April 18, 2014

FDA Warning Letters Emphasize CAPA, Design Issues

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

The FDA focused its regulatory laser beam on the Midwest and overseas in the latest wave of medical device warning letters.

Enraf-Nonius B.V., a device maker based in the Netherlands but doing business in the U.S., was hit in several areas, including:

Failure establish and maintain device controls in relation to acceptable validation during a clinical trial, failure to set up procedures to determine whether device changes require validation or verification, and failure to document post-production design changes.

As is so often the case in FDA warning letters, CAPA again reared its head. In the July 5 letter, the device maker was charged with several alleged CAPA shortcomings. These include failure to establish a process that makes certain corrective actions are noted and take steps to prevent the issue from happening again, and failure to address illegible, missing and/or incorrect component codes.

Back here at home, Pennsylvania-based firm Lenfest Media Group was advised in a July 1 letter that its product claims lack FDA clearance or approval. Lenfest markets its WaxVec that it claims “gently draws dirt particles and moisture out of your ear quickly and safely.

warning640In Ohio, x-ray systems-manufacturer Meridian Medical Systems was hit with CAPA violations, and alleged design history violations, including:

  • A design plan for the project
  • Established or approved design inputs/outputs for the system
  • Verification or validation testing for the system
  • Design transfer
  • Risk management for the system
  • Design reviews

The firm was also warned for allegedly not having a handle on its suppliers, an issue that the FDA appears to be focusing on more and more. It could be, in part, because more and more domestic firms and outsourcing device manufacturing work overseas.

Completing our latest round-up, we travel to Turkey, where FDA issued a June 27 warning letter to Aygun Cerrahi Aletler A.S. Surgical Instruments Co., with charges of CAPA shortcomings and several other issues, including failure to establish and maintain procedures to ensure that the device design is correctly translated into production specifications, and failure to establish and maintain procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation.

 

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Jeff Mazik joins AssurX as Vice President, Life Science Solutions

 

Jeff Mazik, Vice President, Life Science Solutions

Jeff Mazik, Vice President, Life Science Solutions

AssurX is pleased to announce the appointment of Jeff Mazik as Vice President, Life Science Solutions. Prior to joining AssurX, Jeff served as IT Head, Manufacturing & Engineering Systems for Alcon (a Division of Novartis). Jeff worked at Alcon for 15 years, and was responsible for the global rollout and support of many varied global software systems in the areas of Quality Management, Engineering, Manufacturing, Corporate, and Safety/Security/Environmental Affairs.

During his tenure at Alcon, Jeff helped implement and/or oversee the global use of many varied software solutions, including the rollout and use of over 60 CATSWeb processes, the implementation of physical access security systems to all plants, a global corrective and preventative maintenance solution, an eMSDS solution, global ERP initiatives, Business Intelligence solutions, as well as corporate projects such as CCTV systems, and the Point of Sale solutions for the company’s cafeteria and company store.

Furthermore, from 2008 to 2012 Jeff served as one of Alcon’s 9-person core team in the start-up of the Alcon Singapore Manufacturing plant. He was intimately involved in the initiation, planning, design, development, construction, commissioning and startup of Alcon’s first Asian-based aseptic pharmaceutical drop-tainer filling plant in the Republic of Singapore. As such, he oversaw the implementation and validation of multiple applications and was responsible for the design and implementation of the entire IT infrastructure for this new pharmaceutical manufacturing plant, including plans for cable tray trunking, network drops, communication room design, and audio/video conferencing technology. As the IT Manager for this new plant, he was also responsible for determining the policies and procedures for the operation of the new IT department: including processes required to meet FDA, HSA, and other regulatory guidelines for pharmaceutical and medical device companies.

Prior to his career at Alcon, Jeff consulted for a Division of IBM (ShowCase Corporation), implementing Business Intelligence and Data Warehousing tools to healthcare providers. Prior to IBM, Jeff was the Director of Implementations for McKesson Provider Technologies (previously Enterprise Systems, Inc.) implementing software solutions for Materials Management, Operating Room Scheduling, and Finance in Hospitals across the United States.

In 2003, Jeff won AssurX’s Customer of the Year, and has seen CATSWeb used in many varied ways to meet regulatory and business needs. He is excited to be able to help all of AssurX’s Life Science customers better realize the value of CATSWeb to meet their business demands in this constantly changing and evolving industry.

 

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You’ve Got eMDR Questions; FDA Has (Some) Answers

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

In a new 47-page guidance the FDA appears to be doing its best to cover the waterfront for medical device manufacturers who need to better understand the complex Medical Device Reporting (MDR) requirements. Topics range from the big picture (who is subject to this rule) down to specifics (how many times must a manufacturer call a user facility for information before it can close the file).

