October 8, 2015

FDA Warning Letters Hit Device Makers Over CAPA, MDR Failures

Michael Causey, Editor-in-Chief, Association of Clinical Research Professionals

Michael Causey, Editor-in-Chief,
Association of Clinical Research Professionals

It’s been a little while since we checked the FDA’s outgoing mail tray to find out what inspectors are looking for – and often finding – during their visits in the first half of 2015

We start with a rather hefty June 12 letter to AG Industries in St. Louis, hit for a number of alleged 820-related shortcomings, including:

  • Failure to promptly review, evaluate, and investigate complaints related to a Medical Device Report (MDR) review and file an MDR with the agency for what it deemed one of perhaps several “serious complaints.” FDA found AG’s response “inadequate” because the firm labeled the incident to be not life threatening, where the agency clearly has some doubts.
  • Failure to adequately validate according to established procedures for a process those results can’t be verified by additional testing.
  • Failure to adequately establish procedures for finished medical device acceptance.

FDA says about ten percent of the nearly 210 complaints the firm has received since early 2013 are still open. Specifically, it called out a complaint that AG received in August 2013.

Note: Throughout the letter FDA says AG’s characterization of its CAPA problem as minor “appears inappropriate.”

fancyFDAlogoInsulin Management System manufacturer Insulet Corporation had a relatively easier time of it in a June 5 letter. FDA hit the firm for devices it alleges are adulterated because the methods used in, or controls of, the manufacture, packing, storage, or installation don’t meet FDA good manufacturing practice (cGMP) requirements of its Quality System regulation.

FDA fired back that the firms April 16 response was not adequate and advised the firm that “regulatory action” could be initiated without further notice unless the Massachusetts-based firm takes prompt action to correct violations FDA alleges in the warning letter.

In New Jersey, FDA called out Ultrafiler-maker Nephros for alleged failure to document evaluation of its suppliers. Like Insulet, the firm was also criticized in the May 27 letter for not including required info of complaint investigations.

Bothell, Washington-based Thorn Dental Laboratory LLC was challenged in a June 2 letter of a number of CAPA-related fronts, including:

  • An inability to produce CAPA procedures for review during the inspectors’ series of inspections in February.
  • Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit.
  • Failure to establish and maintain procedures to ensure that all purchased or otherwise received product and services conformed to specific requirements such as failing to maintain adequate documentation of suppliers, contractors and consultants.
  • Failure to establish and maintain procedures for finished device acceptance.
  • Misbranding its anti-snoring/sleep apnea devices.

Our final letter in this go ‘round’s review focused on Irvine, California-based Insightra Medical, maker of catheters and hernia implants. The agency said the firm’s devices are adulterated because Insightra failed to control its facilities in terms of manufacture, packing, storage, or installation.

Insightra was hit with a number of MDR shortcomings, including failure to establish internal systems that provide for “timely transmission” of complete medical device reports.


Medical Device Makers Express Optimism About Future — But QA Worries About US Regulatory Burden

Michael Causey, Editor-in-Chief, Association of Clinical Research Professionals

Michael Causey, Editor-in-Chief,
Association of Clinical Research Professionals

Crystal may be clear, but crystal balls, at least metaphorically, are certainly not. The late, great political columnist David Broder with The Washington Post used to run a column at the end of the year tallying up where he had guessed correctly – and where he’d missed the mark. Not many columnists have the guts to do that.

A survey taken earlier this year found that some 75% of more than 5,000 medical device professionals felt “very or somewhat positive” about business prospects for 2015. Those numbers are pretty much in line with the findings of the 2014 survey, conducted by our friends at The Emergo Group.

Taking a closer look at the 2015 numbers, it’s clear that domestic device makers feel better about their prospects than do counterparts in the EU – and this was before Greece really started to tank.

Casting eyes around the globe, it turns out device makers in Asia were even more optimistic than those in America. Still, confidence among Asian device makers fell to 77% in 2015, from 83% in 2014. It’s interesting to note that, even then, concerns about a slowing Chinese economy don’t reflect an increasing edginess about the state of things in the world’s most populous nation.

