Michael Causey, Editor & Publisher, eDataIntegrityReport.com

One of my favorite all-time bands, The Kinks, have a fantastic tongue-in-cheek song called “Have a Cuppa Tea” that satirizes the British belief that a good hot cup of tea will solve all of the world’s problems.

• 820.198 Complaint files
• 820.90 Nonconforming Product
• 820.80 Acceptance Activities
• 820.200 Servicing
• 820.22 Audits
• 803 Medical Device Reporting (MDR)
• 806 Reports of Corrections and Recalls…

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Deciphering the FDA is a bit like trying to understand what the old USSR was up to in the days of the Cold War.  In those days, it was called Kremlinology, or the study of a complex, secretive organization.  We need a catchphrase for those of us today who try to figure out what the FDA means when it says something, or what it means when it says nothing, or what it means when it tells you what it means. You get the idea.

The FDA has been talking a lot of late about transparency. Its 2011 initiative is an agency attempt, it says, to open up about how it does business. FDA is accepting comments on it until February 28.  The jury is still out on whether this initiative will accomplish much.

Our latest piece of FDA evidence is CDRH’s 2012 Strategic Priorities.

CDRH devotes the Introduction of the document about looking ahead to patting itself on the back for its 2011 achievements, e.g. its report, “Understanding Barriers to Medical Device Quality,” that reviews the challenges that the FDA and industry face in supporting well‐integrated, best‐quality manufacturing practices and strategies that industry and the FDA can take to overcome these barriers.

CDRH also reminds us that “to complete this work [in 2011] our staff went above and beyond their already demanding workload. This is a remarkable achievement.”

Good to know.

In 2012, CDRH says it will continue to emphasize four priority areas:

1. Fully Implement a Total Product Life Cycle Approach
2. Enhance Communication and Transparency
3. Strengthen Its Workforce and Workplace
4. Proactively Facilitate Innovation to Address Unmet Public Health Needs

CDRH promises in 2012 to “improve” its premarket programs. By April 1, it pledges to begin its Triage of Pre-market Submissions Pilot to “increase submission review efficiency and better manage the pre-market review workload.”

And by the end of the year, CDRH pledges to publish a proposed rule to clarify the circumstances under which it could rely on clinical studies conducted in and for other countries. CDRH also says it will finalize all guidance documents it has issued as part of its overall plan to improve its premarket programs.

We’ll keep an eye on these and other promises throughout the year and report back as FDA hits or misses its own targets.

Patrick Stone, President, TradeStone QA

In the age of electronic documents and electronic signatures, the FDA is still defining and providing guidance for 21 CFR Part 11 concepts it began in 2003.  It seems we all really need to catch up.

Now that FDA provides small business webinars and blogs about “the most pressing public health issues of the day”, it is refreshing to note that FDA does not deem all electronic records as regulated; however with human clinical trials, most if not all records are reviewable (investigator discretion).

Basic concepts like hybrid records (paper based, e-records) and meta-data (audit trail data-points) should be well defined by now and not mysterious to industry.  Enforcement discretion still applies for most Part 11 electronic review by FDA investigators.

The new risk based approach will need to be well documented and defined before approval is granted by the respective review division.  In 2007, FDA provided the most up to date guidance and current thinking on computer systems used in human clinical trials.

Once you can establish and document these three risk based controls you are ready to begin your clinical trial. The risk based approach continues throughout all phases of your clinical trial.

Companies conducting clinical trials in the all-electronic environment with e-patient source, e-case report forms, and scanned regulatory records may find that costs go down. You have spent multi-millions in assets to implement validated e-systems so now you may use “alternative monitoring” methods for your monitoring controls.

Human clinical trials can be monitored from a desk if your monitoring plan is deemed acceptable to the review division. You do not necessarily have to pay travel expenses for multi-site monitoring anymore. Here is the game changing draft guidance for “Oversight of Clinical Investigations  A Risk-Based Approach to Monitoring” and I have also included the link for the 2012 Small Business webinar “Electronic Source Documentation in Clinical Trials” here.

There’s more to this subject and we’ll revisit it again.

