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Medical Device

Evaluation & Regulation

Strengthening Our National System for Medical Device Postmarket Surveillance

Catherine Gebhardt

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Table of Contents

Introduction ……………………………………………………………………………………………………………… 3

Definitional Report ……………………………………………………………………………………………… 4-7

Glossary………………………………………………………………………………………………………….…….. 8-10

Informative Report ………………………………………………………………………………………….. 11-18

Set of Instructions ……………………………………………………………………………………………..….. 19

FAQs ……………………………………………………………………………………………..……………..….... 20-23

Works Cited ……………………………………………………………………………………………………… 24-25

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Introduction This report is provided by the U.S. Food and Drug Administration and the Center for Devices and Radiological Health. The Food and Drug Administration (FDA) is a sector of the United States Department of Health and Human Services. As a federal agency, the FDA is responsible for protecting and promoting public health through the regulation of food safety, prescription and pharmaceutical drugs and medications, vaccines, and for the purpose of this report, medical devices. The Center for Devices and Radiological Health is also responsible for protecting and promoting public health by assuring patients and providers have timely and consistent access to safe, effective, and high-quality medical devices. A medical device is an instrument used to diagnose, prevent or treat diseases and conditions. As opposed to medicinal products that treat the body through chemical action within or on the body, medical devices act in other ways. Medical devices vary in purpose and scope, but several examples include wheelchairs, pacemakers, hearing aids and prosthetic limbs. The design of medical devices constitutes a major sector of the field of biomedical engineering, and the process of designing manufacturing these devices has many stages of regulation and screening. The FDA classifies different classes of medical devices based on their complexity, characteristics and potential for harm if misused. In the United States, Class I devices are subject to the least regulatory control, Class II devices are subject to special controls for which general controls alone cannot ensure safety and effectiveness, and Class III devices are those for which general and special controls are insufficient. These devices need premarket approval in addition to scientific reviews to ensure safety and effectiveness. Regardless of the class designation of a medical device, it is required to go through postmarket surveillance (PMS). PMS is the practice of monitoring the safety of a pharmaceutical drug or medical device after it has been release on the market. PMS can further establish or refine the safety of a drug or device after it is used in the general population by large numbers of people with wide variations of medical conditions. Data gathered from PMS is reviewed to highlight potential safety concerns. This report seeks to establish a stronger system for medical device postmarket surveillance in the United States to further improve the effectiveness and regular monitoring of medical devices in our nation. By evaluating the current FDA medical device PMS system, a new and improved system is presented for future use.

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Definitional Report Medical Device

A medical device is a piece of equipment used to improve the lives of the users by diagnosing, preventing, and treating medical conditions. These instruments are very important to today’s medical field. Without them, numerous illnesses would go undiagnosed, treatments would not be done, and lives would be lost. Some examples of medical devices include wheelchairs, pacemakers, hearing aids and prosthetic limbs. Many things you see in a hospital or doctor’s office are also considered medical devices: tongue depressors, x-ray machines, and medical lasers. While drugs can be used to prevent and treat illnesses, they are not considered medical devices. A physician may use a tongue depressor to help diagnose someone with strep throat, a stethoscope to diagnose a cardiac problem, or an x-ray machine to diagnose a broken bone. The devices used to diagnose medical conditions may be simple (a tongue depressor) or complex (x-ray machine), but they are important no matter their complexity. After a medical device has been used to diagnose a patient, another device may be used to prevent a condition from occurring or reoccurring. For example, when a cardiac problem is diagnosed, a pacemaker could be put into place to prevent further complication. A shunt in the brain prevents a buildup of spinal fluid, and an insulin pump prevents the buildup of sugar in the blood stream by infusing the body with insulin. In this instance, the insulin pump is a medical device, however the insulin itself is not. When a medical condition has been diagnosed and can no longer be prevented, it needs to be treated, if possible. When the x-ray machine shows that someone has broken a bone, a cast can be used to hold the bone in place until it heals. The cast is an example of a medical device used for treatment. There are also medical devices that do not diagnose, prevent, or treat conditions, but merely help the user continue with their daily lives. Contacts, used to correct near-sightedness or far-sightedness, are an example of this type of medical device. Also, prosthetic limbs, canes, and walkers are in this category. Cosmetic medical devices, such as breast implants, braces, and dermal fillers, are also not used to diagnose, prevent, or treat medical conditions. Instead, these devices are used to enhance the user’s appearance. These medical devices are not necessary for the health or well being of the user. Businesses that are involved in the production and distribution of medical devices in the United States are required to register with the FDA on an annual basis. The business must pay a fee and submit a premarket submission number if the device requires premarket approval. This allows the FDA to prepare for and respond to public health

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emergencies by knowing the location of medical device related businesses and their manufactured devices.

