December 8, 2016

FDA Touts Improved IDE Review Stats

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

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

Ironically, FDA is sometimes wary of issuing guidances out of concern it will appear it is imposing new rules that will stifle innovation, says Ken Skodacek, Policy Analyst, Clinical Trials Program, Center for Devices and Radiological Health (CDRH). Of course, the tension here is that many in industry hold off implementing a new program with confidence out of fear the FDA won’t like its approach, e.g. mHealth and 21 CFR Part 11.

The agency is trying, with a renewed vigor, to find that balance between giving industry direction without making it feel handcuffed.

fancyFDAlogoStill, the FDA must be doing something right given stats it released last week (September 25). Here are some of the results Skodacek and team are boasting about:

  • Nearly 75% of IDE Studies are now fully approved within two cycles, compared to 63% last year and just under 15% in FY 2011.
  • The median days for full IDE Study Approval has dropped to thirty. That’s down from 101 in FY2014, and way down from the 442 days it took in FY 2011.
  • Teleconference of in-person meetings are now offered to all sponsors of a disapproved IDE within ten days of the decision.
  • Overall, there was a 50% increase in the number of Early Feasibility Study (EFS) submissions for the first nine months of FY 2015 when compared to FY 2013. Skodacek urged device makers to take advantage of this offering and noted there are no costs or user fees association with it.
  • EFS approval rates jumped up 100% between FY 2015 and FY 2013.
  • The number of EFS submissions increased in six of seven ODE review divisions during the same time period.

Skodacek noted that the FDA is genuinely working to change its review approach and genuinely wants to be an inspiration, not a roadblock, when it comes to innovation. For example, CDRH notes in a new blog post that it has trained review staff to give them a better understanding of the challenges of conducting a successful device trial. More than 100 reviewers have gone on-site to visit trial sponsors.

Skodacek said he couldn’t emphasize enough the value of in-person, or teleconference, communications. Emails and snail mail are fine ways to share some information, but the most effective way to best understand FDA expectations, and to help them understand your rationale, is face-to-face whether it’s live eyeball-to-eyeball, or virtual communications.

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FDA’s New 510(k) Guidance Emphasizes Software as Device Factor

Russ King, Managing Partner, Methodsense

Russ King, Managing Partner, Methodsense

The path to medical device commercialization requires FDA approval, which most often means filing a pre-marketing notification, also known as a 510(k). The FDA has specific criteria for accepting a 510(k), and they just released their new acceptance policy. This new standard, which will be effective October 1, 2015, replaces the old FDA Refuse to Accept Policy for 510(k) Guidance of 2012.

The purpose of this Guidance is to explain the FDA’s procedures and criteria in assessing whether a 510(k) submission meets a minimum threshold of acceptability and should be accepted for further review. Using the pre-market notification, or 510(k) process, the FDA evaluates whether or not the submission demonstrates substantial equivalence to a predicate device and that the device is as safe and effective as its predicate.

softwareInterestingly, the old 2012 Guidance mentions “software” only 18 times. The new 2015 Guidance uses the word “software” 33 times. Additionally, the new Guidance is more specific about the acceptance criteria around software. There is now an entire section (section H) dedicated specifically to device software. This section covers:

In only 3 years’ time, the new Guidance has dramatically increased its focus on software, indicating the FDA’s growing concerns around medical device software. As the FDA gets a handle on software-dependent medical devices, manufacturers will be faced with a quality framework that addresses FDA’s concerns. We’re already seeing this with 21 CFR Part 11, IEC 60601-1, PEMs and IEC 62304. I foresee additional regulations emerging as the FDA further seeks to meet the challenges of software as a medical device, increased communications between hospital networks and devices, devices that increasingly rely on software for Basic Safety and Essential Performance, and the constantly growing challenges to cybersecurity.

Keeping a finger on the pulse of these changing regulations is going to be critical. What potential challenges do you see as the industry becomes more technology dependent? Please comment below or feel free to email me directly at rking@methodsense.com.

