April 12, 2013
If you have been listening to the industry trade associations and reading the trade press, you know FDAs cGMP (current good manufacturing practice) inspections are growing more detailed over time. FDA is inspecting not only manufacturers, including private label manufacturers, but also distributor/marketers that do no manufacturing, but simply order product to be manufactured under their brand names.
A simple way to prepare for FDA inspections is to read the warning letters FDA posts weekly on its website. Go to the FDA Home Page, read and ensure your quality assurance (QA) department reads as well to ensure they are in compliance with the teaching.
During an FDA inspection, at least one person should accompany the inspector at all times. FDA has the authority to inspect and to review documents required to be kept by the cGMPs. FDA does not have the authority to interrogate, but its inspectors will interrogate. No answers should be given unless they are provided by someone who knows and can assess their potential impact on the company and determine whether to answer or not. Any deficiencies noted as the inspection takes place should be corrected at once, if that is possible.
At the end of the inspection, during the closing interview, the inspector will issue an FDA 483 Notice of Observations if any violative conditions were noted during the inspection. Responding to the 483 begins during the closing interview. Your company should have two representatives present. First, if any condition noted on the FDA 483 was corrected during the inspection, ask the inspector to note that in handwriting on the form. Second, if you do not understand how the observation relates to the cGMP regulatory requirement, ask the inspector to explain which cGMP regulation covers the observation. Third, ensure you understand each observation and if not, ask questions. Do not try to talk your way out of the observation or to explain your positionthat is best done after careful thought and with the help of someone experienced in addressing FDA observations.
You have 15 working days from the receipt of the FDA 483 to respond. Once you know you are going to receive significant observations, you should contact the counsel or regulatory consultant that you are going to work with in preparing your responseyou need to be certain of their availability. Prepare a working draft of the response. List each observation and the applicable cGMP regulation that applies. Assign one person or a group knowledgeable of the subject area of each observation to begin drafting the response.
To avoid a warning letter, an FDA 483 response must talk the talk and walk the talk. First, your responses cannot simply promise compliance, they must show compliance. If FDA has observed that you do not have a written master manufacturing record (MMR) for each unique formulation of a dietary supplement that you manufacture, develop those MMRs and provide them to FDA in response. Second, for items that you cannot respond to immediately, provide a response that respects FDAs observation, e.g., here are the MMRs for five products, signed off on and in place, and no product will be manufactured unless there is an MMR in place for that specific product. Then update FDA as to your efforts 60 days thereafter. Third, if FDA has observed, for example, across all products, that you do not have a validated process for confirming the absence of microbial contamination in your manufacturing, then you should show FDA that you have contracted for or sought bids for that process validation. Fourth, all responses should cite the cGMP regulatory requirement from 21 CFR Part 111 so that FDA knows you have seen and understand the requirement.
A successful response to an FDA 483 tells FDA that you understand the issue, provides the written documentation showing you have addressed the issue, and follows up to provide FDA with later developed compliance information as required.
Anthony L. Young has more than three decades of experience in food and drug law. He is a partner at Kleinfeld, Kaplan and Becker LLP.
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