Stuart Hart, MD, MBA, MS, FACOG, FACS

Dr Hart is Chief Medical Officer of Innovation, USF Health Center for Advanced Medical Learning and Simulation (CAMLS), Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology, University of South Florida Mor

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	Dr Hart is Chief Medical Officer of Innovation, USF Health Center for Advanced Medical Learning and Simulation (CAMLS), Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology, University of South Florida Morsani College of Medicine, Tampa. He reports receiving salary/honoria and fees from Covidien and Boston Scientific, and performing contracted research for Cooper Surgical, Covidien, and Stryker.

	Dr Armstrong is Preclinical Research Administrator, CAMLS Innovation Center, USF Health, Tampa. He has no conflicts of interest to report with respect to the content of this article.

	Physicians provide knowledge, technical expertise, and clinical experience to invent and innovate medical devices. The importance of the physician’s contribution to this process, although long implicitly understood within the medical community, was recently objectively demonstrated in a study that showed that physicians participated in approximately 20% of the 26,000 medical device patents filed in the United States from 1990 to 1996.

 These patents received higher generality scores (representing the breadth of the patent) and on average 2.5 more citations than non-physician-generated patents. This study confirmed that “physicians are deeply engaged in the discovery stage” of medical device innovation.

	Ob/gyns are especially well positioned to identify clinical problems representing unmet medical device needs because they treat a variety of medical and surgical patients. It is not uncommon for ob/gyns to experience many “eureka moments” during their careers, when they feel that they have just come up with the next multimillion-dollar invention. Many physicians do not realize that the path to commercialization of a medical device is oftentimes arduous and expensive, and requires knowledge of business, law, engineering, and regulations.

	Invention and innovation are not synonymous. Invention is the “eureka moment” when you dream up the next great medical device, and any subsequent work that goes into developing the idea, such as creating drawings or building a prototype.

	Invention transforms into innovation when this new idea is used to develop a useful device that enhances patient care, improves performance of a surgical procedure, reduces costs, or improves access to care in underserved areas. Thus, innovation (bringing a device to market), and not just invention (the idea), creates true value.

 Invention takes resources (time, money, expertise, etc.) to create, whereas an innovation creates value (improved outcomes, revenue, etc.).

	So how can physicians who have great ideas for new devices become innovators by successfully commercializing their concepts? Although the process of commercializing a medical device can be overwhelmingly complex, here we provide a general overview to help clinicians develop a basic understanding of the process.

	Once you have an idea for a new medical device, investigate its viability. Many factors are important to the success of a new medical device, ranging from creating a financially sustainable business model to obtaining intellectual property to protecting the idea.

	Physician inventors also need to consider into what class their devices fall. A device’s classification determines the regulatory requirements for FDA approval to sell and market it in the United States. The goal of FDA approval is to determine whether a device can be used safely and effectively according to its intended indication. Therefore, classification is risk-based and depends on reasonable assurance of safety and effectiveness.

	Class I devices pose the lowest risk, and Class III devices the highest. Regulatory requirements thus increase by class. All medical devices are regulated under General Controls, which include registration of the devices and manufacturers, conformance with Good Manufacturing Practices, maintenance of appropriate records and reports, and assurance that the devices are not adulterated or misbranded. Additional controls are required for Class II and III devices (Table 1). The FDA website provides extensive information on these requirements.

	An appropriate Intellectual Property (IP) strategy is important to ensure that the device does not encroach on a previously granted patent while providing the developers with the right to exclude others from making and selling it. A US patent does not grant the inventor the right to make his or her device, but rather, the right to exclude others from doing so.

	Filers should survey previously granted patents and the medical literature for any “prior art” that could be used to disqualify a patent application. Prior art entails any knowledge available to the public, including previous US and international patents, previously disclosed research, or concepts in the medical literature or public domain. The device must be useful, new, and nonobvious to a person having ordinary skill in the area of the invention. A US patent grant term is 20 years from the date of filing of a nonprovisional patent application.

	A typical strategy for IP protection is to first file a provisional patent application because it is relatively inexpensive, does not require the filer to determine the claims of the patent, and establishes an early filing date with a 12-month priority benefit. Because the lifespan of a provisional application is just 12 months, in order to continue to pursue patent protection, a nonprovisional patent application must be filed before the provisional one expires.

	While you may choose to simply file a US nonprovisional patent application (the United States is usually the largest market), you may also file an international patent application, known as a PCT application. In 2013, the United States transitioned from “first to invent” to “first to file.” Under this system, if 2 inventors simultaneously invent the same device, the US Patent and Trademark Office (USPTO) will determine priority based on the filing dates, rather than the date of the invention.

