medical device Industry

Martell Winters Shares Expertise with University Students

martell_winters_3Martell Winters, consultant and senior scientist at Nelson Laboratories, is now instructing a course at Brigham Young University (BYU) entitled “Industrial Microbiology and Sterilization.” The course is limited to juniors, seniors, and graduate students and is focused on providing a thorough review of microbiology in the medical device industry. For years BYU has provided an excellent education in the department of microbiology and molecular biology. However, it was recognized that a good foundation in industrial microbiology and sterilization microbiology was missing.

Martell worked closely with Dr. Rich Robison (professor and Department Chair) and Hyrum Shumway (graduate student and TA) at BYU to develop a comprehensive curriculum to cover such topics as FDA regulatory requirements, validation concepts, terminal sterilization (including EO, radiation and steam), reusable medical devices, aseptic processing, water treatment, and biological evaluations/biocompatibility. Also incorporated into the course are several company tours to medical device manufacturers, Nelson Laboratories, a water treatment plant and a hospital central processing department. This is an exciting program as it will give students an opportunity to learn from industry experts as well as great preparation for those who want to enter into the medical device/pharmaceutical/sterilization industries.

Martell is an industry leader in microbiology and sterilization and has over 20 years of experience working with companies to improve their processes.  He is also an active committee member of many working groups for multiple regulatory bodies, and has been integral in the creation of multiple standards in place today. His expertise in these areas makes him well qualified to develop and teach this course.

3D Printed Devices and Biocompatibility

By: Matthew R. Jorgensen, PhD; Audrey P. Turley, B.S., RM(NRCM), CBA(ASQ)

3-D Blog Post

The use of three-dimensional (3D) printing techniques to address challenging fabrication problems has become mainstream over the past decade. While this rich resource has extended fabrication of personalized medical devices to the limit of our imagination, the myriad materials and morphologies available present a unique concern from a toxicological perspective. A range of standalone 3D printers are commercially available with compatible materials ranging from plastics to oxides and metals. Raw materials used in the fabrication process often have highly customized properties, achieved through the use of proprietary additives and specific microscale morphologies which can affect the overall biocompatibility of the finished device. Therefore, 3D printed medical devices require versatile approaches to the assessment of their biocompatibility that consider several factors which will be addressed in turn over this four-part blog series:

  1. Possible additives to raw materials which enhance workability
  2. Details of the material curing process
  3. Post-printing finishing and rinsing processes
  4. Time allowed for aeration between device manufacture and use

Possible additives to raw materials which enhance workability

3D printed plastic materials can be grouped by the printing technology used; generally either photolithography or direct writing of thermoplastic materials. In both of these cases, one or more materials are printed in tandem with a sacrificial filler material that provides structural support during the printing process. Photolithographic methods use a mixture of polymer precursors called photoresist which polymerize into a durable solid on exposure to light. If the photoresist requires light with intensity above a certain threshold, extremely fine resolution on the order of hundreds of nanometers is possible by scanning tightly focused laser light through the photoresist. Direct writing involves the partial melting of raw materials through a heated nozzle into fine layers. The structure and support material are deposited layer by layer, gradually building from the ground up. A compromise between photolithography and direct writing is also possible. In a process similar to inkjet printing, which produces thousands of colors by mixing three or four primary colors, different combinations of photoresists can be mixed and printed followed by exposure and polymerization with UV light.

Each technology for 3-D printing of plastic involves materials with highly customized properties, enabled by their unique chemistries. Photolithography involves polymer precursors, photosensitizers, other additives, and solvents. Following exposure, precursors and reaction byproducts remain embedded in the structure raising concerns regarding their potential to leach out during clinical use. Thermoplastics used in direct writing processes include plasticizers and other additives essential for their workability but which may cause concern as some of these additives are not biocompatible. Following melting and drawing through the writing nozzle, the additives are redistributed through the material and the surface area is increased exponentially. These processes increase the availability of potential toxicants to their surrounding matrix in the body and potentially a clinical exposure risk if not understood.

