Application of FDA Form 483

FDA Form 483 can be issued to:

• Pharmaceutical Manufacturers (cGMP)
• 503B Outsourcing Facilities (cGMP), and
• 503A Pharmacies

We are well aware of the application involving manufacturers in the pharmaceutical industry and more recently to 503B Outsourcing Facilities required to follow cGMPs, but why the 503A Pharmacies?

Even though pharmacies, including compounding pharmacies, are inspected by state boards of pharmacy in each state, the FDA has the authority to and has become proactive in conducting its own inspections and, when necessary, taking enforcement actions to protect public health. During the inspection, the FDA will note on the Form 483 any observation of issues that may endanger patients. Next week, we will look at some specific findings in 503B and 503A pharmacies.

Now, we will look at FDA Warning Letters, which may ultimately follow the 483s if not adequately addressed.

General FDA Warning Letters

When FDA finds that a facility has significantly violated FDA regulations, FDA notifies the facility. This notification is often in the form of a Warning Letter. The Warning Letter identifies the violation, such as poor manufacturing practices, problems with claims for what a product can do, or incorrect directions for use. The letter also makes clear that the company must correct the problem and provides directions and a timeframe for the company to inform FDA of its plans for correction. FDA then checks to ensure that the company's corrections are adequate. Matters described in FDA warning letters may have been subject to subsequent interaction between FDA and the recipient of the letter that may have changed the regulatory status of the issues discussed in the letter.

Warning Letter Close-Out Letter Program

FDA may issue a Warning Letter close-out letter ("close-out letter") once the Agency has completed an evaluation of corrective actions undertaken by a firm in response to a Warning Letter. A close-out letter may issue when, based on FDA's evaluation, the firm has taken corrective action to address the violations contained in the Warning Letter.

A close-out letter will not be issued based on representations that some action will or has been taken. The corrective actions must actually have been made and verified by FDA. Usually, the standard for verifying that corrections have been implemented will be a follow-up inspection. If the Warning Letter contains violations that by their nature are not correctable, then no close-out letter will be issued. Future FDA inspections and regulatory activities may further assess the adequacy and sustainability of these corrections. Should violations be observed during a subsequent inspection or through other means, enforcement action may be taken without further notice. The FDA office that issued the Warning Letter will issue the close-out letter, and that office may be contacted for information on a particular Warning Letter.

More next week.