Warning Letters: Roadmap to Corrective Action

Facilities should understand the importance of this “early-warning” message from FDA.

Following an unsatisfactory facility inspection, the FDA has the ability to give individuals and firms an opportunity to take voluntary and prompt corrective action in response to deficient findings before it initiates an enforcement action. FDA uses the Warning Letter to achieve voluntary compliance and to establish prior notice.

A Warning Letter is a written communication from FDA notifying a responsible individual, firm, or facility that the agency considers one or more products, practices, processes, or other activities to be in violation of the laws that FDA enforces. The Warning Letter states that the failure to take appropriate and prompt action to correct and prevent any future repeat of the violations noted in the Warning Letter may result in an administrative or regulatory action. Although serious noncompliance is a catalyst for a Warning Letter, a Warning Letter is informal and advisory. The issuance of a Warning Letter embraces the FDA policy that, when consistent with the agency’s public health responsibilities, it is appropriate to afford individuals, firms, and facilities an opportunity to take appropriate and prompt voluntary corrective actions prior to the initiation of an enforcement action.

The agency position is that Warning Letters are issued only for violations of regulatory significance. Significant violations are those violations that may lead to enforcement action if not promptly and adequately corrected. A Warning Letter is the agency’s principal means of achieving prompt voluntary compliance with the Federal Food, Drug, and Cosmetic Act (the Act).

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. Consequently, responsible individuals should not assume that they would receive a Warning Letter, or other prior notice, before FDA initiates enforcement action.

A Warning Letter constitutes official but not final, agency action. Observations will be classified Official Action Indicated, OAI, whenever a Warning Letter is issued. This procedure provides greater consistency and uniformity in the classification system and regulatory policy.

A Warning Letter is considered a public record and is posted on FDA’s website for public viewing. Warning Letters are issued by FDA field offices and will detail the problems found during an inspection and steps that the recipients need to take within 15 business days of receipt of the letter. Including directions for the preparation of a written response that details the corrective action plan and plan submittal instructions.

A facility that fails to respond to a Warning Letter or to correct problems promptly may be re-inspected by FDA at a cost to the facility. The facility also may be subject to an enforcement or administrative action that could include a directed plan of correction, suspension or revocation of its licensing, civil money penalties, an injunction, and other regulatory or administrative actions to ensure that it corrects the violation(s).

Warning Letters generally cause manufacturers to quickly and cooperatively correct problems. In some cases, this may mean that the product needs to be temporarily removed from the market or production must be stopped until the problem is resolved. In other cases, the problem may not require the manufacturer to stop its product from being sold. As with other product safety decisions, completely removing a product from the market, based on the problems justifying a Warning Letter, can also be dangerous to people who need the product. Warning Letters often help to solve product problems without having to remove necessary products from the market.

When necessary, for drug manufacturers who receive Warning Letters, FDA may withhold approval of a new drug from that manufacturer until identified manufacturing problems that may affect the new drug are corrected. In addition, for foreign drug manufacturers who receive Warning Letters, FDA may refuse to allow the manufacturer’s drug to be imported for sale in the United States until the problems that may affect the drug are corrected.

In cases when FDA finds that a manufacturer is either unwilling or unable to effectively remediate problems after receiving a Warning Letter, the agency can take additional measures to protect public health. For instance, FDA can quickly issue a press release or consumer alert to notify the public not to use the product. Additionally, FDA can take legal action to seize batches of a drug or to stop a company from further manufacturing and distributing the drug.

Observations of regulatory significance generally reflect systemic issues. Observations that indicate a systemic issue generally are accompanied by the following type of language;

• sterility is not assured
• process is not validated
• you failed to follow procedures
• investigation is incomplete
• you failed to include other batches
• did not address the reason or root cause

Remedial plans will need to include instance specific corrective actions for these types of violations and also preventative actions designed to address the larger systemic issues.

Generally, Warning Letter responses will include;

• A direct response to each issue noted in the warning letter
• Evidence and/or documentation to support the corporate opinion if it differs from that of the FDA
• List of actions already taken
• List of future actions planned, accompanied by a detailed timeline
• A commitment to correct the systemic issues, with language that makes it very clear those system failures are well understood

In summary, the Warning Letter program while seen by many in our industry as a negative event, is a tool that was designed to give us a chance to have direct feedback from FDA, and an opportunity to be the leaders of our own improvement. The change that follows a Warning Letter is often a painful process, but it helps to remember that this process allows us to evolve and improve, without depriving the public of critically necessary therapies.

If your organization finds themselves in this position, be an active agent of change, and embrace the intent of the regulations – to help us help our patients – as safely and effectively as possible!

Gina Guido-Redden
Chief Technical Officer
Coda Corp USA
(p) 716.751.6150 (f) 716.751.6193
[email protected]


“Quality is never an accident; it is the result of high intention, sincere effort, intelligent direction and skillful execution. It represents the wisest of many alternatives.”


Post a comment or leave a trackback: Trackback URL.

Post a Comment

Your email is never published nor shared. Required fields are marked *


You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <s> <strike> <strong>