You Just Got An FDA Warning Letter – What Should You Do Next?

By Ed Miseta, Chief Editor, Clinical Leader

Alan Minsk, partner and Food and Drug Practice leader, Arnall Golden Gregory LLP

You took your time selecting a CMO partner. You prepared a quality agreement specifying each company’s responsibilities, and you did your best to monitor the quality of the product they produced. But somehow you still managed to receive a FDA-483 (Notice of Inspectional Observations) or a warning letter. What do you do now?

Attorney Alan Minsk, partner and leader of the Food and Drug Practice for law firm Arnall Golden Gregory LLP, believes your response is critical to satisfying the concerns of the FDA — and putting the situation behind you as quickly as possible. The timing of your response is the first issue you must consider.

“When the FDA issues a warning letter, it expects an answer within 15 days,” says Minsk. “That is the understood rule. If you don’t respond within 15 days, it can be perceived as though the company doesn’t consider the matter serious, which can lead to more significant enforcement.” You don’t want haste to make waste, he warns, but remember this is a government agency, and you do not want to thumb your nose at them. At the same time, he cautions responders to not feel as if they need to respond the next day. The goal should be to put together a thorough and efficient response in a timely manner.


Look At The Bigger Picture

Minsk recommends a response that addresses the specific issue and at the same time tries to read between the lines and address the bigger issue. “When the FDA issues a FDA-483, they do not write down every possible concern,” he says. “Generally, they are giving you examples of violations. If you don’t address the bigger issue, you are likely submitting a response that will not satisfy the FDA.” For example, the 483 might state a cap was left off a bottle. You could easily submit a response stating the cap was put on the bottle. But if that is the extent of your response, the FDA will likely find it to be inadequate. “The FDA will look at that and start asking questions,” says Minsk. “They will want to know why it happened, if there are other bottles that may also be uncapped, and if you investigated why it happened. You need to show the FDA that you are looking at the bigger picture, and will prevent not only this recurrence, but will investigate similar situations and fix them as well.”

A phrase often heard is that sponsors need to be in a “state of control.” The FDA wants to know that a company has its operations, as well as its contractors, under control at all times. The more responsive a company is in looking at other possible issues, the better able they will be to convince the FDA that they “get it.” It will appear you are taking proactive actions to become a better company.

Set Reasonable Deadlines

When setting deadlines for making needed improvements, Minsk recommends making them reasonable. “Don’t tell them you will have everything fixed in a week if that is not possible or is not going to happen.” He cautions. “They do not want to hear platitudes. If all of the issues are minor, perhaps you could have them fixed quickly. But if the observation is such that it will take two months to fix, don’t tell them you will have it done in a week.”

Giving unreasonable deadlines will only tell the FDA you do not have a true sense of the issue. Minsk believes that will not impress them. “They will have to assume that you are either ignorant or lying,” he says. “And neither one looks good. They do not expect everything to be taken care of yesterday. They want to know you have a game plan in place.”

Minsk also recommends that letter recipients focus on the most important observations first. Get them taken care of as soon as possible, providing completion dates for each observation. ”If your response convinces them that you understand the issue and are taking care of it, the FDA will be more inclined to allow the company time to resolve the agency’s concerns.” 

Finally, Minsk believes that no response should be submitted before it is reviewed by an internal quality assurance (QA) team. That team should review the response to see what it is saying will be done, whether the company is able to do it, and has the financial resources to get it done. “All of these things need to be considered,” he says. “Because most responses will involve QA, they need to be involved. Too often we find they are nothing more than an afterthought.”

You can contact Minsk through his website. For more information you can also go to www.expertbriefings.com.