Postmarket Surveillance

Postmarket: after something has entered the market Surveillance: the monitoring of behavior, activities or other changing information for the purpose of influence, managing, directing or protecting Postmarket Surveillance (PMS) is the process of monitoring the safety of a pharmaceutical drug or medical device after it has been released on the market and is accessible to the general population. For the purpose of this report, we will focus on PMS in terms of medical devices. PMS is an important aspect of the science of pharmacovigilance, which relates to the collection, detection, assessment, monitoring and prevention of harmful effects caused by pharmaceutical products. The etymological roots for the word "pharmacovigilance" are: pharmakon (Greek for drug) and vigilare (Latin for to keep watch). Essentially, PMS keeps watch for adverse effects caused by medical devices and is concerned with identifying potential hazards to minimize the risk of harm in the future. Postmarketing surveillance uses a number of approaches to monitor the safety of approved devices, including reporting databases, prescription and event monitoring, electronic health records, patient registries and record linkage between health databases. These data are reviewed to highlight potential safety concerns in a process known as data mining. In the United States, postmarketing surveillance falls under the jurisdiction of the Food and Drug Administration (FDA). The FDA also has a premarket review process that seeks to ensure risks associated with medical devices have been screened and minimized before the devices ever enter the market. However, once medical devices enter the market and are widely used by doctors or other healthcare providers with their patients, new issues arise. PMS serves as an additional safeguard in protecting patients that are treated using such medical devices. By continuing to screen and monitor the safety and effectiveness of these devices once they are on the market, the FDA can more quickly identify poorly performing devices, safety problems and potential unforeseen harms and risks associated with using such devices. This regulation process ensures the development of new devices or use of existing devices is safe and effective. Medical device postmarket surveillance presents unique challenges compared to drugs and biologics due to their greater diversity and complexity, the cyclical nature of product development, the learning curve associated with adopting the new technology and the relatively short product life cycle.

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In the wake of several high-profile questionable device performances, regulatory agencies are placing greater emphasis on postmarket surveillance as a way of handling and improving risk management procedures and protecting public health in the future.

Unique Device Identification

A Unique Device Identification (UDI) is an integral part of a well-organized and efficient post-market surveillance system of medical devices. At its most basic, a UDI is “a unique numeric or alphanumeric code that consists of two parts” that must be included on device labels and packages (UDI Basics). These parts are a device identifier (DI) and a production identifier (PI). The DI is used to distinguish the labeler of the device, and the specific version or model. This is the more general identifier to mark a category of medical devices. The PI is conditional, and it is used for more specific identification. Information on the PI can include the lot or batch number of a device, the serial number of a device, the expiration date of a device, the expiration date, or the “distinct identification code” that is required for biological material (UDI Basics). Using this two-part system, devices can easily be located by category and labeler, and then individually referenced or identified by the specific information on the PI. This will allow reports on faults in specific devices and bugs in categories of devices to be easily documented and filed. In order to promote a cohesive labeling system, the UDI’s will all be assigned by a system operated FDA-accredited issuing agency. (UDI Basics) There can be multiple issuing agencies at work, so long as each one has been approved by the FDA as able to satisfactorily label medical devices so they are each properly and uniquely identified. They will do so using the “Global Unique Device Identification Database (GUDID). This database will have a standardized set of elements for each UDI. The database only contains the DI, so the individual issuing agencies must generate the PIs. (UDI Basics) At the moment, there are three issuing agencies working to label UDI’s for the FDA (UDI Issuing Agencies). One final stipulation for UDIs is that they must be provided in two different forms. The first of these is plaintext, basic numbers and letters that are easily read and understood by humans. The second is a form using “automatic identification and data capture” (AIDC). This is defined as “any technology that conveys the UDI…in a form that can be entered into an electronic patient record…via an automated process” (UDI Basics). This means that the information contained in the UDI should be encoded in something like a label or a tag, anything that can be easily scanned and quickly entered into a computer system. This will aid efficiency in dealing with the large number of unique medical devices used across the country every day. A well-run UDI system is integral to the FDA’s plans for improving their post-market surveillance system. Without an easy way to categorize and identify medical devices both as individuals and as groups, there would be no organized way to file reports on medical devices to run the surveillance system, and the country would be left with

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useless groups of data with no connection to reality. The division of DIs and PIs in the UDI will help to organize the reports even further, as they will allow the surveillance system to organize reports first by category then by individual medical device, the same way a library organizes books by genre then by author. The labeling system together with the AIDC will allow the FDA to build an efficient and well-informed system.

Registry

A registry is a system that collects and maintains structured records on a specific disease, condition, procedure, or medical product for a specified time period and population. There are a number of different kinds of registries in the medical realm. Product registries include patients who have been exposed to a specific medical device, biologic, or drug product. Health services registries contain patients who have had a common procedure, clinical encounter, or hospitalization. Disease or condition registries are characterized by patients having the same diagnosis. Registries are generally run and organized by private organizations in the various sectors of health care. The FDA itself does not create nor maintain individual registries. Instead, they partner with numerous registries around the world to collect data and assess the performance of medical products and procedures. Doing so allows the FDA to create a history of, and find similarities in diseases or medical device malfunctions. The FDA has a set of guidelines and requirements for creating certain registries. Voluntary registries are not mandated to follow the guidelines but the FDA strongly encourages them to do so in an effort to make the process of data collection swifter. Well-designed registries provide unique insights into device performance and device-associated clinical benefits and risks. Patient information contained in each registry is kept private through a system of firewalls in the host’s main hard drives. Though the FDA stresses the importance of keeping registries, it does acknowledge that time need not be wasted creating registries for devices with well-understood benefits and risks. By maintaining registries for key products and new market releases, the FDA will be able to enhance the overall postmarket surveillance of these devices.

