For Medical Device

Uncertain Times for Medical Devices - Regulatory and Clinical Advice
by Ron Warren, Principal Consultant, Regulatory Services, Medical Device Consultants, Inc.

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There is no shortage of discouraging news these days for the medical device industry. We continue to hear how the recession is curtailing investment and venture funding of new medical technologies. Many start-ups find they are unable to attract new funding for projects or have to delay major expenditures for product development. Moreover, FDA is under new leadership and promising increased enforcement in food and drug programs and is taking a hard look at device programs, particularly the 510(k) process. Despite the headlines, there are activities that can be completed to keep your device development process moving forward.

A pre-IDE meeting with CDRH is particularly important in the current environment at FDA.

Although the economic downturn has put increased pressures on medical device companies to curtail spending and has limited the available sources of venture funding, there are opportunities to continue product development activities while avoiding significant capital expenditures. Given the lengthy approval process for many devices, it is prudent to continue to add value to the technology and demonstrate incremental progress toward premarket review and approval. To that end, there are numerous regulatory and clinical activities that may be undertaken that do not necessarily require large outlays of capital to complete. Even though the U.S. regulatory environment for devices is in midst of potentially significant changes as FDA examines its policies and programs, taking steps to add a degree of clarity to your product development pathway may be helpful in attracting investments for your product.

Get Early Informal Feedback from FDA

In regard to regulatory tasks that may add value, a firm may consider conducting a pre-IDE meeting with CDRH. For fiscal year 2010, there are no user fees to have a pre-IDE meeting and the pre-IDE process provides an opportunity for a company to meet informally with the FDA review staff to gain a better understanding of the regulatory pathway for a particular device, especially one that offers new technological features or new intended uses. The process usually results in the company having a better grasp of the preclinical and clinical testing required to support the FDA review process. The pre-IDE process can normally be completed in 60 to 90 days and will allow a company to describe the regulatory pathway with more clarity to potential investors.

This process is particularly important in the current environment at FDA. In September, the FDA commissioned the Institute of Medicine to evaluate the premarket 510(k) clearance process. This is in response to reports from within CDRH that certain products were allowed by Agency management to be cleared through the 510(k) process rather than the more stringent PMA process recommended by CDRH review staff. Despite this uncertainty it is imperative for device companies to continue developing and maintaining a collaborative approach with CDRH for new medical devices. The pre-IDE process remains a valuable tool in getting early FDA feedback on key issues particularly for innovative devices in which there are no obvious predicate devices or for new intended uses. Topics that are typically addressed in the pre-IDE process include:

  • Need for further pre-clinical testing
  • Comments on clinical study design
  • Suggestions on proposed indications for use
  • Need for feasibility or pilot clinical studies
  • Suggestions on preclinical testing
  • Discussion on proposed regulatory pathway
  • Whether planned studies are significant risk

While the pre-IDE process is non-binding and informal, it provides a device sponsor the opportunity for early collaboration with CDRH. This interaction is important because a device company can get more clarity of the likely data requirements and review process before making significant expenditures for preclinical and clinical studies. More importantly they can get some insight into whether a new product is a likely candidate for a 510(k), or because of technological features, device risks or labeling claims, the agency is more likely to require a PMA.

Product Modifications vs. Original Submissions

For device manufacturers with existing medical devices, a cost-effective option for product development is to consider product enhancements or added features rather than bringing a brand-new device to market. When faced with economic pressures and an uncertain regulatory landscape, a useful approach is to make incremental modifications to an already cleared or approved product. A number of changes to an existing product might be possible without the need for a new regulatory submission. These might include minor design changes that improve the reliability of the product or reduce the costs of manufacturing (e.g, a new source of raw material). The FDA has guidance documents that provide help in deciding when a device modification should trigger a new submission. Product and process changes that might be considered to help improve the company bottom line include:
  • Process changes to reduce scrap rates or improve reliability
  • Evaluation of lot size, QC sampling requirements
  • Qualification of alternative suppliers for lower cost raw materials
  • Extension of shelf-life for in process manufacturing materials and final product

From a regulatory perspective, the company can be strategic and creative in its approach to managing the change process. First and foremost, the company needs to establish a documented change control policy through which it consistently evaluates whether the proposed change could affect the safety and effectiveness of a device. This policy needs to take into account the FDA guidance on 510(k) and PMA changes but also needs to be linked to a well-defined design control system. From there the company can evaluate all planned changes to a product or process and strategically decide which changes could be made with appropriate testing and documentation and which changes would more than likely require a new 510(k) or PMA Supplement. In this regard the company can make minor incremental changes to existing products and submit new 510(k)s or PMAs at defined stages of development when the economic or regulatory environment is more favorable.

