FOOD AND DRUG ADMINISTRATION MODERNIZATION ACT OF 1997 (FDAMA)¹

Over the past 25 years, a series of laws changed the medical device regulation landscape. FDAMA marked the FDA’s first steps into the modern age and began a series of legislative initiatives aimed at streamlining the device approval process, while still maintaining appropriate standards for safety and efficacy. According to the FDA, this piece of legislation instituted the “most wide-ranging reforms in agency practices since 1938.”² These reforms included codification of an alternative, streamlined path for 510(k) approval of certain devices (the “Third-Party Review Program”). Under the Third-Party Review Program, the FDA accredited certain outside private parties (“Accredited Persons”) to conduct the primary review of 510(k) reports for “low-to-moderate risk” devices.³ This program did not permit Accredited Persons to review 510(k) reports for Class II devices “intended to be permanently implantable or life sustaining or life supporting” or that require clinical data under 510(k), or for any Class III device. Instead, Accredited Persons were permitted to review 510(k) reports for any Class I device that was not exempt from 510(k), as well as 30 different Class II devices.⁴ Notably, FDAMA obligated the FDA to issue a final determination regarding a device’s initial classification within 30 days of receiving a recommendation from an Accredited Person.⁵ This legislation benefited the FDA, the public and medical device manufacturers in that it relieved the FDA of some of its burdens (which, in turn, permitted the FDA to focus its resources on higher-risk devices), and it offered manufacturers a faster method for obtaining clearance. Consistent with this spirit of safety, speed and efficiency, FDAMA also directed the FDA to conduct priority review of devices: (1) that represented breakthrough technologies, (2) that had no approved alternatives, (3) that offered “significant advantages over existing approved alternatives,” or (4) whose availability was in the “best interest of the patients.”⁶

FDAMA’s importance is not limited to the Third-Party Review Program or its priority review provisions. This legislation is also noteworthy in that it changed the scope and obligations of post-market surveillance. As noted in the preceding section, SMDA compelled the FDA to require manufacturers to conduct postmarket surveillance on any device that: (1) was “a permanent implant the failure of which may cause serious, adverse health consequences or death;” (2) was “intended for a use in supporting or sustaining human life;” or (3) “potentially present[ed] a serious risk to human health.”⁷ The FDA had discretion to order surveillance if it determined that it was “necessary to protect the public health or to provide safety or effectiveness data for the device.”⁸ Under that statutory scheme, the FDA required postmarket surveillance on 18 devices.⁹ FDAMA altered the landscape of postmarket surveillance in that the FDA, itself, was no longer compelled to order manufacturers to conduct postmarket surveillance.¹⁰ Instead, the FDAMA granted discretion to the FDA to order any manufacturer of a Class II or Class III device to conduct postmarket surveillance if: (1) the failure of the device would “be reasonably likely to have serious adverse health consequences;” or (2) the device was intended to be “implanted in the human body for more than one year;” or (3) the device was intended to be “a life sustaining or life supporting device used outside a device user facility.”¹¹

MEDICAL DEVICE USER FEE AND MODERNIZATION ACT OF 2002 (MDUFMA)¹²

MDUFMA was borne from Congress’s two-pronged realization that “prompt approval and clearance of safe and effective devices is critical to the improvement of the public health” and that this could not be accomplished without additional FDA funding.¹³ The FDA has succinctly (and broadly) described MDUFMA as the program under which “The FDA collects fees from manufacturers seeking to market medical devices, which helps the agency improve the timeliness, quality and predictability of its overall premarket review program.”¹⁴ Prior to MDUFMA, “The FDA’s medical device program suffered a long-term, significant loss of resources that undermined the program’s capacity and performance.”¹⁵ MDUFMA helped remedy that situation by providing additional funds for postmarket surveillance ($3,000,000 in 2003; $6,000,000 in 2004; and “such sums as may be necessary” for 2005 forward).¹⁶

MDUFMA did more than simply increase the FDA’s funding. It continued the Third-Party Review Program through 2007,¹⁷ and also expanded the program to include the inspection of manufacturing facilities for Class II and Class III devices.¹⁸ MDUFMA required device manufacturers to “prominently and conspicuously” place their name or symbol on devices, unless the FDA determined that it would not be feasible or would jeopardize the device’s safety and effectiveness.¹⁹ MDUFMA also introduced electronic labeling and registration of devices.²⁰