In a perfect world, the FDA would pick an intelligent, telegenic representative and provide this information in a live Q&A format with follow-up questions from the audience. Until that day, we’ve got to rely on the new guidance, published July 9, 2013.

MDR is FDA’s mechanism to work with medical device companies to identify and monitor adverse events, with an eye to detecting and correcting problems as quickly as possible.

Medical device makers are required to report when one of its devices may have or could contribute to a death or serious injury. Device makers have between five and 30 days to report, depending on the severity of the potential adverse event.

eMDR, Electronic Medical Device Reporting

The Electronic Medical Device Reporting Process (Source: AssurX, Inc.)

We won’t try to summarize the entire document here. Instead, we’ll highlight some of the more interesting FDA “answers” to its questions.

  • How should you handle a voluntary report when you don’t know the source of it? FDA says to first evaluate the complaint to see if it is a reportable event. Base that determination on in-house information, and consider contacting a user facility, importer or other initial reporter related to the alleged event. “Your decision about whether or not the event is an MDR reportable event should be based on the findings of your evaluation,” the agency says.
  • What is a ‘remedial action,’ and are those reportable to FDA and included as part of the more urgent 5-day report? The short answer is yes. FDA wants medical device manufacturers to attack problems with a wide lens. “FDA does not consider an action taken to correct only a single device involved in an MDR reportable vent to be a remedial action.” In other words, don’t forget CAPA and root cause analysis.
  • What does FDA require for developing, maintaining, and implementing written MDR procedures? FDA says medical device manufacturers must include internal systems that provide for: timely and effective identification, communication, and evaluation of events; a standardized review process or procedure; and timely transmission of complete reports to the FDA.
  • What information contained in an MDR report is subject to public disclosure. The bad news: All of it. The good news: FDA, before releasing a MDR report subject to a Freedom of Information Act request, will delete information covering trade secrets, personal medical information, and names and other identifying information of a third party that voluntarily submits a report, e.g., physicians and other health care professionals.

Comments are due in early October. Submit them to www.regulations.gov. Include the docket number (1828) with comments. Short URL for the draft guidance document: https://federalregister.gov/a/2013-16395

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FDA Turns Regulatory Flashlight on Compounding Pharmacies

Patrick Stone

Patrick Stone, President, TradeStoneQA

The latest round of 483 notices of observation forms are out and most of the headlines are all about sterile compounding pharmacies in compliance hot water.  The FDA is now specifically targeting sterile compounding pharmacies for compliance and surveillance inspections. The individual State Pharmacy Boards are less likely to shield local firms in the wake of New England Compounding Center. (NECC). FDA has expanded its unhindered self-appointed access to sterile compounding pharmacies. It does not appear that FDA is limiting its inspections to large hospital system operations. The agency also appears to be targeting smaller regional firms, too.

With well over a hundred pharmaceuticals on the shortage list , sterile compounding pharmacies are more critical then ever. The normal size sterile bags are turned into numerous admixtures for many different drugs, which in turn helps alleviate the shortage. For instance, when treating children you have to turn an adult sized sterile drug into a child size dosage for administration; one big bag turns into three small ones. Otherwise only a portion of the large bag would be used on one patient and then discarded. Some of the drugs on the shortage list can’t be manufactured by a compounding pharmacy, but these operations may be able to stretch out some critically short drugs until more supplies may be manufactured.

The citations issued by FDA have very similar tone and compliance issues.

compounding pharmacyFor example, this Texas firm’s 483 from March 2013 is a laundry list of remediations. I don’t mean to single out this firm, because many other firms have similar citations. But this 483 shows that the main agency concerns include preventing microbial, pyrogen, and viral contaminations (maintaining aseptic environment). Operational configuration (enough hoods for amount of admixtures), employee aseptic technique (media fills), and product stability programs were all noted as deficient. Validations were also lacking for environmental monitoring and decontamination procedures. These are all basic cGMP requirements most pharma manufacturing companies spend much of their resources on. Sterile compounding pharmacies operate close to USP 797 standard but fall way short of FDA cGMP requirements for sterile drug manufacturing.  The above listed 483 Web page is from this FDA weblink:

Ready or not the sterile drug compounding pharmacies will now get a crash course in drug manufacturing 101. FDA will continue to conduct surprise audits on medium and large sterile drug compounders and inspect them as they would a cGMP manufacturer. Why would FDA investigators treat a compounding pharmacy like a manufacturer? FDA does not currently have a sterile compounding pharmacy training course; instead, they have a sterile drug manufacturing training course. It is that simple and until there is a distinction or separate training class offered, we will see more of the same. FDA inspectors are trained to use the USP 797 guide but they still inspect the firm using the 7356.002 Compliance Program Guidance Manual (CPGM) for drug manufacturers.

