Surviving An Audit By The Food And Drug Administration

Friday, December 13, 2013 - 15:54

An audit by the Food and Drug Administration (FDA) can prove intimidating and burdensome for any company. Audits may last for multiple days and be disruptive to a firm’s normal operating procedure. In a worst-case scenario, negative audit results may affect the viability of an entire company. Fortunately, there are steps that can be taken to minimize disruption and maximize the potential for a positive audit outcome.

What Triggers An Audit?

If your company manufactures or processes any FDA-regulated products, then it is possible that the company will receive an audit notice and subsequent visit from the FDA. Inspections occur for a variety of reasons; however, routine inspections account for about 80 percent of the audits performed each year. The routine audits are a result of random site selection or focus on a site that has submitted a New Drug Application or a Pre-Market Application.

Any FDA audit is a nerve-wracking prospect, but tensions can be particularly high when audits are prompted by a reported problem. These targeted “for cause” audits can technically occur for almost any reason. A few red flags that tend to catch the FDA’s attention include:

  • Conducting a large number of studies or a study outside of the company’s area of focus or expertise;
  • Submitting safety and efficacy data which is inconsistent with other studies;
  • Conducting a highly publicized study;
  • Conducting a study with a large number of enrollees or a short enrollment window;
  • Having an unlikely number of subjects with a specific diagnosis in a certain geographical area;
  • Complaints regarding an alleged violation of FDA regulations, company protocol or human rights; or
  • Evidence that an investigator has a significant financial interest in the product.

Sometimes the FDA’s red flags are actually red herrings, as the situations listed above may legitimately arise in the routine course of the company’s business and be of no or little concern. In that case, the best offense is a good defense. As discussed in more detail below, prepare your employees for the audit as a means of protecting your company.

How To Handle An Audit

First, upon receiving notice of an impending audit, do not panic. You will typically receive between 5 and 14 days’ notice before an inspection actually takes place. Do not try to postpone an audit without a valid reason as this may serve to increase the FDA’s level of scrutiny once the audit commences. You should appoint a knowledgeable person in the firm, such as the plant or production manager, to accompany the investigators when they arrive at the site. Prepare an office or room with a large table and copy machine and make them available to the FDA personnel. Typically, inspectors will examine the production process, analyze certain documents, collect samples, and interview members of the staff.

If copies of documents are requested:

  • Remove subject identifiers from the copies you provide to the inspectors;
  • Retain a copy for your records;
  • Stamp "confidential" on the inspector copy and "copy" on yours;
  • Only provide the documents that are specifically requested.

The inspector may ask to interview a member of the staff. Here are some important do’s and don’ts to keep in mind when answering an inspector’s questions:

Do

  • Be honest;
  • Be clear and concise;
  • Only answer the question that is being asked; and   
  • Keep a log of all questions that are asked.        

Don't

  • Guess or speculate;
  • Argue with the inspector;
  • Volunteer information that is not specifically asked for; or
  • Be afraid to say, “I don’t know.” You can refer the inspector to someone else who might know the answer.

Companies conducting clinical trials, especially those involving human subjects, are highly scrutinized by the FDA. It is essential for a company to follow its protocol and make sure everything is properly documented. In particular, be prepared for the FDA to review the following items, all of which are routinely examined during an audit:

  • Adequacy of communications with the Institutional Review Board (IRB), including the initial submission, continuing reviews, adverse event reporting, progress reports, etc.;
  • Completeness of accountability documentation for the receipt, storage, administration and return of the investigational product;
  • Compliance with the study protocol and documentation that each deviation/amendment received IRB and sponsor approval;
  • Appropriateness of the informed consent process and the consent forms;
  • Adequate monitoring of the site and communications of the sponsor;
  • Prompt and complete reporting of adverse events to the IRB and sponsor; and
  • Compliance with record retention requirements.

At the conclusion of the audit, the investigator will discuss any significant findings and concerns with the company’s management. The FDA will then issue a report, the Form 483 that documents any conditions or practices, which, in the investigator’s judgment, indicate areas of concern. The findings contained in the Form 483 should be used as a guide for corrective action. While there is no requirement that a company should formally respond to the Form 483, it is strongly encouraged as a means of documenting the company’s response and corrective action plan, if any.

Preparation Tips

The best way to prepare for an FDA audit is to have proper procedures in place before you receive a call from the FDA.

If you have not done so already, your company should:

  • Develop and implement Standard Operating Procedures (SOP). This will improve consistency and let every staff member know what the expectations are. However, the SOP should not be so detailed that it does not allow for some flexibility.
  • Keep a detailed checklist to verify that each step of the process is completed and document anything that varies from protocol.
  • Manage your data effectively. Important documents and other data should be readily accessible.
  • Run test audits. Have your internal auditors, compliance staff, and/or third parties perform mock FDA inspections. Do not be afraid to make changes to your SOP when appropriate after the test.
  • Provide training for all employees about applicable regulations and FDA procedures. A good start may be providing them with a copy of this factsheet!

Companies should be prepared for an FDA audit at all times. The sooner you start putting procedures and protections in place, the better chance you will have of emerging from an audit unscathed. Your senior management, internal auditors, legal counsel and compliance team should develop the standard operating procedures. You should also encourage employees to comment on your procedures to ensure that the procedures are practical and easily implemented.

The FDA provides numerous resources on its website regarding inspections, current regulations, and the approval process. Take advantage of these free resources. If your company is still unsure about compliance, contact the FDA or your legal counsel. Always err on the side of caution and try to anticipate problems before they arise. Inspections are only unpleasant for those who are unprepared.

Douglas A. Grimm, FACHE, chairs the Health Care Practice Group at Stradley Ronon. He represents health care systems, with an emphasis on regulatory counseling in the areas of compliance planning, government investigations, health information privacy and security, health information technology, peer review/medical staff and certificates of need, development of new service lines, licensure and provider enrollment, and insurance issues.

Please email the author at dgrimm@stradley.com with questions about this article.