08.20.2019 Robert Fenton
Oct 11, 2016 • Pat Flanders
What should I expect when the FDA comes knocking?Complying with FDA, ISO and other regulatory guidelines protects individuals when they engage with health care products, but it demands a great deal of work on the part of labs, product companies and manufacturers.
Because life sciences companies must have FDA approval to sell their products in the United States, they have to agree to inspections of their facilities, processes, and documents. When FDA officials inspect the facility of a company or review its documentation and processes, they're looking for issues with how a company complies with regulatory requirements. When the FDA finds issues, they will issue a 483 letter which documents and communicates concerns discovered during these inspections.
No one wants to be on the receiving end of a 483 letter, but fortunately the FDA provides a protocol for correcting mistakes and reporting updates. The FDA will ultimately determine whether or not an organization can bring their product to market, so it is wise for recipients of a 483 letter to respond and address their issues. The first thing to understand is that the FDA seeks quality in how companies develop and deliver life sciences products; quality is how those products are created, how documentation and tracking is handled, and how the product is tested and ultimately prepared for the market. The emphasis on quality is where many companies fall short of the FDA's requirements.
While fixing quality issues will delay product development, it is important that, in the process of rectifying their issues, the offending company take measures to respond appropriately in a way that will enable them to continue with their work. It is recommended that the first thing life sciences companies do is address quality as a foundational element of the way they work. That said, some companies will find themselves in a position of neglecting quality issues; hence the 483 letter.Problems can be fixed, but communication with the FDA must happen first. We strongly encourage life sciences companies to consider the following in how they approach their written response to the FDA:
- Put time on your side: Once you receive the 483 letter, your organization has 15 days to reply in writing. That's plenty of time as long as you create a timeline for how you will respond. This means you must create a timeline, assign tasks for who will provide necessary data in the response, and ensure that reviews and approvals are done so you do not miss the 15-day deadline.
- Be direct, but be humble: You just got served a warning, so it is in your best interest to first acknowledge the reality of the situation. Then, address each issue individually and very clearly. This is not your opportunity to get pedantic or solve problems. Simply detail the problems and show an indication that you are aware of them and eager to fix them.
- Prioritize: As you go through each issue, you should know your business and product well enough to be able to prioritize the issues and communicate that you will address them accordingly. The FDA likes to see that you've given serious thought to their findings and will look more favorably upon your situation if you are candid about what needs to be fixed.
- Accentuate the positives: It is important to emphasize where you're going, not necessarily where you've been. To that end, let the FDA know that you are taking steps to remedy the issues they are concerned about. Include relevant documentation that demonstrates not only a willingness, but actual execution towards finding a resolution.
- Don’t play the blame game: Clearly some problems have been uncovered, hence the letter. However, there's no need to take rehash it all. Simply emphasize the corrective action you will take, and be detailed. This indicates you are working on making things right. If you start to accept fault, you will likely be under even more scrutiny.
- Get on the mend: Be specific about the steps you'll take to correct the issue(s). This should communicate that you are already working on fixes and that you're serious in your efforts to complete product development and testing. An indication of thoughtfulness and purpose will help the FDA understand that you are capable of getting past your hurdles.
- Dispute when necessary: It certainly may be the case that a mistake was made by the inspector. If you think you were unfairly evaluated, explain that in your response. Be diplomatic, and be thorough. Explain the issue that was discovered, provide some background on what you feel may have been missed, and offer something similar to an agreement. Perhaps you'd like to be re-evaluated. Maybe you can provide documentation or proof that the issue in question is actually just fine in its current state. Be direct but tactful.You can also file an official dispute; the one for the pharma industry is straightforward and helpful.
- It actually is all about you: The purpose of a 483 letter is not just to get you to correct problems. If issues exist, it is incumbent upon you and the organization to take a critical look at your processes and correct them so they don't happen again. Consider the 483 letter as a reason to reevaluate how you manage quality, and then improve upon those things that have been problematic. The FDA's Operations Investigations Manual is a helpful tool in learning what they look for and how they expect organizations to adhere to quality standards.
- Ask for help: It may be that you're at a loss for how to move forward. Maybe it's because your quality management processes are not adequate, or perhaps it has to do with being unable to fully understand the scope of the needed corrections. Either way, you only have 15 days to get a response, so you should immediately seek help by contacting FDA headquarters in order to get clarification.
- Plan ahead: After submitting your response, you will need to wait for feedback from the FDA before you can officially move forward. There's clearly going to be a lag, but you should spend that time preparing for the different possible scenarios. You may get the green light to return to business as usual, or you may need to adapt your plans and processes to adhere to a different way of working. Spend time with your team, plan for next steps, and be prepared to retool and re-engage.