X-ray of hipIn the U.S., smaller companies actually felt a bit more optimistic than their big brothers and sisters. But mid-size and big shops were a little less thrilled about the future, likely due to “regulatory and pricing pressures,” Emergo notes.

The study burrowed down to quiz more than 2,000 QA/RA professionals for their thoughts on current and prospective regulatory trends. Just over one-third of American respondents said they expect the process of gaining regulatory approval will be tougher than it was a year ago. The study says about 3.5% think the regulatory process is getting easier, though I’ve personally never found or spoken to any of those people!

Not surprisingly, the QA/RA pros in the U.S. said their country was one of the toughest when it comes to regulatory approval. Even the FDA sometimes acknowledges that, as we noted in an earlier blog when FDA’s Center for Devices and Radiological Health Jeffrey Shuren noted the agency is sensitive to this and trying to make some pro-industry changes.

We’ll check back with Emergo – and Shuren – later in the year. Let’s see if we can find some of that Broder confidence where folks circle back and reassess their predictions.


Study: FDA 510(k) Approval Process Now Averages Over Six Months

Michael Causey, Editor-in-Chief, Association of Clinical Research Professionals

Michael Causey, Editor-in-Chief,
Association of Clinical Research Professionals

If you’ve got six months – and nerves of steel – here’s some good news: You have a 61% percent chance of getting your medical device approved by the FDA. That’s one nugget of interesting data to be found in a recent Emergo group report that analyzed some 15,000 device clearances between January 2010 and December 2014.

We’ve blogged about this quite a lot over the past four years or so, and it looks to be another case of the more things change the more they stay the same. Back in June 2011, we reported on an Emergo study which found that in 2006 it took about 96 days to get clearance. By 2010 that number had leapt to 132. Today, Emergo reports that “it now averages about six months.” Blame for this trend is slung around between industry and regulators – each time FDA says it’s made a big step forward, industry tends to toss these kind of stats back in the agency’s face.

FDA can’t exactly point to any kind of consistent improvement. It approved 3,173 devices working their way through the 510(k) maze in 2014, which was up nearly 5% from 2013, but pretty much in line with 2011 and 2012. Check back in a year or two to see if 2014 was the start of a positive trend.


Radiological and Orthopedic devices are usually the fleetest of foot in the race for approval, averaging about 140 days last year, that’s up from 135 in 2013. Overall, about 22% of devices are cleared within three months.

The study also finds that third party reviewers tend to work more quickly than internal agency reviewers. While not all devices qualify for this program, think about grabbing it if you can. Your device might clear in 68 days, on average, or more than 110 days faster than with an internal FDA reviewer.

Note: FDA doesn’t release data about submissions rejected, withdrawn or abandoned by the submitter. Emergo’s analysis doesn’t include devices subject to the Pre-Market Approval (PMA) process.

So, still trying to figure out how your new medical device might fare in today’s FDA climate?

A fun new tool from Emergo just might sweep aside some of the fog. Simply plug in (or look up) your device product code, then sit back and let the tool tell you an estimate approval time based on similar products that have gone through – and survived – the process.

Unfortunately, you probably don’t need any kind of online tool to tell you one thing: The FDA’s 510(k) approval process keeps getting slower and slower and slower…


FDA Issues Deadline Reminder to Medical Device Companies on Electronic Medical Device Reporting

Tamar June

Tamar June, VP, Strategic Marketing, AssurX, Inc.

Looks like it’s crunch time for medical device manufacturers. Whether they submit one or 10,000 medical device reports (MDRs) to the FDA per month, they are required to go all electronic come August 14, 2015. No faxes, no mailed in reports, no more burned CDs. Device manufacturers have two choices. Either use the eSubmitter, or utilize the HL7 ICSR. Both go through FDA’s Electronic Submissions Gateway.

If device manufacturers haven’t yet setup their ESG accounts, they better get started right away. It takes at least two weeks to get on board with FDA, as well as additional time to test the submissions. FDA issued another reminder and an updated implementation package this morning:

fancyFDAlogoOn August 14, 2015, the eMDR final rule goes into effect, requiring manufacturers to submit medical device reports (MDRs) to the FDA electronically rather than in paper form. Electronic submission expedites report processing and reduces the burden of data entry on the FDA, manufacturers, and importers. There are two options available to all reporters for submitting eMDRs: eSubmitter or Health Level 7 Individual Case Safety Reports (HL7 ICSR).