Evaluation of the biocompatibility of 3D printed devices should consider chemicals which are novel additives to otherwise well-known materials, as well as byproducts of the polymerization process. The availability of these chemicals for extraction into the matrix surrounding the device must be evaluated along with an assessment of their potential toxicological impact on a case-by-case basis.

Tune in next week to learn more about the details of the material curing process and the role it plays in the biocompatibility of 3D printed medical devices.

FDA Proposes Ban on Powdered Surgeon’s Gloves, Powdered Patient Examination Gloves, and Absorbable Powder for Lubricating a Surgeon’s Gloves

Sterilization-of-reusable-trayFDA is proposing to ban powdered surgeon’s gloves, powdered patient examination gloves, and absorbable powder for lubricating a surgeon’s gloves. The Agency determined that an unreasonable and substantial risk of illness or injury may occur from using these medical products and the risk cannot be corrected or eliminated by labeling or a change in labeling.

Electronic comments are encouraged for docket number FDA-2015-N-5017 RIN 0910-AH02 and can be submitted via this link.

The Federal Food, Drug, and Cosmetic Act (FD&C Act) of 1976 states that any device presenting an “unreasonable and substantial risk of illness or injury” that cannot be, or has not been, corrected or eliminated by labeling or a change in labeling must be banned. FDA has been considering banning the use of powder on gloves since 1997 when it issued the Medical Glove Powder Report. At that time, FDA decided that the benefits of using powder with surgical and patient gloves outweighed the risks. Since then, FDA has received many citizen petitions regarding the use of glove powder.

As a reaction to the 1998 petition to review its stance on the use of powdered gloves, FDA reconsidered a ban on powdered gloves in 1999. Three main factors kept the ban from taking effect: (1) A ban would not address exposure to natural latex allergens from medical gloves with high levels of natural latex proteins; (2) a ban of powdered gloves might compromise the availability of high quality medical gloves; and (3) a ban of powdered gloves might greatly increase annual costs by almost as much as $64 million over the alternative approach proposed by FDA in the “Draft Guidance for Industry and FDA Staff: Medical Glove Guidance Manual.”

FDA is yet to finalize the ban. The Agency possibly has not received all the information regarding the risks and benefits of powdered gloves, so Nelson Laboratories, Inc. is encouraging anyone who is interested in this topic to submit comments to FDA via the link above.

Nelson Labs: A Full, Life-cycle Microbiology Testing Lab

Nelson LabsNelson Laboratories is a leading provider of full, life-cycle microbiology testing services for the Medical Devices, Pharmaceutical, Tissue and Natural Products industries. While we are known for exceptional quality and rigorous testing standards, we are also keenly aware of the bigger picture. It’s what we call The Science of Success™.

At the MD&M West 2016 trade show, Jeffery Nelson was asked to explain who we are and what we do. Watch this video to see what he said.

 

Estimated Economic Impacts of the Two Year Moratorium on the Medical Device Excise Tax

We may be seeing an increase in activity from medical device manufacturers as a result of the Consolidated Appropriations Act, 2016 (Pub. L. 114-113) which lifted the Medical Device Excise Tax for two years beginning January 1, 2016. Since January 1, 2013, manufacturers and importers have been paying a 2.3 percent tax on the sale price of taxable medical devices (some exclusions include eyeglasses, contact lenses, hearing-aids, retail items, etc.).

“What most taxpayers don’t realize is, even though the 2.3 percent tax seems like a small number, it is significant to manufacturers,” states John Bolinder, VP marketing & communications at Nelson Laboratories.  “For a mid-size company in the $10 million to $50 million range that sells commodity items in a competitive MedTech market place, the profit margins are only 6 to 10 percent, so the effective tax is closer to 20 to 30 percent since the 2.3 percent tax is taken from top line revenue, not earnings. That is a tremendous erosion of earnings and capital for small and mid-size firms. Many firms had to make significant cuts in spending, R&D and payrolls to pay the tax. Hopefully legislators will realize how much of a burden this tax is to device manufactures and continue to assess alternatives so that MedTech companies can spend these funds on innovation and improving the quality of life.”

