Six New FDA Enforcement Policies: How They Impact You

For Life Science Companies

Marla Phillips

On August 6, 2009, FDA Commissioner Dr. Margaret Hamburg publicly announced the FDA's new enforcement strategy. This strategy involves six new policies that went into effect on September 15, 2009. What are the policies and what do they mean to you?

It is important to note that there is no regulatory requirement to respond to 483 observations.
1. The FDA will set post-inspection deadlines. Firms will generally have no more than 15 working days in which to respond to serious violations before the FDA moves ahead with a warning letter or enforcement action.
  • Impact: The way this enforcement policy reads, it seems as though the FDA will issue a Warning Letter if a firm does not respond to 483 Observations within 15 days. This is confusing, and fortunately, is not an accurate interpretation. The policy was announced based on historical issues where the FDA would find serious GMP violations and intended to issue a warning letter. However, the firm would submit updates beyond 15 days, as well as submit subsequent updates on a periodic basis. With each update, the FDA would stop its process in order to review the responses to see if the expectations for GMP compliance were being met. This process would drag out the issuance of a warning letter, when really one had been warranted many months beforehand.

    It is important to note that there is no regulatory requirement to respond to 483 observations. Therefore, a warning letter will not be issued just because a firm does not respond in a timely manner, or respond at all. However, if the FDA feels that the violations are serious and wants to issue a warning letter, they will only review responses from a firm if they are sent within 15 days. It is important to respond not only in a timely manner but also to have action items that address the issues with the overriding systems that allowed the violations to occur. This is the firm's opportunity to demonstrate to the FDA that the compliance issues uncovered by the FDA are understood and comprehensive action plans are being put in place to remediate the issue and to avoid future occurrence.

2. The FDA will take responsible steps to speed the issuance of warning letters. FDA's Chief Counsel will limit warning letter review to significant legal issues, therefore allowing most enforcement letters to move forward through a more streamlined process.

  • Impact: since firms now only have 15 days to respond to FDA inspection findings, as stated in policy #1 above, the speed at which the FDA operates internally has very little impact on the actual outcome other than timing. Historically, the longer the FDA took, the more opportunities firms had to send in multiple responses in an effort to demonstrate that action items were completed and implemented as planned. However, once the FDA heads down the path of warning letter, there is very little a firm can do now to stop the train.

3. The FDA will seek to work more closely with our regulatory partners to develop effective risk control and enforcement strategies. This action is mainly focused on the food industry, where local, state, and international offices have more authority than the FDA to take action quickly.

  • Impact: hopefully greater safety for us as consumers once suspect food is out in the market.

4. The FDA will prioritize enforcement follow-up. After a warning letter or product recall, the FDA will make it a priority to follow up with appropriate action.

  • Impact: This policy could impact a firm in a couple of different ways.

Firms that are engaged in high risk products (i.e. sterile products or products that are necessary for patients) can expect that the FDA will prioritize the re-inspection of their facility in a timely manner. The FDA will be coming in sooner to verify that the firm has completed commitments and they will ask for a demonstration that the actions were effective. There is less time to implement a corrective action and see the benefit of that action. Corrective actions need to be thorough and the firm needs to have an understanding during CAPA development as to how they will measure the effectiveness of that CAPA.

Firms that are not engaged in high risk products may experience a delay in having the FDA return to the facility to verify that corrective actions were sufficient and that the firm is considered to be within compliance expectations of the FDA. This can be challenging if the firm is in the process of submitting applications for drug products (whether NDA or ANDA applications). As we know, pre-approval inspections require that the firm operates under GMP expectations in addition to verifying the scientific aspects and data of the product in question. A second way this can be challenging is for firms that are dependent on investor money and market confidence to survive. These firms are heavily reliant on a stamp of approval from the FDA in order for them to secure additional funding to continue or in order to get their one and only product on the market to start generating revenue. Delays from the FDA in these examples are constantly analyzed/interpreted by market investors.

