In our previous installment, Tamil Arasu, former investigator with FDA, detailed preparations that a firm can make in advance of an FDA inspection, as well as details on the types of inspections that FDA performs on drug firms. In today’s post, Tamil will describe appropriate conduct during an inspection, including both the personnel that will interface with the investigators as well as critical backroom support.

During the Inspection

A brief introductory presentation by management that covers the history of the company, the site’s compliance history, organizational chart, headcount, hours of operation, list of products, list of major equipment and software, and facility layout should be performed on the first day that FDA is on site. This will help the investigator get familiar with your site before walking into the facility for inspection. Also, inspection should include a facility tour which will most likely happen on the first day of the inspection.

Present FDA investigator’s questions to site personnel in the “Backroom” and prepare responses to the questions before meeting with the FDA investigator. Ask for clarification if the questions or requests are vague. Listen carefully to what you are asked and respond directly to the question. Make sure you understand the question before you answer. Answer questions accurately and succinctly and do not elaborate and/or do not guess. Do not delay, deny, limit or refuse an FDA inspection as it may lead to further actions by the Agency as they are considered prohibited behaviors and may cause a drug to be considered adulterated as described in the FDA guidance document, titled, Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug Inspection.

FDA Documents Request

It is not uncommon to receive a document request from the FDA investigator, particularly before an international inspection. If you receive such a request and you have doubts about the content, ask for a clarification. Some investigators ask the firm to have all the requested documents to be ready on the first day of the inspection. Individual preference among FDA investigators in collecting documents varies to large extent, with some preferring electronic documents and some preferring hard copies and others preferring both formats. It is common for FDA investigators to request electronic documents in a CD, DVD, or USB format.

Documenting the Investigator’s Request

It is a good practice to document all the requests made by an investigator during the inspection. Document Room staff roles and responsibilities should include:

  • Recording, prioritizing, and tracking of document requests
  • Retrieving and reviewing documents
  • Sorting documents
  • Staging documents for investigator review
  • Ensuring that complete records and copies are kept of all documentation provided to the investigators
  • Tracking all documents entering and leaving the inspection room

Backroom Support

Although it might seem like all the important activities occur in the front room, the effectiveness of the backroom management can often be the key deciding factor in whether an inspection has a successful outcome. (There is a reason why the backroom is commonly referred to as the “war room”.) A well-prepared and well-organized backroom is one of the most crucial elements of FDA inspection management, enabling your firm to respond quickly and appropriately to any FDA investigator’s request.

General Conduct During FDA Inspection

Here are some general recommendations for the employees to follow during the inspection:

  • Escort the FDA investigator to the conference room upon arrival
  • The senior-most person on site to receive Form FDA 482 (only for domestic) should verify the accuracy of FDA 482 contents; if a 483 is issued, they will also receive it at the closing of the inspection
  • Explain site rules including all safety rules
  • Ensure that site personnel are available when FDA investigator arrives daily
  • At start of the day, ask the lead investigator for the agenda for that day
  • Request a daily wrap-up for discussing any potential FDA concerns
  • Periodically ask the investigator(s) if he/she has received the information requested
  • Avoid unrelated discussions in the room with FDA investigator as this may distract the FDA personnel
  • If a concern voiced by an FDA investigator is valid, acknowledge that fact and commit to correct in a timely manner
  • Provide evidence of corrections made during the inspection
  • It is proper to provide information during the close-out meeting on corrective actions taken to any observations.

Daily Wrap-up Meeting

According to the FDA’s Investigations Operations Manual (IOM), “Investigators and analysts should make every reasonable effort to discuss all observations with the management of the establishment as they are observed, or on a daily basis, to minimize surprises, errors, and misunderstandings when the FDA 483 is issued. This discussion should include those observations, which may be written on the FDA 483 and those that will only be discussed with management during the closeout meeting. Industry may use this opportunity to ask questions about the observations, request clarification, and inform the inspection team what corrections have been or will be made during the inspection process. Investigators are encouraged to verify the establishment’s completed corrective actions as long as the verification does not unreasonably extend the duration of the inspection”. As the IOM recommends meeting on a daily basis, in general, FDA investigators are usually not averse to conducting a daily wrap-up meeting. The firm should ask for one.

Close-out Meeting

It is critical that the most senior person available at the facility is sitting at the table during the closeout meeting with the investigators. This is important in demonstrating that your firm is taking the inspection findings seriously and interested in learning the inspection outcome in order to address the deficiencies in a timely manner. The close-out may include sample collections, affidavits (domestic), and issuance of a Form FDA-483 Inspectional Observations. In addition to the Form FDA 483, the investigator may also verbally discuss minor deficiencies with the management and may include the discussion items under the “General Discussion with Management” heading in the Establishment Inspection Report (EIR).

Qualified consultants can provide onsite support during FDA inspections, assist in backroom management, and provide inspection preparedness training. The contributions that a 3rd party can make during an inspection can be invaluable and are certainly worth the investment to increase the chances for a positive inspectional outcome.

Our next installment will discuss what happens after the inspection ends and will provide tips on responding to a 483. Stay tuned to this page!