MEDICAL DEVICES TECHNICAL CORRECTIONS ACT OF 2004 (“MDTCA”)²¹

MDTCA cleaned up MDUFMA by clarifying language that the FDA described as “potentially confusing” as well as instituting changes on a more substantive level.²² MDTCA dispelled any doubt that the FDA has the authority to withdraw the accreditation of any Accredited Person if it determined that he or she had a financial conflict of interest with the owner or operator of an establishment inspected by the Accredited Person.²³ It also specified that the FDA can “suspend an establishment’s eligibility to use third-party inspections if the FDA finds the establishment is substantially not in compliance with statutory requirements.”²⁴ This act trimmed some of the statutory requirements of third-party inspections²⁵ and further modified MDUFMA to allow for inspections to be completed in phases within a two-year period.²⁶ MDTCA delayed implementation of MDUFMA’s requirement that devices bear the manufacturer’s name to give “the FDA and industry more time to determine how best to implement [this requirement], … [a] task [that] is still considered very challenging.”²⁷

MEDICAL DEVICE USER FEE AMENDMENTS OF 2007 (“MDUFA II”)²⁸

MDUFA II was part of the Food and Drug Administration Amendments Act of 2007 (FDAAA).²⁹ FDAAA was hailed as “landmark FDA legislation.”³⁰ At the time MDUFA II was passed, Dr. Randall Lutter, the FDA’s Deputy Commissioner for Policy, commented that the fees collected under MDUFA accounted for a large part of the FDA’s total budget, and that the continued existence of this funding was “crucial for the Agency’s ability to efficiently and effectively carry out some of its most essential public health functions.”³¹ Dr. Janet Woodcock, then the FDA’s Deputy Commissioner for Science and Medical Programs and Chief Medical Officer, observed that the FDA “spend[s] a lot of time – we spend at least 50% of our time on safety throughout the product life cycle.”³² It is no wonder that MDUFA allocated significant funds to the FDA for postmarket safety surveillance ($7,100,000 in 2008; $7,455,000 in 2009; $7,827,750 in 2010; $8,219,138 in 2011; and $8,630,094 in 2012).³³ MDUFA also continued the FDA’s Third-Party 510(k) review program through 2012.³⁴ It further authorized the FDA to establish regulations regarding a unique device identification system for medical devices (with some exceptions).³⁵

In addition to including MDUFA II, FDAAA was an important piece of legislation because it mandated the collection of adverse-event information in an electronic format.³⁶ As Dr. Woodcock noted:

[W]e get the vast majority of our reports from the manufacturers. What changes here is not a new requirement on healthcare professionals, but rather mandate that the FDA work with the healthcare systems and others to get the data that is now available in electronic form and use that. Because that data is much more complete. We think that only about one in 10 serious adverse events are reported to the FDA now, whereas if we were using a healthcare system that really captured all its patients, we could probably find most of them and also know how many people are actually taking the drug or using the device. So this is actually a totally new approach.³⁷

This “totally new approach” dramatically changed how adverse–event data is collected and analyzed. In fact, the FDA’s active surveillance system, the Sentinel Initiative, was established as a direct result of FDAAA.³⁸ Presently, Sentinel uses information collected from healthcare information facilities to monitor the safety of drugs. However, Sentinel will eventually be used to survey the safety of medical devices as well.

MEDICAL DEVICE USER FEE AMENDMENTS OF 2012 (“MDUFA III”)³⁹

MDUFA III was part of the Food and Drug Administration Safety and Innovation Act (FDASIA).⁴⁰ According to the FDA, “[u]ltimately, MDUFA III represents a commitment between the U.S. medical device industry and the FDA to increase the efficiency of regulatory processes in order to reduce the time it takes to bring safe and effective medical devices to the U.S. market.”⁴¹ As one might expect, device user fees were continued under MDUFA III. It is anticipated that the FDA will collect over $595,000,000 in fees over five years ($97,722,301 in 2013; $112,580,497 in 2014; $125,767,107 in 2015; $129,339,949 in 2016; $130,184,348 in 2017).⁴² MDUFA reauthorized the third-party review of 510(k) submissions and inspection of manufacturing facilities through 2017.⁴³ However, MDUFA III also sought to improve both the device approval process and the outcome of the process. For example, as outlined in the MDUFA III commitment letter, the FDA sped up the device review process by establishing objective criteria for its “refuse to accept” and “refuse to file” checklists, with those checklists being published prior to finalization.⁴⁴