	While anyone can write, file, and receive a patent, most investors will need legal counsel before funding a startup company based on a medical device idea. A full patent can take several years to be granted and cost tens of thousands of dollars in legal and filing fees, but it is highly recommended to use a patent attorney when commercializing or licensing a device. The cost of a patent is relatively small compared to the total cost of commercializing a device. It will also provide some legal protection against imitators even during the patent-pending phase.

	If you have determined that your idea is viable, the next step is to transition into the Research and Discovery (R&D) phase. Key components for a successful R&D phase are building a multidisciplinary team, designing, prototyping, proof-of-concept testing, and iterative redesigning. Closely monitor your budget during this phase because the costs can escalate quickly. The initial R&D phase is considered “nonregulated,” meaning that design and testing do not need to be controlled under a Quality System.3

	For most physician inventors, funding is limited for the R&D phase, which can make affording a large design team challenging. So, the first major decision a physician inventor has to make is whether to hire his or her own development team or use a medical device engineering company or consultant. Each approach has pros and cons, so speak with multiple experts to determine which approach is best for you. In either case, the team should be composed of people with expertise in at least these areas:

	• Human factors engineering and usability 

	• Clinical and scientific knowledge in the medical field of intended use  

	• Regulatory affairs and quality assurance

	• Intellectual property and business law

	When looking for team members, first evaluate your own skills. Do you have a business or engineering background that supplements your clinical expertise? Next, look for partners who can fill expertise gaps. Many experienced medical device professionals will lend their expertise in exchange for an equity stake in your venture. The technology underlying your device will determine the level of expertise needed within the team.

	If you have a complex product, such as a Class II combination product that includes a mechanical design and drug delivery system, the engineering and scientific expertise needed will be quite different from that needed for a simple Class I device.

	Because the exploratory R&D phase is not regulated, many first-time inventors neglect the regulatory and quality assurance requirements early in the process. Involving regulatory and quality experts from the beginning will save time and money later as the project enters the regulated Design & Development phase, which will require compliance with FDA and international regulations.

	During the R&D phase, the focus should be on prototype function, not necessarily aesthetics (design and performance characteristics will be refined later). Computer-aided design (CAD) software often is used to develop 3D models of a prototype. Identify the most appropriate prototyping method for the project, because cost and functionality vary greatly depending on the method.

	Proof-of-Concept (POC) testing of the prototype determines if the device can function as designed. Initial POC testing is generally done using benchtop engineering. For example, if a device is designed to clamp an artery without causing damage, the POC testing may include repeatedly clamping a simulated vessel containing a pressure transducer to show that the maximum pressure did not reach the threshold for vessel damage.

	If the prototype does not pass POC testing, a second round of design and prototyping may be needed. The process of revising the prototype design in response to test results is called iterative redesign. It is always more cost-effective to make design and functional changes early on.

	At this point, there should be enough information to define the general characteristics of the device, which will later become the design and performance specifications in the Design & Development phase. These specifications will then guide the development and testing processes and substantiate the claims on your device for regulatory approval. Now that you have a functional prototype and have reached the end of the R&D phase, determine whether you want to proceed with commercialization.

	To proceed with commercialization of your device, you must enter a process strictly governed by a Quality Management System (QMS), which is a framework of policies and procedures for how products are developed and manufactured. This system is regulated by the FDA’s Good Manufacturing Practices.9 A QMS guides the entire development process, resulting in a Design History File (DHF). The DHF is the compilation of all design, testing, and manufacturing information related to the final product. A regulatory agency such as the FDA can then audit the DHF and the facilities that helped develop and manufacture the device to ensure that the product is safe and effective.

	Design control documents specify each function the device will perform and the corresponding engineering specifications (ie, “the device will atraumatically grasp a vessel” and ”the maximum compressive force shall not exceed 10 N”). These specifications are often modified throughout the development process, but the changes must be properly performed and documented according to a QMS for later review by regulatory agencies.

	For example, if an initial engineering specification states that the maximum force of a surgical clamp is 10 N but the force requirement is changed to 5N, testing must be performed and documented to demonstrate that the new design meets the new specification. This verification testing is a crucial part of the development of nearly every medical device. However, verification testing does not prove that the device meets the user’s requirements. Validation testing is used for that purpose. Think of the 2 types of testing in this way: Verification means the device meets design specifications and validation means the device meets user needs.

	Other types of testing that may be required include usability engineering/human factors engineering (UE/HFE), nonclinical testing, and clinical testing. Although it’s not a new field, UE/HFE has become increasingly important for FDA approval of medical device applications. The goal of usability testing is to understand how people interact with technology and to identify potential use error patterns that may harm users or patients. A use error is “an act or omission of an act that results in a different medical device response than intended by the manufacturer or expected by the user.” Usability testing evaluates the people who use the device, the device/human interface, and the overall environment in which the device is used.

	Nonclinical device testing is governed by Good Laboratory Practices (GLP) as well as other international standards.