It is estimated by the Congressional Research Service that companies paid out $2.4 billion in 2014. What effect will this have on the medical device industry? Time will tell, but many manufacturers have already stated that they are increasing investments back into their companies which will fuel growth in the MedTech sector.

Improving Medical Device Approval Timelines

The business of getting medical devices to market is a complex web of variables including the laboratory testing we do at Nelson Labs. We know that an intimate knowledge of regulatory behavior, draft guidance and guidance documents can significantly improve our client’s medical device development and market introduction timelines. However, those who are developing novel devices, the trailblazers creating entirely new categories of medical devices, face a more difficult, expensive, and risky path to market. This device development “no man’s land” lacks regulatory guidance, and research indicates a 41% increase in time to market approval, causing many medical device manufacturers to stray from developing novel, life saving devices, and instead sticking to the known regulatory path.

Two important studies have been released this year highlighting the significant difficulties new device manufacturers face due to fragmented data systems (Recommendations for a National Medical Device Evaluation System), and a lack of regulatory guidance from FDA for unique devices (Innovation Under Regulatory Uncertainty: Evidence from Medical Technology). One argues for harmonized data systems for improved device surveillance and product transparency for doctors, patients, device manufacturers, regulators, etc. The other suggests more FDA guidance is needed to help streamline the process for novelty devices that have no precedent to help reduce regulatory uncertainty and thereby encourage greater medical device innovation.

Jim Dickinson’s article, Two Eminent Reasons to Speed Device Approvals, which recently appeared on MD+DI’s blog, provides a nice overview of these important reports and the benefits of adopting their recommendations. Below you will find Mr. Dickinson’s article in its entirety. You may also visit www.mddionline.com for the original article.

 

 

 

 

 

 

 

 

 


Two Eminent Reasons to Speed Device Approvals
Two studies point to the need for a more efficient, informed medical device approval process at FDA.
By: Jim Dickinson, MD+DI contributing editor

Their pedigrees and their scholarship couldn’t be faulted—two deeply researched studies emerged in the dog days of August when most Washington policymakers were away, each providing potent reasons for speeding up the FDA approval process for medical devices.

The first, with no fewer than 26 authors from diverse professional settings in academia, industry, clinical practice, informatics and government, came from FDA with far-reaching recommendations to integrate existing and developing data systems and registries to “promote continuous accrual of benefit/risk and safety knowledge from invention to obsolescence.”

Entitled Recommendations for a National Medical Device Evaluation System—Strategically Coordinated Registry Networks to Bridge Clinical Care and Research, the 146-page FDA task force report foresees ultimate deliverables that “should include better, more efficient regulatory science-based decisions in conjunction with device information dissemination customized to stakeholder groups, including patients, clinicians, professional societies, regulators, manufacturers, payers and others . . .”

The second, an unrelated 56-page working paper from Harvard Business School assistant professor of business administration Ariel Dora Stern aided by 23 acknowledged collaborators from other schools, industry and FDA, provides a compelling case for getting on with those recommendations.

Blaming “regulatory uncertainty” at FDA, her research finds that early mover medical device innovators spend 34% (7.2 months) more time getting FDA approval than do follow-on imitators that come along later—the opposite of what market entrants experience when introducing new drug products.

“Back-of-the-envelope calculations suggest that the cost of this delay is upwards of 7% of the cost of bringing a new high-risk device to market,” Stern writes, observing that this deters small companies from even trying.

The voluminous extramural FDA report builds on a 2012-published agency overview, Strengthening Our National System for Medical Device Postmarket Surveillance and in the process seemingly opts for a dash of political correctness, eschewing forever the prickly word “surveillance” in favor of the less polarizing word “evaluation.”

But the name change is more than just semantics, the report insists. By broadening surveillance into evaluation, the national system could “organically both add efficiency and better inform the ability for manufacturers to use [safety signals] as engineering targets and to convincingly demonstrate signal mitigation with newer, better device designs that reach the public faster . . .”

Critical to the national system’s success will be strategically integrating existing device registries, electronic health records, administrative claims data and mobile device outputs “to produce a complementary network whose whole data composite in fact could support ongoing and robust device evaluation.”