Additionally, FDASIA improved the regulatory scheme for medical devices. For example, it clarified the “least burdensome” standard” for premarket approval under section 515 and premarket notification under section 510(k).⁴⁵ Regarding premarket approval, FDASIA defined “necessary” data considered by the FDA in evaluating device effectiveness as the “minimum required information that would support a determination…that an application provides reasonable assurance of the effectiveness of the device.”⁴⁶ Insofar as premarket notification is concerned, FDASIA specified that the “necessary” information requested by the FDA in evaluating substantial equivalence is the “minimum required information that would support a determination of substantial equivalence between a new device and a predicate device.”⁴⁷ FDASIA also required the FDA to provide a “substantive summary of the scientific and regulatory rationale for any significant decision” by CDRH concerning 510(k) reviews or reports, applications under section 515, and applications for exemption under section 520(g).⁴⁸ FDASIA provided applicants with a remedy if they disagreed with the decision: “supervisory review” of the decision.⁴⁹ FDASIA further directed the FDA to institute a program to improve the device recall system that would at least collect trend information regarding the number and types of device recalls, the identity of devices that are most frequently recalled, and the causes of device recalls.⁵⁰ The program is also to include, inter alia, the creation of criteria to evaluate the effectiveness of the correction or action plan for recalls and establish a system to “routinely and systematically assess information relating to device recalls.”

FDASIA modified the de novo application process⁵¹ and revised the reclassification procedure for devices.⁵² Generally the de novo process was revised by permitting a person to request the FDA to classify a device if that person determined that there was “no legally marketed device upon which to base a determination of substantial equivalence.”⁵³ If there was, in fact, such a legally marketed device, then the FDA could decline the request for classification. The FDA could also decline the request if it determined that the device was not low-to-moderate risk “or that general controls would be inadequate to control the risks and special controls to mitigate the risks cannot be developed.”⁵⁴ FDASIA permitted the FDA to reclassify a device based on new information. This may be initiated either sua sponte by the agency or by petition of an interested person.⁵⁵ A Class III device may be reclassified:

• to Class II if “special controls would provide reasonable assurance of the safety and effectiveness of the device and that general controls would not provide reasonable assurance of the safety and effectiveness of the device.”⁵⁶
• to Class I if “general controls would provide reasonable assurance of the safety and effectiveness of the device.”⁵⁷

THE NEW 510(K) GUIDANCE DOCUMENT

On July 28, 2014, the FDA released a new guidance document titled The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications.⁵⁸ The purpose of this guidance is to “identify, explain and clarify each of the critical decision points in the decision-making process the FDA uses to determine substantial equivalence.” ⁵⁹ We hope to provide you with an article discussing this new guidance document in an upcoming edition of Pro Te.

CONCLUSION

The medical device industry has come a long way since the Pure Food and Drugs Act of 1906. From “devices” such as height-stretching machines and nose straighteners to state-of-the-art heart valves. The FDA has to meet the challenge of keeping up with the ever-growing number of medical devices. There is a definite legislative trend toward “greater speed and efficiency” of device approval, without sacrificing safety or efficacy. From an aerial view, the programs flowing from these various legislative efforts carry with them a sense that the FDA is groping for near-omniscience (e.g., electronic collection of adverse event data, the Sentinel Initiative, the recall improvement program, etc.). Hopefully, these statutes and initiatives will continue to facilitate the development of new, life-improving medical devices.

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[1] Food and Drug Administration Modernization Act of 1997, 105 P.L. 115, 111 Stat. 2296.

[2] See http://www.fda.gov/AboutFDA/WhatWeDo/History/Milestones/ucm128305.htm.

[3] FDAMA, § 210; Implementation of Third Party Programs Under the FDA Modernization Act of 1997; Final Guidance for Staff, Industry and Third Parties (2001), http://www.fda.gov/MedicalDevices/Device
RegulationandGuidance/GuidanceDocuments/ucm094450.htm, Last accessed August 7, 2014.

[4] FDAMA, § 210; Implementation of Third Party Programs Under the FDA Modernization Act of 1997; Final Guidance for Staff, Industry and Third Parties (2001), http://www.fda.gov/MedicalDevices/Device
RegulationandGuidance/GuidanceDocuments/ucm094450.htm, Last accessed August 7, 2014.

[5] FDAMA, § 210.

[6] Id.

[7] SMDA, § 10.

[8] Id.

[9] U.S. Food and Drug Administration, SMDA to FDAMA: Guidance on FDA’s Transition Plan for Existing Postmarket Surveillance Protocols, (November 2, 1998), Available at http://www.fda.gov/downloads/MedicalDevices/
DeviceRegulationandGuidance/GuidanceDocuments/ucm106754.pdf. Last accessed August 7, 2014.

[10] U.S. Food and Drug Administration, FDAMA, § 212; SMDA to FDAMA: Guidance on FDA’s Transition Plan for Existing Postmarket Surveillance Protocols, (November 2, 1998.), Available at http://www.fda.gov/downloads/MedicalDevices/
DeviceRegulationandGuidance/GuidanceDocuments/ucm106754.pdf. Last accessed August 7, 2014.

