701 Pennsylvania Avenue, NW Suite 800 Washington, D.C. 20004 2654 Tel: 202 783 8700 Fax: 202 783 8750 www.advamed.org Division of Dockets Management (HFA-305) Food and Drug Administration 5630 Fishers Lane, Room 1061 Rockville, MD 20852 RE: : Agency Information Collection Activities; Proposed Collection; Comment Request; Safety Assurance Case Dear Sir/Madam: The Advanced Medical Technology Association is pleased to comment on the Food and Drug Administration s (FDA s or the Agency s ) Paperwork Reduction Act of 1995 Collection of Information associated with the FDA s requirement for submission of Safety Assurance Cases (SACs) for infusion pump manufacturers. AdvaMed represents manufacturers of medical devices, diagnostic products, and health information systems that are transforming health care through earlier disease detection, less invasive procedures, and more effective treatments. Our members produce nearly 90 percent of the health care technology purchased annually in the United States and more than 50 percent of such technology purchased annually around the world. These members range from the smallest to the largest medical technology innovators and companies. Nearly 70 percent of our members have less than $30 million in sales annually. Executive Summary: AdvaMed believes that the FDA Center for Devices and Radiologic Health s requirement for infusion pump manufacturers to submit SACs (in addition to the 510(k) and PMA required elements) should be eliminated. Revised standards and new guidance documents have eliminated the need for the redundant examination of safety, which is what the SAC is a summary of the essential performance and supporting evidence already required in a 510(k) and PMA. AdvaMed Responses to the Office of Management and Budget Paperwork Reduction Act Questions AdvaMed responds to several of the Office of Management and Budget (OMB) Paperwork Reduction Act (PRA) questions below. (1) Whether the proposed collection of information is necessary for the proper performance of FDA s functions, including whether the information will have practical utility? Bringing innovation to patient care worldwide
Page 2 of 12 Since FDA initially imposed the requirement for submission of SACs in conjunction with infusion pump manufacturer s 510(k) submissions in its draft guidance entitled Total Product Life Cycle: Infusion Pump Premarket Notification [510(k)] Submissions on April 23, 2010 1, FDA has issued 21 guidances (see the attached table) which apply broadly to all device types or have special relevance for infusion pumps. Examples of such guidance includes: cybersecurity in premarket submissions, postmarket management of cybersecurity, electromagnetic compatibility, use of ISO 10993-1 on evaluation and testing within risk management processes, design considerations for home use devices, and application of human factors and usability engineering. In addition, since the requirement for SACs was first imposed, a number of standards with which infusion pump manufacturers comply (see attached table) have been significantly strengthened to require higher levels of product safety, usability and risk management including, among others: ANSI/AAMI ES60601-1:2012, IEC 60601-2-24:2012 Infusion Pump Basic Safety and Essential Performance, IEC 60601-1-2:2014 EMC, IEC 60601-1-8:2012 Alarm Systems, IEC 62366:2014 Usability and ISO 14971:2007 Risk Management. The third edition of IEC 60601 which FDA now recognizes has been revised so that a substantial portion of safety testing must encompass the risks related to design as well as the risks related to performance. We note that any additional information required by the assurance case is already addressed in standard IEC 60601-2-24. Thus, compliance with this standard along with the other applicable standards should be seen as having, in effect, created an assurance case for an infusion pump. The attached list of recent FDA final guidance documents go beyond the scope of SACs and in fact, reflect FDA s latest thinking, particularly with respect to management of risks. All SAC verification and validation data is based on compliance with the abovementioned and additional standards and guidance which is already being supplied to FDA in the 510(k) or PMA. The requirement to submit a SAC means this data must be restructured into the assurance case format which is simply a restatement of what is already provided. There is no added benefit to repeating this information in a SAC. Agency familiarity with what each consensus standard contains and/or addresses, rather than delineating each possible hazard separate from the standards (a long and lengthy process) is a better use of both the Agency and industry s time and resources. Importantly, due to these new guidance documents and strengthened standards, infusion pump 510(k) and PMA submissions, including declarations and verification and validation evidence for all the elements of SACs, make SACs redundant and duplicative. The assurance case or proposed collection of information for infusion pumps is not necessary to demonstrate substantial equivalence of infusion pump 510(k)s or safety and effectiveness of PMAs, nor does the SAC information have practical utility. We have a number of additional concerns with the requirement for SACs that we believe demonstrate that they are not necessary for the proper performance of FDA s functions: 1 FDA imposed the SAC requirement in violation of Good Guidance Practice (GGP) while the Total Product Life Cycle: Infusion Pump Premarket Notification [510(k)] Submissions was still in draft.
