What To Do If You're Issued a Form FDA 483


Virtually any company involved in the manufacture of pharmaceuticals, biologics, or devices can be subject to receiving an FDA 483.

As such, pharmaceutical executives should understand the significance of receiving a Form FDA 483 and different ways of handling it.

What is a Form FDA 483?

A Form FDA 483 is list of observations made by the FDA Investigator that indicate to the Investigator deficiencies from compliance with GMP. The FDA 483 can also be a prerequisite to an FDA Warning letter.

The FDA 483 that is issued to the most responsible person at the company at the conclusion of an inspection.

Investigators from the Food and Drug Administration's Office of Regulatory Affairs issue the form when they observe practices that can adulterate the pharmaceuticals, devices, or biologics being produced.

On the form, the inspectors identify any deficiencies or violations that they find to report to the managers. FDA Investigators list the issues in order of significance.

The issues consist of short and long statements based on the relevant regulations or citations in a database used by FDA. These statements, which are in plain language, identify each specific objectionable issue.

Some examples include equipment used to manufacture or produce a pharmaceutical product is not appropriately designed to facilitate operations for its intended use or "procedures designed to prevent contamination by microorganisms were not followed." Multiple citations can exist for a given regulation.

The inspectors look up a specific citation in their database on the basis of its short description and enter its long description onto the Form 483.

If a citation for a given regulation is not in the database, they enter it manually. Then they read and discuss each deficiency with the senior managers. Investigators attempt to make certain that the managers understand the meaning of the issues.


Key Points About Form 483s

There are a number of things pharmaceutical and device executives should know about a Form 483.

1. The form is not an all-inclusive list of issues that inspectors may have found

The inspector may have omitted issues that are of questionable importance or for which the significance is not known.

2. It does not constitute a final determination of violation

It only provides documentation of what the investigators found when they inspected the facilities .. The Food and Drug Administration looks at the information on the Form 483 and on another internal FDA document written by the Investigators called the Establishment Inspection Report when determining what actions to take.

It is up to the company to determine the measures must be taken by their firm to resolve the issues that the inspectors noted.

What to do if you're issued a Form 483

1. Respond verbally at the end of inspection

Responding verbally to the findings at the end of an inspection are the first steps in addressing a Form 483. During the closing meeting at the end of the inspection executives should:

• Clarify any misunderstandings, and

• Identify any issues that were rectified during the inspection

2. Prepare a written response within 15 days

Within fifteen days the FDA-483 was issued, executives should prepare a written response. Although it's not required, one should always be sent, as a good response can prevent the FDA from issuing a Warning Letter.

In the response, executives should explain the following:

• That they understand the importance of the findings and how they pertain to quality.
• The corrective actions that they are taking to rectify the issues.
• Root causes of the deficiencies
• A detailed proposal of the corrective actions you plan to carry out.

If the firm cannot implement the changes immediately, they should provide an appropriate time frame for implementing them with target dates if possible.

The plan for correcting the issues should be as specific. They should explain to the FDA that all of the global changes have been addressed. Provide hard copies of any records showing corrections if possible. The firm should expect the agency to follow up on promised corrections during the re-inspection, which will usually occur within the first year following issuance of the FDA-483.

How to prevent a Form FDA 483

To avoid being issued a Form 483, executives should take the following steps:

• Make certain that valid and reliable quality control and quality assurance systems and procedures are in place and meet all FDA GMP requirements

• Make certain that personnel are appropriately trained in Good clinical Practices, Good Manufacturing Practices, and Good Laboratory Practices

• Make certain that records are accurate and up-to-date

• Conduct regular internal or contract audits to identify gaps


Although pharmaceutical and device companies want to avoid receiving a Form FDA 483, executives who receive them can ameliorate the situation by taking the appropriate and well designed corrective actions.

These include responding to the Food and Drug Administration in a timely manner, implementing changes to address issues and improve quality, and assuring all corrective actions have been implemented and the problems corrected.

Need help?

If you've been issued a Form 483 and need assistance crafting an adequate response, contact us today. Our FDA compliance consultants have firsthand experience with FDA regulations. Want to learn more about how we can help? Grab our free whitepaper: The Benefits for Pharma Companies of Working with an FDA Compliance Consulting Firm

Topics: Process, FDA Warning Letters, FDA regulatory consultants, Compliance Consulting, Global Regulations