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  • EXPEDITING THE DRUG APPROVAL PROCESS: AN ANALYSIS OF THE FDA MODERNIZATIONACT OF 1997Author(s): Deborah G. ParverSource: Administrative Law Review, Vol. 51, No. 4 (Fall 1999), pp. 1249-1266Published by: American Bar AssociationStable URL: http://www.jstor.org/stable/40710059 .Accessed: 11/06/2014 01:22

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    ACT OF 1997

    Deborah G. Parver*

    Table of Contents

    Introduction 1249 I. Background 1252 II. Provisions of FDAMA that Expedite the Drug Approval Proc-

    ess 1258 A. The Reinstatement of PDUFA 1258 B. Expediting Study and Approval of Fast Track Drugs 1 26 1 C. International Harmonization 1263

    III. Potential Public Health Consequences Related to Expedited Drug Review 1264

    Conclusion 1266


    Since the 1970s, the Food and Drug Administration (FDA) has been highly criticized for the length of time needed to approve new and benefi- cial drugs.1 The FDA is often chastised for its overly bureaucratic drug ap-

    * J.D. Candidate, 2000, Washington College of Law, American University; B.A., University of Michigan, 1996. Articles Editor, Administrative Law Review, 1999-2000. The author would like to thank her family and friends for their constant encouragement and support.

    1. See Michael D. Green, Safety as an Element of Pharmaceutical Quality: The Re- spective Roles of Regulation and Tort Law, 42 St. LOUIS U. L.J. 163, 164 (1998) (noting that due to "contemporary criticism" of "overcautious" drug approval process, current re- form proposals focus on acceleration of new drug approval).


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    provai process,2 and for causing the United States to lag behind other countries that have expeditiously approved and marketed new therapies.3 Although concern has been voiced for years regarding the drug approval process, Congress did not prioritize comprehensive FDA reform until after the congressional elections of 1994.4

    After three years of debate, Congress passed the FDA Modernization Act of 1997 (FDAMA),5 which instituted major reforms to the Federal Food, Drug, and Cosmetic Act of 1938 (Act of 1938).

    6 Through FDAMA,

    Congress emphasized that the FDA's mission is not only to prevent the distribution of unsafe products, but also to review and approve new drugs in a timely, manner.

    7 Accordingly, Congress set forth numerous provisions

    2. See S. Rep. No. 105-43, at 6 (1997) (stating that FDA's requirements for clinical testing and its review of new products have grown time-consuming, complex, and costly); see also Doug Bandow, Deregulation: The FDA Can Be Hazardous to Your Health, Fortune, Nov. 1996, at 56 (concluding that American drug manufacturers could discover and market new medical treatments if federal government eased its "stultifying regulation" by removing its "roadblocks" to development, testing, and marketing of new drugs).

    3. See Richard A. Merrill, The Architecture of Government Regulation of Medical Products, 82 Va. L. Rev. 1753, 1754 (1996) (finding that unfavorable comparisons in terms of access to new drugs are often drawn between United States and its major trading partners such as Northern Europe, Canada, and Japan). This delay in drug approval is commonly referred to as the "drug lag."

    4. See Margaret Gilhooley, The Administrative Conference and the Progress of Food and Drug Reform, 30 Ariz. St. L.J. 129, 133 (1998) (stating that legislative and executive branches focused on regulation without undue hardship to FDA). "Every administration in the past 20 years has recognized the need for modernizing the FDA's product approval sys- tem to bring into better balance the need to facilitate the development, testing, and timely approval of safe and effective products that benefit the public." S. Rep. No. 105-43, at 10 (1997).

    5. Pub. L. No. 105-115, 111 Stat. 2296 (1997) (to be codified at 21 U.S.C. 310). FDAMA has been described as '"the most important change in drug regulation in twenty years.'" Charles Marwick, Implementing the FDA Modernization Act, 279 JAMA 815 (1998) (quoting Sharon Smith Houston, Deputy Commissioner for External Affairs of FDA).

