What happens when an FDA Form 483 is issued?

[John Robinson]

One of the chief aims of the FDA is to ensure the protection of public health and making sure that select types of organizations comply with the provisions of the Food, Drug and Cosmetic Act. It enforces these aims by conducting periodic inspections of the facilities and types of organizations that come under its purview. The FDA is empowered by the terms of the Federal Food, Drug, and Cosmetic Act, Sec. 704 to carry out these inspections to meet its stated intent. These organizations include:

• Clinical trial sponsors
• Clinical trial investigators
• Institutional Review Boards (IRB)
• Facilities that are involved in the business of manufacturing, processing or packing of FDA-regulated products

When the FDA finds that the organization is not meeting the set requirements; it issues either a Form 483 or a Warning Letter to the organization at the conclusion of the investigation. The first of these steps is the Form FDA 483. It is used to list the observations made from the inspection, in which it documents and communicates its concerns that it observes during its inspections. The FDA in its website says that the FDA Form 483 is issued to the management of the company “when an investigator(s) has observed any conditions that in their judgement may constitute violations of the Food Drug and Cosmetic (FD&C) Act and related Acts”.

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How does the FDA observe its findings?

The FDA ensures that there is no subjectivity in the matter of its observations, which is the prelude to issuing the company an FDA Form 483. There are no grey areas or any kind of arbitrariness on the part of the FDA investigators when they carry out their observations.

The FDA investigators are thoroughly trained to ensure that their observations are noted on the FDA Form 483 in a clear and specific format before it is issued. These are based on the thorough and demonstrable observations that the investigator makes. These observations should reflect that the “food, drug, device or cosmetic has been adulterated or is being prepared, packed, or held under conditions whereby it may become adulterated or rendered injurious to health.”

An issued FDA Form 483 contains all of the inspector’s observations and judgments made during the inspection. It will clearly specify the areas in which the organization fell short of regulatory requirements and expectations. When an FDA Form 483 is issued, it calls for a response within 15 working days of the issue. Although a written response is not a mandatory requirement; it constitutes good practice and is preferred. The response has to detail the reasons for the shortfalls and ways by which the organization will remedy them.

If the organization does not file a satisfactory response to the FDA Form 483 violations within the specified time period, it is issued a Warning Letter. The Warning Letter is the next action the FDA takes to elicit a response. The organization has to file a response to it within 15 working days. If it wants more time, it will have to ask for it in writing. If the FDA Form 483 and Warning Letter fail to evoke a proper and satisfactory response within this period, the FDA may proceed to take the appropriate legal action against the organization. Based on the nature and gravity of the deviations, these legal actions could include suspension or cancellation of the manufacturing license, withholding of the product approval, or even shutting down the business.