 The term “nonclinical” or “preclinical” refers to testing that is performed on living nonhuman systems. In addition to the FDA regulations, the use of nonhuman subjects in medical device testing is dependent upon regulations and oversight by national and local organizations.

	Clinical testing of a medical device is regulated by the FDA through Good Clinical Practices (GCP).

 Testing involving human subjects is generally reserved for new and potentially dangerous medical devices. Before a medical device can undergo clinical testing, an Investigational Device Exemption (IDE) may be required by the FDA depending on whether it is considered a nonsignificant or significant risk device. Regardless, all clinical studies require Institutional Review Board (IRB) approval.

	Depending on the type of device, the FDA application will vary, as will the amount of required testing.

 Table 2 lists the regulations, FDA applications, and device classes associated with different types of testing.

	Once the DHF has been completed, you will need to obtain regulatory clearance to market and sell your device. In the United States, a medical device is required to follow the CFR and be approved by the FDA, which requires evidence that the device is safe and effective. In most other countries, ISO standards are used. In Europe, a CE mark denotes conformance with all European laws regarding the device. This is similar to receiving FDA clearance in the United States. Because demonstrating conformance to European directives is often more expeditious than the regulatory path in the United States, many medical devices enter the European market first.

	A review of 510(k) applications between 2010 and 2014 by the Emergo Group showed the average length of time to FDA clearance was 167 days, with a 22% chance of device clearance in 3 months, and a 61% chance in 6 months.

 Because the number of complex high-risk devices is growing, PMA applications took longer for approval-around 246 days in 2012, according to the Regulatory Affairs Professionals Society.

	While many applications are cleared on the first submission, the FDA frequently submits letters of deficiency to applicants who have not provided sufficient information. Once again, investing in a team with all the needed expertise, including knowledge of regulatory and quality assurance, will help ensure that the process is timely and cost-effective.

	The final phase of the medical device lifecycle is Post-Market Surveillance. The FDA requires that manufacturers monitor the safety and effectiveness of marketed medical devices and report that information to the FDA. The FDA tracks manufacturer-reported and publicly reported adverse events in the Manufacturer and User Facility Device Experience (MAUDE) Database. If significant post-market issues are noted, the manufacturer may be required to recall a device until there is sufficient evidence that those issues have been remediated.

	1. Chatterji AK, Fabrizio KR, Mitchell W, Schulman KA. Physician-industry cooperation in the medical device industry. 

	2. Barriers to innovation in the field of medical devices: background paper 6. World Health Organization, Geneva, August 2010.

	3. Overview of device regulation. FDA.gov. 

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/

	4. Classify your medical device: device classification panels. FDA.gov. 

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/ClassifyYourDevice/ucm051530.htm

	5. Learn if a medical device has been cleared by FDA for marketing. http://www.fda.gov/MedicalDevices/ResourcesforYou/Consumers/ucm142523.htm.

	6. General information concerning patents. USPTO.gov. http://www.uspto.gov/patents-getting-started/general-information-concerning-patents.

	7. America Invents Act (AIA) frequently asked questions. USPTO.gov. http://www.uspto.gov/patent/laws-and-regulations/america-invents-act-aia/america-invents-act-aia-frequently-asked.

	8. Mugan J. Prototyping: comparing prototype techniques. MDDI Medical Device and Diagnostic Industry News Products and Suppliers. 

	9. Good manufacturing practices. FDA code of federal regulations, title 21, part 820. 

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?cfrpart=820

	10. Draft guidance for industry and Food and Drug Administration staff-applying human factors and usability engineering to optimize medical device design. FDA.gov. 

http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm259748.htm

	11. Good laboratory practices (non-clinical testing). FDA code of federal regulations, title 21, part 58. 

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?cfrpart=58

	12. Device advice: investigational device exemption (IDE). FDA.gov. 

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/default.htm

	13. Information sheet guidance for IRBs, clinical investigators, and sponsors: frequently asked questions about medical devices. FDA.gov. 

http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf

	14. CFR-Code of federal regulations title 21. FDA.gov. 

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=814&showFR=1

	15. How long it takes the FDA to “approve” a 510(k) application. Emergo Group. 

http://www.emergogroup.com/resources/research/fda-510k-review-times-research

	16. FDA data show the worst is over for 510(k), PMA applications. RAPS.org. 

http://www.raps.org/regulatoryDetail.aspx?id=8533

	17. Device post-market surveillance. FDA.gov. 

http://www.fda.gov/MedicalDevices/Safety/CDRHPostmarketSurveillance/default.htm

Articles

Financial sustainability, intellectual property rights, and protection of the idea are all considerations for physician inventors who want to create new medical devices.

Author | Stuart Hart, MD, MBA, MS, FACOG, FACS

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