Today, the FDA released an updated implementation package with the system requirements to enable manufacturers that chose the HL7 ICSR submission option to prepare for and test eMDR submissions.

As a reminder, both eSubmitter and HL7 reporting options transmit MDRs to the FDA using the FDA Electronic Submission Gateway (ESG), a secure entry point for all electronic submissions to the Agency.

Manufacturers should consider registering for an ESG account and submit a test submission as soon as possible to ensure that they are electronic submission compliant by August 14, 2015, regardless of which transmission method they choose. Manufacturers may begin testing their submissions as early as June 29, 2015.

Information on the FDA ESG and steps to obtain a production account, please visit the Electronic Submissions Gateway page.

For more information about how to prepare for eMDR, please visit the FDA eMDR page.

After this deadline, there will be no more extensions. Even if device manufacturers rarely submit reports, they need to make sure they are ready just in case.


FDA’s Shuren Works to Assure Device Industry Innovators

Michael Causey, Editor-in-Chief, Association of Clinical Research Professionals

Michael Causey, Editor-in-Chief,
Association of Clinical Research Professionals

Calling it something of a “culture change” at the Center for Devices and Radiological Health (CDRH), Director Jeffrey Shuren said his team is working hard to find ways to speed approval of new medical devices by, in part, placing more stress on patient needs when looking at high-risk devices.

If potential users believe a product’s benefits outweigh its potential risks, Shuren said the agency is more likely to approve it today. “We want to make the U.S. a much more attractive market for medical device innovations,” he told attendees at this month’s Drug Information Association (DIA) convention in Washington, D.C., acknowledging that America has some of the toughest standards blocking the way between device manufacture and approval.

Jeffrey E. Shuren, M.D., J.D., Director, CDRH

Jeffrey E. Shuren, M.D., J.D., Director, CDRH

Shuren pinned a lot of his hopes on the Medical Device Innovation Consortium (MDIC), the first public-private partnership devoted to the advancement of regulatory science in the medical device industry. MDIC aims to coordinate the development of methods, tools, and resources used in managing the total product life cycle of a medical device to improve patient access to cutting-edge medical technology. It will hold its annual meeting September 25 in D.C.

Boasting 49 members, including large and small device companies, PhRMA, venture capitalists, consumer groups, FDA and NIH, MDIC has been active over the past year or so, holding a slew of meetings across the U.S. (and Japan), spreading the good word of innovation.

Shuren also talked about the FDA’s May guidance which offers additional detail regarding how it will consider patient needs as it weighs risk/benefit calculations. “We’re looking to find ways to reduce medical device time to market,” he said. CDRH is making “changes in our approach” as evidenced by the guidance and the FDA’s work with MDIC, among other things, Shuren stressed.


FDA Moves UDI Initiative Further Down the Production Line

Michael Causey, Editor-in-Chief, Association of Clinical Research Professionals

Michael Causey, Editor-in-Chief,
Association of Clinical Research Professionals

We, and others, like to take the FDA to task for missing deadlines or behaving in ways that are sometimes difficult to fathom. But it’s only fair to give equal space to something when they seem to get it right. Take the Agency’s Unique Device Identification System (UDI).

Readers of this blog might have different experiences with it – and we’d like to hear about them, good or bad – but you’ve got to tip your hat to FDA because they’re trying to get it right.

Last month, FDA launched the Global Unique Device Identification Database (GUDID), a searchable website containing a listing of all UDIs. Expectations, both from industry and the agency, are high for this system implemented to simplify the identification of many regulated medical devices used by patients in the United States.