Will this push to regulate sterile compounding pharmacies make the drug shortage better or worse? Will compounding sterile operators invest in the capitol it takes to make a validated aseptic facility with anterooms and appropriate gowning procedures?

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

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Expert: Cool Down on Hot CAPA

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

It’s no secret that FDA inspectors hone in on a medical device company’s Corrective and Preventive Action Program (CAPA) during an inspection.

But a leading certified body says many companies may have overreacted and made things unnecessarily difficult for themselves.

“Audits we’ve researched show the FDA has found CAPA deficiencies” at a company, says John DiMaria, Product Market Manager at BSI Group America Inc.

Irony: DiMaria says it’s usually not a a problem of a company doing too little.  “They take a ‘better safe than sorry’  approach” where they label almost any anomaly a problem that triggers their CAPA machinery. In other words, they are doing too much.   “They launch into a ten-step procedure that requires management sign-off” and a whole lot of other time-consuming activities.

Irony #2: By labeling too many small problems as potentially big CAPA issues, medical device companies often overwhelm themselves and “struggle” to give enough attention to the “preventive” part of CAPA. Medical device companies try to deal with so many “CAPAs” that they end up being sloppy with some, e.g., not closing the loop on an investigation.  It’s not company chicanery; it’s honest overload. But try telling that to an FDA inspector.

Image converted using ifftoanyFull disclosure: We may have helped contribute to that overreaction with our numerous blogs emphasizing FDA’s fixation on CAPA. Warning letter stats clearly show an FDA focus on CAPA.  However, DiMaria delivers a helpful reminder: Don’t throw a full-blown CAPA investigation at a minor, one-off mistake.

Instead, he advises medical device companies to have a strong investigative process up front. “If something small happens, say human error, you should have the data in place to show it doesn’t warrant a corrective action,” DiMaria notes.

“Understand the magnitude of the problem,” DiMaria adds.  “Sometimes it’s not a system problem at all.

Think of it as eating right and getting enough exercise, rather than calling a surgeon every time you’ve got a minor ache.

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Taste’s Like Chicken — With a Side of Bacteria

Kim Egan

Kim Egan, Founder, Saltbox Consulting

FDA’s latest Annual Meat Report is out.   It analyzes foodborne bacteria in retail meat, particularly salmonella, campylobacter, enterococcus and E. coli.   Salmonella causes typhoid.  Campylobacter causes spontaneous abortions in animals and opportunistic infections in humans.  Enteroccus can cause meningitis and E. coli is the most common source of food poisoning.

Suffice to say, the news is bad.

The number of antibiotic resistant microbes in retail meat is going up, not down.   Over half of all retail meats – 55.7 percent — test positive for E. coli.  Contrary to popular belief, pork chops have the lowest prevalence – 30.4 percent – while ground turkey has the highest at 76.7 percent.  In fact, pork and beef came out rather well in this report, relatively speaking, compared to retail chicken and ground turkey.  Chicken and turkey do so badly, in fact, that it is amazing anyone eats retail poultry at all.

T-boneThe report also analyzes the extent to which these food contaminants are resistant to antibiotics, and assigns p values to measure statistical significance.  In other words, FDA made sure its findings are real and not the result of chance.  It turns out that:

  • Over a third (33.5 percent) of the contaminants in retail chickens and almost a fourth (22.4 percent) of those in ground turkey are resistant to third-generation cephalosporins.   Third-generation cephalosporins are supposed to be effective against hospital-acquired infections, pneumonia, and meningitis.
  • Almost half (40.5 percent) of contaminants in retail chickens and over half (58.4 percent) of those in ground turkey are resistant to ampicillin.  Ampicillin is supposed to be effective against staph infections, strep, and the flu. FDA said the change in ampicillin resistance in turkey from 2002 to 2011 is a “highly statistically significant” result.
  • Tetracycline resistance in poultry is up.   Tetracycline combats cholera.  So, that’s more bad news.
  • Gentamicin resistance in retail chicken and turkey is higher than that in beef and pork, or 20 percent compared to 5 percent.  We use gentamicin to fight staph infections, along with  the pathogens found in decomposing animal matter, sewage, manure soil, and human and animal feces.

On the theory that The Truth Will Set You Free, we can expect FDA to do something about this, right?  No.  Prediction: All FDA will do is write more reports and approve ever more powerful antibiotics for animals.

Makes you a little sick to the stomach, doesn’t it?