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Glossary Quantitative In terms of research, numerical or measurable data with information about quantities; information that can be measured and written down with numbers; as opposed to qualitative, which is relating to, measuring, or measured by the quality of something rather than its quantity. Directly Identifiable Patient Information Also referred to as personally identifiable information (PII); any information that can be used on its own or with other information from accessible sources to identify, contact, or locate or to identify a patient in context; it includes information that is linked or linkable to an individual; examples: full and common name, home address, email address, date of birth or birthplace, face, fingerprints or other genetic information, handwriting, telephone number, driver’s license number or vehicle registration plate number, social security number, credit card information, etc. Query Used in the context of a clinical trial for a request for clarification from a sponsor or sponsor's representative to an investigator on a data item collected for a clinical trial, to resolve an error or inconsistency discovered during data review; a request for information from a database; a form of questioning in a line of inquiry; can be used to call attention to an item in order to question its validity or accuracy. Data Transparency The ability to easily work with data no matter where the data is located or where it originated from; also the guarantee that the data you’re working with is accurate and from a legitimate source. Sentinel Initiative A proactive, electronic system that will allow the FDA to track the safety of drugs, biologics, and medical devices after they’ve reached the market by complementing existing systems the FDA already has in place; enables the FDA to query data and evaluate possible safety issues and health risks quickly and securely; launched in May 2008 and will be developed and implemented in stages. EHR (electronic health record)

An electronic version of the traditional health record that consists of a patient’s medical history, diagnoses, medications, immunization dates, allergies, etc.; allows a patient’s health record to be obtained instantly and securely to authorized users.

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Methodological Relating to a set of methods, rules, or ideas that are important to a science or art; pertaining to methods. Semantic text mining A method of using a computer program to quickly derive high quality semantic information from a text. Used by the FDA to identify “safety signals” or problematic patterns in medical device reports, semantic text mining will quickly run through thousands of reports, searching for predefined patterns that suggest problems with medical devices. Safety signal A signal is a pattern of associations or unexpected occurrences in large databases. A safety signal is any pattern found in a database that indicates a potential safety risk. For example, a pattern of a certain medical device systematically failing in specific environments. Repository A location where information is stored. Medical device reports would be separated into relevant information, which could then be located in a repository that anyone with clearance could access and draw data from. Note that the FDA does not want to create a repository of information, preferring to keep the data control local. Iterative Occurring in cycles. When a process or product is iterative, it tends to repeat itself in a cyclical fashion. Each iteration could potentially lead to an increase or improvement in utility, so iterative does not necessarily mean static. Generation In terms of evidence, the act or process of generating; origination, production, or procreation. Synthesis The combining of constituent elements of separate material or abstract entities into a single or unified entity. In reference to evidence, the collection of evidence and data from multiple sources.

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Appraisal The act of estimating or judging the nature or the value of something or someone. When used with evidence, a measure of it’s relevance, importance, and urgency.

Interoperability In healthcare, the ability of different information technology systems and software applications to communicate, exchange data, and use the information that has been exchanged.

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Informative Report FDA and Medical Device Regulation The FDA regulates a broad range of medical devices, including complicated, high-risk medical devices, like artificial hearts, and relatively simple, low-risk devices, like tongue depressors, as well as devices that fall somewhere in between, like sutures. FDA has authority to regulate medical devices before and after they reach the marketplace. When FDA reviews a medical device prior to marketing, the FDA will either:

1. "Clear" the device after reviewing a premarket notification, otherwise known as a 510(k) (named for a section in the Food, Drug, and Cosmetic Act), that has been filed with FDA, or

2. "Approve" the device after reviewing a premarket approval (PMA) application that has been submitted to FDA.

However, there is no such simple process for reviewing medical devices post-market. Because of the constant and increasing need for these medical devices, the FDA and regulatory agencies are primarily concerned with streamlining the path to market for medical devices and bringing safe and effective technologies to patients as quickly as possible, and are less attentive to post-market evaluation of these devices (Riley). While the current system emphasizes FDA review prior to marketing a medical device, the postmarket surveillance system has been largely neglected, leading to question whether the current PMS is optimally structured to meet the challenges of rapidly evolving medical devices and the changing nature of health care delivery and information technology. However, to best develop innovative, lower-risk medical devices, it is crucial to implement post-market evaluation to further assess the safety and effectiveness of these new technologies. Current Postmarket Surveillance System Medical device postmarket surveillance is known to be a difficult field to adequately document and report. The diversity of medical devices presents a challenge when it comes to organizing reports and documentation in a way that presents the information sensibly. The short product life cycle also presents a challenge, as devices are often altered and off the market before the errors can be documented and addressed. In addition to this, medical device production is cyclical in nature—manufacturers will often abandon an approach for a new one, and then pick up the old approach again in the future. This means problems with the devices have the potential to appear again in the future if not addressed. The current FDA postmarket surveillance system attempts to address each of these challenges and create an organized database using five tools:

1) Medical Device Reporting (MDR) Medical Device Reporting is the FDAs method for collecting information on malfunctioning medical devices that have potential to cause injury or other medical error. Each year, hundreds of thousands of reports are submitted from a variety of

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sources, some required and some voluntary. Parties required to report medical device malfunctions include manufacturers, importers, and device user facilities (Medical Device Reporting). Voluntary reporters, including healthcare professionals, patients, caregivers and consumers, are strongly encouraged to submit reports that document errors, product quality issues and therapeutic failures. This includes individual healthcare professionals, patients, caregivers, and consumers.

