The QMN Weekly Bulletin
Medical Devices / Inspections and Audits

Begin Form 483 Response by Analyzing Symptoms of Quality System Failure

Nov. 25, 2016

A response to a Form 483 is not a routine or informal communication and should be given the same attention and care you would give to defending your company from a federal indictment — because that’s what a 483 actually is.

Essentially, a 483 is a written indictment issued by a federal law enforcement officer (the FDA investigator) informing a company that it is in violation of the law. It’s the warning that comes before enforcement action, and a company’s response to the observations listed in a 483 is its chance to head off the FDA before the agency takes that action.

The purpose of the response is to make your case to the FDA: Convince the agency that you take its warnings seriously, are committed to improvement and have a solid, detailed plan for fixing your deficiencies. Unfortunately, the FDA provides no guidance on what it expects to see in a response. Even worse, the agency gives you only 15 days to deliver it.

Report on Effective 483 Responses

FDAnews has recently published a report — Effective 483 Responses: Focus on CAPA Violations — that provides the advice the agency does not: from the 15-day deadline to the audience the response should address to such practical matters as proofreading your draft.

The report explains that the most important step in developing a response is analyzing the observations in the 483. Most of the time, 483 observations reflect symptoms or signals of a quality system failure. Look at every aspect of the quality system, including training, oversight, recordkeeping and auditing. You need to make sure the plan you present in your response is fully corrective and preventive. And make sure to consider short-term actions or controls to maintain a state of control until the fully corrective actions are in place.

Following through on commitments is another critical part of the response. The FDA will review and verify whether all of those commitments made in the response have actually been met. It’s important to operate in a very coordinated, open-communication mode so everyone involved understands the commitments and progress toward meeting them.

While enforcement of quality system regulations is not cookie-cutter, and outcomes vary by the unique circumstance of the particular case, there are some common truths to be found in any collection of 483 responses:

  • Respond on time
  • Get upper management involved
  • Strike the right tone
  • Describe the immediate response
  • Cover each CAPA cited in the observation
  • List the root cause of each cited CAPA mistake
  • List corrective and preventive actions for each cause
  • Address cited mistakes on a systemic level
  • Consider the potential impact on non-CAPA quality subsystems
  • Describe training and other implementation actions
  • Specify implementation dates or timetables
  • Describe verification efforts
  • Provide documentation
  • Invite feedback
  • Provide regular implementation updates

The 479-page FDAnews report provides full explanations of the best practices listed above and provides expert evaluation of the responses to 28 Form 483s.

Everyone breathes a sigh of relief when the FDA investigators depart. But if they left behind a Form 483 pointing out deficiencies and noncompliances, that’s when the work really starts. This management report, Effective 483 Responses: Focus on CAPA Violations, will show you the FDA's exact CAPA observations in each 483 and put them side-by-side with the company’s response. You’ll see how firms handled particular issues, especially the tone and language they used.

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