Preparing FDA Response
Responding to the FDA Warning Letter and 483 Observations
One of the paramount objectives of a medical device or drug manufacturer is to avoid receiving an FDA Warning Letter. If there is a stronger word, I will use it. Make every effort to avoid receiving a warning letter in the first place. There is nothing more costly and detrimental than attempting to fix a problem after it has already occurred. Therefore, avoid it at all costs.
The primary reason for mock FDA inspections is one of the steps that will help. Don’t wait until you receive a notification of an FDA inspection for a mock inspection. Again, we cannot overstate the importance of complying with the FD&C Act to avoid receiving an FDA Warning Letter. More importantly, you will need to hire a qualified FDA Consultant, such as a former FDA investigator who specialises in medical devices and pharmaceuticals.
FDA WARNING LETTER RESPONSE
Official Action Indicated (AOI)
FDA RESPONSE TO FORM-483
Inspectional Observations
What is an FDA Warning Letter?
The US FDA is a federal law enforcement agency. Therefore, if you are a medical device, in-vitro diagnostic, drug, dietary supplement, food, or biologic company and violate FDA laws or regulations, the FDA may issue a warning letter.
It’s a formal notification to document the violative conditions you are committing, whether intentionally or unknowingly.
However, it’s not the only tool the FDA has to enforce the FD&C Act, but it is one of its most effective tools.
The FDA Warning Letter is an official public record. Anyone who has access to the internet can see warning letters. Of course, any personal or other confidential information has been redacted, but they are public records, which means your competitors can use them against you. Also, news media, consumers, and even lawyers can access warning letters. Get the idea? Therefore, don’t take the chance of bad publicity and put your company in jeopardy.
When does the FDA Issue its Warning Letter?
The federal agency issues FDA Warning Letter to the violators of the Federal Food, Drug, and Cosmetic Act (FD&C Act) or United States Code, Title 21. It’s a form of formal warning that you are in violation of a specific law. The letter could be triggered by poor manufacturing practices, unsubstantiated claims for a product’s intended benefit, improper directions for its use, or other adulteration or misbranding conditions. For example, if the manufacturer or distributor of dietary supplements claims that their product prevents or cures a certain condition. Another example is poor manufacturing practices, such as the failure to validate a sterilisation process.
Responding to a Letter
The FDA Warning Letter clarify that you must correct the violations, including details of how and when you must do so. Therefore, you must present a plan including corrective actions that you will take by writing a response letter or meeting with the assigned Compliance Officer. However, a meeting with a compliance officer is not necessarily better than writing a response letter. In fact, one session or one response letter may not be sufficient and may be subject to subsequent interaction.
An FDA Warning Letter can be received unexpectedly.
There is no specific timeframe or guideline for when the FDA will issue its warning letter. It can come a few months after the close of an FDA inspection. Or it may appear out of the blue without an onsite inspection. Just because the FDA did not inspect you or you did not receive Form-483, Inspectional Observations, does not mean you are exempt from receiving a warning letter.
Warning Letter & Close-Out Letter
If you received a warning letter from the FDA on or after September 1, 2009, the FDA might issue a close-out letter if your response to the warning letter is satisfactory. It includes your actions to correct violations listed on the FDA Warning Letter. Of course, the assigned Compliance Officer must verify and accept all corrective actions. This is the reason you should seek a professional to write the response to the warning letter. The FDA may issue a close-out letter once they conduct another onsite inspection to verify that you have corrected the violation according to the regulations. However, the agency may employ stronger enforcement action without further notice if your corrective actions are inadequate during a subsequent inspection.
The Implications of the FDA Warning Letter
Receiving it can have several consequences. Additionally, it could lead to immediate complications for your company in its business operations.
- For an international company, the FDA may put your company on its import detention list. This is to prevent your “violated” products from being distributed in the United States.
- For a domestic company, you may not be able to sell your products to federally funded businesses, including hospitals. Sometimes, it can cause you to shut down your manufacturing operations until violations are resolved.
How to Avoid FDA Warning Letter
If any consultant claims they can completely safeguard you from receiving a warning letter from the FDA, that is a clear indication that you should steer away from them. No one can make such an egregious claim. However, you can minimise the chance or the significance. How? Educate, train, practice, and practice again with your staff. This is where we come in. One of the tools we use is the mock FDA inspection. Even if it’s too late for a mock inspection and you have already received a warning letter, we can still assist you in effectively remediating the situation.
Our FDA consultant was a former FDA field Compliance Officer. Therefore, we can help you to understand the seriousness of the violations and how to correct them as best you can. In addition, we may even have to involve other specialists and experts during the process. It may not be a one-person task. But we can help you because we know where to start. Please note that remediating an FDA Warning Letter can take months or even years. Therefore, you must not spare anything to prevent it from being issued in the first place. Please note that the warning letter is serious; additionally, there may not be a second warning letter.
Still Not Convinced?
This analogy is not the best approach, but it may help you understand the seriousness of a warning letter. Imagine, for example, that you are a renowned oncologist. A recently diagnosed cancer patient comes to you for treatment. Suppose the patient asks you if you can cure their cancer. Your answer will most likely depend on the seriousness of the cancer. If the cancer is “fixable” and in the early stage, you may tell the patient that you can’t promise, but you can try. Of course, it may take a few months or even years. Inform the patient that cancers can return even after remission. This is the patient with a curable form of cancer. Do you still think a mock FDA inspection is too expensive or redundant? Consider taking proactive steps to avoid receiving an FDA Warning Letter by contacting us today.
A Side Note
Please note that this article does not represent the FDA or its position. The FDA may update its regulatory policies from time to time. Therefore, this article may not be up-to-date. Please check the FDA website for up-to-date policies and guidelines. In addition, this article is written based on experiences working as a field and Center Compliance Officer. As such, we do not claim that we can remedy your current conditions or situations with the FDA. We are here to act as a consultancy and for advisement.
