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Businesses that manufacture FDA-regulated products are not the only ones that can be inspected by the U.S. Food & Drug Administration at any time. FDA also inspects clinical trial sites (studies in humans) and nonclinical laboratories that conduct animal, plant or microorganism studies used in FDA applications for drugs, biologics, or devices.
FDA enforces many regulations that affect clinical trial and laboratory sites, including good laboratory practices, good clinical practices, human subjects protection and requirements for institutional review boards and clinical investigators. FDA also conducts inspections to audit data used in approval applications.
FDA investigators follow the same basic procedures whether they're inspecting a large manufacturing plant or a small clinical trial facility. Herein lies the challenge for those smaller facilities. Clinical trial and laboratory sites are more likely to be inexperienced with FDA inspections than are manufacturers, and operations of all sizes and types have learned the hard way that inexperience can result in less than optimal interactions with an investigator.
Preparing for FDA inspection is important for all regulated operations as it positions the facility (and its employees) to handle an inspection effectively, and reduces some of the apprehension that occurs whenever FDA arrives for an inspection.What to Expect: Inspectional Processes
Federal law allows an FDA investigator who provides written notice (called a Form 482) and shows appropriate credentials to enter a regulated establishment. FDA has broadbut not unlimitedauthority to inspect equipment, materials, products, labeling and certain records.
An inspection can be comprehensive, focused on a specific issue or set of issues, or in response to a reported problem. More than one investigator may be involved. Investigation techniques may include observing operations, examining equipment, reviewing documents, collecting product samples, and interviewing employees.
At the end of the inspection, if the investigator believes conditions deviate from FDA requirements or violative products exist, the investigator will issue a notice of inspectional observations (called a Form 483). The investigator will review the 483 and each observation with management-level personnel, and may ask management representatives for comment. About 45% of domestic inspections conclude with a 483.
Observations on a 483 are not a final agency judgment on a facility. As a result, a written response can significantly affect whether FDA takes further action after an inspection.Effective Preparation
Preparation for FDA inspection should begin long before an investigator arrives. Key components include:Employee Training.
Training should cover FDA regulatory requirements and inspection processes for the type of operations at the facility. Designation and Training of Personnel to Accompany the Investigator.
These representatives should be carefully selected both for their knowledge of the site's operations and their ability to interact appropriately with the investigator. They should be familiar with the site's inspection policies, and understand that FDA's inspection authority, while broad, is not unlimited. It does not encompass certain records, such as product formulas, and does not expressly provide for the taking of photographs. Additionally, only certain activities at nonclinical laboratories are subject to FDA inspection.Standard Operating Procedures (SOPs).
Create written SOPs that include the following: what happens when an investigator arrives; roles and responsibilities of each person involved; processes for retrieving requested documents; activities permitted and not permitted during the inspection; how the inspection is documented by the site's personnel; and follow-up and response procedures after the inspection ends.Mock Inspections.
Although a mock inspection cannot fully prepare one for the real thing, a simulated inspection helps identify possible weaknesses in the SOPs and provides personnel with a better appreciation of both the questions that they may be asked and the seriousness of the inspection process.
Regular review and updating of the SOPs and mock inspections can help the organization improve its inspection preparedness as well as its operations.Dos and Don'ts
Effective inspection preparation requires a multi-faceted approach. But communication issues can be just as critical, as these dos and don'ts suggest.
Do be professional and confident. Don't become argumentative or, worse, hostile. Attitudes are important. If management is seen as "uncooperative," the investigator may well become suspicious and more zealous.
Don't tell the investigator that an inspection isn't possible that day because the owner is on vacation, and suggest they return next week.
Do balance cooperation with wariness. Although an initial presentation about the facility's operations and a tour can be useful in setting a positive tone, wait for the investigator to make specific requests before providing records, samples, labels and the like. Respond to requests appropriately, but do not offer other materials that might relate to another matter pending with FDA but are unrelated to the request.
Do provide timely and carefully prepared written responses to 483s, and to any letters issued by FDA regarding violations identified as a result of the inspection. Often, it is appropriate to include a plan for corrective action. FDA wants to see that management is taking these issues seriously.
Patricia Kaeding, an attorney, was an associate chief counsel at the U.S. Food & Drug Administration from 1993-2003. FDA & Your Business appears monthly on WTN.