Such structures have been called “coordinated registries networks” or CRNs—even though not all of their members are actual registries, the report notes.

“Functionality of CRN structure and governance should be guided with the objective of meeting the needs of multiple stakeholders including patients, clinicians, healthcare systems, FDA, registry owners, and industry partners,” it says.

“Functionality, leveraging and linking of participating registries and other entities,” the report goes on, “should promote ongoing device evaluation, increase patient and device data and outcome information quality, modulate added work load through dual-purposing existing workflow, and so reduce cost and enhance overall efficiencies and timeliness associated with regulatory milestones.”

Examples of contemporary devices that could be profiled by CRNs, the report says, include hip and knee replacement devices, spine surgery procedures/devices, vascular procedures/devices (peripheral, abdominal aortic aneurysm repair, carotid and vascular access/catheters), cardiac valves, atrial fibrillation ablation procedures/devices, implantable rhythm and heart failure devices, coronary stents, robotic and other minimally invasive surgery devices, ophthalmic procedures/devices, and surgical mesh.

“The success and sustainability of CRNs, and of the national system itself,” the report concludes, “will depend on the actively promoted transformation of the contemporary medical device innovation ecosystems from a landscape of fragmentation, skepticism, and distrust to a culture of good will and partnering in every aspect of the CRN and national system’s development and operations.”

All of this adds up to efficiency gains in a regulatory system that now is far from that. Another word for efficiency is “speed”—in this context, speed of processes that currently don’t work together well. The FDA report wants these processes to become a smooth “continuum.”

As an authoritative description of how badly everyone needs this, Stern’s Harvard Business School working paper discovers that, contrary to many expectations, technological novelty is largely unrelated to FDA approval time for a high-risk device.

Instead, she says, approval time is “meaningfully reduced by the publication of objective regulatory guidelines.”

PMA content and format uncertainty at FDA, Stern writes, “is easiest to think about in a scenario in which a product and its functionality are known to the regulator, but evaluation criteria have not been formally articulated or informally established by precedent. This can be seen in the case of drug eluting stents (DESs), which were first sent to the FDA for approval in 2002.

“It was not until 2008, however, after five different DESs had submitted applications for regulatory approval and four had already been cleared, that the FDA published a formal guidance document, detailing what criteria it would use to evaluate DESs moving forward.”

This document and others on another eight unique medical devices (pacemakers, implanted cardioverter defibrillators, electrodes, heart valves, lasers, occluders, catheters and stents) provided objective regulatory guidance that allowed average approval times for subsequent entrants to fall by about 40% (6.1 months), Stern’s paper says.

“These findings,” she writes, “have implications for other emerging categories of medical technology such as tissue engineered products and the applications gene therapies, as these are all contexts in which there is a large degree of uncertainty about the content and format of new product applications and, as a corollary, around how to evaluate new products.

“This uncertainty is the result of both a short (or nonexistent) regulatory history for these types of products and a dearth of formally or informally established regulatory criteria. In these new product categories, regulatory approval times for a given product are similarly likely to be substantially protracted until a time when objective product evaluation criteria are formalized and made available to innovators.”

Stern cites a 2010 survey of the medical device industry by Josh Makower et al that found that for roughly 20% of companies the average cost of bringing a high-risk medical device to market was about $94 million.

“Assuming a discount rate of 11.5%,” she writes, “the results suggest that the opportunity cost of the delay associated with being the first entrant in a product code is probably around $6.7 million, or more generally, upwards of 7% of the total cost of new device development.”

Stern’s analysis of FDA data suggests, she says, that by even the most conservative estimate “the resolution of procedural uncertainty through the publication of formal guidance is associated with a 6.1 month (approximately 185 day) reduction in regulatory approval times”—or an average 41% reduction.

In other words, as others have also found, familiarity with FDA protocols is more important than technical knowledge for predicting a medical device firm’s successes.

Moreover, Stern and the FDA task force together make it obvious that fusing diverse knowledge systems need not further retard the route to market but should actually have the opposite effect.