2) Medical Product Safety Network (MedSun) MedSun is a network that partners Clinical Sites across the US with the FDA, allowing them to share medical report information interactively. Composed of over 280 hospitals, the network strives to “identify, understand, and solve problems with the use of medical devices” (MedSun). This program provides a two-way street for information to flow between hospitals and the FDA by way of an online database that accepts and stores medical device reports. When a report is entered into the system, MedSun researchers begin working to diagnose the problem. Reports on why the problem occurred and how to fix it are then entered into the database with the incident reports, so that other members of the network can preemptively fix the problem.

3) Post-Approval Studies A post-approval study is an optional study that can be requested by the FDA when performing a premarket approval. Currently run by the Division of Epidemiology, these studies are used to “assess device safety and effectiveness” in the real world. Although devices are very thoroughly tested before they are given premarket approval, these tests take place in a very carefully controlled setting. Once the device is approved, mass-produced, and bought for use, thousands of new factors are introduced. There is no way to account for every possibility for error the device might encounter in the real world prior to production, so a post-approval study does the necessary job of checking on the devices to make sure they work just as well when implemented for long-term real-world purposes outside of the lab. The projects currently undergoing post-approval studies can be found online (Post-Approval Studies).

4) Postmarket Surveillance Studies Often referred to as “522 studies” post-market surveillance studies are studies that take place when a device is reported as causing or having the potential to cause serious injury. The FDA orders the study to diagnose and fix the problem, so it can be prevented in future productions of the device.

5) FDA Discretionary Studies An FDA discretionary study can cover the purposes of both post-approval studies and post-market surveillance studies, as the field covers monitoring device performance post-production and investigating reports of malfunctioning devices. Since the FDA conducts the studies, they have access to privacy-protected data sources that other studies might not be privy to. This includes national registries, Medicare, Medicaid, and electronic health records. In addition to these five main tools, the FDA uses a few other approaches in their system, including Registration and Listing, Recalls, Device Tracking, Enforcement

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Actions, Restrictions of Devices, and Removal of a Device as a Predicate. These all allow the FDA to control and restrict the flow of medical devices, remove potentially dangerous medical devices, and to keep tabs on their status post-production. The Sentinel Initiative Announced in May of 2008, the Sentinel Initiative is a plan laid out by the FDA with the intent to create a national system for monitoring medical device safety after is passes through FDA approval. The Initiative will require the FDA to work with medical entities across the country to obtain scattered health data and integrate it with the data already gathered by current surveillance systems. This will allow the FDA to monitor post-market medical devices in real time, reporting and diagnosing errors sooner, more effectively, and with wider coverage. The updated post-market surveillance system envisioned with the Sentinel Initiative is vital to the continued improvement of our medical system for several reasons. The first is efficiency. It was previously mentioned that one challenge found with medical device post-market surveillance is the short product life cycle of medical devices. An updated surveillance system will allow the FDA to monitor medical devices in real time or near real time, meaning problems can be reported, diagnosed, and solved much sooner. This will help with another challenge, the iterative nature of medical device production. If problems are solved when they first appear, they will be easier to spot if they return in a later iteration of the device. Finally, the addition of a Unique Device Identification system with the Sentinel Initiative will solve the issue the current system faces with de-identification of devices. A new identification system is crucial to collecting data that can be used and implemented in the real world. FDA’s Vision for Postmarket Surveillance These mandatory and voluntary adverse event reports, along with data from other sources, can provide critical information that helps improve patient safety. FDA’s vision for medical device PMS is the creation of a national, up-to-date and efficient system that serves four primary functions (CDRH Updated and Next Steps).

1. Communicates timely, accurate, systematic and prioritized assessments of the benefits and risks of medical devices throughout their marketed life using high quality, standardized, structured, electronic health-related data.

2. Identifies potential safety signals in real-time from a variety of privacy-protected data sources.

3. Reduces the burdens and costs of medical device postmarket surveillance. 4. Facilitates the clearance and approval of new devices, or new uses of existing

devices.

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Proposed Actions To serve these functions, the FDA proposed four specific actions that use existing resources to strengthen the medical device postmarket surveillance system in the United States. The proposed actions to strengthen this system are as follows: 1. Establish a Unique Identification System and Promote its Incorporation

into Electronic Health Information • As discussed above, a Unique Device Identifier (UDI) is a unique alphanumeric code

that consists of two parts: the device identifier (DI) that is specific to the device or model of the object and the product identifier (PI) which contains information specific to the object.

