September 2, 2015

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.

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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.

emergo510k

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…

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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.

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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.

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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.

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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.

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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.

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Avoid Common Medical Device Software Development Life Cycle, IEC 62304 Pitfalls

Russ King, Managing Partner, Methodsense

Russ King, Managing Partner, Methodsense

IEC 62304, the international standard that defines software development lifecycle requirements for medical device software, was developed from the perspective that product testing alone is insufficient to ensure patient safety. It provides a common framework for medical device manufacturers to develop software components. Conformance with this standard demonstrates that there is a software development process in place that fulfills the requirements of the Medical Device Directive.

If your medical device has software that regulates its functionality in a way that contributes to Basic Safety or Essential Performance, then you will need to comply with IEC 62304. This standard requires all aspects of the Software Development Life Cycle (SDLC) to be appropriately managed to ensure patient safety, including:

  • Development and code reviews
  • Risk management
  • Configuration management
  • Incident and bug resolution
  • Validation
  • Maintenance

dnachainThe most common mistake medical device manufacturers make is failing to assess which elements of risk their software mitigates. These are the elements that must be addressed by IEC 62304. For example, what would happen if the creator of a hoist didn’t properly vet the software that signaled the hoist to lower the patient at a certain speed? If a patient were lowered too quickly – or not at all – there would be a risk management nightmare. Since software plays a role in the Basic Safety functions of the hoist, it must comply with 62304’s requirements.

Common software functionality manufacturers fail to recognize as IEC 62304 compliance issues include:

  • Alarms and Alerts often an Essential Performance requirement because they are intended to detect abnormalities
  • Speed & Position Sensors use of software to limit range of motion, speed and force, which are Basic Safety concerns
  • Algorithms remove the software and the device is no longer able to operate as intended, resulting in the algorithms being part of Essential Performance 

It is critical to have clearly defined processes for your company and your Software Development Life Cycle, in particular. IEC 62304 identifies several expectations related to the information that should be included in your SDLC procedures, including:

  • Documentation of your process – document management is essential for meeting compliance goals
  • Software of Unknown Pedigree (SOUP) – manage your SOUP appropriately
  • Document Development – make certain you are sufficiently resourced to support document development needs
  • Version Control & Updates – clearly define software updates and how software will be maintained in a validated state.

Medical device manufacturers frequently seek 3rd party software development assistance. However, the manufacturer remains responsible for the device software. Important areas to consider when contracting out your software development include:

  • Supplier Management Processconfirm that your software vendor complies with IEC 62304 and their processes are reviewed during vendor audit
  • Quality Agreement – confirm that:
    • It defines vendor responsibilities and IEC 62304 Deliverables
    • Vendor procedures used for software development will be provided to you and the test lab for review
  • Establish your SDLC – at minimum, your process will define acceptance criteria (i.e. IEC 62304 compliance and deliverables) from your vendor

Once you know you must comply with IEC 62304, how do you go about preparing? To start, know that compliance with this standard is defined as implementing all of the processes, activities and tasks identified in the standard in accordance with the software safety class. 62304 itself does not prescribe a particular organizational structure or specific format for documentation. Compliance is determined by a review of all required documentation, including the risk management file.

IEC 62304 file will be reviewed to ensure:

  • It contains all required documentation including a risk management file
  • Procedures meet the requirements of the standard
  • Each check list item is satisfied
  • A product review is conducted and further a review of the relevant software segments if it has been decided that the software performs Basic Safety or Essential Performance for your device

If you get caught in any of the above-mentioned pitfalls, you’ve probably got a problem. You will either not receive a report at all, or will receive a report that says you failed somewhere in IEC 60601-1 or IEC 62304.

Because the standards are voluntary in the US, you don’t necessarily have to make product changes. However, for each “fail,” you will be required to provide justification for each deviation. If you have valid justification, your device should still attain regulatory approval from the FDA, although developing this justification can be a lengthy process in itself. In the end, though, you may find it more efficient to comply with IEC 62304.

Download your IEC 62304 action list here. 

