From 1978 52nd On the Street album, Billy Joel sings: “Honesty is such a lonely word, everyone is so untrue; You hardly ever hear honesty, and mostly that’s what I need from you. ”Although we don’t want to start this bulletin on such a melancholy note, we thought of the texts because we recently had customer inquiries from the Food and Drug Administration.
Part of our daily work is helping customers respond to FD-483s, Warning Letters, and other compliance and enforcement actions from the FDA and similar regulatory agencies. Sometimes regulators like the FDA request a meeting or, in the case of the pandemic, a phone call. Depending on a number of factors we’ll be discussing, this call or meeting can be a potential opportunity for the company to break free from a near-fatal experience, or, unfortunately, it can speed the company up to a likely consent decree or something similar devastating consequences.
In this bulletin, we will share some of our shared experiences, both from 28 years of external advice and more than 12 years of working with the FDA. That is not is an exhaustive list, and we do not intend to suggest that simply following these steps is a guarantee of success. However, we believe that it increases the likelihood of success and, conversely, minimizes failure. Our list is in no particular order.
1. No current public health risk
First and foremost, the responsibility and primary role of the FDA is to do everything possible to ensure that the products it regulates do not harm consumers. If for no other reason than this, conduct an evaluation and determine whether, based on the concerns raised by the FDA, a company should evaluate the products it is currently marketing in order to minimize any risk to the public. If such concerns exist, the results and actions taken should be reported to the FDA as soon as possible.
2. Credibility is key
It is imperative that the senior management company shows the FDA that it can count on it to fix its problems and minimize repetition. This credibility factor becomes even more acute when a “repeat observation” is referred to in an FD-483 or warning letter. The agency expresses concerns that the company either “does not understand the underlying problem” or “does not fix it” – both of which are not good. Frustration, fueled by growing concerns that the company may sell products that cannot be guaranteed to be safe or effective, is beginning to spread to the FDA. To avoid further escalation, the company must definitely demonstrate that: (1) it recognizes the regulatory and qualitative issues and concerns related to specific legal “observations”; (2) an appropriate investigation was conducted to identify the root cause of each specific observation; (3) Measures that are suitable for addressing and eliminating every root cause of an observation and for preventing their future occurrence have been developed and implemented (e.g., CAPA-like actions); and (4) the implementation and effectiveness of the Action Points were monitored and, if necessary, deliberate modifications made.
3. Control status
In conjunction with the above, many in the industry may have heard of the term “Control Condition”. The FDA wants to know the company is sticking its act of quality together. The company’s Quality Unit (“QU”) should be well organized, trained and fully empowered by management to make final decisions regarding Good Manufacturing Process (GMP) requirements, disposition and release of the product to the market . Standard operating procedures should be based on the Federal Food, Drug, and Cosmetic Act, FDA regulations, written agency guidelines, and appropriate industry standards (and all of these, of course, must be followed). The QU should review and approve all of these documents.
Decisions to do (or not to do) something should be thoroughly discussed internally by senior management and documented. It should be a Rhyme and reason, based on scientific evidence and supported by data on why the company acted this way. It is important that the decision-making approach is consistent and thoughtful. While the FDA may not agree to the final decision, the company will be in a better position than if it acted arbitrarily or reached an ex-post, reactive conclusion.
It is important to remember that, in our experience, with a few exceptions (e.g.(Data Integrity FDA thinks it is being lied to) The FDA wants the company to voluntarily achieve compliance. The agency does not want more aggressive enforcement measures (e.g., injunction, product seizure), which requires intervention by the Department of Justice and is more time-consuming.
4. Compliance culture
This is another phrase that many in the industry have likely heard. “Compliance” cannot just be a word on a bumper sticker or on the canteen walls. “Compliance” has to be just as important as “Sales”. Not only is non-compliance an illegal act, but it’s business damaging, which a meeting or call to the FDA often reveals. It is not uncommon for the FDA, during such a call, to ask the company if they are recalling a product or that a pending product application might delay approval. It has happened that a warning was issued during the meeting or the call itself.
Senior management must demonstrate to the FDA that they are involved in resolving issues and will take all necessary steps to achieve and maintain compliance. This doesn’t necessarily mean just spending money or hiring consultants, but maybe that Not release of products if they do not meet final product specifications or are otherwise unsuitable for sale.
5. Be prepared
For the call or meeting and any subsequent FDA inspection that is inevitable after a poor inspection or government call, the company should be prepared for the “why” questions – “why did company x” and “why did this Company not “and?” The company should also expect that not all FDA staff may have read the PowerPoint presentation or documents the company prepared for the meeting. Some officials will, but many will not, so that the company may have to review some of the material even though the session only lasts an hour.
Make sure the correct staff is present at the meeting to answer the questions posed by the FDA. If the company employees present don’t know a specific answer to a question, it is better to respond to it that the company will reply as soon as possible, rather than bluffing or making up something. In addition, a company should be receptive to a valid suggestion for improvement from the FDA. The meeting is a dialogue and the agency tries to help where it can. If it’s a good idea and something can be improved, check your ego at the door and accept the recommendation or improvement. And since the FDA will likely re-inspect the company in a few months, it’s a good idea to re-examine the proposal as the agency will wonder if the company has listened.
Finally, when a company responds to the FDA, be it an FD-483, a warning letter, or questions during a regulatory meeting, it should try to see the bigger picture, not just the specific area of concern or observation. Of course, the company needs to address the specific problem, but it is important to recognize that the concern raised is only one example cited. The company should demonstrate to the FDA that it recognizes this as an example and has (or will review) similar areas to assess whether there might be larger areas for improvement. This forward-looking approach touches on many of the other high-level issues discussed earlier (e.g., Control status, compliance culture).
There is no playbook for making an government call or meeting when a compliance issue arises. However, there are some high level issues and specific points that we remind our customers about that we believe will fuel success and, conversely, if left unaddressed, will maximize failure. Credibility, trust, control status, compliance culture, and willingness are some (but not all) of the key points companies need to consider when preparing for these nerve-wracking, but potentially opportunistic meetings to prove to the FDA that they are compliant with quality standards.