Amid continuing debate about the timing and shape of the Senate’s food safety bill (the House passed a version in July 2009), comes a new issue that affects companies in the food, drug, device and cosmetic industries.

Several months ago, FDA Deputy Chief Counsel for Litigation Eric Blumberg told industry representatives at the FDLI Annual Conference that the agency is prepared to dust off the three-decade-old “Park Doctrine” to augment FDA’s continuing efforts to ratchet up its enforcement profile. The doctrine stems from the United States Supreme Court’s decision in United States v. Park, 421 U.S. 658 (1975). In principle, it allows the government to pursue misdemeanor charges against a corporate officer for alleged violations of the Federal Food, Drug, and Cosmetic Act, regardless of whether the officer is aware of the existence of a violation, as long as the officer holds a position of responsibility so that that individual could have initiated preventive or corrective action and, for whatever reason, failed to do so.

Park represents a strict liability standard, so no warning letter is required. FDA need only request that the Department of Justice file charges based on FDA’s conclusion that an officer is guilty of misconduct, which is effectively defined as failing to know what FDA believes one should have known. In sum, what an executive does not know can be more than harmful.

The scale of punishment for misdemeanors ranges from one year in prison and/or a maximum fine of $100,000 for each count, ranging to much higher where injury or death are involved. Courts can impose mandatory prison sentences, and if FDA believes a substantial risk of injury or death is involved, judges can increase the length of prison sentences.

At a time when corporate resources are stretched, the entire spectrum of regulatory compliance issues has become every bit as critical for senior management and counsel as the other bet-the-company issues that confront each company on a day-to-day basis.

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

FDA Extends Comment Period for Proposed Neurological Device Regulations
The FDA has announced that it is reopening until September 7, 2010, the comment period for the proposed rule and guidance published in the Federal Register of April 5, 2010 (75 FR 17093). The document proposed to amend certain neurological and physical medicine device regulations to establish special controls for these class II devices and to exempt some of these devices from premarket notification requirements. More information is available here and here.

Device Industry Calls for Closer Coordination Between FDA, CMS
Members of the device industry are calling for closer coordination between FDA and CMS related to the competitive bidding process. Stakeholders have said that the two agencies sometimes send mixed messages, due to their different approaches to devices, and particularly for sophisticated therapy products for home use, with CMS focused on pricing and the FDA focused on support services and safety issues, including labeling and training. Members of industry have indicated that they hope that new FDA guidelines on home-use devices will make certain that suppliers ensure that training and support are provided as part of their bids.

FDA Weighs New Approach to Regulation of DTC Genetic Tests
In the wake of a recent GAO report finding that direct-to-consumer genetic tests are providing inaccurate results to the public, the FDA has indicated that it is considering an approach to regulating the tests that would increase oversight without creating heavy reporting burdens on individual companies. The agency’s potential approach, as currently envisioned, would not require the developers of certain diagnostics to submit data on their individual diagnostics, if a manufacturer had previously provided information on the overall indication of the diagnostic to the FDA.

Pharmacies Calling for Removal of Reimportation Amendment from Food Safety Bill
Pharmacies are ramping up their efforts to encourage lawmakers to remove an amendment to the food safety legislation, offered by senator Byron Dorgan, that would allow for the reimportation of drugs from Canada and Mexico into the United States. Pharmacies are stating that the safety of such drugs cannot be ensured and that the use of reimportation means that individuals would not be consulting with a pharmacist at the time that they obtain the drug. Some are speculating that the amendment, which Dorgan also attempted to introduce in the health reform legislation, could prevent the passage of the overall bill, and are thus encouraging its removal.

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

I’ve got to admit, despite months (or years?) of hearing from those inside and close to the FDA that the agency intended someday to begin actual enforcement of 21 CFR Part 11, I was beginning to have my doubts.

No one likes to be told he’s crying wolf or acting like Chicken Little squawking about the sky falling.

Finally, however, the FDAs CDER division issued a blandly worded release that may have some serious repercussions for regulated drug companies:

The FDA “will be conducting a series of inspections in an effort to evaluate industry’s compliance and understanding of Part 11 in light of the enforcement discretion described in the August 2003 ‘Part 11, Electronic Records; Electronic Signatures — Scope and Application’ guidance (Guidance). The Agency intends to take appropriate action to enforce Part 11 requirements for issues raised during the inspections that do not fall under the enforcement discretion discussed in the Guidance.”

That’s about all they said publicly, but it’s a mouthful after waiting a long long time for any agency activity backing the Part 11 rule.

While this announcement focuses on drugs, don’t be surprised to find a similar action coming soon on the device side.

“I’d expect FDA inspectors to focus on Part 11, too, when they inspect device manufacturers,” agrees former FDA inspector Ken Miles.

When it comes to preparing for FDA inspections, Ken says he’s a big fan of the Boy Scouts motto: Be prepared.

