Here are some tips — some simple, some a bit more complex — for responding appropriately to 483 letters:
[b][COLOR=“blue”]-Get your response in on time and in writing. You have 15 days, so ensure that final proofing and substantive editing is done at least by day 10.
-In the first paragraph of the response letter, be explicit in your understanding of and desire to comply with FDA regulations.
-Respond individually to each item that was addressed in the Warning letter. Be specific. Do not try to solve all issues in one paragraph or your response may be rejected, prompting further action from the FDA.
-Respond by importance – that is, respond individually to items most likely to impact product quality. These items may not be the first on the form, but they should be first in your response.
-Be detailed yet concise, but provide support documents to accompany your cover letter. Outline how and when each deficiency will be corrected (rather than how you feel the deficiency came to be), and provide documentation of a corrective action commitment from the person responsible for it.
-Use positive statements; avoid language that implies fault. Make it clear in your tone that you regard each item in the 483 as an opportunity to fine-tune your quality and compliance systems.
-Include reference to how you will be forwarding evidence to support the correction. For example, “will use a validated monitoring and alarming system to provide reports on temperature recordings taken at 10 minute intervals month-by-month.” Product specifications and protocols of applications you use to create records can be provided in your support documents to accompany your corrective action plan.
-If the inspector noted something that you feel was an isolated incident, note it in your response. However, be 100% certain that you can back this up and that your data is complete and accurate. If you find some of the observations were in error, there is a formal dispute resolution process outlined in the agency’s "Guidance for Industry - Formal Dispute Resolution: Scientific and Technical Issues Related to Pharmaceutical CGMP.
-Be proactive. Reassess your internal compliance programs — Why were 483 deficiencies not detected internally? Mention this in your response letter, noting your commitment to QC/QA audit management. If you need to fine-tune your quality systems, a good place to start is the guide to what FDA inspectors are looking for, which is contained in the agency’s Investigations operations manual.
-If you need clarification, seek it—in writing and from the correct party. Ideally, when the investigator handed you the Form 483 after the inspection you asked a lot of questions to clarify each observation. Try to be sure you understand each deviation before the inspector leaves your facility and make notes while he/she is explaining their observation. If your questions involve policy, contact the FDA headquarters — don’t contact your local FDA because policy is set at HQ. [/color][/b]
And… 10.5. You may need an industry expert. There are many companies who specialize in creating and implementing regulatory strategy, whether from the ground up or from your existing quality and regulatory systems. If it’s worth doing, it may be worth hiring someone who knows how to do it really well. As regulatory compliance issues grow more complex, many companies have been created to provide solutions in common compliance areas like: response to agency queries and help with agency meetings, regulatory gap analysis & remediation, internal GLP/GMP auditing and pre-approval inspections.