Author: cmdeyoung

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 We know that an intimate knowledge of regulatory behavior, draft guidance and guidance documents can significantly improve our client’s medical device development and market introduction timelines.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 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.

Alternatives To In Vivo Biocompatibility Testing

Reconstructed human epidermis (RHE) for in vitro skin irritation and sensitization testing.

Reconstructed human epidermis (RHE) provides an accurate and reliable test system for in vitro skin irritation and sensitization testing.

By: Daniel Olsen, Senior Laboratory Analyst II, Nelson Laboratories

The landscape of biocompatibility assessment of medical devices is an ever-changing and evolving one. Recently, there has been a lot of effort put into the development of alternatives to in vivo biocompatibility testing. Expanding technological capability and increased scientific understanding of the key events in complex biological responses is making this shift to in vitro alternatives possible by enabling the development of accurate, sensitive, and reliable test methods.

Because of the large amount of toxicological data available and increased sensitivity compared to animal tests, the advanced chemical characterization of medical device extractables is largely being seen as a potential replacement for many in vivo systemic toxicity endpoints. This is reflected in Figure 1 of ISO 10993-1, which lists chemical characterization as a first step in the biological evaluation of a new medical device.

Another area that is making great progress in the transition to in vitro alternatives is that of skin irritation and sensitization testing. A number of in vitro test methods for assessing skin irritation and sensitization have been validated and approved for use in chemical, cosmetic and pharmaceutical testing1-3. Many of these methods are being successfully adapted for use in medical device assessment. The final preparations are currently underway for a round-robin validation of in vitro skin irritation testing for medical devices. In addition, recently published research shows promising results for in vitro sensitization using medical device extracts4.

Nelson Laboratories is committed to scientific advancement and is actively engaged in research to assist in the development of safe and reliable in vitro alternative methods. We believe that this transition will be largely beneficial to medical device manufacturers, testing laboratories, and end users.

For more information on these important developments Daniel recommends you read Evaluation of an In Vitro Human Dermal Sensitization Test for Use with Medical Device Extracts, Better Animal Testing Alternatives Are Coming to U.S., and review Nelson Labs’ 2015 SOT poster presentation, Extractable Positive Control for In Vitro Skin Irritation Testing of Medical Devices.


  1. OECD. Test No. 439: In Vitro Skin Irritation.  (OECD Publishing).
  2. OECD. Test No. 442C: In Chemico Skin Sensitisation.  (OECD Publishing).
  3. OECD. Test No. 442D: In Vitro Skin Sensitisation.  (OECD Publishing).
  4. Coleman, K. P. et al. Evaluation of an In Vitro Human Dermal Sensitization Test for Use with Medical Device Extracts. Applied In Vitro Toxicology 1, 118-130, doi:10.1089/aivt.2015.0007 (2015).

Evaluating The Impact of Change with Chemical Characterization

Analyst performing FTIR Test to identify residuals

Analyst performing FTIR Test to identify residuals.

When dealing with orthopedic medical devices, even small changes in the manufacturing process or device materials can impact patient safety. With these changes comes the risk of introducing new compounds that may leave residue on the device or leach harmful compounds that put the patient at risk. Because of the high patient risk, the biocompatibility of the device must be re-evaluated after any change.

The most thorough method to determine the effect of a change is to repeat the biocompatibility tests that were performed in the original submission to bring the device to market. However, this can be costly and time-intensive. One alternative is chemical characterization testing. Chemical characterization test methods characterize the device materials and determine the compounds that may leach or extract from the device. Chemical characterization, combined with specific biocompatibility tests, is a more cost effective and efficient way to evaluate the impact of a change in the manufacture of a device.

Common changes orthopedic device manufacturers encounter are generally outside of their control. These changes include alterations to the device material or vendor supply. Internal changes are also implemented to improve the device or the manufacturing process which can impact the biocompatibility of the device.

When a change occurs, the manufacturer must evaluate the impact of the change on the device as a whole. A few key characteristics of evaluating change include:

  • Evaluate any new material or compounds that could be introduced to the patient as a result of that change.
  • Evaluate how much the change affects the patient contacting portion of the device.
  • If the affected portion of the device does not have direct patient contact there may be less testing required than a change that would affect the direct patient contacting surface areas of the device.
  • If a processing change has occurred, evaluate whether or not the new process removes residuals as effectively as the original process.

Because every orthopedic device is unique, there are many ways to assess the impact of a change. The potential impact to the patient must be evaluated with any change and chemical characterization is one way manufactures can evaluate that change.