[11] U.S. Food and Drug Administration, FDAMA, § 212; SMDA to FDAMA: Guidance on FDA’s Transition Plan for Existing Postmarket Surveillance Protocols (November 2, 1998),. Available at http://www.fda.gov/downloads/MedicalDevices/
DeviceRegulationandGuidance/GuidanceDocuments/ucm106754.pdf. Last accessed August 7, 2014.

[12] Medical Device User Fee and Modernization Act of 2002, 107 P.L. 250, 116 Stat. 1588.

[13] Id., § 104.

[14] See http://www.fda.gov/MedicalDevices/Device
RegulationandGuidance/Overview/MedicalDeviceUserFeeandModernizationActMDUFMA/ucm109317.htm, last accessed August 7, 2014.

[15] See http://www.fda.gov/MedicalDevices/Device
RegulationandGuidance/Overview/MedicalDeviceUserFeeandModernizationActMDUFMA/ucm109149.htm, last accessed August 7, 2014.

[16] MDUFMA, § 104

[17] MDUFMA, § 202.

[18] Id., § 201.

[19] Id., § 301

[20] Id., §§ 206, 207.

[21] Medical Devices Technical Corrections Act of 2004, 118 Stat. 572; 108 P.L. 214.

[22] Summary of the Medical Devices Technical Corrections Act (November, 2004),. Available at http://www.fda.gov/downloads/MedicalDevices/Device
RegulationandGuidance/Overview/MedicalDeviceUserFeeandModernizationActMDUFMA/ucm109131.pdf. Last accessed August 7, 2014.

[23] MDTCA, § 2(b)(1)(B).

[24] Summary of the Medical Devices Technical Corrections Act (November, 2004),. Available at http://www.fda.gov/downloads/MedicalDevices/Device
RegulationandGuidance/Overview/MedicalDeviceUserFeeandModernizationActMDUFMA/ucm109131.pdf. Last accessed August 7, 2014.

[25] Medical Devices Technical Corrections Act of 2004, § 2(b)(1)(C).

[26] Id., § 2(b)(1)(C)(ii)(I).

[27] Id., § 2(c)(1); Summary of the Medical Devices Technical Corrections Act (November, 2004),. Available at http://www.fda.gov/downloads/MedicalDevices/Device
RegulationandGuidance/Overview/MedicalDeviceUserFeeandModernizationActMDUFMA/ucm109131.pdf. Last accessed August 7, 2014.

[28] MDUFA II, 110 P.L. 85, 121 Stat. 823, §§ 201-230.

[29] Food and Drug Administration Amendments Act, 110 P.L. 85, 121 Stat. 823.

[30] FDA Media Teleconference, Food and Drug Administration Act of 2007 (September 27, 2007),. Available at http://www.fda.gov/downloads/NewsEvents/
Newsroom/MediaTranscripts/UCM123579.pdf. Last accessed August 7, 2014.

[31] Id.

[32] Id.

[33] MDUFA II, 110 P.L. 85, 121 Stat. 823, § 215.

[34] Id., at § 221.

[35] Id., at § 226.

[36] FDAA, § 905.

[37] FDA Media Teleconference, Food and Drug Administration Act of 2007 (September 27, 2007). Available at, http://www.fda.gov/downloads/NewsEvents/
Newsroom/MediaTranscripts/UCM123579.pdf. Last accessed August 7, 2014.

[38] See http://www.fda.gov/Safety/FDAsSentinelInitiative/ucm149340.htm. Last accessed August 7, 2014.

[39] MDUFA III, 112 P.L. 144, 126 Stat. 993, §§ 201-208. See also: “There is an App for That: Adverse Event Reports and the Sentinel Initiative,”, Pro Te Solutio, Vol. 7, No. 2 , June 2014.

[40] Food and Drug Administration Safety and Innovation Act of 2012, 112 P.L. 144, 126 Stat. 993.

[41] See http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/
SignificantAmendmentstotheFDCAct/FDASIA/ucm313695.htm. Last accessed August 7, 2014.

[42] § 203(b)(3).

[43] Section 611, 612.

[44] MDUFA III Commitment Letter. Available at er, http://www.fda.gov/downloads/MedicalDevices/
NewsEvents/WorkshopsConferences/UCM295454.pdf. Last accessed August 7, 2014.

[45] FDASIA, § 602.

[46] Id., at § 602(a).

[47] Id., at § 602(b).

[48] Id., at § 603.

[49] Id.

[50] Id., at § 605.

[51] Id., at § 607.

[52] Id., at § 608.

[53] Id., at § 607.

[54] Id., at § 607(a)(3).

[55] § 608 (a).

[56] Id.

[57] Id.

[58] See http://www.fda.gov/downloads/MedicalDevices/Device
RegulationandGuidance/GuidanceDocuments/UCM284443.pdf. Last accessed August 7, 2014.

[59] Id.

Finis