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FDA Pilot Program Encourages Quarterly Malfunction Summary Filings

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

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

FDA will be taking applications starting Sept 1, 2015, looking for makers of class I and suitable class II medical devices to participate in a pilot program to file malfunction reports in summary form quarterly. Get on the stick, though, if you are interested: there are only nine slots.

Under FDA’s Medical Device Reporting on Malfunctions, the agency hopes to streamline some reporting procedures. It wants any reports to include a “narrative text” with sufficient detail for a reviewer to understand what happened. The agency also expects to hear about subsequent investigations and corrective actions as necessary to address the situation(s).

fancyFDAlogoThere’s a carrot, too: manufacturers accepted into the pilot will be granted an exemption or variance from, or alternative to, the usual reporting requirements under 803.5 and 803.52 for covered devices. Accepted candidates can withdraw from the pilot program at any time. FDA can drop participants, too.

Pilot participants will be expected to submit FDA 3500A forms that cover a summary of malfunction events tied to a unique device problem code or set of codes within the quarterly timeframe, and for a particular device model number and/or catalog numbers.

The program was announced via an August 18 notice in the Federal Register. For more information, contact William C. Malone, Center for Devices and Radiological Health, 10903 New Hampshire Ave., Bldg. 66, Rm. 3236, Silver Spring, MD 20993-0002, 227pilot@fda.hhs.gov.

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US Drug Shortage Hits Patients, Pharmacies Hardest

Patrick Stone

Patrick Stone, President, TradeStoneQA

The corner drug store is not currently affected by many drug shortages; instead, the pain is being inflicted on a vulnerable group of patients in hospitals today. The FDA drug shortage list is “officially” under two hundred; however, the pharma warehouse industry pegs the list a bit higher: at approximately 250 drug products. This list includes drug container closure systems like sterile intravenous bags (IV). It is important to include the component shortages because these also impede mitigation strategies in place at many of the nation’s hospital systems. Hospital compound pharmacies can formulate these admixtures even in short supply — but not without the IV bag components. The drug shortage list has fallen by almost half in the past three years but there is no quick fix here for underlying challenges.

For now, compound pharmacies may have to drastically expand and improve current facilities to fill sterile admixture demands. New supply chains for many generic drugs and IV drugs will have to go online with documented patient safe compliant manufacturing systems.

The new drug inspectorate team investigators at FDA will not be casual with their inspection approach, neither will they be in a big rush to give a clean bill of health to the facilities under inspection. Quality by design inspection approaches over the quality systems model will globally standardize regulatory expectations.

PharmaceuticalsHospitals have adopted shortage mitigation plans that include stockpiling drugs on the shortage list and requesting manufacturers to extend the expiration dates through longer stability indicating studies. The current inspection focus will be on sterile compound pharmacies and overseas generic manufacturers. The current focus on compound pharmacies will turn up many sterile compliance gaps and limited sterile bench top space to meet these sterile drug shortage mitigation plans. Hospitals may consider storing stockpiled drugs together and otherwise better networking with each other so that close expiration dated stock is sent to hospitals with instant use demand.

Simply waiting passively for supply chain improvement will be a painful endeavor. FDA may have to consider fostering domestic growth mitigation supply chain strategies for the Pharma industry. The current focus will be for FDA to bulk up international offices in the generic drug manufacturing sector of the world for increased supply.

Drugs on the shortage list include antibiotics, pain relief (CNS), cancer (chemo), epinephrine, and IV drugs and total nutrition IV components (TPN). Click here for the official current drug shortage list.

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’s UDI Initiative Continues to Roll Forward

Jeff Mazik

Jeff Mazik, Vice President, Life Science Solutions, AssurX

With the close of the 7th Annual UDI Conference in Baltimore late last month, FDA took another big step forward in providing an electronic library of medical device information. During the conference, FDA shared a number of milestones completed in the last eight months since the previous conference.

