At their core, IVD studies are not significantly different from other medical device studies, as they aim to gather evidence about the safety and efficacy of a product in an ethical manner. The FDA classifies IVDs as reagents, instruments, and systems used in the diagnosis of diseases and the determination of a state of health. This can include products which are used to collect, prepare, or examine specimens from patients.

From the FDA’s perspective, IVD studies can be exempt from IDE requirements (21 CFR 812) under certain circumstances when all the following criteria are met: the IVD itself is non-invasive, the IVD does not require an invasive sampling procedure that presents significant risk to the patient, the IVD does not introduce energy into a subject, and the IVD does not stand alone as a diagnostic product or procedure. If all the above criteria are met and the investigational device is properly labeled, an IDE exemption can be obtained.

It’s important for medical device companies to understand exactly what the FDA is referring to with each of the specific IDE exemption requirements. An IVD is considered ‘non-invasive’ if it does not actually pierce or otherwise enter the body past certain limits if introduced via a canal or cavity. Testing that requires blood drawn from a vein is also considered non-invasive, as well as the use of ‘surplus’ tissue and fluid samples gathered for non-investigational purposes.

Likewise, the FDA considers an IVD that poses ‘significant risk’ to a study participant to be any device that plays a substantial role in determining or treating a health condition, or which could itself be detrimental to the health of a patient. This includes the potential for misdiagnosis resulting from IVD use and false positive results that can lead to unnecessary confirmatory testing and/or treatment. IDE exempt trials must not rely on any data gathered during the course of testing to make treatment or clinical decisions. Instead, personnel must employ an already-established means of diagnosis when managing the health condition in question.

All IVD studies must follow FDA labeling requirements, with the device in question bearing a disclaimer that states “For Investigational Use Only – The performance characteristics of this product have not been established.” IVD studies must also adhere to the same human subject protections as any other clinical trial as described in 21 CFR, Parts 50 and 56 (“Protection of Human Subjects” and “Institutional Review Boards”). This includes the de-identification of any leftover human specimens.

In our next post in the IVD series, we will take a look at protocols, plans, and data validity as applied to IVD studies.

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Lisa Dye
Benjamin Hunting
Aptiv Solutions Blogging Team

In June of this year, the FDA published the draft guidance, “Applying Human Factors and Usability Engineering to Optimize Medical Device Design,” which provides methods for identifying, evaluating, and understanding use-related hazards.

The advantages of optimizing device design through application of HFE/UE extend beyond improved safety. Many medical device manufacturers have found that the application of HFE/UE in the design of their products reduces the need for modifications and costly updates after market introduction and offers competitive advantages. With increased safety, the likelihood of incurring expenses associated with product recalls or liability is reduced; when HFE/UE approaches are used in the design of medical devices, particularly if the perspective of users is taken into account, the overall ease of use and appeal of a device can simultaneously be enhanced.

The draft guidance identifies the three steps to successfully incorporating HFE/UE into the design control process:

• Identify anticipated use-related hazards and unanticipated use-related hazards and determine how hazardous use situations occur.
• Develop and apply strategies to mitigate or control use-related hazards.
• Demonstrate safe and effective device use through human factors validation testing.

Information on how to follow these steps is provided in the guidance and gives the industry an insight into the process.

Aptiv Solutions can assist medical device manufacturers with incorporating HFE/UE into their design controls process and can assist them with our contacts with companies that conduct human factors and usability testing.

Benjamin Hunting
MDCI Blogging Team

According to The New York Times, $3.3 million in political donations have been made by financial funds associated with medical device investment to both Democrat and Republican candidates and committees since 2006.  The Times further clarified that 20 percent of these funds were specifically earmarked for initiatives aimed at reducing the amount of FDA red tape required to bring a new product to market.  The latest embodiment of this sentiment has been the support thrown behind Representative Erik Paulsen of Minnesota, who is sponsoring legislation that would further streamline FDA approval of innovative medical devices.

This blog has covered the efforts of Representative Paulsen and other members of Congress in the past.  Information concerning the increased attention being paid by the investment community to the medical device approval process is new and indicates that the FDA could be facing a multi-pronged offensive on the part of companies, financial institutions, and practitioners who want easier access to potentially revolutionary medical technologies.  Both the Senate and the House of Representatives have seen an increase in the number of bills introduced that are aimed specifically at accelerating FDA approval of medical devices, while the number of public hearings concerning the same regulatory procedures also continues to grow.