• UDIs will provide an unambiguous method for classifying devices in Electronic Health Records (EHRs). In turn, this will allow studies and researchers to easily access information about the performance of individual medical devices through the health records, without the time it would usually take to pull together a clinical study. Additionally, this method of device identification should improve accuracy of information, and allow medical professionals to easily identify malfunctioning medical devices and remove them from production.

2. Promote the Development of National and International Device Registries for Selected Products

• A device registry is a collection of data that maintains structured records of medical

devices, their uses, and their errors. The FDA plans on keeping this system of individual registries, but creating a network that allows information to be drawn from the registries and shared with those who need it for research.

• Registry creation and maintenance can be both costly and inefficient. To solve this, FDA is attempting to identify the device registries that are more important. This is decided by analyzing patient need, degree of patient exposure to the device, how uncertain real-world performance will be, and cost of the registry and device.

• In order to implement the plan, the FDA is sponsoring a workshop for Medical Device Registry experts. The goal is to develop certain desirable aspects in the registry and registry production. Firstly, they wish to leverage experience and expertise to facilitate registry development. Next, they will to establish common demographic, clinical, procedural, and device-based data elements. The third goal is to develop and share methodological tools for privacy-protected data collection. The fourth and fifth goals are to enhance interoperability with EHRs and claims data, and to enhance incorporation of registry data into EHRs and vice versa. Together, these goals will promote up-to-date and well-integrated registries, improving the accuracy of studies. Six is to develop criteria that automatically decide whether a registry is eligible for post-approval studies, which would increase system efficiency. Finally, the FDA wants to create sustainable business models, identify priority medical device types for inclusion in registries, and adopt well-adjusted registry governance structures. All three of these goals support a well-run, well-informed registry system.

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3. Modernize Adverse Event Reporting and Analysis A lack in enforcing voluntary reports and the limitations and restrictions of reporting systems, the FDA suggests updating and improving the system for adverse event reporting and analysis by implementing the following: Develop automated reporting systems

• By automating adverse event reporting systems, this would facilitate the efficient and timely submission of reports with as little effort as possible required by the reporter. Minimizing the work required to submit an adverse event report would improve the response rate of voluntary reporters. The Adverse Spontaneous Triggered Events Reporting (ASTER) study demonstrated that facilitated, automatic reporting increased the number and quality of reports. Increased reports also more regularly alerts the FDA of potential device-related concerns. This way, the FDA can respond in a timely manner to the device and can more promptly choose the appropriate course of action to handle the device.

Increase electronic reports • Electronic reporting of device-related adverse event reports also enhances the

timeliness, quality and efficiency of both reporting and PMS. Electronic reporting also significantly reduces data entry costs and increases the rate at which reports are sent to and received by the FDA. Additionally, the FDA could pilot programs to automatically report to the FDA through electronic health records and incident reporting systems.

Develop a mobile application for adverse event reporting

• The FDA has also recognized the increased role mobile phones and applications play in everyday life—and the potential role they may play in improving public health. The FDA anticipates this tool would also increase voluntary report submissions by healthcare providers and patients.

Modernize the medical device adverse event database

• The database currently in use—the Manufacturer and User Facility Device Experience (MAUDE) database—contains reports from the past 20 years of use. MAUDE serves as an electronic filing system that archives huge volumes of data in such a way that a computer program can search and select pieces of data, such as information on medical devices that may have malfunctioned or caused a death or serious injury. However, MAUDE is antiquated and unable to handle the volume and complexity of device reports and cannot work seamlessly with mobile applications. Therefore, the FDA is working to develop a new adverse event reporting system with expanded capacity and modern capabilities and will pilot an initial functional release the FDA Adverse Event Reporting System (FAERS).

Rapidly identify safety signals

• Using automated, computerized methods can very effectively evaluate patterns of occurrences concerning medical devices can potentially identify safety issues

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more quickly than traditional signal detection methods. With these methods, the FDA is also implementing data mining tools to enhance the identification of high quality adverse event reports and report trends. By implementing data mining, the FDA can use pattern recognition algorithms to sift through large amounts of data to discover previously unknown patterns or problems.

4. Develop and Use New Methods for Evidence Generation, Synthesis and Appraisal The FDA also seeks to implement the strategic development of innovative methodological approaches for evidence generation, synthesis and appraisal. With an updated systematic analysis of the study of medical devices, the FDA can identify gaps in current efforts to promote data standardization and the seamless linkage and exchange of data between registries and data sources. In 2010, the Center for Devices and Radiological Health launched the Medical Device Epidemiology Network (MDEpiNEet), an initiative through with the Center and other, external partners such as device user facilities can share information and resources to enhance understanding of the safety and effectiveness of medical devices after they are marketed (US FDA Medical Device Epidemiology Network Initiative). This exchange of information with MDEpiNet aims to develop new ways to study medical devices that improve the understanding of their safety and effectiveness throughout their life cycle. Approaches are also being taken to protect personal health information, maintain data security and integrity, assure confidentiality of proprietary information, preserve intellectual property and maintain transparency. By developing new tools for interpreting post market evaluation information, the FDA can improve the efficiency and quality of information about benefits and risks of products and can translate obscure, disconnected data into knowledge that will help make better-informed decisions. To do this, the FDA has several proposed approaches: Quantitative decision analysis to evaluate benefits and risks

• The CDRH is exploring quantitative analysis to better evaluate the benefits and risks of medical devices. By using statistics and numerical data, risks can be evaluated in a more consistent and reliable way both before and after medical devices are marketed. With more consistent and reliable data, individuals can make more informed healthcare decisions regarding medical devices.

