An MD&DI May 1998 Column
DEVICE SAFETY STANDARDS
FDA is working hand in hand with the Global Harmonization Task Force to ensure the development of internationally acceptable device safety standards.
The Global Harmonization Task Force was formed in September 1992 to facilitate alignment of various technical requirements for a quality systemsbased approach to regulating medical devices. Since that time, the group's scope has expanded to include other aspects of the regulatory process as well, resulting in the creation of five subcommittees or "study groups." Study Group 2 (SG2), the subject of this article, concentrates on postmarket vigilance and surveillance. Specifically, the group was formed to "examine the requirements for the reporting of adverse incidents involving medical devices, postmarket surveillance, and other forms of vigilance and to recommend ways of harmonizing the requirements," and to "promote the dissemination of relevant information." The following discussion summarizes current SG2 efforts and examines the impact SG2 recommendations will have on FDA policies.
Study Group 2 first met in February 1996 under the chairmanship of FDA Office of Surveillance and Biologics (OSB) director Larry Kessler, ScD. Participants included 10 government and 13 industry professionals from Belgium, Canada, France, Germany, Japan, the United Kingdom, and the United States, as well as representatives from the Emergency Care Research Institute (ECRI), EUROM VI, the European Confederation of Medical Devices Associations (EUCOMED), the Coordinated Committee of the Radiological and Electromedical Industry (COCIR), the International Standards Organization Technical Committee (ISO TC) 210, the European Commission (EC), Medical Devices Canada (MEDEC), the Japan Federation of Medical Devices Association (JFMDA), the Health Industry Manufacturers Association (HIMA), and the National Electrical Manufacturers Association (NEMA). At that time, members generated a list of specific tasks that needed to be accomplished, most notably to define how and when to report adverse events, to develop examples of reportable events, and to establish guidelines for postmarket reporting among users, manufacturers, and competent authorities (such as FDA). In addition, the group would harmonize the language of medical device reporting requirements and identify elements and requirements for device nomenclature. Lastly, the group would maintain member information, examine the feasibility of electronic data interchange (EDI) for adverse event reporting or transmission of regulatory affairs data, and communicate regularly with other committees, groups, and organizations whose efforts might affect or be affected by SG2 efforts. SG2 finalized its mission statement at its second meeting, held in May 1996.
The documents SG2 has sent to the Global Harmonization Task Force include GHTF-SG2 N5: SG2 Controlled Documents Log; GHTF-SG2 N6: Comparison of the Device Adverse Report Systems in USA, Europe, Canada, Australia, and Japan; GHTF-SG2 N7: Minimum Data Set for Manufacturer Reports to Competent Authority (CA); GHTF-SG2 N8: Guidance on How to Handle Information Concerning Vigilance Reporting Related to Medical Devices; GHTF-SG2 N9: Global Medical Devices Vigilance Report; GHTF-SG2 N21: Adverse Event Reporting Rules for Manufacturers; and GHTF-SG2 N16: SG2 Charge and Mission Statement. Other ongoing projects include an umbrella document, use error document, vigilance criteria document, and examples of which adverse events require a report to the competent authority.
Because these documents represent harmonization guidance, they are expected to undergo periodic changes to reflect refinements in the knowledge of medical devices; thus, documents are never designated as "final," but rather as "final draft."
Regulatory Overview and Comparison. The regulatory overview document GHTF-SG2 N6 represents a vital and necessary first step in appreciating the similarities and differences among the various regulatory systems around the globe. The document briefly summarizes the various elements of medical device reporting in the countries participating in SG2. The European countries have been represented collectivelyreflective of the European Union guidelines and directives.
The document contains 11 main sections that delineate the purpose of the reporting program, who must report, when reports must be filed, what constitutes a reportable event, what provisions exist for not reporting an event, and what information to include in a report. Also covered are applicable forms, content of the forms, the role of the competent authority, definitions, and the entity responsible for investigating the adverse event. This document was compiled by a subgroup of SG2 members and provides the basis of information from which other guidance documents have been drawn.
Umbrella Document. The SG2 umbrella document (GHTF-SG2 N12), renamed Precís, provides an executive summary of SG2 deliberations, links the individual documents generated by SG2, and explains the current status and future direction of the committee, including proposed work in postmarket surveillance and communication (such as nomenclature and EDI). The document also delineates the transition from independent systems to an integrated international system, the proper structure and authority of a harmonized vigilance system, and suggestions to consider when creating future vigilance systems.
