Complying with FDA 21 CFR Part 111 – Understanding the Process of FDA Inspections, FDA Form 483 & FDA Warning Letter Responses

July 11, 2012 By

What is FDA Form 483? The FDA has started conducting inspections of establishments that manufacture, process, pack, or hold dietary supplements without prior notice to determine the establishment’s compliance with laws administered by the FDA1. During an inspection, the FDA is looking for compliance with cGMPs (current Good Manufacturing Practices). The cGMPs are outlined in Title 21 CFR Part 111 of the Code of Federal Regulations, focusing on manufacturing processes and quality control.

The FDA Inspector records observations of non-compliance with cGMPs, if there are any. In such cases where there are observations the FDA officer will provide the establishment owner with a FDA Form 483 which includes the name of the firm, the date(s) of inspection and the observations recorded by the Inspector2.

What happens after an FDA Form 483 is issued?

After an FDA Form 483 is issued the establishment is allocated 15 days in which to provide an adequate response to all identified observations. In the context of FDA language, the word “adequate” is defined as providing both corrective and preventative actions to observations, as well as setting reasonable timelines for the change(s) to be effected. If a company either does not respond within the 15 day allotted time frame or if the FDA considers the response to be inadequate, then the 483 is escalated to a Warning Letter, which is made publicly available on the FDA’s electronic reading room (

According to the FDA definition, a Warning Letter is correspondence that notifies regulated industry about violations that the FDA Inspectors have documented during its inspections or investigations. Typically, a Warning Letter notifies a responsible individual or firm that the Agency considers one or more products, practices, processes, or other activities to be in violation of the Federal Food, Drug, and Cosmetic Act (the Act), its implementing regulations and other federal statutes. Warning Letters should only be issued for violations of regulatory significance, i.e., those that may actually lead to an enforcement action if the documented violations are not promptly and adequately corrected. A Warning Letter is one of the Agency’s principal means of achieving prompt voluntary compliance with the Act.

If response to FDA Form 483 is adequate

If no observations are made or an adequate response is provided to the FDA Form 483 then the FDA provides the inspected establishments with a final inspection report, called an Establishment Inspection Report (EIR), which includes:

  • Brief history of prior inspectional findings, including any action taken by FDA or corrective action taken by the firm in response to a previous inspection
  • The officer’s narrative report
  • Any refusals, voluntary corrections, or promises made by the firm’s management
  • Copies of forms the FDA issued to the firm during the inspection, including the FDA Form 483

Although an FDA inspection process can be a hassle for many companies, it does provide a great benefit in promoting an establishment as a cGMP compliant facility ensuring consumers that the establishment is producing quality dietary supplements that are safe and compliant with US FDA regulations.

In conclusion, ensuring that you are in compliance with cGMPs on a daily basis by performing regular audits with a solid quality control and quality assurance program in place can help get you ready for when the FDA knocks on your door for an inspection and possibly help avoid a troublesome Form 483 or Warning Letter.

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