Evidence assessment by combining data from diverse data sources • Combining medical device performance data with clinical outcome data would

also significantly improve the efficiency of PMS. With common data standards, this combining of data from separate sources becomes easier, more straightforward and seamless. Implementing these data standards--which includes information describing procedures, guidelines and usage requirements--provides a comprehensive, up-to-date, benefit-risk analysis of any medical device at any point in its life cycle.

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Automated signal detection

• Modern software and techniques can better compare device performance and clinical outcomes among marketed products, as well as identify early signals of concern. The use of automated signal detection can better identify potentially underperforming or even harmful products.

Refinement of process for signal detection and management • A safety signal is information that suggests a new, cause-related association

between a medical device and an event or set of related event. With signal detection, unwanted or unexpected effects associated with a product can be identified promptly.

By implementing these proposed changes, the FDA can provide more timely and comprehensive benefit-risk profiles of devices, allowing the public and healthcare providers to make more informed decisions. Figure: Contrasting the Current and Future States of Medical Device Postmarket Surveillance Figure C-2 found in the back of the document uses four separate examples to illustrate how an updated Postmarket Surveillance system would differ from the current system. These examples include evaluation of a potential safety signal, a need for a postmarket study, identification of a potential safety signal, and facilitating the expansion of a labeled indication. Evaluation of a Potential Safety Signal: Problem: A certain neurological implant needs to be replaced soon after operation. Comparison of Solutions: Using the current system, all companies that manufacture this implant must conduct a 522 study. Problems gathering data and finding patients mean the study takes years. Under the future system, health care systems voluntarily access electronic health records (EHRs) using UDIs. They give the information to the FDA, and the data is analyzed in a manner of weeks. Need for Postmarket Study Problem: CDRH approaches FDA for approval of arterial implant. Short-term studies are positive, but long-term data is unavailable as of yet. Comparison of Solutions: Using the current system, a new registry for storing long-term information must be created, and patients have to be recruited for the study. Study has difficulty recruiting patients because other implants are available without the study involvement. Under the future system, observations on the implant are automatically incorporated into an existing registry when patients come in for a checkup. The company can use this information to conduct a study over 5 years. Identification of a Potential Safety Signal Problem: CDRH approves permanent cerebral implants to treat stroke patients, and needs to monitor reactions.

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Comparison of Solutions: Using the current system, the CDRH will have to wait for medical device reports to be filed. Often, these reports will be incomplete. Under the future system, automated surveillance software will provide real-time analysis of similar devices, so CDRH can be on the lookout for safety signals, and analyze them if they appear. Facilitating the Expansion of Labeled Indication Problem: CDRH approved device to treat male incontinence after prostate surgery. Manufacturer believes device can treat other types of incontinence as well. Comparison of Solutions: Using the current system, the manufacturer will have to complete a new clinical trial. Under the future system, the manufacturer can analyze information from electronic health records using UDIs, and submit a report with this information. In short, the examples given in the graphic theoretically demonstrate that the future system of postmarket surveillance will be significantly more efficient than the current model. Conclusion The FDAs current postmarket surveillance system uses a well-defined, multifaceted approach to gathering information about medical devices after approval. The different branches of the system work to keep track of potential flaws in the devices so that these devices can be removed from the market and future errors can be fixed. Despite this, the current system is too slow to address most problems before the devices are replaced with new equipment on the market, and the de-identification system erases data such as the device manufacturer, which hinders research into the problems and dampens the usefulness of the data. Implementing a stronger postmarket surveillance system will improve the quality of medical devices and their uses across the United States. Using the Sentinel Initiative, the FDA hopes to create a collaborative system that allows local healthcare systems to handle and share their own medical data. This distributed form of data handling will replace a central repository, allowing the handling of medical records to be more dynamic, and more efficient in turn. This implementation will also encourage more complete medical device records, as each locality is closer to the problem and better able to fill in the details of the occurrence. Reforming the device identification method by implementing a Unique Device Identification system that keeps the manufacturer’s information, the device’s medical category, and the individual device labels will make it easier for the information to be gathered and used once a diagnosis of the problem is made. Finally, collecting data from multiple sources and automating and improving signal detection will provide the system with a significantly larger database of information to search through, and allow it to comb through the data looking for patterns more efficiently and more accurately, leading to an overall improvement in the state of America’s medical devices.