Patrick Stone, President, TradeStone QA

Will 2012 be a Mayan prophecy year of doom and gloom at FDA or will they get the job done for US/global public safety? According to the FDA website, 2012 will be a year of global regulatory operation and enforcement with emphasis on medical devices, drugs, and food products. Will the 2012 budget from congress for FDA provide the necessary funds as supplemented by MDUFA and PDUFA to complete this global mission?

Third party audits may be a new driving force in the completion of this bold global mission as with the European Union ICH mandates. How will FDA review the third party audits and enforce them accordingly?

The growing pains of letting go of the steering wheel may take FDA some time to get used to. Trusting international “accredited” third party audits may take some time for FDA to digest, too. FDA is used to being in the driver seat for all aspects of firm review and enforcement especially for medical devices and drugs. There may be an uptick in regulatory action internationally and some more supply chain shortages in both medical devices & drugs due to expanded review process.

Domestically, FDA will try to inspect the few medical devices & drugs manufacturing firms left within our borders. The focus may be on dietary supplements and food firms in order to meet congressional mandates for the Food Safety Modernization Act (FSMA). I can only hope that FDA mandates better labeling for our food products with strict guidelines on labeling the percentage of that food product which is imported.

According to FDA,”Nearly two-thirds of the fruits and vegetables–and 80% of seafood–eaten domestically come from outside the U.S.”

As consumers we need to be able to make informed decisions about the food we eat and where it is harvested. Processed foods are not labeling the percentage of imported ingredients within their product. FDA should also focus on human clinical research domestically with an emphasis on training inspectors to complete this goal. We may have lost domestic manufacturing for medical devices & drugs — however human clinical trials have not decreased at the same rate.

Clinical trials must be conducted domestically in order for the test article to be marketed in the US. Logic should dictate that FDA review more of these medical devices & drug human clinical trials. Unfortunately political appointees with no FDA experience lead the mission here, so logic and science are not always a driving force. The field investigator can only do what they are told not what is logically necessary to complete the public safety mission.

Crystal balls aside, let’s hope 2012 is a better year for the FDA.

Read more about FDA’s 2012 inspectional and enforcement trends here.

Patrick Stone is the author of Bubble Gum Badge – An FDA His-Story. You can also follow him on Twitter.

Patrick Stone, President, TradeStone QA

Here’s an idea: More FDA inspections outside the US, at a lower cost.

How?

If FDA trained other countries health organizations to conduct FDA business with Memorandums of Understanding (MOU), less money could be used to travel with more inspections completed. This training could be accomplished online and by going out with FDA International Investigators. The EMA should have a MOU if their model is similar to FDA’s. The advent of all electronic review should alleviate the need for more international inspections.

I admit I may be over-simplifying the issues with training monies and bringing foreign inspectors to US training facilities. But I think the basic idea holds water.

Host nations can send their inspectors for knowledge sharing and training with justifiable beneifits to the host nations public health. FDA can also video link for training, as is done currently for new hire training.

Unfortunately, innovative options are scarce at the FDA Senior Executive Service level (SES) and the old way of doing business is ingrained into the government model. For the short term FDA will try to increase international inspections in all program areas with a focus on food work.

I’ve observed many international drug and device firms receiving warning letters and multiple item 483 forms. If this current warning letter trend continues, the blame may fall on lack of FDA regulatory guidance.

The core mission of FDA is to protect the US public from harmful health products. Sending FDA field Investigators to where the products are manufactured and undergo human clinical trials is one of the only ways to accomplish the core mission. Ensuring that field investigators are proficient for the task and seasoned investigators stay engaged will be the challenge.

The international firms with compliance issues should be reviewed by their country’s FDA equivalent for cross training on regulatory compliance.

On the job training is used here at home as a component of new hire training. FDA will have to think outside the box if Congressional Mandates for International travel are to be met.

Congress must also understand that it is not only the amount of funds that insure successful international travel, it is also about proficient field investigators as well.

I have faith that FDA field staff will answer the challenge because they always do.

Patrick Stone is the author of Bubble Gum Badge – An FDA His-Story. You can also follow him on Twitter.