Page 3 of 12 As we have noted in previous OMB PRA comments on this topic, FDA s requirement for SACs for infusion pumps goes beyond the statutory requirement to demonstrate substantial equivalence to a predicate device. For this reason, imposition of SACs for infusion pumps (or any other device) must be imposed via a change to the regulations (i.e., a special control). FDA has failed to issue a special control and yet it continues to require SACs. We continue to believe that assurance cases are not a proven risk management tool. Strong risk management processes are already in place in the device sector to mitigate device hazards. Companies that have implemented SACs have indicated their use is not driving different infusion pump design decisions or additional risk-based controls. FDA should carefully consider its current objectives for requiring assurance case reports. While the assurance case requirement may make 510(k) and PMA infusion pump submissions easier for ODE reviewers, SACs require burdensome and significant changes to manufacturer s risk management practices. In addition it increases the volume of submission documentation by approximately 2,500 pages on average. We believe the costs and resources required for SACs and the difficulties and challenges associated with implementing SACs has and will continue to increase manufacturer time to submission of 510(k)s and PMAs and has not shortened FDA review times of infusion pump submissions (for modified or new products). This delays patient access to newer and innovative infusion pumps. Infusion pump manufacturers now follow global guidance, BSEN 14971:2012 which has advanced the state of the art of risk management. FDA would do better to leverage and recognize this standard rather than requiring SACs. (2) The accuracy of FDA s estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used? AdvaMed is concerned that FDA has failed to take into consideration industry s estimate of the burden which was compiled by members with direct responsibility for implementing and managing SACs members with first-hand knowledge of the costs and man-hour burdens and resources associated with SACs. FDA s estimate of 112 hours per submission is a gross underestimate of the burden per response. In May, 2014, we estimated that 2,948.8 2 man-hours were required to implement all aspects of SACs. We again surveyed our members who make a range of infusion pumps with varying features and differing risk and complexity levels and found the following: 2 A man-month is 172 hours, and it represents a single person working 40 hours per week over the period of 1 month (4.3 weeks). Man-hours are calculated by multiplying the number of people working on a project by the number of months they worked to complete the project.
Page 4 of 12 Safety Assurance Case (SAC) Resource Costs and Related Factors Number of Man-Hours to develop SAC for a new or legacy pump Cost of developing a SAC for a new or legacy pump (includes software and/or use of consultants) Number of pages of 510(k) Average and Worst Case Average 2,792 hours Worst case 3,640 hours Average $486,110 Worst case $1,938,000 Average 15,672 pages Worst case 30,000 pages Number of pages of SAC Average 2,582 pages Worst case 15,000 Number of Man-Hours to update SAC for a modified product Cost of maintaining, archiving, updating SAC for a modified product Number of pages of 510(k) for a modified product Average 1,240 hours Worst case 2,420 hours Average $76,073 Worst case $200,000 Average 16,300 pages Worst case 30,000 pages Number of pages for a SAC for modified product Average 538 pages Worst case 1,068 pages (4) Ways to minimize the burden of the collection of information on respondents, including through the use of automated collection techniques, when appropriate, and other forms of information technology. Given the burdensome nature of compliance with the submission of SACs, which duplicates all aspects of infusion pump 510(k) and PMA submissions, FDA should eliminate the requirement for SACs.
Page 5 of 12 In closing, thank you for the opportunity to provide comments on this Paperwork Reduction Act Collection of Information. Please don t hesitate to contact me if you have any questions. I can be reached at tfederici@advamed.org or 202-434-7208. Sincerely, /s/ Tara Federici Vice President Technology and Regulatory Affairs Attachments cc: William Maisel, Acting Director, Office of Device Evaluation
Page 6 of 12 Title 1 Factors to Consider When Making Benefit-Risk Determinations for Medical Device Investigational Device Exemptions - Guidance for Investigational Device Exemption Sponsors, Sponsor- Investigators and Food and Drug * List of Guidance Issued by FDA Since Implementation of the Safety Assurance Case Requirement Date Issued FDA Organization Subject 1/13/2017 CDRH Premarket IDE, Clinical- Medical Status 2 Medical Device Accessories - Describing Accessories and Classification Pathway for New Accessory Types - Guidance for Industry and Food and Drug 3 Postmarket Management of Cybersecurity in Medical Devices - Guidance for Industry and Food and Drug Administration Staff 4 Factors to Consider Regarding Benefit-Risk in Medical Device Product Availability, Compliance, and Enforcement Decisions - Guidance for Industry and Food and Drug 12/30/2016 CDRH, CBER Premarket, Laws and Regulations 12/28/2016 CDRH, CBER Labeling, PMA, Premarket, Postmarket, Safety, Emerging Technology 12/27/2016 CDRH Postmarket, Combination Products, Adverse Event Reporting, Safety, Laws and Regulations, Recall, HUD/HDE, PMA, IDE