Figure 1. This draft decision tree, part of a larger draft document, helps the manufacturer determine whether a competent authority would require a report for a particular adverse event.
Manufacturer Reporting Decision Tree. Figure 1 shows a draft of the manufacturer reporting decision tree, which is designed to help manufacturers evaluate the information about an adverse event. Answering the questions posed by the decision tree in sequence will determine whether a competent authority would require a report. The tree is part of a larger draft document, Adverse Event Reporting Rules for Manufacturers and Their Representatives. It is absolutely essential that individuals understand the larger document before attempting to use the abbreviated decision tree. Competent authorities recognize that manufacturers may not know much about the cause of the reported problem. The decision tree should help manufacturers understand the considerations and rationale behind the decision to file a report with the competent authority, anticipating that the investigation may need to continue.
When manufacturers reach a question that cannot be answered or for which the answer is unknown, the decision tree guides them toward reporting. However, if the firm determines that the adverse event is not linked to the device, no report is required. The documentation supporting such a determination should be filed. In concluding that no report is necessary, the guidance document notes that such a determination is based on the expectation that manufacturers will begin to report similar findings if the same or similar types of adverse events become more prevalent.
Manufacturer Reporting Rules. GHTF-SG2 N21 consolidates guidance on considerations to be included in determining reportability of an event, rules for reporting, a schematic summary in the form of a decision tree, and examples of actual scenarios to facilitate clarity.
Use Error Considerations. Document GHTF-SG2 N18 identifies the various circumstances that constitute use error or user error. Categories include intentional and unintentional uses and misuses of the device as well as use of the device for nonlabeled indications. These categories are not intended to assign blame for product problems; rather, they should help to identify potential means of resolving problems. Still to be addressed are issues such as the impact of device design, off-label applications of a device, reuse of devices, and planned failure modes.
Minimum Data Set for Manufacturer Reports to the Competent Authority. Document GHTF-SG2 N7 defines the essential elements that must be reported by the manufacturer to a competent authority based on which ones were deemed vital by each participating competent authority. The document lists the least amount of data desired; it does not reflect all the information required by a competent authority, nor is it intended to do so. In the future, SG2 may also define both an optimum and a maximum data set, although such a project is not on the current agenda.
Dissemination of Information. Two documents address the dissemination of adverse event information. The first, GHTF-SG2 N8, instructs manufacturers when and how to inform the public of an adverse event. The other, GHTF-SG2 N9, provides guidance on how to exchange information between competent authorities.
GHTF-SG2 N8 gives primary consideration to confidentiality. The guidance document states that competent authorities should not disseminate information concerning actions taken, or actions to be taken, as a result of a medical device related adverse event unless a threat of immediate danger is perceived. The document provides criteria to help the competent authority make the necessary determinations prior to releasing data, but it recommends that the manufacturer be given primary responsibility for the dissemination of information under the supervision of the competent authority, which should assist as necessary. The competent authority may alternatively disseminate the information itself when appropriate.
Potential recipients of the information have been defined as other competent authorities, manufacturers, distributors, the health-care system, health-care facilities, end-users and patients, professionals and academics, and the public at large. To ensure that these groups are reached in a timely manner, health authorities should have access to registries for manufacturers and distributors of medical devices and their authorized representatives as well as for health-care providers, hospitals and health-care facilities, and hospital owners and administrators.
SG2 has developed a form for use in disseminating information from one competent authority to another so that standard details will be collected. To reiterate, report confidentiality is the highest priority and, because it is, special considerations of how to protect confidentiality are incorporated in the mutual recognition agreements between the United States and other participating countries.
Document Control Log. The document control log (GHTF-SG2 N5) provides a ready reference to those documents that have been given a control number, been placed in the SG2 master files, and are now available for dissemination. This document lists all the projects currently under way in SG2, as well as the official SG2 minutes and agendas.
IMPACT ON FDA
FDA is strongly invested in harmonization and has already incorporated some harmonization concepts into the 1996 medical device reporting (MDR) regulation. Meetings and discussions with the EC have confirmed that its basic reporting priorities are consistent with FDA priorities. FDA still sees room for growth in the area of common, well-recognized, and sometimes medically foreseeable adverse events. Under certain circumstances, new information about such events adds little to the depth of knowledge about the device in question, its use, or patient outcomes associated with its use. For example, having received vast numbers of reports about breast implants, FDA has come to recognize that additional reports may not provide much new data or information about adverse events or patient outcomes.
