In the musical “Oliver!” based on Charles Dickens’ novel, a poor child draws the ire of his caretakers when, after a meager portion of food, he famously holds out his bowl and says, “Please, sir, I want some more.”

Consumer advocates and others would argue today that we don’t necessarily need more food  – but they would hold out their bowl for more food regulation, especially from the FDA.

It’s not as if we need reminders that there are some serious shortcomings when it comes to how some food manufacturers operate (and how the FDA regulates them), but a recall of more than 200 million eggs this week gives us one whether we’d like it or not.

There’s been growing pressure on the agency to tighten its regulation of food, and it is starting to look like proposed federal legislation is going to deliver just that.

Most Capitol Hill watchers are predicting the Food Safety Modernization Act will come to a vote after the Labor Day recess. It’s likely to pass, though there is some debate about a few proposed amendments including one that would ban outright the usage of BPA, the plastic lining found in cans and in other packaging. Some pundits say attaching the BPA ban would kill the whole bill.

The FSMA would give the FDA greater authority regulate food and place a greater legal burden on food manufacturers to be more transparent when it comes to how they control their product from conception to landing on your dining room table. In other words, food manufacturers would have a lot more quality control work on their, well, plate.

A timely summit last week featured representatives from the Pennsylvania Dept of Agriculture and Dept of Health as well as the Grocery Manufacturing Association.  Led by Dr. Rene Massengale, Associate Professor of Biotechnology, who heads Food Safety and Quality Assurance Academic program at Harrisburg University of Science and Technology, Dr Massengale said industry has generally reacted positively to the potential changes coming from Capitol Hill.

While industry is supportive in principle to the idea of increased food regulation, Dr. Massengale said there is some nervousness out there about what kind of regulations finally emerge from any new Congressional law. Another wrinkle: Some manufacturers of relatively lower risk items, say candy versus eggs, are saying to feds “leave us alone, we already do this well,” she says. Her event attracted representatives of companies and organizations participating in the food supply system including agricultural growers and producers, food processors, food distributors/wholesalers/ retailers and members of related trade associations, as well as middle and upper-level managers from small and medium-sized organizations and managers, directors or owners responsible for food safety and product quality, such as HACCP, QA/QC, and process control professionals.

So, is “more” on the way?

It’s beginning to look that way.  Watch this space in the coming months as track the FSMA’s progress on Capitol Hill.

For more information

Request “The New FDA Drive for Food Safety” paper here.

Blog:  http://foodsafetyquality.blogspot.com/

You can follow Dr. Massengale’s frequent updates on Twitter here:  http://twitter.com/RDMassengale

Weighing patient safety against encouraging medical innovation is no easy task. The FDA has been struggling with it off and on, mostly on, since its creation in 1906 (yes, I had to look it up). It took very gross meat and a crusading Upton Sinclair to force the FDA’s very existence. Hopefully we won’t need anything so dire to effect some positive change this time around.

Over the past decade most critics have said the agency has been too understaffed to effectively regulate the F(ood)and D(rugs) of its name. When it comes to assessing its medical device activity, it’s a bit tougher to analyze. But that just might get a little bit easier. Last week the FDA unveiled two big evaluations containing recommendations that address three key objectives of the agency’s public health mission as it relates to medical devices – foster device innovation, create a more predictable regulatory environment, and enhance device safety.

The Center for Devices and Radiological Health (CDRH) assessment consists of two preliminary reports. The first focuses on ways to strengthen and clarify a premarket review process called the 510(k) program for medical devices that do not need to undergo a full premarket approval review. The second evaluates CDRH’s use of science in decision-making, with an eye toward adapting to new scientific information, while maintaining regulatory predictability necessary for innovation.

The two documents overlap in several places and cross-reference information. Both are available here.

“Having FDA 510(k) clearance is a big milestone, one which further validates” a company’s products, notes WellDoc CEO Ryan Sysko. He’s just been through the 510(k) approval process with a happy outcome (approval in July).

“We found the FDA to be very open and willing to talk, willing to offer guidance,” Sysko says. His advice to other young companies is “first thing, call the FDA, talk about your product and what it is trying to accomplish, and get a sense of the regulatory climate.”

Make sure the FDA understands your technology or product so they can better understand how doctors and patients use it, stresses Sysko. Also it important to put quality system programs in place early on and have strong employee training programs, Sysko adds. “It is absolutely critical to show the FDA your good work, too” he emphasizes. FDA on audits wants to see SOPs, document control, training records, among other items, and you’d better be ready to demonstrate it.

Back to what the FDA did last week.

CDRH established two staff committees on these issues in late 2009 as part of its 2010 strategic plan. The committees collected and reviewed input from public meetings, open dockets, data analyses, and input from CDRH staff over the course of several months to prepare the complementary evaluations.