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Set of Instructions

The following instructions describe the steps that can be taken to file Medical Device Reports electronically. By submitting MDR’s electronically, the FDA will be able to process and analyze common incidents with much greater speed. 1. Visit the website www.fda.gov/medicaldevices 2. Download the required 3500A form onto your computer and open it. Reports from manufacturers must be made within five days of becoming aware of a malfunction. 3. Fill out the manufacturer report number. This number this is the unique identifier used by the manufacturer for the report and follow up reports. 4. Complete the patient information section detailing initials, age, sex, weight, and date of event. If there are numerous patients suffering from the same issue, fill out the appropriate number of patient information forms and attach them all in the file. 5. Explain the adverse event or product problem. An adverse event is described as: any incident where the use of a medication (drug or biologic, including human cell, tissue, or cellular or tissue-based product (HCT/P), at any dose, or a medical device (including in vitro diagnostic products) is suspected to have resulted in an adverse outcome in a patient. Product problems are considered any report regarding the quality, performance, or safety of any medical product. This category is selected when reporting device malfunctions that could lead to a death or serious injury if the malfunction were to recur. 6. Describe the severity of the patient’s condition. (Ex: Death, Life-threatening, Hospitalized, etc.) 7. Report any and all suspect products or other devices that may have had a role in causing the incident. Include name, dose, consumption frequency, model number, and manufacturer as applicable. 8. Return back to www.fda.gov/medicaldevices and select ‘Submit MDR.’ When prompted, upload the completed file and select ‘Submit’.

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FAQs (Frequently Asked Questions)

1. Do medical devices require FDA approval? Most medical devices do not require FDA approval. However, all manufacturers and distributors must register their establishments with the FDA. The registration information must be verified annually. In addition to the establishment registration, the manufacturers must list their devices with the FDA. Higher classified devices may require premarket notification, and the highest classified devices may require a premarket approval. If the device is to be used in a clinical study or trial, an Investigation Device Exemption (IDE) can be given. These can be used to obtain data required to support a premarket notification or premarket approval. Manufacturers must also undergo FDA inspections to assure compliance with the Quality System/ Good Manufacturing Practices requirements; they must accurately and effectively label their products, and report any incidents and/or malfunctions related to the product. 2. What are the different classifications of medical devices? There are three classes of medical devices: Class I, Class II, and Class III. 3. How does the FDA classify medical devices? The FDA classifies medical devices based on their risk factor. Class I devices present the lowest potential for risk. They are usually simpler in design than the other classes. Class II devices have a higher potential for risk and may be subject to special labeling requirements, performance standards, and postmarket surveillance. Devices that provide insufficient information to determine a reasonable assurance of safety and effectiveness are classified as Class III devices. 4. What are examples of medical devices? Bandages, examination gloves, and hand-held surgical instruments are a few examples of Class I medical devices. Some examples of Class II devices are wheelchairs, infusion pumps, and surgical drapes. Replacement heart valves, breast implants, and implanted cerebellar stimulators are examples of Class III devices. 5. What is a premarket notification submission? A premarket notification submission (or a 510(k)) is sent to the FDA by a medical device manufacturer before the manufacturer puts their device on the market. The FDA may approve the device immediately, or may require premarket approval before the manufacturer can market their product. The FDA does not require premarket approval in most premarket notification submissions. 6. What is a premarket approval application?

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If the FDA does not immediately approve the premarket notification submission, a premarket approval application must be submitted. The premarket approval application must contain sufficient, valid, and scientific evidence that assures the device is safe and effective. 7. What regulations apply to medical device clinical investigations? Medical device clinical investigations must comply with the FDA’s human subject protection requirements, Investigational Device Exemptions requirements, Financial Disclosure for Clinical Investigators requirements regulations, and any other regulations that can be applied to the investigation. 8. Can a physician use an unapproved device in an emergency? A physician can use investigational devices in an emergency if the patient has a life-threatening condition and needs immediate treatment, no alternative treatment for the condition currently exists, and there is no time to get FDA approval for the use. The FDA also expects the physician to have substantial reason to believe that the patient will benefit from the unapproved device. The physician should also obtain informed consent from either the patient or a legal representative, clearance from the institution with respect to their policies, an assessment from a physician that is not involved in the case, and authorization from the IDE sponsor if an IDE exists for the device. 9. Can a patient with a serious illness or condition have access to an unapproved device

outside a study? Unapproved devices can also be used in non-emergency situations. However, prior FDA approval is needed before the device is used. If the FDA grants approval and the device is used, the patient should be monitored to detect any complications from the device. A follow-up report should also be sent to the FDA that summarizes the patient’s outcome. 10. What are the steps I should take to get my medical device approved? Step 1: Register your establishment with the FDA Step 2: Pay the registration fee Step 3: List your device(s) with the FDA Step 4: Submit a premarket notification, if needed Step 5: Submit a premarket approval application, if needed IMPORTANT: All registration and listing information must be submitted electronically, unless a waiver has been granted. 11. What are problems or concerns with the current postmarket surveillance system? One problem with the current system is the limitations of medical device reporting. Incomplete data, inaccurate data, under-reporting of events, and lack of report timeliness are a few of these limitations. Also, records lack manufacturer or brand-

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specific device identifiers and cannot be leveraged to perform meaningful medical device postmarket surveillance. 12. When is postmarket surveillance required? Every device should go through some process of postmarket surveillance. However, the CDRH has the authority to order a Postmarket Surveillance Study if:

• Device failure would be reasonably likely to have serious adverse health consequences;

• The device is expected to have significant use in pediatric populations; • The device is intended to be implanted in the body for more than one year; or, • The device is intended to be a life-sustaining or life-supporting device used

outside a device user facility. The FDA may also order postmarket surveillance as condition of clearance of a device that is expected to have significant use in pediatric patients.