Kim Egan is the Founder of Saltbox Consulting, a firm that provides legal and compliance advice to entities regulated by FDA and USDA.  She can be reached at kim.egan@saltboxlaw.com and on Twitter at @saltboxlaw.

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FDA 483s: We Read’em So You Don’t Have To

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

The FDA is taking its act overseas – and isn’t liking some of what it found.

The latest batch of 483s has a decidely international flair: Italy, Japan and Canada had the pleasure of hosting FDA inspectors in recent months. Three foreign firms were found wanting by the agency in a number of areas.

In the land of Christopher Columbus, and the birthplace of artificial hearts and artificial insemination THD S.p.A., a maker of rectoscopes, anescopes, proctoscopes and Doppler systems devices, was issued a March 26 warning letter for failing in several cGMP areas. For example, the FDA inspector cited a failure to:

  • Establish and maintain procedures for receiving, reviewing and evaluating complaints by a formally designated unit.
  • Review and evaluate all complaints to determine whether an investigation is necessary.
  • Establish and maintain procedures for implementing corrective and preventive actions (CAPA). Here the company was singled out for a lack of documentation. The firm’s Dec. 12 response was deemed inadequate by the FDA.
  • Establish and maintain acceptance procedures for verifying the device design.
FDAlogoSailing to the land of the original cherry blossoms and the birthplace of the Sumo Wrestler, the FDA hit Japan’s Eiken Chemical with a March 13 warning letter. It got off to a bad start with the FDA by failing to get Premarket Approval (PMA) for its fecal occult blood testing devices.

Eiken was also told it didn’t adequately validate device design, and properly handle complaints.

Closer to home, Canadian firm Safecross First Aid, manufacturers of first aid kits and their components, was accused in a March 26 warning letter of misbranding. It was also hit for failure to develop, maintain and implement written Medical Device Reporting (MDR) procedures.

It’s also worth noting that Safecross fell victim to the FDA’s “if it’s not documented, it didn’t happen” mantra. The warning letter chastised the company for failure to establish procedures for quality audits and ensure their effectiveness. According to the warning letter, Safecross’s Quality Manager said the firm had conducted certain quality audits.  However, FDA said the company had not documented dates or results of the audits.

In FDA speak, that means they don’t count, whether they happened or not.
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FDA Shows More Flair in Latest 483 Round-up

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

The latest batch of 483s issued by the FDA shows a bit more variety than the last few we’ve reviewed.  We’ve noted in many earlier 483 review reports that the agency has been consistently fixated on corrective and preventative action (CAPA) programs. And there was some of that in this new group.

However, we found more variation here than we’ve seen in many moons.

For example, a December inspection of Stingray Surgical Products in Boca Raton, FL resulted in an interesting 483 for the manufacturer. Specifically, FDA inspectors found “a process whose results cannot be fully verified by subsequent inspection and test has not been adequately validated according to established procedures.”

FDA also hit Stingray for not having “any requirements (only preferences) for purchasing control of components which do not contact the patient.”

Stingray was also found wanting in its design risk analysis program.

warning640Back in California, an October – November inspection of Ra Medical Systems faulted the company for not reviewing design output before release. Also, inspectors issued a 483 because “the acceptance status of product was not identified to indicate conformance or nonconformance with accepted criteria.”

Going farther afield, an October inspection of Karl Storz Video Endoscopy Estonia Ou did find a number of problems with our old CAPA friend at their operation.

Even there, the device maker was also cited for inadequate quality audit procedures, control product not meeting specified requirements, and document control procedures.

Have you sensed a different vibe from inspectors during any recent inspections at your shop? We’d love to hear your story. Anonymously, of course. Drop us a private email at blog@assurx.com.

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Part II: Next Practices for Selecting an Enterprise Quality System

John Moroney of AssurX, Inc.

John Moroney, VP, Sales, AssurX, Inc.

Note: In part one, we looked at how to approach the selection process, assess vendor capabilities, and find the right philosophical “match” for your particular organization. In part two, we’ll take you through next practices for scoring vendors, conducting an effective vendor search, and clearly defining project scope and costs.

Beware of how to measure. Companies frequently will devote significant effort and elaborate scoring methods to grade vendor functions resulting in very precise but ultimately irrelevant scores. Academic studies of software project success indicate that product functionality contributes less to success than the customer and vendor implementation team and process.  Keep the assessments simple and double check major variances with the team members and the vendor.

One approach to avoid feature/function obsession is to develop scenarios for vendors to demonstrate. Select one to three primary areas of business improvement (CAPA, Customer Complaints, etc), develop an outline of how the team would like these processes to be and review the outline with key vendors. This may result in a more detailed scenario for each vendor to demonstrate, or simply request the vendors to show how they would support the original description.

