Being prepared

    Critical points to managing an FDA inspection
    By Karen Dixon
    A U.S. Food and Drug Administration (FDA) inspection is a careful, critical, official examination of a facility to determine its compliance with certain laws administered by the regulatory agency. Inspections may be used to obtain evidence to support legal action when violations are found. Therefore, given the criticality of the event, you must be prepared.
    Investigator will review your processes and procedures, document and collect information, and observe your operation while its under production. At your firm’s closeout meeting, the inspector will communicate potential violations to key management personnel.
    FDA authority in a tobacco inspection
    Your firms’ inspections will be performed by the tobacco operations staff of the FDA’s Office of Regulatory Affairs. These staff members may also be accompanied by representatives of the agency’s Center for Tobacco Products who are subject matter experts. Most of these individuals will have some type of life science degree, but they could also be engineers, chemists or microbiologists. Their background usually entails investigative techniques, evidence development, law and regulation training, and laboratory methods and techniques.
    This team will be acting on Section 905(g) of the U.S. Federal Food, Drug and Cosmetic Act (FDCA), which directs the FDA to inspect “every establishment registered with [the FDA] … engaged in the manufacture, compounding or processing of a tobacco product.”
    It will also act on Section 704(a)(1) of the FDCA, which states that the FDA has the authority to inspect any factory, warehouse or establishment in which tobacco products are manufactured, processed, packed or held.
    This authority requires the FDA to inspect each establishment at least once in a two-year period that begins the date you registered your facility with the FDA, as well as every two-year period thereafter.
    The importance of inspection preparedness
    The key to inspection preparedness is having a thorough inspection plan. The inspection tour is hosted by a key production manager or quality-control manager, and this person should be well-trained on tour routes, how to respond to the investigator and the rights of the firm during the investigation. As part of the inspection, be prepared to demonstrate written records of how the company is meeting all of the agency’s requirements, such as identification of who holds the key roles during the inspection as well as how the company meets all training requirements for those that play key roles. In addition, having key trained support personnel behind the scenes managing the requests in a “war room” is critical to a successful, well-controlled inspection.
    The opening of an inspection generally begins with your firm providing a brief (15–20 minutes) overview of your facility and production process. Having an accurate and updated presentation ready at all times will help you to have a smooth first interaction with the lead investigator. Some information that should be included in this presentation is: the firm’s contact information, who the most responsible individual on-site is, the firm’s history, a description of the facility and operations, the number of employees, hours of operation and an organization chart of top management officials. You should also include a list of the regulated products manufactured at your site.
    Also, be ready to have standard requests ready and on hand. Some of these requests include:

    • product listings
    • largest volume brand manufactured
    • diagram of facility layout
    • index of your standard operating procedures
    • copy of procedures for sanitation, pest control and water monitoring
    • CV or job description for key members of management team

    Managing the Inspection Process
    As mentioned earlier, you can help set the tone for the inspection by preparing a well-conducted reception and opening meeting. Make sure your receptionist or security team know who to contact when the investigators arrive, ensure the most responsible person at the site is immediately available to greet the investigators and accept the notice of inspection (FDA form 482), and have department managers and quality-control managers lead the meeting. Do not keep the FDA investigator waiting or delay the initiation of the inspection.
    Ensure that your meeting room is an appropriate size to handle the number of attendees and that it is also out of the employee traffic routes. This room must be in a quiet place and have a desk large enough to spread out papers and to take. It should also be equipped for your slideshow presentation.
    A well-trained site visit manager is imperative. This is the one contact that will take the request and direct the questioning to the right subject matter experts. The site visit manager should:

    • understand your company’s policy on taking photographs within the facility
    • understand the guidelines on tax and legal requirements for product removal
    • closely monitor and remain with investigators throughout the inspection
    • assure all questions and requests are fully addressed
    • assure all document requests are fulfilled
    • provide instruction to the inspection team and war room
    • provide expertise on quality issues

    The designated note taker(s) should also have training in the accurate capturing of pertinent data. Having good notes on the inspection will help with responding to any observations, assessing how you can improve upon the handling of future inspections, and the review of the establishment inspection report (EIR). The note taker should understand that it isn’t necessary or even feasible to attempt to record everything that is said. Rather, recording key questions and responses to those questions as well as indicating any concerns the company has about meeting investigator’s expectations are the types of key information to note. Also, if you have more than one investigator, assign a specific note taker to each investigator. This will ensure that all discussions are covered.
    The purpose of the war room is to manage and oversee the logistics of the inspection.
    A leader should be assigned to direct the employees within the room. This room should receive all FDA requests. In addition, all documents going in and out of the FDA room must pass through this room. The requests being fulfilled should be fully reviewed for accuracy to ensure that they completely answer the request from the FDA. A file containing all copies of documents should be created, and copies should be kept in the order in which they were fulfilled, including the time requested and the time submitted.
    A team, including the site visit manager, should accompany the FDA investigators within your facility at all times. This team should know the FDA’s authority over records, photographs, signing of documents and access to employees. Always obtain duplicate samples if the FDA takes samples of your products or labeling, and be sure you are provided form 484 documenting the samples.
    If during the inspection the FDA submits an affidavit to you, remember that you are not required to read or sign it. Do not even listen if the investigators begin to read it and refer the FDA to your legal counsel. Remember this is a serious interaction. Remain calm and exhibit control. Most companies adopt a policy of never signing any documents during an FDA inspection.
    The FDA may provide a daily closeout discussion with you. If during this closeout you determine there was information or data previously provided to them that needs to corrected or clarified, this is the time to correct and provide a clear explanation to the investigator. This is common, as there is a lot of information being reviewed throughout the day.
    While interacting with the FDA, it is important that all employees support the preparation efforts by ensuring that all work areas are orderly and that equipment and instruments are clean and calibrated. All records and logs should be filled out completely, accurately and legibly at the time of performance.
    Employees should be honest and direct. “I don’t know” is usually an acceptable answer if you are asked a question for which you have no responsibility. Refer the question to someone whom is a subject matter expert. Employees should be professional, courteous and cooperative. Employees should be trained to never volunteer information or guess on a response. They shouldn’t provide any misleading information or be confrontational or argumentative.
    After the inspection, which can last many days or sometimes weeks, the lead FDA investigator may provide the site with an FDA 483 form. This is a listing of objectionable conditions that the investigator feels need to be corrected. Post-inspection you should provide a letter to the FDA addressing the 483 observations. It is best to respond within 15 working days (not required) so as to minimize the risk of receiving a 483 warning letter from the FDA. If you do receive a warning letter, you are obligated by law to respond within 15 working days from receipt of the letter. Your responses must be thorough and supported by data and documentation. Remember, the FDA will confirm all of your committed corrections. You will also need to address the scope of each observation systemically.
    If the FDA is satisfied with the inspection and the site’s response, the FDA inspection team will prepare an EIR that will include the scope of the inspection, general topics of the inspection, FDA form 483 findings and any promised corrections at time of the inspection. This report will arrive via mail generally within a reasonable amount of time. The receipt of the EIR is an indication that the FDA considers your inspection closed.
    In conclusion, well-trained employees having a detailed and well-developed procedure and preparation is critical to a successful and efficient FDA inspection. Performing mock FDA inspections on a routine basis using an internal team or third party will keep your established process current and FDA-ready.
    Karen Dixon is an independent consultant at EAS Consulting Group.