Protecting public health remains the number one concern at the FDA, but the Administration is also actively seeking to do what it can to balance the need to approve advanced, cost-saving treatments and devices with its duty to keep Americans safe from the harm that could be caused by inadequately tested products.  There is also the question of whether the interests of venture capitalists have taken into account the broader scope of the medical device safety issue, given that typical investment strategies involve cashing out after a product has initially hit the market.  One thing is certain: with so much dialogue sparked concerning FDA regulatory and approval practices, the current atmosphere in Washington could be more primed than ever for an evolutionary step forward in medical device regulations.

Benjamin Hunting
MDCI Blogging Team

Several interesting points were made within the “Pulse of the Industry” report that indicate the direction in which the medical device business specifically, and healthcare in general, is moving.

A renewed emphasis on outcomes will require that companies shift their focus from moving as many units as possible to marshalling the resources needed to demonstrate definite improvements in health outcomes for a specific product. Advertising and promotion of medical devices will by necessity move to complement this new approach, which could very well become the yardstick by which an organization’s success is judged in the industry – especially with regard to hospitals and health care decision makers increasingly restrained by smaller purchasing budgets.

Medical device companies will also face a challenge in sustaining innovation in the face of a dramatically changing financial and regulatory environment.  Over the course of 2010, global medical device venture capital investment dropped by 13 percent compared to 2009.  The effect was even more pronounced in the United States, which saw a 15 percent reduction in venture capital financing during the same period.  Combined with pricing pressures and an uncertain future regarding the FDA regulation of high tech medical devices, developers will have to make strategic choices concerning the amount of investment made in uncharted areas of the industry.

With these challenges and uncertainties, innovative device developers can benefit by taking a “phased,” or step-wise, approach through the FDA process. By investing in an initial FDA regulatory strategy/review, which may include a pre-IDE or pre-submission meeting, companies can take the first steps to build a positive relationship with their future FDA review team. They will also have an objective outline of their expected regulatory pathway, including FDA concerns and issues and top-level budgets for collecting the most useful clinical data to present to future investors and partners.

Benjamin Hunting
MDCI Blogging Team

Some medical device companies may have initially passed over the FDA announcement as it was described as being applicable specifically to drug trials as described in the Food and Drug Administration Amendments Act 801(b)(3)(a).  However, the FDA has stated that the Final Rule, which went into effect March 12, 2011, applies to both medical device trials and clinical drug trials, with only a few exceptions.  The specific regulation can be found in 21 C.F.R. Part 50.25.

What does this mean for medical device companies currently in the process of organizing a clinical trial?  At the outset, it means that all informed consent forms must include the following text, supplied by the FDA:

“A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law.  This Web site will not include information that can identify you.  At most, the Website will include a summary of the results.  You can search this Web site at anytime.”

Trials which are already underway will not be required to re-consent participants in order to incorporate the modified forms.

The law, which comes with a one-year grace period for implementation, assigns the responsibility for collecting informed consent to a trial’s investigator.  However, medical device companies should take note that once the forms have been gathered, it is usually necessary for the trial’s sponsor to take the initiative in posting the trial description information to ClinicalTrials.gov using the Protocol Registration System (PRS).  Moving forward, this simple added step should not be overlooked by medical device manufacturers engaged in clinical trial research.

Benjamin Hunting
MDCI Blogging Team

According to an article published by MDDI Online, on average small medical device companies found themselves in the pre-IDE stage 3.4 months longer than their larger counterparts.  Even more startling is the fact that larger companies faced close to 50 percent less 510(k) review time (330 days for organizations with fewer than 100 employees, 177 days for those with more than 100 employees).

The Medical Device Manufacturer’s Association (MDMA) claims that this disparity in approval times is driving more and more product launches to the European market, where well over 60 percent of small medical device companies are successful in their pursuit of initial clearance.  Exported product launches bring with them exported jobs and a brain drain of institutional knowledge that could end up staying in Europe in order to continue to benefit from the more welcoming regulatory environment that it has to offer.

The FDA has publicly stated that one of the biggest reasons for increased delays during the 510(k) medical device approval process has to do with the amount of time that companies take to respond to information requests on the part of the Administration.  This reality affects both large and small medical device manufacturers, but larger companies have greater resources to draw on in addressing these requests, which puts them in a better position to move through the pre-IDE process more quickly.  Big medical device manufacturers are also typically more capable of absorbing the financial burden of medical device approval delays due to their more diversified cash flow situations.

The FDA argument regarding the quality of 510(k) submissions and the increased need for additional information to clarify incomplete or confusing applications is nothing new.  The unbalanced effect that current FDA review and clearance practices has on smaller medical device companies, however, is alarming.  Smaller companies spearhead innovation, and given that the industry is currently up in arms over regulatory hurdles that are pushing more and more researchers out of the U.S. and into Europe and Asia where product approval is quicker and more efficient, the impact of these 510(k) delays cannot be overstated.  The FDA might call for higher quality submissions as a solution for rectifying the situation, but the focus on this one particular symptom of what is currently wrong with the pre-market approval process runs the risk of missing the bigger picture implications of maintaining the status quo in the American market.