    6. Pub. L. No. 75-717, 52 Stat. 1040 (1938) (coditied as amended at 21 U.S.C. 301 (1994)).

    /. ee Larry k. mot & uaniei k. waiamann, tooa ana urug Aaministranon Moa- ernization Act of 1997: Medical Device Provisions, 53 FOOD & DRUG L.J. 267 (1998) (de- tailing history of FDA's regulation of medical devices). In 1989, the Secretary of Health and Human Services chartered the Advisory Committee on the FDA to examine the mission, responsibilities, and structure of the FDA. See S. Rep. No. 105-43, at 8 (1997). The Com- mittee found that:

    [T]he agency should be guided by the principle that expeditious approval of useful and safe new products enhances the health of the American people. Approving such products can be as important as preventing the marketing of harmful or ineffective products. This is especially true for people with life-threatening illnesses and for dis- eases for which alternative therapies have not been approved.

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  • 1 999] FDA MODERNIZATION ACT 1 25 1

    in FDAMA that will expedite the drug approval process considerably, such as: reinstating the Prescription Drug User Fee Act of 1992 (PDUFA),8 fa- cilitating the accelerated approval of drugs for serious or life-threatening conditions,9 and promoting the FDA's cooperation with other countries to harmonize regulatory requirements.10

    Despite Congress's apparent interest in expediting the drug approval process, FDAMA is indicative of Congress's reluctance to strip the FDA of its monopoly over prescription drug approvals.11 For instance, although FDAMA expressly allows the FDA to contract out to accredited third par- ties to review and approve applications for low to moderate risk medical devices,12 FDAMA does not contain any provisions that expressly provide for third party review of new drug applications.13 Utilizing outside experts to review new drug applications may contribute significantly to expediting the approval process, but the FDA is highly unlikely to allow third parties to review drugs for approval.14

    This Comment analyzes provisions of FDAMA that focus on expedited drug approval, and discusses the tension between the public health interest in the production and approval of safe and efficacious drugs and the need for an accelerated drug approval process. Part I examines the background of the modern drug approval process prior to the passage of FDAMA, in-

    Id. 8. Pub. L. No. 102-571, 106 Stat. 4491 (1992) (codified as amended at 21 U.S.C.

    379g-h (1994 & Supp. Ill 1997)). 9. See 1 12, 1 1 1 Stat. at 2309-12.

    10. See 410, 1 1 1 Stat. at 2372-73. 1 1 . ee Michael I. Krauss, Breaking the FDA s Drug Approval Monopoly: Implications

    for Tort Law and Consumer Welfare (visited Sept. 23, 1998) [hereinafter Krauss].

    12. See 210, 111 Stat. 2342-45 (1997) (to be codified at 21 U.S.C. 360(m)). The FDA has classified medical devices into one of three regulatory classes. Joel Hoffman, The Food and Drug Administration's Administrative Procedures, in FOOD AND DRUG Law 18 (Richard M. Cooper ed., 1991). Class I devices are generally not used to support or sustain life, and do not pose a potentially unreasonable risk of injury or illness. Id. When general controls, "such as the misbranding and adulteration provisions, are insufficient in regards to a device, and a pre-marketing approval requirement would be burdensome," those devices are classified as Class II devices and performance standards are set. Id. Finally, Class III devices require pre-market clearance, they are used to support or sustain life, and they may present a "potential unreasonable risk that cannot adequately be regulated by a performance standard." Id.

    13. See 415, 111 Stat. at 2377-78 (allowing outside contractors to review applications but not requiring FDA to use outside experts or to issue any guidance documents or regula- tions to mandate this provision).

    14. See generally 143 Cong. Rec. S 12,24 1-42 (exemplifying Congress's difficulty in codifying third-party approval of low-risk medical devices because of public health con- cerns).

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    eluding a discussion of the 1962 Amendments to the Federal Food, Drug, and Cosmetics Act , and the Prescription Drug User Fee Act of 1992. Part II analyzes certain provisions of FDAMA that are directed at expediting the approval process. Part III evaluates FDAMA's effect on public health is- sues in light of the expedited review process. This Comment concludes that FDAMA's implementation will expedite the drug approval process; however, the FDA must actively ensure that public health will not suffer as a result.