5. The FDA will be prepared to act swiftly and aggressively to protect the public. The FDA will consider immediate action without the issuance of a formal warning letter when necessary.

  • Impact: Not necessarily new, just greater emphasis and perhaps greater empowerment to the Districts to act when they feel it is necessary. There are multiple examples of firms being issued a consent decree without having been issued a warning letter first. Again, this is not new, just restated.

6. The FDA is developing a formal warning letter "close-out" process. If the FDA can verify the effectiveness of corrective actions (typically through re-inspection), then a close-out letter will be issued to signify closure of the warning letter issues.

  • Impact: This is extremely important for companies that are not as established as big pharma. Receiving a close-out letter signals a clear indication to industry and investors that the FDA is truly satisfied with corrective actions and that warning letter issues are resolved. As stated above in # 4, the FDA might not re-inspect in a timely fashion if the firm is not manufacturing high risk products. The lack of receiving a close-out letter in a timely fashion may be incorrectly interpreted by the industry and investors as assuming the FDA has significant GMP concerns that are still unresolved.


The best line of defense is always to be prepared (whether we are talking about sports or business). How can a firm be prepared as it relates to these enforcement policies? First of all, understanding these policies, as well as how the FDA will enforce them, is a step in the right direction. Most importantly, however, and easier said than done, is to ensure compliance to begin with. In an effort to determine if the systems within your firm would meet FDA expectations, there is a process that can be followed that is tedious and time-consuming, but one that should only have to be done once in its entirety, assuming the systems are subsequently maintained. That process includes the following top-down progression:

  1. Ensure that Quality Policies are in alignment with the sections of the Code of Federal Regulations (CFR) that are applicable to your firm's line of business.
  2. Verify that Standard Operating Procedures (SOPs) are in place that would allow full implementation of the Quality Policies and therefore the requirements of the CFR.
  3. Ensure that SOPs are detailed enough and clear enough to ensure employees are able to consistently implement what is asked of them.
  4. Ensure appropriate training is conducted and documented based on a risk assessment of the activities required by the SOPs. In some cases, read and understand is sufficient, whereas the opposite end of the spectrum requires demonstration of skills through formal qualification.
  5. Verify that practice on the floor is in alignment and is compliant with SOP requirements. If not, it may be the SOP that needs to be changed or better training devised for employees.

And of course, the above progression is not all that would be required to feel confident in the Quality Systems established by your firm. Constant oversight of the systems through thoughtful audits and meaningful performance measurements will assist the Quality Council in identifying areas of concern before non-compliance occurs. It is always critical to ensure that changes are assessed versus the impact to the overall system. And finally, a firm needs to be aware of the constantly evolving expectations of global regulators.

The best line of defense is to have excellent quality oversight now to ensure that the systems in place are compliant, functional, and effective. Then your firm won't have to worry about getting a warning letter in the first place. Easier said than done but more critical now than ever.

Dr. Marla A. Phillips joined Xavier University in 2008 as the Founder and Director of Med-XU. Med-XU is an organization within Xavier University that utilizes the ethical and neutral ground of the university to identify and develop initiatives that bring global regulators and industry together in an effort to collaboratively address issues faced by the Medical Device and Pharmaceutical industries. Since 2005, Dr. Phillips has worked with former FDA Investigators to conduct mock FDA inspections of pharmaceutical firms on a global level and has provided technical consulting assistance related to manufacturing, packaging and laboratory operations. Dr. Phillips started in the industry in 1996 when she was employed by Merck & Co., where she quickly took on positions of increasing responsibility, culminating in the position of Head of Quality Operations at the Merck North Carolina facility in 2000. Dr. Phillips holds a B.S. in Chemistry from Xavier University and a Ph.D. in Organic Chemistry from the University of North Carolina - Chapel Hill. Contact Dr. Phillips at 513-745-3073 or by email at