If you are working at a GMP or GLP manufacturer or laboratory you will need to know what to do when the FDA's inspectors come to visit.
The quality control director here at Avomeen Analytical Services has put together a brief outline in order to help you be prepared for such a visit.
What might cause the FDA to visit?
- Company recently made the national public news.
- Association with a company that has recently been put under consent decree.
- Company is a major competitor of another company that just recently had an audit.
- Customer or public complaint filed against one of the company's products or services.
- Selected as part of a regional area audit that year.
- They can appear when they want but will visit at least once every two years.
What should be done when the FDA arrives?
- FDA inspectors should present a 482 notice of inspection
- Verify credentials as the FDA inspectors will need to prove identification.
- Ask the purpose of the visit.
- Escort inspectors to a meeting room that does not contain any information on the company or its clients. Typically the FDA can be asked to wait up to 15 minutes, either in the lobby or the meeting room. This time is crucial to allow the company to get organized.
- Communicate internally with management and externally with Sponsors if the audit is due to a Sponsor submission.
- In the first 15 minutes, while the FDA is waiting
- Gather all employees (or department heads for a large company) in a central location
- Distribute jobs that will be completed in the next 10 minute time frame including
- Empty all trash cans (field inspectors can and will reach in and ask about papers, printouts, etc)
- Turn off all computer monitors (no need to stimulate questions; make them ask)
- Close all notebooks
- Put away all confidential information
- Shut office doors
- Ask what is the cause for the audit:
- Such as a follow-up to a prior observation or a pre-approval inspection as a consequence of a submission.
- Is this a general inspection.
- Directed study specific.
What will they look at?
- Rejected batches
- Laboratory controls
- Overall facility
- Building, equipment, materials, cleaning procedures, HVAC, etc.
- Tour of facility
- Corrective action procedures
Who are the individuals that perform inspections for the FDA?
- Typically field inspectors are people with a few years prior experience within the industry before moving to this entry level position at the FDA.
What authority do they have?
- Inspectors are given authority from the federal government
- Given power from the federal government they can enforce actions on manufacturing and testing facilities that fail to meet federal regulations on (GMP) Good Manufacturing Practices and/or (GLP) Good Laboratory Practices.
- They have the authority to perform:
- Warning Letters
- Issue 483
- Consent Decrees
- Fines & Restitution's
Some of the reasons a 483 may be issued:
- Poor documentation showing why a product or test failed.
- Lack of investigation into failure (12-15% of 483's are related to poor laboratory investigations).
- Poor training records or organizational charts.
- Improper labeling of lab books, samples, or chemicals.
- Not following SOP's.
- Insufficient protocols.
- Out-of-specification (OOS) results
Why respond to a 483?
There is no law or regulation stating that a company must respond to a 483. However, by responding in writing within 15 business days, the company could possibly mitigate an FDA compliance decision for further action, such as a warning letter. This response should include the acknowledgement of the inspector's observations, the steps taken to correct the problem areas, and a completion date for corrections.
What the FDA looks for when visiting?
- Inspect company SOPs to verify compliance of the quality system to GMP requirements.
- Verify that the laboratory or manufacturing staff comply with the SOPs.
What to expect:
- The FDA will request the following:
- Organizational Charts.
- Quality System Manuals (including all SOPs).
- Management organization charts.
- Personnel training records to verify:
- Personnel maintain proper knowledge to perform their duties.
- What annual testing and certifications administered?
- Employees understanding of company's policies and (SOP) Standard Operating Protocols.
- Facility Design and engineering operations and diagrams.
- Quality control department and systems SOPs.
- Validation Programs and Plans for all instruments used.
- Material controls for manufacturers.
- Documentation on Deviations, Investigations, CAPA, and E-Checks.
- Customer's complaint reports.
- Executed test methods & batch records, logbooks, and technical reports.
- CPATs and/or Annual Report on trending (manufacturers only).
- Environmental controls: - monitoring.
How should employees respond to questioning?
The FDA will ask general questions for specific reasons. These may include:
- Questions about the FDA, GMP, or SOPs - these are to probe your required regulatory knowledge and understanding of how your company complies
- Questions about your workload and the availability of instruments - it is a requirement of GMP that one have sufficient staff, space, and instruments to do the work. You can answer that you are busy, but if several employees state they are overwhelmed, a 483 will likely result
- What are you doing? Good answers may include "I'm following my method and protocol," or, "I'm doing an HPLC for a client sample." A poor answer would be one which gets into technical details encouraging more questions or give an indication you do not fully understand what you are doing.
- Provide only what is asked - Don't guess/estimate, volunteer information, or provide misleading information.
- Listen to questions - Don't assume that you know the question, listen fully to the question and answer only after it is fully stated. Be confident, but if you don't know, say so.
- For questions on procedures refer inspectors to written procedures.
What the FDA cannot ask about:
- The FDA cannot ask about any confidential information. In a general audit, they cannot ask about Sponsor specific projects or methods or ask to see notebooks. In a Pre-approval inspection, they cannot ask to see work related to other client projects.
- They cannot ask about your financials, clients, or investors.
- They cannot ask to see internal audit findings, including peer review or QA review questions. These are considered part of your compliance process. They can only ask to see final work product, reports and notebooks. They can ask to see compilations of QA statistics and actions regarding CAPAs.
- Research data.
- If the FDA requests a document you have twenty minutes to locate the document or it is considered lost.
- The agency realizes that mistakes can be made in trying to comply with an SOP, however three observations of the same issue is considered a quality systems problem, and may result in a 483.
- Even though many independent laboratories are not also manufactures they are still bound by the GMPs. While they do not release a product to the public they are still part of the process of product testing and development and are audited in a similar way as manufactures.
Avomeen Analytical Services is a FDA-Registered, DEA-Licensed, cGMP-Compliant testing laboratory. We perform non-routine testing and analysis services with an investigative mindset to answer complex problems like product failure, new product innovation, contamination analysis, and more for entrepreneurs, manufactures, distributors, and other laboratories. Our specialty is in the area of chemical and material identification services, specifically deformulation and reformulation services. Our chemists are also experts in the areas of product failure analysis, new product formulation services, method development & validation, and litigation support services.
Dr. Shri Thanedar, Ph.D, is the CEO and Chief Chemist at Avomeen Analytical Services. He has over 20 years of experience serving as chief scientist or expert witness on over 20 litigation support projects involving chemical analysis, product failure analysis, reverse engineering, and polymer and rubber analysis.
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