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

That sound you heard last week was the device industry sighing and maybe even applauding lightly when the FDA announced  it was seeking the public’s input on a plan to identify and harness a web of outside experts who may help it speed device approval.

As Reuters reported, FDA formed a pilot committee of experts, which will run through December 30 and expand the pool of vetted sources the agency already has on tap. It’s all part of the FDA’s effort to reform the 510(k) medical device review process. Some say the agency isn’t tough enough in protecting the safety of device users; others say the agency is stifling innovation and sending more jobs overseas.

Device manufacturers we spoke to were guardedly optimistic about this and other recent FDA moves. “We support the creation of such a network, providing that the FDA ensures that the experts do not have any personal or professional ties or conflicts of interest with the products / manufacturers / specific device industries they oversee,” Kelly Roman, Vice President at Fisher Wallace Laboratories, told us.

“We are aware that current Panel members that the FDA works with on PMA and reclassification matters may have these types of ties and conflicts,” Kelly continues. “It is difficult to retain top experts who have no vested interest in the fate of the industries they oversee, but ensuring that the process is completely free of bias is essential to the FDA’s mission and to public health.”

She suggests that, as with Panel members, FDA should “provide the full professional biographies of network experts. “ She also called on the agency to provide a forum by which the public may raise concerns over potential conflicts of interest on a case by case basis, and provide some process by which these concerns are officially addressed.

“This will help provide transparency and resolution to conflicts of interest that will inevitably arise. As of now, there is no clear, prescribed way to address such issues.

But Charlie Chi, Ph.D., former CEO and co-founder of OtisMed (now part of Stryker Orthopaedics), is a medical device industry entrepreneur and inventor flat out thinks it’s a bad idea for the FDA to get involved in new medical technologies.

Chi doesn’t think any company would want the FDA to get involved in every step of the product development cycle. In addition, he thinks it would take longer and be more costly for companies to develop new medical devices even though the approval process might be faster.

Chi noted that most U.S. companies are now going to Europe/Asia first to launch their new products because the approval process is quicker and less stringent than in the U.S. Yet, the failure rate is actually less than here in the U.S. He thinks the FDA should follow a review and approval process similar to other countries around the world.

Doug Mowen, Accenture

Accenture’s Doug Mowen feels the pain of both sides and urged the medical device industry to take a “wait and watch” approach. “There has been so much noise around FDA and these issues, but I believe the FDA has now heard everyone loud and clear.” He and his team work with medical device firms to handle 483s and other FDA-related dealings.

Doug sees some reasons for optimism because the FDA does seem to finally understand the medical device industries concerns. “If the FDA is able to reform a few things in the 510(k) process and make it more transparent, that will be such a positive thing.”

With over 15 years of experience in the Life Sciences industry, Doug has worked broadly across the medical technology industry, assisting major MedTech companies with compliance in key areas including emerging markets, supply chain, and pricing and customer profitability. Most recently Doug developed a research paper “Achieving High Performance: Reinventing Medical Technology for a Dramatically Different Future,” addressing how global regulatory issues are changing the overall business landscape for MedTech.

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Under pressure from all sides, the beleaguered FDA keeps announcing new reorganization initiatives, name changes and all sorts of stuff that would be funny if it was scripted by the same team handling Steve Carell’s departure from “The Office” and the ushering in of the new James Spader era.

Unfortunately, in real life these things aren’t always so funny. The FDA has been mocked in many quarters for its failure to maintain a balance between protecting the public safety and encouraging innovation among device and drug companies.

The list of FDA reorg moves made in just the past year would fill pages of old-fashioned newsletter space, but suffice it to say that the FDA has made a lot of changes and shows no signs of stopping.

Question: Should device and drug manufacturers care?

Short answer: Yes.

Question: Do the FDA changes mean more inspections and enforcement action for device and drug manufacturers.

Short answer: Yes.

We’ve spoke with several drug and device company compliance officers in the past few months, and without exception we’re told that dealings with the FDA have become more time-consuming and frequent. Not surprisingly, none wanted to go on the record for fear of further irritating an already irritating (to them) agency.

“I didn’t like the FDA’s approach five years ago, but now I miss those days,” a mid-size device firm compliance officer recently told us, only half jokingly.