13. Can I submit an adverse event report? Yes. The FDA receives adverse event reports from healthcare professionals (physicians, pharmacists, nurses, etc.) and from consumers (patients, family members, lawyers, etc.). Adverse event reports can also be sent directly to the products’ manufacturers. When the manufacturer receives an adverse event report, it is required that they send the report to the FDA. 14. What happens to a medical device after an adverse event happens while using it and is reported? CDRH has the authority to order the manufacturer, importer, or distributor of a device to repair or replace it or to refund its purchase price if, after affording an opportunity for a hearing, CDRH determines that:

• The device poses an unreasonable risk of substantial harm to the public health; • There are reasonable grounds to believe that the device was not properly

designed or manufactured with reference to the state of the art as it existed at the time of design or manufacture;

• There are reasonable grounds to believe that the unreasonable risk was not caused by failure of a person other than a manufacturer, importer, distributor, or retailer of the device to exercise due care in the installation, maintenance, repair, or use of the device; and,

• Notifying device users would not by itself be sufficient to eliminate the unreasonable risk, and the repair, replacement, or refund is necessary to eliminate such risk.

15. Are medical devices recalled as a result of postmarket surveillance? CDRH has the authority to issue a recall or "cease distribution and notification" order, if, after providing the appropriate person with an opportunity to consult with the agency, CDRH determines that “there is a reasonable probability that the device would

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cause serious, adverse health consequences or death.” The order may require the appropriate person to immediately:

• Cease distribution of the device; • Notify health professionals and device user facilities of the order; and, • Instruct these professionals and device user facilities to cease use of the device.

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Works Cited Internal: Riley, Karen. "FDA to Improve Most Common Review Path for Medical Devices." Press Announcements. Food and Drug Administration, 19 Jan. 2011. Web. 14 Nov. 2014. "U.S. Food and Drug Administration." CDRH Plan of Action for 510(k) and Science. N.p., n.d. Web. 17 Nov. 2014. <http://www.fda.gov/AboutfDA/centersoffices/officeofmedicalproductsandtobacco/cDrh/cDrhreports/ucm239448.htm>. "U.S. Food and Drug Administration." Medical Device Epidemiology Network Initiative (MDEpiNet). Web. 17 Nov. 2014. <http://www.fda.gov/medicalDevices/scienceandresearch/epidemiologymedicalDevices/medicalDeviceepidemiologynetworkmDepinet/default.htm>. "U.S. Food and Drug Administration." Medical Device Reporting (MDR). Web. 16 Nov. 2014. <http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm>. External: “522 Postmarket Surveillance Studies.” U.S. Food and Drug Administration. Food and Drug Administration, 09 Sept. 2014. Web. 25 Nov. 2014. <http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/PostmarketRequ

irements/PostmarketSurveillance/default.htm>. Center For Devices And Radiological Health, and U.S. Food And Drug Administration. Strengthening Our National System for Medical Device Postmarket Surveillance: Update and Next Steps (n.d.): Apr. 2013. Web. 12 Nov. 2014. <http://www.fda.gov/downloads/MedicalDevices/Safety/CDRHPostmarketSurveillance/UCM348845.pdf>. “Data Transparency Definition.” PC Magazine Encyclopedia, n.d. Web. 16 Nov. 2014. “FDA’s Sentinel Initiative.” U.S. Food And Drug Administration, n.d. Web. 16 Nov. 2014. “Frequently Asked Questions About Medical Devices.” Information Sheet Guidance for IRBs, Clinical Investigators, and Sponsors. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Devices and Radiological Health (CDRH), Center for Biologics Evaluation and Research, Jan. 2006. Web 16. Nov. 2014. "MedSun: Medical Product Safety Network." FDA: US Food and Drug Administration. Food and Drug Administration, 18 June 2014. Web. 25 Nov. 2014. <http://www.fda.gov/medicaldevices/safety/medsunmedicalproductsafetynetwork/>.

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“Methodological.” Merriam-Webster. Web. 16 Nov. 2014. "Office of HIPAA Privacy & Security." What Is Personally Identifiable Information (PII)? | Privacy | at Miller School of Medicine. University of Miami Health System, n.d. Web. 12 Nov. 2014. “Overview of Device Regulation.” U.S. Food And Drug Administration, n.d. Web. 16 Nov. 2014. <http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/> "Post-Approval Studies." Post-Approval Studies. Food and Drug Administration, 24 Nov. 2014. Web. 25 Nov. 2014. <http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma_pas.cfm>. "UDI Basics." U.S. Food and Drug Administration. Food and Drug Administration, 30 Sept. 2014. Web. 25 Nov. 2014. "UDI Issuing Agencies." U.S. Food and Drug Administration. Food and Drug Administration, 30 Sept. 2014. Web. 25 Nov. 2014. <http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/UniqueDeviceIdentification/UDIIssuingAgencies/default.htm>. "U.S. Food and Drug Administration." About the Center for Devices and Radiological Health. Web. 16 Nov. 2014. <http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/default.htm>. “What is an electronic health record (EHR)?” Health IT, n.d. Web. 16 Nov. 2014.