    I. Background The FDA's regulatory authority over drugs has increased tremendously

    throughout the agency's history.15 The Federal Food, Drug, and Cosmetic Act of 1938 (1938 Act) was Congress's first piece of legislation that authorized the FDA to promulgate rules and regulations.16 The 1938 Act also created a pre-market approval requirement for new drugs.17 A drug manufacturer was required to inform the FDA of its "new drug"18 by sub- mitting a new drug application (NDA), which, in effect, gave the FDA time to approve the drug before releasing it into the market.19 If the FDA did not affirmatively respond to the NDA within sixty days, the manufacturer could proceed with further testing and development.20

    After the implementation of the 1938 Act, Congress passed additional statutes that broadened the FDA's regulatory authority.21 Specifically, the 1962 Amendments were instrumental in changing the drug approval proc-

    15. See generally Hoffman, supra note 12, at 1. Prior to the Food, Drug, and Cosmetic Act of 1938, the FDA merely was responsible for the policing of statutory violations such as the shipment or delivery in interstate commerce of adulterated or misbranded food. Merrill, supra note 3, at 1762. Also, a drug manufacturer could market and develop drugs without the FDA's involvement, and if the FDA doubted the safety of a drug, the FDA had the bur- den of proving that the drug was dangerous. Id. at 1797.

    16. See Hoffman, supra note 12, at 16. 17. See id. 18. A "new drug" is defined as "any drug the composition of which is such that such

    drug is not generally recognized, among experts qualified by scientific training and experi- ence to evaluate the safety of drugs, as safe for use under the conditions prescribed, recom- mended, or suggested in the labeling thereof." 201(p)(l), 52 Stat. at 1041-42.

    19. See Merrill, supra note 3, at 1762 (reporting that 1938 Act did not apply to drugs that were not new, and manufacturers could dodge regulations by introducing a drug made up of materials that were "generally recognized as safe").

    20. See Richard M. Goodman & Paul D. Rheingold, Lawyer's Drug Handbook 30 (1967) (stating that unless FDA found and reported to manufacturer that it lacked suffi- cient information to determine drug's safety, drug would automatically be approved).

    21. See S. Rep. No. 105-43, at 6 (1997) (describing various acts and amendments passed to expand "regulatory reach").

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    ess.22 Under the 1962 Amendments, a "new drug"23 could not be marketed unless the FDA found that it met certain safety and efficacy standards.24 Moreover, the FDA gained control over the design and structure of clinical trials, and required manufacturers to prove that a new drug was effective under the "substantial evidence"25 standard.26 Thus, the FDA had the ulti- mate authority over drug approval, and, consequently, manufacturers began to adapt to the FDA's slow approval process.27

    Development, testing, and subsequent approval of a new drug could take

    approximately fifteen years.28 Several factors contributed to the lengthy approval process.29 The FDA, however, was primarily responsible for the

    22. See Hoffman, supra note 12, at 16 ("The purpose of the 1962 Amendments was to strengthen the laws to keep unfit drugs off the market in the first instance and speed their removal should they reach the market.") (quoting S. Rep. No. 87-1744, at 8 (1962)). The 1962 Amendments were passed in response to the Thalidomide tragedy in Europe. See Merrill, supra note 3, at 1764 n. 35. Thalidomide was a sedative prescribed to pregnant women, and it caused severe birth defects. Id. Most commonly, children were born with a flipper-like arm or leg. Merrill, supra note 3, at 1765 n.3 5. Id. The United States escaped the tragedy because the FDA had not approved the new drug application. Id. Dr. Frances O. Kelsey, the reviewer of Thalidomide, was awarded the Presidential Award of Distin- guished Federal Civilian Service from President Kennedy. See Elizabeth M. Rutherford, The FDA and "Privatization" - The Drug Approval Process, 50 FOOD & Drug L.J. 203, 212(1995).

    23. Congress expanded the statutory definition of "new drug to include, "any drug that was not generally recognized by experts as safe and effective." See Merrill, supra note 3, at 1765.