Benjamin Hunting
MDCI Blogging Team

AdvaMed called its recommendations a “Competitiveness Agenda,” which is designed to ensure that future medical device innovations are not driven to move outside of the United States but continue to be developed by American companies. Divided into six main points, the Competitiveness Agenda is intended to balance the need to protect the health and safety of the public while ensuring that the pace of technological development is not unduly slowed by an inefficient regulatory bureaucratic process.

Of the six main policy recommendations made by AdvaMed, three were directed specifically at the legislative and regulatory apparatus at the federal level. AdvaMed called on the FDA to reduce the amount of time taken to review and approve medical devices, have the government formally prioritize health and life science innovation, and tailor Medicare and Medicaid reimbursement policies to provide financial support for new treatments. At the same time, private insurers in the U.S. must also be encouraged to develop a more open mind towards the same types of innovative devices.

The second half of AdvaMed’s recommendations focused on the economic aspect of medical device innovation. The Agenda advocated both the adoption of tax policies and credits that favored technological research and development, as well as an increased investment in America’s scientific infrastructure in order to create an environment where discoveries can be brought to market quickly and efficiently. AdvaMed would also like to see the U.S. government take a hard look at its current foreign trade policies and do what it can to influence favorable conditions for American manufacturers and exporters.

There is no question that these recommendations represent sweeping changes from both legislative and procedural perspectives within the medical device industry. The call for changes to America’s economic policies – especially during a time when it is difficult to find a sector of the economy that is not struggling due to the recent financial crisis – could also be seen as a tall order. It is impossible to deny, however, that the United States is running the risk of falling behind Europe and other major medical device development centers in terms of innovation. AdvaMed – and MDCI – feel that it is far from too late to intervene and reconfigure the current medical device environment to foster technological development and improve regulatory policies.

Benjamin Hunting
MDCI Blogging Team

The FDA divides reusable medical devices into three categories according to the degree of risk of infection associated with the use of the device:

• Critical devices, such as surgical forceps, which come in contact with blood or normally sterile tissue.
• Semi-critical devices, such as endoscopes, which come in contact with mucus membranes.
• Non-critical devices, such as stethoscopes, which come in contact with unbroken skin.

The FDA is focusing this new initiative on critical and semi-critical medical devices that are intended for reuse after reprocessing. However, MDCI believes that non-critical devices will be expected to comply with the spirit of the new initiative even if all of FDA’s recommendations will not be applicable.

The FDA’s initial guidance for reprocessing reusable medical devices was released on February 27, 1996. In the intervening years, innovation in the medical device industry has increased the number and complexity of reusable medical devices on the market. However, a complex design often makes adequate reprocessing difficult to achieve, and the science of reprocessing has not kept pace with the speed of design innovation.

The FDA has become concerned with the number of well-publicized incidences of patient infection attributed to faulty reprocessing. In a statement made to before the Committee on Veteran’s Affairs, United States House of Representatives on May 3, 2011, Anthony D. Watson, BS, MS, MBA (Director, Division of Anesthesiology, General Hospital, Infection Control, and Dental Devices Office of Device Evaluation) pointed to 80 adverse event reports involving inadequate reprocessing and 28 reports of infection that may have resulted from inadequate reprocessing that were filed with the Agency from January 1, 2007, to May 11, 2010.

FDA Launches Reusable Medical Device Reprocessing Improvement Initiative

On April 29, 2011 the FDA launched the reusable medical device reprocessing improvement initiative and announced a public workshop to collaborate with representatives from other stakeholders, government agencies, manufacturers, and health care providers on future device design and scientific advances in reprocessing. In advance of the workshop, the FDA released an updated guidance document, Draft Guidance for Industry and FDA Staff – Processing/Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling (issued May 2, 2011). This document provides recommendations for developing appropriate reuse instructions to be developed for reusable medical device labeling, and also outlines the validation of these instructions. Areas of particular interest in the guidance include the following:

• Step by step instructions for disassembly and reassembly.
• Identify and address known post-market human factors issues with the reprocessing of your device or similar devices. This requires a search of a number of resources including internal complaints, published clinical literature, and the FDA MAUDE database.
• Validation of reprocessing instructions to ensure that end users can understand and follow them. This is not a validation of the capacity of your reprocessing instructions to successfully clean and sterilize the device. This is a human factors assessment that is used for validation of the usability of the instructions.
• Inclusion of reprocessing risks in risk analysis.
• Addition of reprocessing items to design inputs.
• Addition of validation of reprocessing instructions to design outputs.

