In August, Commissioner of Food and Drugs Margaret A. Hamburg, M.D., outlined her commitment “to prevent harm to the American people” through swift, aggressive, and effective enforcement of FDA laws and regulations at a Food and Drug Law Institute (FDLI) meeting. Last week, FDA officials speaking at the FDLI meeting on enforcement reaffirmed that commitment, warning that “past performance is no measure for future performance” and that companies can expect a “flurry of warning letters.”

FDA staffers have indicated that the agency’s ramped up enforcement efforts will include a holistic and collaborative approach between the agency’s centers in such areas as advertisement enforcement; “blitzes” focused on undeclared allergens, label reviews and warehouse inspections; and data quality.

Among these initiatives, the Center for Drug Evaluation and Research (CDER) has indicated that its approach will include paying closer attention to compliance weaknesses and sloppiness as signs that other reporting could also be sloppy, ensuring proper monitoring of scientific research and data for new drug applications, and working with other centers on matching enforcement priorities.

The Division of Drug Marketing, Advertising and Communications (DDMAC) has also stated that it will dedicate more resources to identifying the most serious violations and getting more actions, through paying closer attention to promotions that could wield the greatest negative impact on public health. DDMAC will also be paying close attention to newly approved products, products with significant risks, or products cited in the past or currently subject to a complaint.

More information on the FDA’s increased enforcement efforts is available at here.

See also: Don’t Ignore 483s…it’s in Your Best Interest to Respond in Writing

See also: The Most Common Drug and Device GMP Items

Mark Mansour is a partner in the firm, Bryan Cave, LLP

FDA Commissioner Margaret A. Hamburg put industry on notice in a brief but well orchestrated rollout of FDA’s new enforcement policy.  The message, in Dr. Hamburg’s own words, is that “the FDA must be vigilant, the FDA must be strategic, the FDA must be quick, and the FDA must be visible.”  On the job now for just shy of three months, Commissioner Hamburg addressed a group of industry representatives, attorneys, consumer representatives, and media at an August 6th event sponsored by the Food and Drug Law Institute in Washington, D.C.

Dr. Hamburg expressed concern about what she described as “unreasonable” delays in FDA enforcement actions in the recent past, and said that “serious violations have gone unaddressed for far too long.”  She observed that that the enforcement process is “too long and arduous when the public’s health is in jeopardy.”

Hamburg laid out a series of steps FDA intends to take, presumably starting immediately:

• Set post-inspection deadlines. The FDA will establish a clear timeline for regulated industry to respond to significant FDA inspection findings, generally giving no more than 15 days to respond to such findings before the agency issues a warning letter or takes other enforcement action.
• Take responsible steps to speed the warning letter process. The FDA will streamline the warning letter process by limiting review of warning letters by the Office of Chief Counsel to those that present significant legal issues.
• Work more closely with FDA’s regulatory partners. In some cases, such as with food safety issues, state, local, and international officials can act more quickly than the FDA. When public health is at risk, the agency will coordinate with its regulatory partners to take rapid action.
• Prioritize follow-up on warning letters and other enforcement actions. The FDA will work quickly to assess and follow up on corrective action taken by industry after a warning letter is issued or major product recall occurs.
• Be prepared to take immediate action in response to public health risks. To better protect the public health, the agency is prepared to act more quickly and aggressively to deal with significant public health concerns and violations. Such actions may occur before a formal warning letter is issued.

Develop and implement a formal warning letter “close-out” process.  If the agency can determine that a firm has fully corrected violations raised in a warning letter the agency will issue an official “close-out” notice and post this information on the FDA Web site. This will be an important motivator for corrective action by manufacturers.

What Hamburg did not address is what will be done to streamline the approval process for medical devices and for other FDA-regulated products, nor did she address the persistent and growing problem of unqualified inspectors roaming plants armed with the authority to enforce.  No one disputes the need for vigorous, predictable enforcement, but FDA’s credibility is not threatened solely by the perception that it cannot keep the marketplace safe.  It is threatened as much by the reality that for those products that require pre-market approval, there is no end in sight to the delays and the absence of sufficient qualified technical staff to evaluate products and therapies and facilitate their release to the medical and patient community.  Ignoring that problem while focusing on regulating to the worst common denominator of the industry, by any a measure a very small minority, may make great headlines. Unfortunately, it leaves unaddressed some of FDA’s major deficiencies.

Mark Mansour is a partner in the firm, Bryan Cave, LLP

Even though there’s no regulatory requirement to respond to an FDA 483 inspectional observations report, it’s in your best interest to do so in writing, according to FDA sources. In a recent presentation by Anita Richardson, Associate Director for Policy Office of Compliance & Biologics Quality, she outlined four reasons for submitting a comprehensive 483 response, and eight suggestions for an effective response.

Four reasons for submitting a well-prepared and timely 483 response:

1. Could possibly mitigate an FDA compliance decision for further action (warning letter, etc.) “As a general rule, a Warning Letter should not be issued if the agency concludes that a firm’s corrective actions are adequate and that the violations that would have supported the letter have been corrected.”
2. Demonstrates to the FDA (and other stakeholders) an understanding and acknowledgement of the observations
3. Demonstrates to the FDA (and other stakeholders) a commitment to correct, i.e. the intent to voluntarily comply
4. Establishes credibility with FDA

Eight suggestions for an effective 483 response

1. Include a commitment/statement from senior leadership
2. Address each observation separately
3. Note whether you agree or disagree with the observation
4. Provide corrective action accomplished and/or planned; tell FDA the plan
   • Be specific (e.g. observation-by-observation)
   • Be complete
   • Be realistic
   • Be able to deliver what you promise
   • Address affected products
5. Provide time frames for correction
6. Provide method of verification and/or monitoring for corrections
7. Consider submitting documentation of corrections where reasonable & feasible
8. BE TIMELY

Good advice. And remember…

“A well-reasoned, complete, and timely 483 response is in your best interest.”