of objectionable conditions. Under the law, your firm is responsible for conducting internal self-audits to identify and correct and all violations of the quality system requirements.”
FDA Warning Letter Instruction: “You should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility. It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the FDA 483 issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems. Your firm should investigate and determine the causes of the violations, and take prompt actions to correct the violations and bring the products into compliance.”
One of the biggest mistakes most manufacturers make is to believe the only thing that is wrong with their Quality Management System is what the FDA pointed out to them in the examples of non-compliance provided by the Investigator in the Form 483. This is a significant error! While the immediate response should first focus on the correction of the issues identified by the FDA, the response must also provide a plan to holistically review the remainder of the QMS to systemically identify, investigate, and address, any other issues of noncompliance that may exist.