Page 7 of 12 Title 5 Public Notification of Emerging Postmarket Medical Device Signals (Emerging Signals) - Guidance for Industry and Food and Drug List of Guidance Issued by FDA Since Implementation of the Safety Assurance Case Requirement Date FDA Subject Status Issued Organization 12/14/2016 CDRH Postmarket, Safety 6 Medical Device Reporting for Manufacturers - Guidance for Industry and Food and Drug 11/8/2016 CDRH Postmarket, Adverse Event Reporting 7 Guidance for Industry and Food and Drug - Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications* 8/24/2016 CDRH, CBER Premarket, PMA 8 Information to Support a Claim of Electromagnetic Compatibility (EMC) of Electrically-Powered Medical Devices - Guidance for Industry and Food and Drug 7/11/2016 CDRH Premarket, Safety, Radiological Health, IDE, HUD/HDE, Emerging Technology, Biotechnology, Anesthesiology Devices, Cardiovascular Devices, Ear, Neurological Devices, Ophthalmic Devices, Orthopedic Devices, Physical Medicine Devices, Radiology Devices
Page 8 of 12 Title 9 Use of International Standard ISO 10993-1, Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process - Guidance for Industry and Food and Drug List of Guidance Issued by FDA Since Implementation of the Safety Assurance Case Requirement Date Issued FDA Organization Subject 6/16/2016 CDRH Premarket, IDE, HUD/HDE, PMA, Safety Status 10 Applying Human Factors and Usability Engineering to Medical Devices - Guidance for Industry and Food and Drug 2/3/2016 CDRH Anesthesiology Devices, Cardiovascular Devices, Dental Devices, Ear, Gastroenterology-Urology Devices, Molecular and Clinical Genetics Devices, Neurological Devices, Ophthalmic Devices, Orthopedic Devices, Physical Medicine Devices, Radiology Devices, Premarket, Postmarket, Labeling, Safety, PMA 11 Submission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile - Guidance for Industry and Food and Drug 1/21/2016 CDRH, CBER Premarket
Page 9 of 12 Title 12 Refuse to Accept Policy for 510(k)s - Guidance for Industry and Food and Drug List of Guidance Issued by FDA Since Implementation of the Safety Assurance Case Requirement Date Issued FDA Organization Subject 8/4/2015 CDRH, CBER Premarket, Administrative / Procedural Status 13 Balancing Premarket and Postmarket Data Collection for Devices Subject to Premarket Approval - Guidance for Industry and Food and Drug 4/13/2015 CDRH, CBER Premarket, Postmarket, PMA 14 Infusion Pumps Total Product Life Cycle - Guidance for Industry and FDA Staff 15 Design Considerations for Devices Intended for Home Use - Guidance for Industry and Food and Drug Administration Staff 16 Distinguishing Medical Device Recalls from Medical Device Enhancements - Guidance for Industry and Food and Drug 17 Content of Premarket Submissions for Management of Cybersecurity in Medical Devices - Guidance for Industry and Food and Drug Administration Staff 12/2/2014 CDRH Premarket 11/24/2014 CDRH, CBER Premarket 10/15/2014 CDRH Postmarket 10/2/2014 CDRH, CBER Premarket
Page 10 of 12 Title 18 The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)] - Guidance for Industry and Food and Drug Administration Staff List of Guidance Issued by FDA Since Implementation of the Safety Assurance Case Requirement Date Issued FDA Organization Subject 7/28/2014 CDRH, CBER Premarket, Administrative / Procedural Status 19 Types of Communication During the Review of Medical Device Submissions - Guidance for Industry and Food and Drug 20 Requests for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with Food and Drug - Guidance for Industry and Food and Drug 4/4/2014 CDRH, CBER Premarket 2/18/2014 CDRH Premarket *Pump sensor systems are Class III devices which require compliance with PMA guidance.
Page 11 of 12 List of Strengthened Standards Number Title Date 1 ANSI/AAMI ES 60601-1 2 UL 60601-1 National Deviations Medical electrical equipment - Part 1: General requirements for safety. Corr. 1 2009, AMD 1 2012 and AMD 2 2012. All R(2012) National Deviations - IEC 60601-1 3rd Edition, for United States 3rd Edition 2005 (R 2012) Consolidated reprint UL 60601-1 National Deviations FDA Recognition Number 19-4 Not found 3 IEC 60601-1-2 Collateral Standard: EMC - Requirements and tests IEC 60601-1-2 19-8 4 IEC 60601-1-6 Collateral standard: Usability 3.1 Edition 2013 Consolidated reprint 5-89 6 IEC 60601-1-8 Collateral standard: Alarm systems 2.1 Edition 2012 Consolidated reprint 5-92 5-96 7 IEC 60601-2-24 Particular requirements for the safety of infusion pumps and controllers. 8 IEC 60529 Degrees of Protection (IP code). Including CORR1:2013 and CORR2:2015 Edition 2.0 2012 Edition 2.2 2013 Not found 9 IEC 62304 Software life-cycle process 2006 13-79
Page 12 of 12 List of Strengthened Standards Number Title Date 10 ANSI/AAMI HE75 General human factors engineering principles 2009 (R2013) 5-57 FDA Recognition Number 11 IEC 62366 Application of Usability Engineering 12 ISO 14971 Application of risk management to medical devices 13 ISO 15223-1 Symbols on Labels and Labeling 1.1 Edition 2014 5-87 2nd Edition 2007 5-40 2012 5-90