One primary goal of the MDR rule is to provide information and insight that can be useful in protecting the public health. FDA would therefore like to maximize the utility of medical device reporting without disregarding the lessons learned from the past, many of which resulted in the regulations and guidances now in existence. The trick is to eliminate noninformative data without losing the useful and important data needed to make informed and scientifically valid decisions.
FDA currently has regulatory provisions for meeting the harmonized manufacturer's decision tree processes relating to the nonreporting of well-established, common, and medically foreseeable events. CFR 803.20(c)(2) provides that "entities required to report under this part do not have to report adverse events for which there is information that would cause a person who is qualified to make a medical judgment (e.g., a physician, nurse, risk manager, or biomedical engineer) to reach a reasonable conclusion that a device did not cause or contribute to a death or serious injury, or that a malfunction would not be likely." In addition, CFR 803.19 provides for exemptions, variances, and alternative reporting requirements and authorizes FDA to permit a firm to amend its reporting procedures, which could incorporate recognition of adverse events that are well documented in, and understood by, both the medical community and the agency.
In fact, in cases where the data are consistently categorized as well known in the medical or scientific literature, FDA encourages alternative reporting methods in order to minimize the reporting impact on both manufacturers and the agency itself. Manufacturers are encouraged to identify and pursue, in writing, whichever alternatives best address current knowledge of adverse events associated with their medical devices. Alternatives to routine 30-day filing of individual reports include a request for exemption from reporting and a request for filing periodic summary reports. Both require a written request along with the documentation ofand rationale forthe request's validity.
In the future, FDA may harmonize the MDR regulation even further by incorporating the above concepts into the regulatory language and thus doing away with written requests. FDA is also actively developing EDI systems for the transmission of data. A centralized database could conceivably house adverse event reports from around the world. Who would establish and maintain such a database is still in question; in the meantime, issues such as data confidentiality, encryption, and translation occupy center stage.
FDA is dedicated to all aspects of global harmonization, of which medical device reporting is but one feature. Liaisons are being developed to facilitate the exchange of information between SG2 and industry groups. These liaisons will further disseminate SG2 information and provide consolidated feedback to help maximize industry input into the harmonization processes.
In addition to the Global Harmonization Task Force efforts, FDA is working on the European Committee for Standardization (CEN) nomenclature project and fostering a smooth transition between the long-established FDA coding and the project's harmonization nomenclature system.
TC 210 WG3 has representatives on SG2, and this formal liaison helps SG2 members understand the activities of WG3 and the transition toward a harmonized nomenclature system. SG2 members have also discussed putting the group's own terms and definitions through the standardization process. Many members feel that SG2 documents have not been adequately reviewed and tested to permit formal standardization. They also acknowledge that standardization is, of necessity, a long process, and may or may not be well suited to the "fluid" documents that are generated by SG2documents that must be frequently reviewed and revised to keep up with medical, technological, and scientific advances and their impact on the use and outcomes associated with medical devices.
WHAT'S NEXT FOR SG2?
A subgroup of SG2 composed of members from competent authorities is developing criteria for determining when to initiate a report from one competent authority to another and defining what constitutes a vigilance case. At the last SG2 meeting in October 1997, it was suggested that another subgroup of competent authority representatives determine what events might initiate an exchange of reports and compile a harmonized list of adverse events exempted from reporting (until the manufacturer notes an increase in the trends of such events or the competent authority invokes a new requirement for reporting previously exempted adverse events). No formal actions have been initiated at this time.
SG2 seeks to share its processes, philosophy, and outcomes with all interested parties and welcomes feedback. European members of SG2 have formed "mirror groups" that update the European medical community about SG2 projects to gather wider industry input.
While the United States does not currently have a similar information- exchange process, the U.S. contingent is also looking for ways to facilitate industry input. Representatives from HIMA and NEMA are active in SG2, and industry representatives are encouraged to communicate with these organizations.
FDA has presented SG2 updates at various meetings of FDLI and the Regulatory Affairs Professionals Society and sponsored a one-day seminar on SG2 for industry groups. The agency also plans to participate in various seminars and presentations and will generally make itself available at industry meetings to share SG2 information and clarify the impact of SG2 guidances.
Deborah Blum is a nurse consultant in CDRH's Office of Surveillance and Biometrics and currently serves as member and executive secretary of SG2.