Linda Sigg, FDA’s Associate Director of Informatics, shared that since the last conference held in October 2014 there has been quite a lot of progress made by her UDI group as well as the Medical Device community. In these past eight months, the number of Device Identification records in the GUDID increased from 33,000 to over 75,000. The number of manufacturer/labeler accounts grew from 240 to 425 accounts and FDA’s UDI Help Desk inquiries doubled to over 8,000 with an increase in their closure rate from 91% to 95%.

This growth was primarily due to the second group of devices requiring to meet FDA compliance due dates by September 24, 2015: those devices classified as implantable, life-saving, and life-sustaining.

UDI LabelingAlso accomplished during this time frame was the launch of the “AccessGUDID” website for public searching and downloading of the “GUDID” repository, finally allowing the fruits of all this collection of data to be visible to the healthcare community, at least for devices currently required to comply.

Mrs. Sigg also announced that upcoming capabilities to watch for was an advanced searching capability within the AccessGUDID system, as well as the implementation and availability of web services for external access to the GUDID. Ostensibly, the web services function will allow labelers/manufacturers and 3rd party vendors to actively integrate and search/download information electronically from the GUDID without the use of the AccessGUDID interface.

As the manufacturers/labelers of implantable, life-saving, and life-sustaining devices get closer to their due date for labeling and GUDID submissions this year, the next group of manufacturers/labelers: Class II devices (that are not implantable, life-saving, and life-sustaining) come to the plate. Accounts and GUDID access for these manufacturers/labelers will start being processed and made available in January of 2016 so as to help this group meet their labeling and GUDID submission compliance date of September 24, 2016. Following this September milestone, the information available in the GUDID will increase substantially. Soon after this milestone, Class I and unclassified devices will have their turn to begin labeling and submitting UDI information to the FDA, in order to meet their compliance date of September 24, 2018.

Also during the conference, guidance on the direct marking of devices was released, and for those devices requiring direct marking (e.g. the device is intended to be used more than once and intended to be reprocessed before each use) there are specific compliance due dates as well. These are posted on the FDA UDI website.

If your business manufactures Class II or Class I devices, be ready to get involved soon. Start planning now, if you haven’t already done so. Don’t wait until FDA grants your company access in order to begin to plan out how you will be compliant in your labeling of your devices, including direct marking (if applicable), as well as planning how to best manage and electronically submit your device’s UDI information to the GUDID system.

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Will New User Fees Fuel More FDA Inspections?

Patrick Stone

Patrick Stone, President, TradeStoneQA

For FY 2016, FDA is requesting $4.9 billion to support our essential functions and priority needs, which is $425 million above the FY 2015 enacted level.  Of the total funding, $2.7 billion is budget authority and $2.2 billion is user fees.  The FY 2016 increase consists of $148 million in budget authority and $277 million in user fees.

User fee monies come from new health care sponsors applying for FDA approval to speed up the time it takes to get an audit scheduled. The user fee monies go toward FDA operating cost and employee payroll.

This means FDA will be expected to conduct more inspections to meet the demands placed on it by collecting user fee monies – but this idea raises a number of questions:

  • Will FDA be able to increase the amount of clinical trial audits globally in order to keep up with the user fee expectations for audit scheduling?
  • fancyFDAlogoHas FDA increased training for bioresearch monitor training and have trained inspectors ready to meet this challenge? FDA’s focus has been on food and tobacco inspections the last few years. The latest’s initiatives have been focused on compound pharmacies, the drug inspectorate, and the “antimicrobial blitz for use in feed lots & human use for resistance strain reducing strategy.”
  • Will FDA also increase the amount of health care products approved for the domestic market as well?

The drug shortage list has remained at high levels for the past few years and this fast track approval change is definitely part of the mitigation effort. Most of the budget increase comes from private industry and new product developers so the government burden is around one hundred and fifty million (2.7 billion total). We can only hope FDA is able to meet the increased demand for audit increases and is not postponing regulatory oversight due to limited trained staff shortfalls.

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 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.

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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 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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