We’ve heard from some medical device firms that scream bloody murder (off the record, of course) about how cumbersome and counter-intuitive the FDA’s 510k system has been. Even the agency admits that “concerns have been raised both inside and outside of the FDA about whether the current 510(k) program achieves its goals of making safe and effective devices available to the public while fostering innovation. Concerns about the program have centered on whether it allows devices to enter the market without sufficient safety and effectiveness evidence and whether a lack of predictability, consistency, and transparency is hindering device development.”

In other words, the FDA seems to understand that the system is broken. Is this a fix? Most say it is a good start, if nothing else. “The challenge the FDA will face is how do we take what’s being accomplished with technology while ensuring patient safety,” Sysko says, noting it’s obviously easier for Apple or Google to launch a new innovation than it is for medical device companies.

FDA makes some effort to defend itself, specifically CDRH, in its announcement. “CDRH uses science to guide its regulation of medical devices across the total product lifecycle,” notes the agency release. “At any stage of that lifecycle, new, unfamiliar or unexpected scientific information may arise that warrants a change in the FDA’s thinking, expectations, and actions.” CDRH says it is trying to find the right balance between the ability to adapt its approach as new science emerges and to provide predictable regulatory pathways.

“Taken together, these preliminary reports show a smarter FDA – an agency that recognizes both sides of our mission to protect and promote public health,” said CDRH Director Jeffrey Shuren, M.D. “The agency is ready to make necessary improvements to support device innovation while assuring patients receive safe and effective devices.

“Even with our significant outreach, it’s important to remember that these recommendations are preliminary,” said Shuren. “CDRH opened another public docket to receive additional comments on both reports. We will make a decision on which recommendations to adopt only after a thorough review of additional comments.”

While the agency has a prime directive to protect patient safety, it doesn’t want to slow or even destroy a medical device that’s ready to roll and ready to help patients. But the agency has often been accused of slowing innovation to the detriment of patient safety. It’s a balancing act, to be sure, and we should at the minimum give the FDA for addressing this and trying to come up with a good solution.

Selected recommendations and the key public health objectives they address include:

Fostering Device Innovation

• The 510(k) report recommends major improvements to the regulatory pathway for lower-risk novel devices that cannot be cleared through 510(k) but which do not warrant the more rigorous premarket approval review applied to higher-risk devices. The report calls for major reforms in the implementation of this process – called the de novo classification process. The recommendations include streamlining the process and clarification of CDRH’s expectations for submissions that undergo this type of review.

• The science report recommends that CDRH make better use of scientific experts outside of the agency by developing a web-based network of external experts using social media technology. This network would help CDRH staff leverage outside knowledge without serving in an advisory capacity.

Enhancing Regulatory Predictability

• The 510(k) report recommends that CDRH develop a guidance document defining a subset of moderate-risk (Class II) devices, called Class IIb, for which clinical or manufacturing data typically would be necessary to support a substantial equivalence determination. This guidance document would help clarify what information submitters should include in their 510(k) submissions so that they can plan accordingly. In addition, this would also help the center’s review staff obtain the type and level of evidence necessary to make well-supported decisions without as much need for time-consuming follow-up requests for information.

• The science report recommends use of a standardized “Notice to Industry” letter that would generally be issued as a “Level 1 – Immediately in Effect” guidance document to quickly communicate when CDRH has changed its premarket regulatory expectations due to scientific information that has emerged about a certain device type. CDRH currently communicates this kind of information through individual interactions during the review process, which can lead to delays. These letters would provide greater clarity to affected manufacturers, in a timelier manner, about CDRH’s expectations with respect to a particular group of devices.

Improving Patient Safety

• The 510(k) report recommends that CDRH consider revising regulations to explicitly require 510(k) submitters to provide a summary of all scientific information known or that the submitter should reasonably know regarding the safety and effectiveness of the device under review. This is not required now for 510(k) submissions and, as a result, relevant information may not be included in an initial submission. This summary would help CDRH review staff to more efficiently make decisions, and potentially avoid extensive follow-up inquiries and questions.

• The 510(k) report recommends that CDRH develop a guidance document that clarifies when a device should not be used as a predicate, such as when the device has been removed from the market because of safety concerns. The report also recommends that the center consider issuing a regulation that would clarify the circumstances under which the center would exercise its authority to rescind a 510(k) clearance to remove an unsafe device from the market and preclude its use as a predicate and also consider whether additional authority is needed.

• Both reports recommend that CDRH build upon public databases to include meaningful, up-to-date information that supports good decision making and promotes the safe use of devices. This could be accomplished by improving the current 510(k) database so that it includes summaries of FDA review decisions, current labeling and photos. In addition, the science report recommends that CDRH build upon the existing transparency website to provide more immediate information on how devices are regulated.

For more information:
CDRH Preliminary Internal Evaluations

CDRH Device Approvals and Clearances: 510(k) Clearances

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.