The new guidance contains a flowchart that includes an overview of the steps involved in reusable medical devices, and it also reproduces FDA-accepted steam sterilization cycle parameters and provides a thorough list of useful references.

Highlights of Public Workshop

At the reprocessing reusable medical devices workshop, the FDA provided a historical perspective on the issues involving inadequate reprocessing, explained the rationale behind the new initiative, and reviewed the draft guidance point by point. One of the most thought-provoking presentations was given by Linda Condon of Johns Hopkins University Hospital. She brought home the challenges healthcare facilities encounter on a daily basis – specifically, the need to effectively reprocess a vast number of medical devices from different manufacturers in the face of outdated, impractical reprocessing instructions, inadequate personnel and facilities, and tremendous time pressures. Other presentations focused on how to properly integrate effective reprocessing into a manufacturer’s quality system, techniques for monitoring reprocessing of complex instruments, and tips for ensuring the efficacy of reprocessing procedures.

Next Steps

On October 11-12, 2011, the FDA and AAMI will co-host a summit on reprocessing. The FDA intends to continue to engage with stakeholders on this issue, and the Administration recognizes that while they can provide guidance documents on device design and the development of effective reprocessing instruction, medical device manufacturers must take the lead and actually implement these recommendations in order to make substantial progress toward the goal of improving medical device reprocessing.

MDCI is uniquely positioned to support medical device manufacturers in the development and validation of reprocessing instructions. MDCI has a broad product experience with reusable non-critical, semi-critical, and critical medical devices. In addition, MDCI has extensive experience with infection control devices (sterilization wraps, process indicators and sterilization technologies) that are required for reprocessing reusable medical devices. Finally, MDCI has developed partnerships with commercial testing facilities and human factors firms with expertise in the procedures involved for the analytical and usability elements of validation of reprocessing instructions.

Lisa King
Cindy Nolte
Suzanne Goodman
MDCI Blogging Team

What, exactly, is covered under the new draft guidance for mobile medical applications? The document applies to any app that is “used as an accessory to a regulated medical device,” or that “transform(s) a mobile platform into a regulated medical device,” excluding apps designed to provide reference materials, log or affect general health, fulfill an administrative role, or which function as a health record system. More specifically, the FDA is looking to regulate medical device apps that display, store, analyze or transmit “patient-specific” medical device data, apps that incorporate functionality similar to currently regulated devices or which integrate with these devices as controllers, and apps that are designed to assist in making clinical or patient health-related decisions via the processing of patient information.

What are some examples of the types of apps that would fall under the heading of these new regulations? The guidance document mentions remote patient-specific data display apps, apps that can control insulin pumps or interact with sensors while gathering patient information, and apps that provide a prognosis based on patient symptoms and other information.

The FDA has stressed that the draft guidance refers exclusively to mobile medical device apps and also that the Administration is not finished with its evaluation of the mobile app spectrum. At a meeting of the California Healthcare Institute this past month, an FDA spokesman indicated that the 510(k) process would eventually only apply to a small subset of anticipated future medical device apps.  Additional mobile medical device use scenarios will be addressed by their own specific guidance documents. The current draft guidance is subject to a 90-day comment period, which will begin this month.

With an estimated 200 million mobile health applications currently available, this area of the medical device industry will require significant federal resources to properly regulate while still maintaining the growth and innovation required to provide Americans with an affordable and safe level of health care. The FDA expects 500 million smartphone users to have medical device apps on their platforms within the next four years, with half expected to be personal monitoring devices.  MDCI will continue to keep a close eye on this impending legislation, as well as any future regulatory changes targeting mobile medical device apps.

Benjamin Hunting
MDCI Blogging Team

Rosina Robinson has been active in regulatory affairs and healthcare delivery for more than three decades, and in that time she has put together over 50 510(k)s as well as many PMA and PMA supplements across a wide range of different medical device product categories. Robinson will be bringing her unique insight to bear on the IOM report by focusing on several important questions and concepts, including:

• Providing an in-depth explanation of the debate surrounding the current 510(k) process and the changes that it has recently undergone.
• Taking a closer look at the IOM’s recommendations regarding the 510(k) process, and examining how they could affect individual companies and the medical device industry as a whole.
• Examining the potential impact of the IOM suggestions on legislative, regulatory, and administrative facets of current FDA policy.
• Providing an assessment of how the IOM report’s recommendations could influence future changes to the 510(k) process.

The webinar will take place tomorrow, August 24, 2011, at 2:00 pm ET/1:00 pm CT/12:00 pm MT/11:00 am PT. The webinar is 90 minutes long and can be accessed at the following URL: http://www.thompsoninteractive.com/site/offer.jsp?promo=00119475&priority=00295701252.

Benjamin Hunting
MDCI Blogging Team