Chemical characterization testing is most effective when the original device configuration is compared to the device after a change has occurred. If the characterization of the two devices is shown to be similar, fewer biocompatibility tests may need to be repeated. A test plan, along with a risk assessment, is the most successful approach to take when evaluating the impact of a change to the overall biocompatibility and patient safety of a device.

For more information on using chemical characterization to evaluate changes in medical device manufacturing we recommend Thor Rollins’ and Alexa Tatarian’s ODT Magazine article, “How to Approach Change in Orthopedic Device Manufacturing,” as well as their complimentary on-demand webinar, “The Power of Chemical Characterization to Assess Changes.” You may also visit Nelson Labs online at for more information about our biocompatibility testing laboratory services.

Nelson Labs Contributes to STEM Education

Nelson Labs STEM Education

Nelson Labs’ WISE Committee is dedicated to sharing the STEM message with young women, informing and preparing them for the career opportunities available in STEM related industries.

Nelson Labs is proud to work in collaboration with the Science, Technology, Engineering, and Math (STEM) Action Center to bring hands-on STEM education exposure to students throughout the state of Utah. The Nelson Lab’ WISE (Women in STEM Education) Committee is one way Jeff Nelson, President and CEO of Nelson Laboratories, and a chairman of the STEM Action Center Board, is supporting STEM initiatives in Utah.

Nelson Labs’ scientists are recognized medical technology thought leaders, serving on the standards committees who develop and perfect the medical device testing standards that help ensure medical devices are safe for patient use. Nelson Labs is leading the industry in the race to acquire regulatory approval of emerging in vitro biocompatibility test alternatives to animal testing. Our scientists are paving new paths for the future of medical device testing, and we are committed to investing in STEM education to ensure the talent of tomorrow is prepared to carry on this legacy of scientific excellence.

Nelson Labs’ WISE Committee has taken an active role in sharing the STEM message to encourage junior high and high school aged young women to become more involved in STEM areas. Since January, when the WISE Committee was formed, scientists from Nelson Labs have participated in multiple conventions to provide girls an up-close look at a day in the life of a scientist. These workshops have given students a chance to work side by side with scientists from Nelson Labs to perform bioburden and calorimetric testing. The students were also able to talk with our industry experts and receive guidance about important skills to develop and classes to take in high school and college en route to a STEM career.

Utah STEM Fest brought together over 12,000 seventh and eighth graders from across the valley to participate in interactive exhibits highlighting opportunities for STEM careers in Utah. Nelson Labs’ booth allowed students to test their knowledge about the organisms and bacteria that live on items they use every day, and examine them closely under a microscope.

Most recently, the WISE Committee’s focus on STEM education took them to two high schools on the Monument Valley Navajo Reservation in Southern Utah. Partnering with Junior Achievement of Utah, the WISE Committee attended career fairs aimed at encouraging Navajo high school students to pursue higher education and careers in the STEM areas. Scientists from Nelson Labs spent time with the students teaching them about the importance of the medical device testing we perform at Nelson Labs, and helping them perform chemistry experiments with liquid nitrogen. Volunteers from the WISE Committee also spoke to several Career and Technical Education (CTE) classes, sharing their passion for science and advising students on ways to pursue STEM careers.

Jeff Nelson believes that inspiring our state’s student population and helping them achieve success with the STEM topics will in turn improve our economy, and encourage businesses to be more competitive.  The STEM program facilitates collaboration between businesses and educators to better prepare students for hi-tech careers.  Jeff is dedicated to encouraging the upcoming generation to become interested and excel in the STEM areas by continuing to support conventions and providing opportunities for students to obtain hands-on experiences with scientists from Nelson Labs.

Visit to learn more about Nelson Labs’ commitment to STEM education.

Why Particulate Matter Testing Matters: Cardiovascular Medical Device Testing

Particulate Matter Testing of Medical Devices

Study Director analyzing particulate matter under a microscope

By: Ryan Lunceford, Particulates Department Manager, Nelson Laboratories

Cardiovascular medical devices undergo particulate matter testing because once implanted, contaminants left on these devices pose serious risks to patient safety including blood clots and stroke. Particulate matter testing evaluates the amount and size of residual material left on the device following manufacture.  Particulate matter testing also evaluates the amount of residual material that may leach off of a medical device into the bloodstream throughout the life of the implant.

To ensure the utmost safety for patients, particulate matter testing of medical devices is done according to two guidance documents: ASNI/AAMI TIR 42, and FDA’s Class II Special Controls Guidance Document for Certain Percutaneous Transluminal Coronary Angioplasty Catheters. EN 45502/ISO 14708 also provides information about permissible levels of residual particulate matter for implantable devices.

