10 Things I Wish I’d Known Before Writing my FDA Response Letter

Don't bury your head in the sand; 
start your response letter ASAP

by Alex Butler

Medical Device Segment Manager, MasterControl 

If you’ve ever received a 483 or warning letter, as I have, you know the chaos that can ensue. The clock is ticking; the FDA requires a response to most compliance notices within 15 business days!

I received a warning letter while working for a leading global manufacturer of dental materials, devices, and instruments. As part of the remediation team assigned to address the citation, which entailed overhauling the company’s entire quality system, I understand that time is of the essence when crafting a response letter and remediation plan. Working many nights and weekends, it took my team eight months to receive our close-out letter, then we spent another year implementing our remediation plan—all while performing our “regular jobs.” It was a grueling process, but I learned a few remediation lifehacks that may save you time and frustration.

#1 Start immediately

Receiving a warning letter is a lot like receiving a notice from the IRS. It’s tempting to ignore it and hope it will go away. It won’t, of course, so don’t waste any time in securing executive support and the right internal expertise. The remediation process is labor-intensive, and timelines are extremely tight. Executive backing will make it easier to compile resources and prioritize company attention. If you have a problem convincing senior management and other stakeholders of the importance of dealing with a warning letter, remind them of the damage it can do to stock prices and brand equity.

Once management is on board, start compiling your remediation team. Identify leaders within each function area (e.g., regulatory, quality, compliance, clinical) that pertains to the observations listed in the warning letter. This team will assist the head of RA/QA in overseeing the response and updating management on progress.

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#2 Enlist outside help, if necessary

If you do not have the adequate internal expertise or resources to address the issue, consider hiring an outside consultant who specializes in regulatory remediation. Smaller companies, particularly those unfamiliar to FDA regulators, can often leverage their consultant’s reputation with the FDA to their advantage. Also, consultants often bring an outsider’s perspective that resonates with management.

We realized pretty early on in the remediation process that we were in over our heads, particularly when it came to training and resolving CAPAs. We hired a consultant, who had previously served as an FDA auditor, to help us draft our response letter and improve our training and event management processes. It was money well spent.

#3 Don’t make assumptions

Assuming that everyone in your company understands quality or abides by the same best practices is likely what got you into trouble with the FDA in the first place. When someone on your remediation team claims something is common sense, beware. In regulated environments, “box ticking” can lead to disastrous results. Remember, mistakes and oversights happen, even in exemplary quality systems.

Quality and compliance must be incorporated, i.e., documented, into your operational strategy and shared with the entire company. Your response SOPs and work instructions must be clear and concise. That’s the first step toward holistic quality management.

#4 Be brutally honest

The day-to-day pressures of running a business can cause an unintentional drift in quality oversight, prompting overworked staff to justify or minimize potential vulnerabilities. Over time, a disconnect occurs between the FDA’s view of a company’s performance and the company’s self-assessment. While it’s tempting to go on the defensive and try to justify or explain what happened, don’t. Regulators are not interested in a justification of why a particular nonconformance may have occurred but what corrective actions you intend to take to remedy the situation—and when.

Your response letter should be transparent and comprehensive, addressing not only the observation(s) itself but also the broader systemic issues implicated by the observation(s). An antagonistic or incomplete response is sure to invite further scrutiny.

#5 Go above and beyond

We performed an audit/gap analysis on every design history file (DHF) the company had compiled since 1998 (23 files total), and a full redo of nine files. Even though the files related to successful products that were not cited in the 483, they did not conform to the new quality system we were developing. Often, 483s are the symptom of a much larger issue. Once root cause is established, you are likely to uncover other potential compliance problems. By being proactive, you show the FDA that you are doing more than the minimum required and committed to continuous quality improvement and compliance.

#6 Divide and conquer

FDA observations can be divided into two categories: one-off observations or systemic observations. Tracking and trending, as well as conducting root cause analysis, will help you determine which type of observation you are dealing with and what corrective action must be taken. Once root cause has been established, assign a competent team member to lead the resolution of each observation. Hold regular response team meetings to monitor progress.

Most one-offs, such as a poor operator performance, can be corrected with surveillance and training. Systemic observations, however, usually (but not always) require deep and broad process changes, which must be addressed in the response. It’s a common misconception that a problem must demonstrate a trend. You can still have a pretty severe product issue—even if it is a one-time occurrence. It’s important to treat each case as critical until you can prove otherwise.

#7 Formally designate department roles

In small companies and startups, it’s common for each employee to wear many hats. However, it’s important to provide the FDA with a list of key personnel and to identify each person’s primary role(s) and responsibilities. For example, although many employees may play a part in the complaint management process, you should designate an official complaints manager and document his or her name and responsibilities. Inadequate handling of complaints is one of the top five reasons for FDA 483 observations and warning letter citations.

#8 Don’t speculate

When crafting an FDA response, make sure you stick to the facts. Don’t speculate or volunteer information unless it can help mitigate a potential observation. The same advice holds true during audits and inspections in which you might be tempted to fill an uncomfortable silence with additional explanation.  Speculation can be a key reason for escalation and enforcement action, so avoid it at all costs.

Report only what you know. Less fact-based data trumps speculation, even when speculation is supported by trending. Don’t say, for example, we have experienced problems shipping this product to humid climates, and this particular issue is most likely due to container sweat—or whatever you think it might be. This is asking for trouble. 

#9 Address timelines—but be realistic

No remediation plan is complete unless it includes progress milestones, which outline the interim steps you intend to take toward resolution, as well as hard deadlines for completing your corrective actions. Be realistic about timelines. Give yourself time to correct the root causes with sustainable solutions rather than Band-Aid fixes.

The key is to show investigators that you understand the consequences of the deviation. Be sure to explain each aspect of the resolution carefully to demonstrate not only a successful resolution to the problem but also the company’s commitment to prevent reoccurrence. Convince investigators that you are remedying the problem to satisfy not only safety and compliance issues, but also because it will make your business better.

#10 Keep an eye out for warning letter trends

You can minimize your chances of receiving future regulatory citations if you keep an eye out for the red flags in your internal procedures and processes that are known to attract the FDA’s attention such as:

  • Long-standing internal quality issues
  • Repeated FDA inspections or observations
  • Failure to submit adverse event reports
  • A large concentration of customer complaints about the same issue, or several complaints about varying issues
  • No trending data or poor trend analysis
  • Dismissal of a complaint because no sample could be obtained
  • Minimizing complaints based on user error, shipping, damage, etc.

Have you ever been part of a remediation team assigned to address an FDA 483, warning letter, or other regulatory citations? If so, do you have any “remediation lifehacks” you can share to facilitate a quick resolution?

As the medical device segment manager, Alex Butleris focused on developing solutions that help medical device companies increase efficiencies, ensure compliance and speed time to market.  Prior to joining MasterControl in 2014, Butler worked as a product development manager for Opal Orthodontics, a division of Ultradent Products Inc., where he helped launch several Class II medical devices, including the Opal Espirit™ Class II Corrector. With more than five years of direct medical device experience, as well as a deep understanding of the FDA’s submission process and audit procedures, Butler is a vital part of the MasterControl product management team. 


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