    24. See GOODMAN & RHEINGOLD, supra note 20, at 31 (1967) (explaining that h DA had 180 days to respond to new drug applications, which are subject to considerable exten- sions).

    25. 21 U.S.C. 355(d) (1994 & Supp. Ill 1997). Substantial evidence was defined as "evidence consisting of adequate and well-controlled investigations including clinical in- vestigations, by qualified experts . . . ." Id.

    26. See Merrill, supra note 3, at 1767 (concluding that FDA was strongest source of guidance for clinical trials in the country and maybe the world).

    27. See id. at 1765. The FDA would often extend the 180-day time period by "re- starting the clock" each time a manufacturer changed an application. Also, reviewers were unwilling to speed up their rulings on completed applications. See id. But see Joshua Wolf Shenk, WARNING: Cutting the FDA Could Be Hazardous to Your Health, WASH. Monthly, Jan.-Feb. 1996, at 17, 22-23 (arguing that despite drug manufacturer's allega- tions that drug approval process became slower and more bureaucratic since 1 962 Amend- ments, pharmaceutical companies' stock has become over a hundred times more valuable).

    28. See PHRMA Publications, Industry Profile 1998 (visited Sept. 23, 1998) [hereinafter PHRMA Publications]. According to the Pharmaceutical Research and Manufacturers Association (PHRMA), it costs an average of $500,000,000 to develop one new drug, and of the 5,000 to 10,000 "chemically synthesized molecules" examined by the FDA, only one ever becomes an approved drug. Id.

    29. See Kenneth I. Kaitlin, FDA Reform: Setting the Stage for Efforts to Reform the

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    time-consuming process.30 The FDA required pharmaceutical companies to submit an investigational new drug application (IND), consisting of the new chemical compound's test information and an evaluation of its safety and proposed biological uses.31 If the FDA accepted the IND,32 the phar- maceutical company would undertake three phases of human clinical stud- ies.33 After all three phases were completed, the pharmaceutical company would submit the new drug application (NDA) to the FDA.34 Although the statutory time limit for the review period was six months,35 the average re- view time for all NDAs was significantly longer.36 In contrast, the FDA codified a provision in 1987 that allowed persons with serious or life- threatening illnesses, such as AIDS, to use investigational new drugs that were still undergoing further clinical trials.37

    Agency, 31 Drug Info. J. 22, 29 (1997). The Tufts Center for the Study of Drug Develop- ment found that pharmaceutical companies often increase clinical development time when they design their pre-clinical and clinical studies to satisfy regulatory requirements in vari- ous countries. Id. Also, drugs aimed to treat persistent, life-threatening diseases typically take longer to develop because of the scientific complexity of the drugs. Id.

    30. See Rutherford, supra note 22, at 213-14 (describing 12-year development and ap- proval process).

    31. See 48 Fed. Reg. 26,720, 26,723 (1983) (codified as amended at 21 C.F.R. 312.23(a) (1999)) (proposed Jun. 9, 1983); see also Rutherford, supra note 22, at 212 (stating that pre-clinical testing process is conducted in laboratory and on animals and usu- ally takes approximately 3.5 years). The pharmaceutical company submits all of its clinical research data on the pharmacology, toxicology, and chemistry of the drug. See 21 C.F.R. 312.23(a)(1999).

    32. When the FDA makes its decision on the IND, it considers the protection of the potential human research subjects, the adequacy of the animal studies, the scientific merits of the research plan, and the qualifications of the investigator. See 21 C.F.R. 312.23(a). If the FDA does not respond to the IND within thirty days, the IND will become effective. Id. 312.40(b)(l).

    33. See Rutherford, supra note 22, at 213. Phase I, which usually lasts one year, in- volves 21 hundred healthy volunteers, and potential side effects are identified and dosages are determined. See PHRMA Publications, supra note 28. Phase II, which lasts about two years, involves 100 to 300 volunteers who have the targeted disease, and the trials mainly evaluate effectiveness. Id. Phase III involves 1000 to 5000 patients (and sometimes thou- sands more) in clinics and hospitals, and it is closely monitored to determine the drug's safety and efficacy. Id. Since the 1980s, the average number of clinical trials has more than doubled, and three times the number of patients were involved in such trials. Id.