FDA Response to Form-483 Inspectional Observations
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- Violation of FDA Laws
- Correct Observations Permanently
- Major or minor, it is still a violation.
During an FDA inspection, investigators may observe objectionable conditions. At the close of the inspection, these conditions are noted on the FDA 483 Observations. They may be violations of FDA laws.
As a medical device or drug manufacturer, you may or may not choose to respond to them. Unlike a Warning Letter, you are not required to respond to them. However, depending on the significance of the observations, I suggest responding to show you are treating them seriously and correcting them. Yet even a well-written response doesn’t mean you are entirely out of the woods if the observations are egregious. It can still be classified as an OAI, meaning you can still receive an FDA Warning Letter or other official action. However, it may take a few months before you get it. Poorly written FDA 483 Observations Responses can negatively impact you.
However, a well-written FDA Form-483, Inspectional Observations, response can neutralise and even remedy it. Therefore, don’t let just anyone write this critical response to the FDA.
Form-482 vs. 483
Form-482 Notice of Inspection is the opening inspection form issued at the onset of the initial inspection. Form-483 Inspectional Observations is the closing form issued at the end of the inspection. So, it’s an official closing of the inspection. Once it’s given to you, they have to reissue Form-482, Notice of Inspection, if they want more information from you. So once you receive FDA 483, you know the inspection is officially closed.
Although Form-482 has to be issued every time they begin an inspection, Form-483 does not. It is issued only when an investigator makes observations during their inspection. Therefore, no written objectionable observation means no FDA-483 Observations.
However, just receiving FDA Form-483 doesn’t mean you failed the FDA inspection.
By the same token, not receiving a Form-483 at the close of the inspection doesn’t mean you have successfully passed the FDA inspection. For example, if an investigator observes something and wants the Center to get involved—for example, Section 510(k)-related—they will not record it on Form-483, Inspectional Observations. Even without a Form-483, you can still get an FDA Warning Letter.
On the contrary, even if you receive Form-483 at the close of the inspection, the inspection could still be a successful one. Therefore, don’t be overly stressed because you received the FDA 483 Observations. However, you don’t want to ignore even the most minutest observation.
The solution is to engage early with someone like us who understands FDA 483 observations.
Our lead FDA consultant is a former FDA field Compliance Officer. His duties included reviewing inspection reports from investigators, Inspectional Observations FDA Form-483, and drafting FDA Warning Letter or other official actions. As such, we can help you write a response letter to the observations.
Taking Copious Notes
It’s imperative that you take copious notes during an FDA inspection. Don’t overlook even a seemingly negligible remark expressed by investigators. For this task, assign an excellent note-taking individual from your company to do nothing but take extensive notes.
If investigators demonstrate an interest in a subject, they may or may not discuss it with their superior, Compliance Officer, or Center. Therefore, the item they notice may not be listed on Form-483, Inspectional Observations. This is one of the prime examples of how you can still get an FDA Warning Letter even without an FDA 483 Observations.
Until a few years ago, investigators would list all observations, even if the report was longer than ten pages. This practice changed in the late 1990s. Investigators were trained to list the top 5-10 most egregious observations. All other minor observations were to go on the report as verbal observations. This is another reason you will need to take detailed notes of the discussion with the investigators. In fact, nothing is minor when it comes to observations.
Response Writing – FDA Form 483 Observations
A well-written response to FDA Form-483 observations is imperative. This is your chance! Don’t waste it with a mediocre or poorly written response letter. It’s an alternative way of having a second chance of inspection.
It’s not exactly a do-over, but it’s still extremely important. Get it right this time!
As such, you want to keep it as realistic as possible. Don’t make any promises you can’t keep. Some people have a misconception of the magnitude of the response letter. Again, it’s not just another formal or company letter. There is no limit to how long or how many pages it can be.
The most egregious violations are repeated violations, regardless of whether they are major or minor.
You don’t get a second chance to violate the same objectional conditions. Sometimes, the second time around, a repeated violation may trigger an “automatic” issuance of an FDA Warning Letter.
Engaging someone like us will help you to understand the observations better. However, please don’t engage us if you are looking for a quick fix.
Partner with RAQA FDA Consulting
First of all, depending on the significance of the violations, we may visit the facility inspected by the FDA. Then, we need to understand the objectionable conditions to offer permanent corrective actions. Remember, you don’t get a second chance with the same violation. Therefore, you will have to fix it so it will never be repeated. The bottom line is, if you learned the lesson the hard way, don’t waste it. Fix it for good, no matter what the cost is. Again, don’t let an unqualified person write the response to FDA 483 Observations. Don’t make a bad situation worse or make it “unfixable.” Remember, a poor response can hurt more than no response at all.
Recently issued 483s are available on the FDA website.
The Next Step
- Firstly, professionals such as RAQA FDA Consultants should be involved. We can help you to get it right. It’s not too late to be truthful or fix problems permanently. However, it may take time.
- Secondly, if you have not learned anything yet, be thorough, resourceful, serious, honest, and, most importantly, truthful.
- Thirdly, get the most responsible individual in your company involved. Most likely, you may have already introduced them to the FDA investigators during the opening section. Commitment from the most responsible individual carries far more weight than multiple middle managers.
- Finally, commit to voluntary compliance to the inspectional observations. The bottom line is that you need to take permanent action to correct any deficiencies noted.
Effective FDA Warning Letter & 483 Responses
Even if you are reading this article and the FDA has not inspected you, engage us as soon as possible to schedule a mock FDA inspection today. The sooner, the better! Stay proactive and minimise the FDA Warning Letter with us.