US Food and Drug Administration (FDA) inspections of drug and devices manufacturing facilities are typically anxiety ridden exercises that can strike fear into even the most seasoned quality and regulatory affairs professionals. And, most manufacturing facilities do not escape these inspections unscathed and are routinely cited, in many cases, for minor infractions.
For those of you who may not be familiar with FDA inspections, manufacturing facilities that produce approved drugs and devices must be inspected every two years for insure regulatory compliance with Current Good Manufacturing Practices (CGMPs). During the inspection, FDA inspectors document “significant objectionable conditions, relating to products and/or processes or other violations of the Food Drug and Cosmetic Act” that they observe. These are known in the industry as Form FDA 483 Inspectional Observations or simply 483. Companies that receive 483s must correct the so-called objections conditions to remain CGMP compliant.
While receiving 483s during an inspection may be routine, it can be overwhelming to inexperienced companies and their representatives. With this in mind, I found a great blog post by Bruce McDuffee, Global Marketing Manager, Veriteq that provides insights on interacting with the agency to manage 483s. He offers the following advice:
“One thing that you should be clear about is that this is not a ‘warning letter’; it is an offer to help you resolve issues and improve your quality system. The FDA may or may not issue a warning letter next if you have not addressed the conditions of the 483 to its satisfaction. Receiving a 483 does not necessarily mean you are out of compliance.
In responding to a 483, your objectives should include these three things; establish credibility, demonstrate acknowledgement and understanding of the observations and the associated requirements and show commitment to corrective actions."
Bruce recommends that you take the following actions when dealing with 483s:
- Get your response in on time or even early if possible. The FDA wants to see the response within 15 days, so plan your review and internal processes accordingly.
- In the first paragraph, demonstrate your understanding of and desire to comply with FDA regulations.
- Respond individually to each item addressed on the form. Give a corrective action and time-frame for implementing.
- Prioritize by first addressing the conditions that will most likely affect product quality.
- Outline how and when each deficiency will be corrected.
- Avoid talking about whose fault the issue is or how it came to be. For example, keep a positive tone and indicate how the quality system will be improved.
- Include any reference documents, such as purchase agreements for a new monitoring system or employment agreement for a new quality manager.
- Keep in mind that there is a formal process available for you to dispute the findings.
- Be proactive in addressing the conditions. For example, address why the deficiencies were not detected internally and what will be done to correct this condition.
- Seek clarification with the inspector when you receive the 483 on the spot. Be sure you understand each objectionable condition before the inspector leaves the site. It may behoove you and your firm to seek out an industry expert if the matters seem complex or if the issues are not able to be resolved by your own personnel.”
While CGMP and regulatory compliance may seem like arcane concepts, they are vitally important and must be clearly understood by companies that are manufacturing FDA-approved drugs and devices. Failure to comply can result in penalties, monetary fines and revocation of a license to manufacture a drug or device.
Until next time….
Good Luck and Good Job Hunting (try regulatory affairs or quality assurance and control)