Areta Kupchyk

Areta Kupchyk, a partner and former FDA-er now at Reed Smith LLP, notes that “where FDA puts their resources typically reflects their priorities and approach to enforcement.  For example, FDA appears to be putting resources in enforcement areas and giving some of those divisions more independent authority from the chief counsel’s office to take action,” she tells us.

“FDA also wants to speed review times for 510(k) submissions, orphan drug designations, and therapeutic biologics (especially biosimilars).  The new acting Chief Counsel, Liz Dickinson, has a strong background in generic drugs and biosimilars and we are very likely to see more focus in this area,” Areta adds.

These FDA changes are mostly going to impact mid- and small-sized companies on the device side, Areta says. “Large pharmaceuticals already basically understand how compliance works and how to do it, but the mid-size device companies in particular don’t have enough experience with quality systems and GMPs,” especially as FDA’s interests and demands seem to keep changing.

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Medical device companies are telling us off the record that they are not particularly optimistic about the FDA’s much ballyhooed new reviewer training programs it unveiled last week.

“If it makes reviewers act more consistently it will be positive but I think the problem is deeper,” a small medical device shop told us this week. Their products are mostly Class I but last year they began a Class II review process.

“Our reviewer left the agency in the middle, and the new guy asked a whole bunch of new questions and even questioned some of the old questions again,” the CEO told us.

His situation is not atypical, according to John Smith, Partner at HoganLovells.  His firm has represented over 500 medical device companies navigating the FDA review process. And what he’s seen isn’t pretty.

“It’s well known in the medical device world that depending on which FDA reviewer is assigned, you may get dramatically different results,” John told us. Like our small medical device shop CEO’s experience, John has also seen the review process change completely when one reviewer leaves and is replaced mid-process.

John’s also seen too many situations where similar Class II products get completely different treatment during their review. “That inconsistency is tough for industry to deal with,” he adds.

“It’s not uncommon for a new member [of the FDA review team] to raise new questions or even go back and look at areas the device company thought were already addressed” by the outgoing reviewer, John says.

CDRH chief Jeffrey Shuren has sometimes downplayed the impact of FDA turnover on the review process, but he generally concedes that the agency needs more help here.

The FDA’s current training initiative is not making any hearts flutter with happiness in medical device land, but John says it is a positive at least in the sense that “the FDA is right to identify this as an issue where resources should be directed.”

For John and others, the impact of this training initiative won’t be clear for months and maybe years. “It sounds like a worthwhile initiative, but we’d like to see the results,” he diplomatically says.  “It’s easy to identify the problem, let’s see if the FDA addresses it.”

But former FDA reviewer Patrick Stone says reviewers will keep leaving unless the agency makes some fundamental changes. “They never praise reviewers or give any positive feedback, and that’s why most reviewers can only take it there for about five years.”

The Senate is also expected to hold hearings in the Fall that will look at how good, or bad, the FDA’s current device review process is and how effectively it balances patient safety with spurring product innovation.

Summer’s over. Back to work.

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Tyra Banks aside, not many 35 year olds look as pristine and buff as they did in younger days.

But if the new Institute of Medicine (IOM) report has its way, the FDA’s 35 year-old 510(k) process should be put out to pasture entirely.

I suppose there’s something to be said for the fact that IOM’s controversial new report seems to have made almost everyone mad.

FDA is reportedly not happy and surprised that it calls for scrapping the current 510(k) system.

Stephen J. Ubl, president and CEO of the Advanced Medical Technology Association (AdvaMed), said industry isn’t happy with it, either. “The report’s conclusions do not deserve serious consideration from the Congress or the Administration. It proposes abandoning efforts to address the serious problems with the administration of the current program by replacing it at some unknown date with an untried, unproven and unspecified new legal structure. This would be a disservice to patients and the public health.”

Ulb goes on, “Numerous academic studies have shown that the 510(k) process is overwhelmingly safe. The IOM committee itself acknowledges that there is no evidence that the 510(k) process is failing to assure safety and effectiveness. Yet the report recommends entirely scrapping this proven process with a vague new plan that contains no useful guidance. It even goes so far as to say that further investment in 510(k) process improvements would not be ‘a wise use of FDA resources.”

