Working with FDA for Successful Outcomes Post-Inspection

The final rule, 21 CFR Part 111 current Good Manufacturing Practices for Dietary Supplements (cGMPs), became the law June 25, 2007. The final date for all companies to be in full compliance was June 25, 2010. Needless to say, the percentage of non-compliant companies is still far too high. There are still companies that have not taken a single step toward implementing the new rules.

In 2014, seven years since the passage of the rule, there are companies that have never heard of the dietary supplement cGMPs.

Prior to the passage of the Dietary Supplement Health and Education Act of 1994 and the cGMPs of 2007, the industry held a negative reputation of unregulated snake oil manufacturers and distributors. FDA was under pressure to remove these products from the marketplace. There was considerable concern because the industry delivered products to market without prior approval as is the rule for pharmaceuticals. Many of these products did not meet label declarations or potency claims. Some of the commonly used ingredients were botanicals which were mostly used in other countries as drug products. Recognizing that there is definitely a place for dietary supplements in support of the public’s health, 21 CFR Part 111 was designed to prevent adulteration by addressing those issues which could have rendered those products unfit or unsafe for human consumption.

Once the rule was passed, the timeframe for compliance was phased in over a period on three years based upon the size of a company. From 2008 until now, FDA inspections also appeared to take a phased in approach regarding the agency’s focal points for compliance. Much of the emphasis was placed on receipt, handling, and testing of raw materials.

It became clear that FDA placed ingredient identity high on its list of importance to ensure correct materials, meeting prescribed quality standards, were being utilized. The responsibilities of quality control personnel, master manufacturing records, and finished product testing were also audited with fervor and intensity, to ensure batch to-batch consistency. A high level of attention was also given to unsubstantiated claims and advertising. Several companies were cited for drug claims on websites or in other forms of advertising.

After six years, these noncompliance areas are still highly prevalent and are still being cited in FDA’s Form 483 observation reports and in warning letters. As a result of this seemingly negligent behavior or total lack of knowledge of the rules, FDA has become frustrated and may increase the use of tools provided to them by the Food Safety Modernization Act including: product seizures, recalls, detentions, consent decrees or physical plant closures and regulatory action against individuals deemed responsible.

So what must industry do to work with FDA to achieve successful outcomes?

The obvious answer is to implement the cGMPs and any other regulations that apply to a firm’s products. However, based upon facts and data published by FDA, this has not been a simple task. Implementation programs by many companies are still “works in process” or even nonexistent. In these cases, there is a good chance that these companies may get a Form 483, a list of observations, or even a warning letter after an inspection.

Let’s say that doesn’t happen and the FDA makes its presence known. First and foremost, the behaviors of management and employees during the inspection, which in some cases has not been cooperative, usually gives an FDA investigator a preview into whether or not the company is sincere and fully committed to compliance. When a Form 483 is issued at the conclusion of an inspection, within 15 days of receipt it is advisable that the company respond in writing to FDA with a corrective action plan. This corrective action report should address each cited noncompliance with documented evidence of practices or procedures that have already been corrected and all compliance activities yet to be implemented with expected completion dates.

The response includes exhibits of documents that confirm the changes have been made or are in process of being made. In cases where facility improvements are required, that cannot be done immediately, it is recommended to submit plans, blueprints, purchase orders, or whatever documentation necessary to support the commitments being made.

For situations where products may be compromised due to construction or leasehold improvement, it is advised to include information describing how these products will be handled during the changeover. It is important here to include expected dates of completion. These dates must be timely, keeping in mind that compliance dates have already passed and products being manufactured under conditions that are not cGMP compliant are adulterated. In such cases where product quality may be affected, FDA may not accept unreasonable dates for achieving compliance.

If the 483 reports or warning letter contains violations concerning claims or advertising, it may be prudent to consult with an attorney or consultant who has had experience working with FDA or FTC in dealing with label declarations, claims, and advertising. This area may bring greater scrutiny and hasten regulatory action than some of the cGMP violations.

It is important to have your entire operation audited for compliance to regulations. Companies shall have management and all employees trained by a qualified person in cGMP requirements as well as any other regulations that apply to your operation. Ignorance of the law is not an excuse. Even if specific noncompliance issues are not observed or noted in the FDA inspection, they will indeed surface during a follow-up inspection and will be indicative that your corrective actions were not all inclusive.

Finally, if your company is registered with FDA as is mandated, and you have not been inspected for cGMP compliance with the current regulations, your inspection is forthcoming. It would be extremely prudent that your company get ready for inspection before the FDA is at your doorstep!