“Check back in August,” FDA spokesman Dick Thomspon told us this week when we asked if the eMDR guidance was coming out anytime soon. “The guidance is not yet complete,” Thompson said. “At this point, I would not expect this to be issued before the end of the summer.”

The FDA has missed several unofficial deadlines for the guidance, others in and close to the agency have told us in recent months. The latest missed deadline was June, when several folks inside the agency told us and others off the record that it was going to be issued that month.

Well, that didn’t happen.

It’s unclear exactly what the cause of the delay is; we’ve heard from those inside the agency who say it’s more about workload and shifting priorities than any guidance content issue, e.g. the eMDR guidance gets shoved off someone’s desk when something else “more important” comes up. More ominously, we’ve also heard some rumblings that the eMDR process is getting a little political much like the Part 11 process did.

At any rate, the agency asked us to check back in August.

Have a nice summer.

Remember that old expression “you get what you pay for”? Well, it’s a cliché, but most of the time these oft-used phrases are oft-used because they have an underpinning of truth. This brings us to the FDA’s free eMDR options for low and high-volume submissions.

In the past few days we’ve connected with a number of folks who either tried it and liked it, tried it and hated it, and/or were afraid to try it because of all the horror stories they heard.

None wanted to speak on the record, but if you are considering going the free route, their comments are, to use another cliché, food for thought.

“We talked to people from several companies and they found creating the files was still considerably more challenging than it should have been,” a medical device QA official told us. Her bottom-line: “We evaluated eMDR in 2009 and were strongly encouraged by others NOT to utilize” it.

On the other side of the ledger (there’s another cliché, for those keeping score), we heard from at least some medical device companies that said the experience was fine. Example: One told us they’d recently filed their first eMDR, and the report was posted on the FDA’s MAUDE database just under a month later.

And it appears the FDA is at least working to improve its eMDR offerings. Earlier this week, for example, the agency issued a bulletin aimed at high volume submitters in its eMDR user group . The agency told those using a gateway to gateway connection using AS2 or thinking of using a high volume solution in the future that the Implementation Specification found in the Health Level Seven (HL7) Individual Case Safety Reporting (ICSR) files has been updated with some important information.

They boiled down to this:

1) Under the section titled “How do I know my submission reached CDRH?” where the 3 acknowledgments sent via the ESG are discussed, they added the following: “For those reporters using a B2B account (i.e. a gateway to gateway connection) using AS2, you should not rely on the “Content-Type” header for determining how the acknowledgments are processed.  Acknowledgments should be processed based on the file extension and actual content, and your systems should be programmed accordingly.”

This was added to address the issue where the content type sent by the Electronic Submissions Gateway (ESG) in test and production differ, the agency explained.

2) Under the section titled “Can I submit attachments?”  the FDA added an instruction:  “Please limit each attachment to 50 MB in size.”

Worth noting: The FDA said anything larger might cause its loading programs to stall.

3) The FDA also added a new question/answer in the FAQ section:
Q:“Electronically submitted adverse event reports do not have all the fields found in the 3500A form able to be mapped. How should we send information that is not able to be mapped to a 3500A field?”

A: “Correct. Some fields such as G5’s check boxes for combination product, pre-1938, and OTC product are not available for mapping. If you would like to indicate this information or any information that is not mapped, please use section H10 (manufacture narrative) to indicate this information.”

Apparently many reporters already have noticed this, but the agency felt it was helpful to have it noted in the implementation file.

The FDA also tried to deal with some other eMDR issues, too, for WebTrader users.

“The FDA Electronic Submissions Gateway (ESG) has heard from trading partners, industry submitters, and ESG account holders about difficulties logging in to the WebTrader portal. The ESG team has been troubleshooting the issue and has found that the large size of some WebTrader inboxes has been causing login difficulties,” the FDA said.

Because many users have left large numbers of old messages in the WebTrader inbox, the FDA ESG staff announced it would delete all messages other than the most recent 20 messages on Monday, June 14th, 2010 at 1PM EDT.

If you haven’t read your messages or if you might want to save them because they have important information from the FDA, you need to open your WebTrader inbox this week and save them to your own computer or a network location your company defines, the agency said. Otherwise, if you don’t read and save your messages before the deadline, all messages beyond the last 20 will be deleted.

The FDA’s other helpful hint: In order to ensure good WebTrader performance in the future, please save a copy of the receipt and acknowledgment files immediately upon receipt and delete copies from your WebTrader inbox or ensure that the WebTrader inbox has a reasonable number of past messages (i.e. <20).

Direct questions/concerns to the FDA ESG staff at esgreg@gnsi.com.

And if you’ve got any great or horrific eMDR experiences to share with us (off the record, if you prefer) please contact me at mcausey@edataintegrityreport.com