GUDIDThe complex infrastructure, which will be phased in over several years marked by a variety of deadlines that began in 2014 and are slated to wrap up in 2020, offers a number of potential benefits, including:

  • Speeding and improving the accuracy of the reporting, reviewing and analyzing of an adverse event.
  • A quicker means to identify a device and extract important information about it.
  • Enhancing analysis of devices on the market by providing a standard and clear way to document device use in electronic health records, clinical information systems, claim data sources and registries. A more robust postmarket surveillance system can also be leveraged to support premarket approval or clearance of new devices and new uses of currently marketed devices.

Ultimately FDA hopes its UDI can become a worldwide model, too.

It’s worth noting that FDA’s former point man for the initiative, Jay Crowley, continues to lead the bandwagon now that he’s ensconced in private practice with USDM Life Sciences. He’s led a number of webinars and given a number of talks that make a persuasive case for the positive impact UDI will have on the device industry. Sometimes, a former FDAer spends the next ten years of his or her career criticizing the very program they led. Not the case with Crowley and that bodes well for UDI.


Large Utilities Power Up with AssurX Enterprise GRC Solution

Tamar June

Tamar June, VP, Strategic Marketing, AssurX, Inc.

Increasingly complicated, and disparate, regulatory requirements and a demand for improved compliance management were driving forces for two major utility companies to find stronger enterprise governance, risk, and compliance (GRC) solutions, says a new report from Blue Hill Research.

The white paper, “Anatomy of a Decision,” looks at the search conducted by two utilities with nearly a million customers spread over multiple states. Subject to strict regulatory requirements from the North American Electric Reliability Corporation (NERC) and the Federal Energy Regulatory Commission (FERC), the size and distribution challenges are daunting, Blue Hill says. It’s arguably even tougher for one of the firms: it has fifty member entities  that must address more than a dozen different sets of requirements.

If one of the GRC carrots is increased efficiency and a stronger competitive posture in the marketplace, one of the sticks is serious regulatory fines for non-compliance. A utility can face $1 million/day fines per violation. That means testing and certification must be robust and demonstrable to meet compliance requirements.

BlueHill-AssurX-GRC-1In the Blue Hill report, two utilities kicked the tires of several solution providers during an extensive search, including IBM OpenPages, Oracle, and AssurX. The respective searches drilled down to six key factors:

  • Depth of understanding of business and regulatory requirements

  • Adaptability and configurability of the solution

  • Vendor’s willingness  to partner with customers

  • Amount of process change required by the implementation

  • Functionality included within the solution

  • Responsiveness and quality of customer support

Both utilities reported going with AssurX, in part, because “they concluded that the provider demonstrated deeper understanding of unique requirements and business operations” facing them compared to other vendors. In addition, the utilities tapped AssurX because of its “deeper out-of-the-box fit to existing processes and ease of configuration.”

For more information on the search and how the AssurX solution is positively impacting utility companies, request a copy of the full report here.


Big Pharma Goes Big for Big Data

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

When it comes to data, big pharma knows what big pharma likes, according to a new survey of giant pharmaceutical companies that included AstraZeneca, Merck, Pfizer and Boehringer Ingelheim. The winners in the data sweepstakes? Claims, electronic health records, health outcomes, real world studies, and registries.

However, no flavors of online or machine-generated data were rated highly by a majority in the project, “Big Data in Pharma,” conducted by Best Practices LLC. Eleven companies and twelve leaders were engaged in the benchmark study designed to produce reliable industry metrics on future and current trends for big data utilization across medical and commercial groups.

Post-launch and customer segmentation studies represented the most common big data projects at play today, with a majority of participants saying that partnerships with payers and data aggregators were “highly impactful.” Health systems were also perceived as valuable partners in each segment.

compounded pillsMedical teams also tended to find more value across data sources when compared to analytics in other functions, the survey found. Best Practices also conducted seven deep-dive executive interviews with selected benchmark participants.

While the majority (58%) reported leveraging a dedicated big data team, it’s somewhat surprising that the remainder said their analytics efforts weren’t centralized to that degree. Less surprising, perhaps, was that these same companies reported the vast majority of their capabilities and governance were based in North America and the European Union. Asia and non-EU countries accounted for less than 20% of local data capability strength.

Respondents, who also included Esteve, Bayer Health Care, Novartis, Janssen, Gilead, and Genentech, said they most valued big data partnerships with payers and data aggregators.