Russ King is President of Methodsense, a consulting firm that helps clients deliver medical and technological breakthroughs by effectively meeting the requirements needed to bring their products to market. He can be reached at (919) 313-3962 or rking@methodsense.com.

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FDA’s Action Plan Demands Some Industry Action, Too

Patrick Stone

Patrick Stone, President, TradeStoneQA

“The following Pharmaceuticals FY 2015 Action Plan (the Action Plan), developed by the Office of Regulatory Affairs (ORA), the Center for Drug Evaluation and Research (CDER), and the Center for Veterinary Medicine (CVM), is intended to facilitate operational and program alignment as FDA transitions to distinct commodity-based and vertically-integrated regulatory programs with well-defined leads, coherent policy and strategy development, and well-designed and coordinated implementation.

That’s the FDA’s plain Jane version of its 2015 Action Plan. But let’s look at some interesting wrinkles not necessarily contained in the document.

The Pharmaceuticals Inspectorate will change the way FDA inspectors conducts audits and how many audits will be conducted in a years’ time. There are some interesting things to note here: First, the Center for Biologics (CBER) is noticeably not included in this reorganization effort. Second, district offices will not be at the helm when it comes to which drug firms get inspected and how compliance OAI & VAI cases are handled. Third, CDER will be assuming the lead role and Center compliance teams will be responsible for industry corrective action plans.

prescription drugsTraditionally, the district compliance team for the drug company took the lead role in compliance strategy and remediation. But now, the inspectors conducting drug audits will be dedicated and certified to conduct inspections. This will reduce errors and enhance the quality of inspections domestically and internationally. This will also increase the number of observations (483 notice of observations), warning letters, and consent decrees.

When a generalist inspector conducts a drug audit they may miss a system wide failure or process control deviation due to a lack of training. By contrast, when a professional team of inspectors with dedicated drug training for a drug firms system conduct an audit, those same compliance issues are not usually missed. This is a positive step in the right direction however building the new drug teams and training them accordingly will take years.

Quality by design (QbD) implementation is looming so this will also affect the training requirements from a system based approach to a QbD approach.

Don’t be caught off-guard by this new way of doing things. The FDA is making some changes here, and regulated firms need to make sure they understand them.

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

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FDA Works to Clarify Device Data Collection Priorities

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

A new FDA guidance issued by the Center for Devices and Radiological Health (CDRH) and Center for Biologics Evaluation and Research (CBER) offers some helpful detail for device firms uncertain if post-approval studies can replace premarket studies at the time of approval for premarket approval applications (PMAs).

The agency says there are some instances where it may consider it acceptable to collect certain data in a postmarket setting rather than premarket.

FDAlogoOne area is mature technologies. For example, a subcutaneous implantable cardioverter defibrillator (S-ICD) has the same basic elements of an ICD, which have been used for decades. Clinical and preclinical evaluations in the premarket setting for the subcutaneous ICD were tailored to collect data on the new aspects and to evaluate functionality of the device, while more detailed safety data is collected in a postmarket study.

Other situations include an urgent public health need, especially in a situation where postmarket testing would do a better job confirming the benefits of a device.

The guidance spells out several other examples where it may be appropriate, including:

  • Migration, an approach used when approval of Class III in vitro diagnostic devices previously approved, licensed, or cleared assay is shifted to another system for which FDA hasn’t evaluated assay performance, is suitable in cases when sufficient knowledge can be gleaned for the documentation of design controls, risk analyses, and prior performance studies on an already marketed system.
  • Confirmation of mitigation effectiveness for a known risk in a post-approval study.
  • Modifying warnings, contraindications, and/or precautions in approved labeling.
  • Approval for an intended population beyond what was fully evaluated in the pivotal trial, with a confirmatory post-approval study.
  • Assessment of long-term performance in a post-approval study.
  • Assessment of rare adverse events in a post-approval study.
  • Confirmation of bench data with clinical data collected in a post-approval study.
  • Where the performance of a particular device type is well-studied, documented, and understood
  • Where long-term outside the U.S. clinical performance data is available but deemed insufficient.
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