Responding to Inadequacies
The obvious intent of an FDA Form 483 or Warning Letter is to promote prompt, voluntary corrective action to inadequacies
uncovered during FDA inspections. The 483 gives inspected facility owners the first opportunity to correct compliance violations
and implement procedures to prevent them from occurring in the future. Warning Letters are issued for significant regulatory
violations that warrant enforcement action if they were not corrected. Often, an inadequate corporate response to a 483 is
followed by a Warning Letter that concludes, "Please advise the Agency regarding your corrective action plan to address the
problems described above..." and sets a firm deadline for a written response.
A Warning Letter opens the door for a company to work with FDA in achieving compliance. Responding to the Letter effectively
is the first step, and it is a critical one, to minimize the likelihood of an FDA enforcement action. Several factors should
be considered in developing a response to an SOP-related Warning Letter, including:
1. Warning Letters can indicate isolated violations or systemic problems throughout an enterprise. Inadequate SOP training
observed by FDA in one job function at one facility may indicate a much broader problem. Understanding the potential scope
of the problem, rather than simply focusing on a specific violation noted in the Warning Letter, will enable the company to
respond to all violations and improve its own compliance performance. If you disagree with the facts or analysis by FDA, or
if you believe no additional actions are necessary for an identified violation, explain your position clearly to FDA. Remember,
however, that FDA has the final word. In a 2004 Warning Letter, for example, FDA responded to the company's assertion that
"The need and adequacy of training is routinely assessed as part of the internal audit program. We have no evidence that there
are systemic training issues." FDA writes, "The production mistakes of two reportedly trained employees, the failure of a
supervisor to properly document employee training, and the failure of your internal audit process to identify these weaknesses,
suggest that there are problems requiring your attention."
2. Prepare a response to the Warning Letter. The response should include specific actions for any identified violation, from
developing new SOPs to monitoring by the quality control unit. Be careful not to promise more than you can deliver. FDA takes
corrective and preventive action plan implementation very seriously. If you have questions about violations, contact the FDA
District Office for additional information, or request a meeting with FDA. Submit a response within the identified timeframe,
typically 15 days.
3. Of utmost importance to FDA is that a company demonstrates an acknowledgement of the seriousness of the observed violations,
a reasonable sense of urgency (with specified target dates), and that corrective actions clearly prove (with data or evidence
where possible) that the compliance issue has been resolved.
Compliance and Performance
Standard operating procedures, whether developed to meet regulatory compliance or to reinforce corporate policies, are critical
to efficient operations, quality control, and regulatory compliance. When properly designed, distributed, and tested, they
provide employees with practical, understandable information that enable safe and efficient job performance. When properly
managed and monitored, SOPs equip employers with a clear view of existing knowledge gaps and potential inefficiencies caused
by inadequate training. And, for any company on the receiving end of a 483 or Warning Letter, they represent an opportunity
to achieve compliance and improve operational efficiency—simultaneously.
DAVID C. PETERSON is director, GMP and Quality Systems EduNeering, Princeton, NJ,08540,1.877.EDUNEER (338.6337),