Start Building Quality System Infrastructure

Another opportunity to advance device development during these challenging economic times is to put incremental efforts into building an infrastructure for quality systems and documentation processes which are critically important to maintain compliance with Quality System Regulations once the device is marketed. At the early stages of development it is prudent to put in place a design control process to document the key design decisions and risk evaluation that will drive the preclinical testing and clinical testing strategies. These documentation activities have the added value of organizing and structuring the key design assumptions, early verification testing results and other development activities so that they are easily retrievable and accessible to those considering investment in the new device. Whether to increase the value of the business or maintain regulatory compliance, developing an infrastructure for quality systems provides a number of benefits including:
  • Formalizing the Design Control Process which is a key system for QSR and ISO
  • Setting the stage for ISO Certification important for international markets
  • Good documentation practices to enhance and complement your intellectual property
  • Establishing a culture of compliance to support the science
  • Creating an infrastructure that protects against business disruptions due to complaints, recalls or regulatory actions

Many small companies view Quality Systems as another burden in an already daunting product approval process. However, long-term success is enhanced when companies embrace quality system requirements to create value and strengthen operational excellence.

Feasibility Studies to Establish Proof of Concept

In regard to clinical studies, the multi-center, randomized, controlled investigation remains the gold standard for Class III devices, yet they are quite expensive to conduct. As an alternative, a firm may consider running smaller pilot or feasibility studies. These studies would require less expenditure but would afford the opportunity to gain early insight into the appropriate intended uses or patient populations for which the device is best suited. Pilot studies provide early evidence of safety, establish preliminary data on effectiveness and positive results help build the case for pivotal study investment. In many cases, a company is eager to start clinical evaluations as soon as possible. However, taking some time to carefully consider the clinical approach may save time and money in the long term. Important questions to consider include:
  • Is the sequence of studies in the program mapped out?
  • Any useful human data available (safety and/or effectiveness)?
  • What are the relevant study endpoints (that match the regulatory strategy)?
  • Is there any controversy about how endpoints are measured?
  • Are the endpoints clinically "relevant" and intuitive?
  • Has a clinically meaningful outcome ("success") been defined?
  • What is the best study design?
  • What sample size is needed for the chosen design?

Having addressed these questions the company would be in a better position to discuss the program with FDA at a pre-IDE meeting and will have a much more productive discussion with the CDRH review staff. This in turn gives the firm a much clearer picture of the likely regulatory pathway and milestones in the product development process.

While the product development, clinical evaluation and regulatory approval of medical devices requires substantial capital investment, the strategies and activities described here are just a few opportunities a firm should consider to add value to an emerging medical technology so that the company is well-positioned and more attractive for significant investment in pivotal clinical trials and regulatory approval efforts as the economic outlook improves.

Ronald S. Warren, RAC, CTBS (AATB), Principal Consultant - Ron has more than twenty-five years of regulatory and clinical affairs experience, with specific expertise in human-derived tissue engineered products and cardiovascular devices. He has coordinated and led multiple pre-IDE meetings and been involved in the submission and preparation of PMAs, 510(k)s, PMA Supplements, and IDEs for various clinical indications. He also has expertise in tissue establishment registration and Good Tissue Practice regulations. Prior to joining MDCI in 2006, he served as executive director, regulatory affairs and quality assurance for Smith & Nephew Wound Management and as head of regulatory affairs at Advanced Tissue Sciences, Inc. Prior to that, he was with Sorin Biomedical, Inc., where he managed regulatory and clinical activities for the company's complete line of cardiovascular and cardiopulmonary products including heart valves, catheters, oxygenators, and blood cardioplegia delivery systems. At Baxter Healthcare Corporation, Edwards Cardiovascular Surgery Division, Ron was responsible for clinical and regulatory activities supporting the company's prosthetic heart valves and biological vascular grafts. He holds a B.S. in biology from the University of California, Irvine and an M.B.A. from California State University, Long Beach. He is a certified Tissue Bank Specialist and is Regulatory Affairs Certified. Contact him at

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