Risk and FDA Inspections: Anticipation, Preparation, Reaction and Conclusion

If you manufacture FDA-regulated drugs, devices, biologics, combination products, dietary supplements, or cosmetics the underlying reason FDA will inspect your facility is to determine if you are in control of all aspects of the operation. It is not enough to have SOPs that state what is supposed to happen. FDA starts with your products and then works backward to determine if all the pieces are in place. For contract manufacturers, the challenge grows exponentially as the number of clients and products increases.
The core of control lies within supplier agreements that delineate who does what, when, where, and how. That’s the easy part. In order to assure that every product that is shipped in interstate commerce is safe and effective a thorough risk plan must be put in place. A risk plan is a document that identifies all known risks associated with a particular product. Where your products are in the continuum of risk, from lowest to highest, will determine how much resources must go into the risk plan in order to assure compliance with all applicable FDA rules. As you start at the lowest level of risk (cosmetics for example), the requirements are more straightforward and do not require pre-approval.

The highest-risk products (injectable medicines for example) require a much higher level of risk mitigation and involve approval of proposed actions prior to selling products. Simple right? The problem is there is a considerable amount of homework needed to control even the lowest risk in your operations. For contractors, the responsibility is shared with the brand owner. Responsibilities under the law cannot be transferred to others. It is important to delineate these responsibilities in comprehensive supplier agreements.

So, how do you get started? First, make sure the risk plan is reviewed by knowledgeable people with experience working in the product class. If you do not have engineers and scientists with experience working at the appropriate risk level FDA expects you to hire experienced consultants. Once top management signs off on a risk plan, the same cadre of experienced individuals should guide the implementation of SOPs required to control the identified risks. A rule of thumb is to control your entire operation at a level appropriate for the highest-risk products.

If you treat lower-risk products with less robust procedures you introduce the possibility of lower-risk products becoming the source of contamination to higher-risk products. This is why high-risk drugs that have been approved through the NDA (New Drug Application) process are manufactured in highly controlled environments without the potential for contamination from other lower-risk products. If you decide to start manufacturing generic drugs, you must tell the FDA what you are doing. When they show up for inspection after you have committed large amounts of capital you better be doing what you told them you would do.

If you are prepared before you start production you will not need to worry about FDA and negative conclusions, because you will already know where you stand. FDA does not expect 100% adherence to all regulations, but you better have a good explanation of why you are deviating and put procedures in place that go beyond basic requirements. Continuous improvement is highly supported by FDA. Your plan to become fully compliant should be based on the risks inherent in your operation. Demonstrating control throughout the lifecycle of any product is the most important principle. This presentation will help you understand the basics of risk planning and preparation for FDA inspection.

Are you ready for the big day? When FDA visits, the more prepared you are the less likely the experience will be a negative one. Put a plan in place so everyone knows what to do when FDA arrives.

What else can happen if your risk plan is inadequate? Recalls. Whether self-generated or FDA-requested, there are a couple of years of an intimate FDA relationship in your future. Risk planning will pay off financially if properly implemented and maintained. As conditions change so do the risks. Revisiting a risk plan is part of management's annual review responsibilities.

• Operating under control
• Supplier agreements
• Risk planning
• Contractor vs. Brand owner responsibilities
• Qualified experts
• Quality Systems
• Adverse events
• Preparation for Inspection
• Recall strategy
• Cost of poor risk planning
• Warning Letters
• CAPA
• Inspection Plan
• Management reviews

Do you review and document risks related to what you bring into your shop and what regulatory responsibilities you have? Do you have sound agreements for all suppliers, including laboratories, terminal treatment facilities, and packaging suppliers? How do you control the risks inherent in each product you touch? All too often, the necessity to "sell, sell, sell" ways the ability to control risks. Getting a process under control requires a first thorough analysis of the risk associated with the product being manufactured.

FDA looks at the risk continuum throughout the entire lifecycle of regulated products. Are you doing your part to assure risks are mitigated in processes you control? Are you aware of the mitigation efforts employed by your suppliers? The time and effort taken to develop a robust risk control plan will pay off by minimizing FDA regulatory problems and ultimately will add to your bottom line. Applying high-level risk management will result in elevating your quality system to an income generator and not just a cost center.

• Directors
• Managers
• Anyone responsible for managing and controlling the safety and quality of FDA-regulated products

John Misock is serving in his fourth career as Senior Consultant with Ceutical Labs, Inc. Flower Mound, TX. He provides regulatory consulting services across all FDA-regulated industries. John retired from FDA in June 2019 where he was an SME in microbiological compliance and manufacturing. Prior to FDA John served in a global capacity with a multinational company responsible for regulatory compliance in all manufacturing facilities. Early in his career, John was Director of a state Food, Drug, and Cosmetics program and also served as Assistant Commissioner of Agriculture.