But IOM’s report seems to have surprised everyone with its stark view of the situation.

“The committee concludes that the 510(k) process lacks the legal basis to be a reliable premarket screen of the safety and effective­ness of moderate-risk devices and, furthermore, that it cannot be transformed into one,” the report says.

IOM believes “the current 510(k) process is flawed based on its legislative foundation. Rather than continuing to modify the 35-year-old 510(k) process, the IOM concludes that the FDA’s finite resources would be better invested in developing an integrated premarket and postmarket regulatory framework that provides a reasonable assurance of safety and effectiveness throughout the device life cycle.”

In other words, junk it. Start over.

Has the FDA’s 510(k) process hindered innovation (as much of the medical device industry maintains), or has it struck the best balance between protecting patients and spurring new ideas?

Sorry, IOM punted on that one. “It is unclear—and the committee concludes that it is indeterminable, given current information— whether the 510(k) process over the last 35 years has had a positive or negative effect on innovation. To answer this question, the FDA should commission an assessment to determine this effect.”

In other words, do another study.

Respected industry attorney and Hogan Lovells Partner John Smith tells us, “the report is extremely disappointing given the time and effort that has been dedicated to this process. The assumptions underlying the IOMs conclusions are fundamentally flawed and those conclusions are vague and highly questionable.”

Specifically, he faults the IOM report for saying the 510(k) process does not evaluate safety and effectiveness. “This is simply not true in FDA’s application of the 510(k) paradigm to new medical devices. Although the standard for clearance is ‘substantial equivalence,’ the agency routinely integrates an evaluation of both safety and effectiveness into its substantial equivalence determinations. In other words, the IOM analysis lacks a ‘real world’ perspective and appears to have relied upon on a very conservative reading of the Federal Food, Drug, and Cosmetic Act, and its implementing regulations to reach this conclusion.”

IOM says scrap the 510(k) system, but some say scrap the IOM report.

“The Institute’s primary conclusion that the 510(k) process should be abandoned completely ignores the considerable debate that lead to its creation and the successful applicable of the 510(k) paradigm over 35 years,” Smith says. “No specific, systemic shortcomings that would justify such a radical restructuring were convincingly identified. Simply put, establishing the 510(k) paradigm was a thorough, thoughtful process and the process served both FDA and industry well since its inception. The Institute also fails to offer concrete recommendations as to potential alternatives, likely reflecting how difficult it will be to improve on the existing 510(k) paradigm.”

Watch the IOM’s webcast unveiling the report here.

Comment period ends September 30. To comment, go here:

Jon Speer, Managing Partner, Creo Quality, LLC

If I look back over the past couple years of business, I notice a common theme from client engagements: addressing FDA-related non-compliance issues. Sure, maybe this is to be expected since our business focuses on the medical device industry. Regulatory compliance is the name of the game and in our wheelhouse of services and expertise.

But I continue to be a little surprised by some of these engagements and how little the client companies are prepared in case the FDA comes for a visit.

If you are a medical device company (or other company regulated by FDA), you should ALWAYS be prepared for visit from FDA. Technically, FDA is supposed to conduct site inspections of registered companies every couple of years. And if you happen to have product issues, expect the nature of the inspection to be quite a bit more stringent.

What can you do to prepare for a FDA inspection?

• Conduct internal audits of your processes per Quality System Regulations (which you should be doing any way).
• Bring in an objective third party at least once a year to thoroughly audit your processes and procedures against FDA regulations.
• Conduct management reviews annually (and I suggest semi-annually). Be critical of complaint handling, CAPA, supplier management, risk management, document control / record management, and design control processes. Be sure these processes are appropriately linked so that data from one process feeds the others.
• Be overly conservative in decision-making processes.
• Consider patient and end-user safety first.
• Follow your own procedures.

Yes, if your company has adequately defined processes and procedures according to FDA regulations and you follow them, you should always be ready for a FDA inspection.

Make sure to follow Jon Speer (@creoquality) on Twitter. He may also be reached via email.