We’ve heard in the past that many FDA inspectors weren’t comfortable yet inspecting or enforcing Part 11 provisions. The result: Very few inspections, and some inconsistent inspectors.

In the coming weeks, we’ll report back on what kind of inspections FDAers are conducting, and how you can best prepare for them.

FDA: Genetic Testing Kits are Medical Devices

The FDA has sent letters to five manufacturers of genetic testing kits stating that the agency is considering the kits to be medical devices. As such, the agency has said that they need to receive approval from the agency before they can be marketed. The House Energy and Commerce Committee has announced that it too is looking into the tests.

FDA Requests Notifications of Intention to Participate in Meetings on PDUFA Reauthorization

The FDA has issued a notice requesting that public stakeholders notify the agency of their intent to participate in periodic consultation meetings on reauthorization of the Prescription Drug User Fee Act (PDUFA). After the statutory authority for PDUFA expires in September 2012, the FDA will consult stakeholders to develop recommendations for the next PDUFA program. Notifications of intention to participate must be submitted by June 25, 2010. The first stakeholder meeting will be held on July 1, 2010, from 9 a.m. to 11 a.m. More information is available here.

FDA Corrects Dental Device Final Rule

The FDA has issued a notice that it is correcting an error in its Final Rule on dental devices, published on August 4, 2009. More information is available here.

FDA Seeks Comments on Labeling Requirements, Premarket Approval, Drug Co-Development

The FDA is seeking comments on the standardized format and content requirements for the labeling of over-the-counter (OTC) drug products. Comments are due by August 2, 2010. More information is available here.  The FDA is seeking comments on requirements for premarket approval of medical devices. Comments are due by August 9, 2010. More information is available here. The FDA also seeks comments on methods to co-develop two or more distinct investigational drugs intended to be used in combination to treat a disease or condition. FDA is planning to develop guidance for industry and other affected parties on the co-development of two or more novel drugs intended to be used in combination (but not as not fixed-dose combinations) and is seeking public input to identify the affected parties’ information needs concerning such co-development. Comments are due by September 7, 2010. More information is available here.

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

Gotta give the FDA some credit here. In addition to its transparency initiative we’ve talk about before, the agency is also trying to remove some of the mystery about how it handles inspections and other inner workings at the FDA. From where I sit, it appears to be a sincere effort and I believe it is helping outsiders better understand what the FDA is trying to do – and how it is trying to do it.

For example, at the second in a new series of monthly online webinars, FDA’s Michael C. Rogers, deputy director, Office of Regional Operations, said today (March 25, 2010)  tried to outline how an FDA inspection tends to work, and what drives inspectors before, during and after an inspection.

As an aside, Rogers also said that the agency currently has about 1,800 total inspectors across its full portfolio, though food gets the bulk of the bodies. He also said there will be more foreign inspections this year, and that the number should continue to grow.

Inspections are based on risk, Rogers said. In other words, the riskier the potential drug, device or food item, the more likely they will be inspected.

Most inspections are unannounced, Rogers said. Before they go on-site, the inspector on inspection team will look at previous inspection reports and identify what corrective actions were promised during prior inspections. They also prepare inspection tool kits with sampling equipment, info to drive inspection based on guidance documents and the Investigation Operations Manual. They also carry a camera to document evidence.

They also conduct “for cause” inspections driven by consumer complaints or other outside activity.

Typically, the inspection begins with a discussion with management to explain the purpose of the inspection, and they try to learn about the corporate structure and any changes made since last inspection. They also ask about complaints, positive tests or returns. Answers to those questions help FDA inspectors focus their on-site efforts.

Next, they go to the physical manufacturing area. They try to observe and understand the on-site process. They ask about acceptance criteria and want specifics on failures, especially the reasons.

Inspectors also draw a diagram of the facility showing the manufacturing process from start to finish. They’re looking for problems in the system and looking to identify critical control points in the manufacturing process.

FDA inspectors then identify procedures in place and assess if company is actually following them. They also look for controls in place to mitigate any contaminated products.

They also look at training and cleaning programs. They also watch employees while they are actually making the product.

If they find evidence of an adulterated product, they collect evidence based on inspector observations and collect samples to prepare their case for possible legal action in court.

At conclusion of inspection, the FDA team meets again with management. They then inform the top company official what is in the official Form 483. That form documents observations during the inspection but does not include final recommendations. They also ask for the firms corrective actions planned or in place to get into compliance.

These corrective actions are taken into account as agency formulates official recommendations.

After the inspection at the firm, the inspector develops a report back at the home office. It includes evidence collected and what the firm has already agreed to do about any shortcomings.

In some cases firms can offer voluntary corrections. But sometimes the agency decides it needs enforcement action such as a warning letter, and can also impose civil and/or monetary penalties.

The webinar was extremely popular. In fact, it “sold out” so many who tried to join it could not get in to the live event. There will be a recording available on Monday March 29.

UPDATE: Slides are now available from this event here in PDF format.