Click here to read more. (registration required)


Congress Crawls Out of 20th Century to Push Bi-partisan ‘Cures’ Legislation

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Just when we’d all decided Washington lawmakers couldn’t do much more than enjoy their own excellent health insurance coverage, tasty bean soup in the Senate cafeteria, and the best parking on Capitol Hill, it turns out they might actually unite to accomplish something pretty big after all.

It’s called the 21st Century Cures Act and its got a lot of device and drug makers excited. It’s been under development since April 2014. Amazingly, the version Congress released recently is almost 50% shorter than the earlier draft. In a city full of bureaucrats who write memos about memos, that’s a pretty incredible feat.

Fresh off a May 15 Congressional vote moving the law closer to passage, Mark Leahey, President and CEO of the Medical Device Manufacturers Association (MDMA), praised Subcommittee Chairman Joe Pitts and Ranking Member Gene Green for their bipartisan work “recognizing the importance of medical technology innovation in answering the pressing challenges facing America’s health care ecosystem.”

Joining AdvaMed, among others, Leahy applauded legislation he says “provides substantive proposals to improve the regulatory process, while addressing ongoing challenges in obtaining adequate reimbursement for the cures and treatments that patients need.”

Among a myriad of potential changes, the Act would clarify the standardization of eligibility information in clinicaltrials.gov, and spur the Department of Health and Human Services to forge ahead with additional public/private partnerships with grants to promote patient advocacy groups and research of disease causes, especially for rare diseases.

SixGroupsAccording to the folks at Hyman, Phelps and McNamara, the new version is broader in terms of Qualification of Drug Development Tools. For example, “it now addresses biomarkers, surrogate endpoints, and other drug development tools; the first discussion draft focused primarily on surrogate endpoints,” reports the firm’s Law Blog. “On the other hand, it is narrower because it does not affect devices. The section also removes many of the formal procedures and timelines from the first discussion draft and provides FDA with more discretion in the development of the program.”

There’s still a lot to dissect from the Act, and, while passage appears likely, some provisions could still be tweaked or cut entirely. But one this is clear: Congress is probably going to shock a lot of us by actually pulling together a relatively bi-partisan piece of legislation and placing it on President Obama’s desk before the end of the year.

Who’d have thought, right? Now, maybe these distinguished men and women can take a hard look at our nation’s infrastructure, tax code, and maybe a few dozen other issues that would also benefit from some good, old-fashioned bipartisan discourse.


Should FDA Get Tougher on IRBs?

Patrick Stone

Patrick Stone, President, TradeStoneQA

The FDA says IRB’s (Investigational Review Boards) are not required to collect a statement of investigator assurance from studies they preside over.

This is troubling. My first question would be how are IRB’s going to assure clinical investigators will abide by requisite 21 code of federal regulations (CFR) and the sponsor approved protocol? How will IRB’s ensure that the protocol they are approving is authorized by FDA for human clinical trials?

fancyFDAlogoClinicaltrials.gov is a great repository and can be a big help here, but only if it used by the IRB’s and updated in a timely manner. In my day as an FDA inspector [1998] we were trained that IRB’s are FDA’s eyes and ear’s because FDA is not going to get to very many clinical investigator audits. Fewer than one percent of clinical trials ongoing domestically are reviewed by the agency.

That’s why I’m a little worried. Why would FDA abandon a last line of defense for patient safety? I’m not sure why the agency takes this position, but luckily for patients, most IRB’s do hold clinical investigators accountable for all HHS requirements (FDA & OHRP) and even conduct quality audits for a small percentage of the clinical trials they preside over. If 21 CFR is the bare minimum requirement for compliance, wouldn’t additional IRB oversight be a big boost to compliance if FDA is not able to review a much higher percentage of the domestic ongoing clinical trials?

There’s another area of concern: A 2013 FDA guidance states that only sponsors and clinical Investigators need to keep track of financial disclosure documents. Financial disclosure should be reviewed by IRB’s especially institutional IRB’s that can easily verify if conflicts of interest exist for clinical investigators under their review.

But let’s save that topic for the next time!

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