A Warning Letter can result from an escalated 483 finding where the FDA investigator felt that insufficient corrective actions or responses were implemented after the issuance of a repeat 483. Typically, a Warning Letter carries prosecutorial weight and means that the FDA may elect to take legal action if not addressed appropriately. Fortunately, a Warning letter still allows the manufacturer to own their own processes and, provided they address the Warning Letters sufficiently to the FDA’s requirements, will allow the manufacturer to continue business as usual. Repeat Warning letters may result in a Consent Decree

First, let’s define what each are separately. A Warning Letter, according to the FDA, discusses matters that may change the regulatory status of the company to whom it is issued. It can potentially result in a recall event, enforced by the FDA, or a negation of prior regulatory approvals. The Warning Letter itself will contain the details or status of the issues discussed in the letter. Warning Letter responses by the FDA may or may not be legal in nature.

Consent Decrees, on the other hand are issued after the FDA has taken legal action and are issued by a Judge (just like a search warrant or an arrest warrant). A consent decree may or may not identify culpability, but requires a response and is a binding judicial agreement that the FDA will control the aspects of the manufacturer that are presented in the decree. This is non-voluntary on the part of the manufacturer and, if the manufacturer refuses to comply, will result in escalated legal activity up to and including the prosecution of individuals and a “Cease and Desist” order issued to the company itself. Essentially, the FDA may chain the doors shut. In most cases, however, the FDA will provide quality and regulatory oversight to the manufacturer and all decisions must be made or agreed upon by the FDA before any product marketing or selling can occur.

Warning Letters are very specific and responses must address every element found in the letter. Recipients have 15 working days (three weeks) to respond to the Warning letter. Like a 483, the recipient is required to put together a corrective action plan (just the plan, not the implementation of efforts) and submit this plan to the FDA. The manufacturer is not to await a response by the FDA before beginning implementation of these remediation efforts, but FDA responses may need to be incorporated into the plans after the fact.

This has just now become company priority No. 1. If the response to your warning letter was insufficient, then that means that whatever you have proposed will not work. You need to go back to the drawing board and/or bring in additional individuals that are experts in the area of the finding to discuss additional remediation efforts. Warning letters are not passive entities and an “explanation” is generally insufficient to get the FDA to change their minds. Appropriate and robust corrective actions are almost always required.

Assess the impact to your products in this case, have you covered everything? If not, expand the remediation efforts to include more products, facilities, or personnel. Bring in a consultant to give you their feedback based on knowledge of the whole industry and the FDA, not just your company. Resubmit a new plan and try again. The FDA rarely takes action (as long as there is no risk to public health), provided you are honestly attempting to address the issues in the Warning Letter.

Not necessarily. The FDA will tell you what it means to you exactly. More commonly, it means that you have to use an FDA individual to approve of your internal decisions affecting quality, regulatory, and marketing while continuing to do business. This will slow the process down considerably, but not necessarily stop your processes. If your consent decree has been issued and you are not following the parameters of the consent decree exactly, you may then have to close your doors if you are ordered to do so by a legal entity such as the Federal Marshals.

In a nutshell, all activities that fall under the auspices of a Consent Decree must be well documented, approved, and retained. The documentation systems for a Consent Decree will still be required to follow the method for all quality documentation (see 21 CFR 820.40). There may be an additional layer of approvals, but all other requirements will still stand.