Selecting an unbiased, qualified testing partner to evaluate particulate matter is fundamental to ensuring cardiovascular devices are safe for patient use. An experienced medical device testing partner like Nelson Labs will help manufacturers create a test protocol incorporating simulated use conditions for the device. The lab will also validate the test protocol to ensure that any particulate matter the device is exposed to is recoverable in the test process. The testing of the device will ideally analyze the interaction of the device with any device accessories, mimic clinical use, and evaluate human factors to determine an accurate real-world particulate count.

While laboratory personnel will help manufacturers create and validate their protocol, the manufacturer is responsible for establishing acceptance criteria. ANSI/AAMI TIR 42 recommends using particulate matter data from a predicate device along with historical test data to establish acceptance criteria.

Following an initial particulate matter analysis, ongoing postmarket surveillance should be considered. Postmarket surveillance offers device manufacturers the assurance that the manufacturing, packaging, and handling processes remain clean long after the initial validation. It also provides the necessary data to address changes or variances that may occur in the manufacturing process over time to ensure maximum patient safety.

In the event that excessive particulate matter is found on the device, further analysis may be required to pinpoint particulate origin and correct the issue. This can be done via a microscopic particle investigation or fourier transform infrared spectroscopy (micro-FTIR) scan to determine the composition of the particulates.

For more extensive information on particulate matter testing for cardiovascular devices, download Nelson Labs’ white paper, A “Particle” of Prevention is Worth a Pound of Cure:  The Significant Benefits of Premarket & Postmarket Particulate Testing of Cardiovascular Devices” from  You may also visit Nelson Laboratories at for more information about medical device testing.

DuPont’s Tyvek Transition: Are You Prepared?

Tyvek Transition

By: Craig Fisch, Study Director, Nelson Laboratories

With DuPont’s Tyvek transition looming, manufacturers should consider performing a packaging validation as part of their implementation strategy.

Nelson Laboratories has been working with the new Tyvek material, testing it according to the ASTM F2638 method, for several years. DuPont has committed to help make this transition process seamless for sterile packaging manufacturers (SPMs), medical device manufacturers (MDMs), and the healthcare industry, carrying the lion’s share of time, money, and resources associated with establishing functional equivalency. For most manufacturers, the transition will not justify a full packaging re-validation – DuPont’s functional equivalency letter may provide much of the necessary justification.

Throughout the Tyvek transition, manufacturers need to be asking, Is the new Tyvek material functionally equivalent once implemented in my unique packaging configuration? A consult with a qualified testing partner early in the implementation process may help manufacturers properly answer this question.

A packaging validation will generally include three components: integrity testing, strength testing, and microbial barrier testing. The options for strength and integrity remain the same, but manufacturers have a new option when it comes to microbial barrier testing – ASTM F2638, Standard Test Method for Using Aerosol Filtration in Measuring the Performance of Porous Packaging Materials as a Surrogate Microbial Barrier.

ISO 11607 Packaging for Terminally Sterilized Medical Devices indicates all sterilizable medical packaging materials need to provide an effective microbial barrier. The method traditionally used to determine if packaging materials meet this requirement has been ASTM F1608, Microbial Ranking of Porous Packaging Materials, and DIN 58953-6.  But the lesser known ASTM F2638 is well suited to testing the filtration efficiency of the new Tyvek material, and should be considered as a viable test option.

ASTM F2638:

  • Intended for porous package testing
  • Is performed using a wide range of flow rates to more accurately mimic real-world exposure
  • Provides quick test results (same day)

ASTM F2638 is a nice addition to the family of package testing methods, as it tests materials at real world flow rates. Or in other words, the standard recommends rates that are more representative of the level of exposure the packaging might endure in a real world setting. It also offers immediate results. Unlike test methods which use live organisms to test filtration efficiency, and therefore need an incubation period, ASTM F2638 uses particles, which means evaluation is based on particle counts which need no incubation, giving a speedy result.

Nelson Labs offers clients unique access to both ASTM filtration efficiency test methods (ASTM F1608, and ASTM F2638), and has the experience and resources to perform the lesser known ASTM F2638 test.  Contact Nelson Laboratories to discuss your package testing needs –, 801-290-7502. You may also be interested in watching Developing Your Packaging Validation and Plan, a complimentary on-demand medical device packaging webinar.

About Craig Fisch: Craig Fisch is a Study Director at Nelson Laboratories. Craig is an expert in ASTM F2638 material qualifications and container closure integrity (CCI) testing. Since 2012, he has overseen integrity testing (ASTM F1929, ASTM F2096, CCI by Dye Immersion), microbial barrier testing (ASTM F2638), and the accelerated and real time aging processes (ASTM F1980) in Nelson Laboratories’ packaging department.