Once the team has narrowed down to the final one or two vendors, it is advisable to speak with customers, but first consider what questions you would like to have answered. This will achieve at least three things:

  • Focus the team on the primary concerns with the vendor/product/project.
  • Assure that the reference company is appropriate.
  • Allow the reference company to have the correct person available.
  • Not miss any key points during the meeting.

This can be an excellent time to hear the lessons learned by the customer – not just about the product or vendor but the project itself and how it has evolved over time.

Quality WhiteboardDefined Project Plan and Costs

At this point the team should have firm costs and establish (possibly with the vendor’s help) a project timeline. If it has not been done already, a business case justifying the project is frequently required to secure executive approval.

The most common source of frustration and delay at this stage is the team not knowing the internal process for getting the project approved. In many companies a capital request and presentation is required. Contracts and agreements usually must be reviewed and/or modified requiring procurement and possibly legal resources. Vendor setup and approvals and possibly background checks may also need to be done. Depending on the company, a separate plan to work through this stage is sometimes helpful.

Often your project is vying with other capital needs for funding. Furthermore, few members of the capital committee or approval executives will know much about your project. It can be useful to create a summary presentation describing the business need for this software, the vendor selection process, general project plan, the benefits and when they will begin to accrue. Include the alternatives as well and the recommendation and consider framing the presentation to address these questions:

  1. Why do anything?
  2.  Why do it now?
  3. Why this recommendation/alternative?
  4. What does the company need to invest – not just money but what resources?

Closing

Embarking on the implementation of a new EQMS is much like any project where change is necessary. Success will hinge on consistent effort and working through obstacles and resource limitations as well as resistance to doing things differently.

Here are some final tips to help ensure success:

  • Secure solid management support – make sure the project leader has been given the time, the resources and organizational support necessary.
  • Get requirements defined, agreed upon and documented – reference and revise frequently.
  • Avoid the geek factor –  beware of flash. Remember, features can often be added later.
  • Don’t let perfection be the enemy of the good – a version 2.0 can come later.
  • Strong team and communication – better to get issues out early.
  • Focus on small wins, quickly – iterate, test and refine along the way.
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Study: FDA Enforcement Growing for Medical Device Companies

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Michael Causey, Editor & Publisher, eDataIntegrityReport.com

Turns out that some paranoid people have a reason to, well, be paranoid.

Researchers from the London Business School issued a report last year finding that many people at work who thought they were being talked about were probably right.

Maybe some in the medical device industry can be forgiven for thinking the FDA has come down harder on them in recent years.  A new study kind of backs their “paranoia,” too.

FDA efforts since 2009 to strengthen key policies has resulted in more medical device enforcement that will have a “long-lasting” effect on the industry, says an independent study from Greenleaf Health’s enforcement and compliance team. It was overseen by former FDA Associate Commissioner for Regulatory Affairs, Michael Chappell.

The Medical Device Enforcement Report focused on four specific area of medical device enforcement data: FDA inspections, 483s, warning letters and product recalls.

Medical Device Recalls

There is a general correlation between CDRH and FDA increasing recall numbers. In 2007, 1,279 medical device products were recalled – that number soared to 3,211 in 2011.

Here’s are some of the more telling stats:

  • Since 2005, CDRH inspections have accounted for 10 – 12% of all FDA inspections.
  • CDRH inspection numbers have increased at a rate consistent with FDA inspection numbers, the report sats. In 2005, CDRH inspected 2,304 facilities compared to 3,369 in 2011.
  • In 2008, CDRH issued 152 warning letters, compared to 200 in 2010.
  • In 2007, 1,279 medical device products were recalled – that number soared to 3,211 in 2011, according to data collected by Greenleaf.
  • Over the last five years, 483s issued to device manufacturers have accounted for 6% of all 483. The number of 483s issued by FDA – for all regulated products – has increased from less than 4,000 in 2008, to nearly 5,000 issued in 2010. The number of 483s issued for CDRH regulated products has remained steady over the 5-year period annually.

Greenleaf’s team suggests that these rising numbers can be attributed to a conscious FDA policy shift that includes more efficient review of warning letters, increased prosecution of misdemeanors, creation of the “Bad Ad” program, and the increased role and responsibility of FDA enforcement officials.

Here’s the $64,000 question: If you are paranoid that something bad is happening to you, and then you learn you may be right and not paranoid, is that a relief?

We’ll let those in the medical device industry speak for themselves on that one.

To purchase the full study, go to www.greenleafhealthllc.com

 

 

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