    34. See id. 35. See 21 U.S.C. 355(c)(l) (1994). 36. See Rutherford, supra note 22, at 213 (finding that FDA averages 30 months to re-

    view an NDA). The average review time for the NDAs approved in 1997 was approxi- mately 16 months. See PHRMA Publications, supra note 28. In fact, the FDA's own "budget justification" for fiscal year 1998 indicated that it takes the FDA an average of 12 months longer than the statutory time limit to review NDAs. See S. Rep. No. 105-43, at 7 (1997).

    37. See 21 C.F.R. 312.34 (1999). The FDA codified this policy as a result of extreme

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    Consequently, drug manufacturers had no choice but to wait until the FDA decided to act on their NDAs.38 The FDA claimed that part of the delay in reviewing NDAs was due to the agency's inability to hire more re- viewers because of budget constraints.39 Subsequently, Congress enacted the Prescription Drug User Fee Act of 1992 (PDUFA),40 which required manufacturers to pay a certain fee upon submission of their NDA.41 The FDA agreed to use the fees to hire additional reviewers, and committed it- self to performance goals that would elicit support for PDUFA from drug manufacturers.42 In order to assess the FDA's success in achieving its goals, PDUFA was only authorized for five years, after which it would be evaluated for reinstatement.43

    PDUFA was successful, and the funds from the user fees have allowed the FDA to hire 600 new drug reviewers.44 Since the passage of PDUFA, the average FDA approval time has decreased from thirty to fifteen months.45 In 1995, FDA Commissioner David Kessler, M.D., reported that

    political pressure from AIDS groups. See Rutherford, supra note 22, at 219. The instant effect of this regulation was to permit more than 4,800 AIDS patients to use zidovudine (AZT) while it was still an IND. Id. The FDA issued another provision that would basi- cally eliminate the need for Phase III review because the manufacturer and the FDA under- went extensive consultation on the design of the clinical investigation of a drug. See 21 C.F.R. pt. 312, subpt. E (1999). As a result, AZT was approved two years after human testing began, as opposed to the typical approval time of six years at that time. See Ruther- ford, supra note 22, at 219-20.

    38. See Merrill, supra note 3, at 1798 (describing approval process as "being held hos- tage" to factors beyond manufacturer's control).

    39. See id. (illustrating other circumstances beyond FDA s control, including compe- tence of reviewers, agency's ability to coordinate with expert advisory committees, and de- mands on reviewers to perform other assigned duties).

    40. See 21 U.S.C. 379g-h. Primarily Senators Edward Kennedy (D-Mass.) and Orrin Hatch (R-Utah) and Representative Henry Waxman (D-Cal.) guided PDUFA, known as the "Waxman-Hatch Amendments," through Congress. Merrill, supra note 3, at 1794. PDUFA did not change the FDA's standards or the drug approval process itself. Id. at 1794-95.

    41. See 21 U.S.C. 379h. The Act established a fee schedule that was subject to infla- tion and was correlated with the FDA's resources. Id. For example, in 1993, an NDA would have a $100,000 fee. That rate would rise to $233,000 in 1997.

    42. In 1992, former tu A Commissioner David Kessler, M.D., set forth the agency s performance goals and commitments in various letters to the House and Senate. See Merrill, supra note 3, at 1795 n. 131. Some of the FDA's commitments included: "(1) to act on completed priority applications and amendments within six months of submission; . . . and (4) to eliminate the backlog of overdue applications within twenty-four months." See id.

    43. See 21 U.S.C. 379g (giving termination date). 44. See 143 Cong. Rec. S 12,244 (daily ed. Nov. 9, 1997) (statement of Sen. Mikulski). 45. See Nancy Lazar, Food and Drug Administration Accelerates Approval Process of

    New Drugs and Medical Devices, 10 LOY. Consumer L. Rev. 20, 21 (1998). The perform- ance goals are not statutorily binding, but PDUFA does require an Annual Report to Con- gress on FDA's compliance with the performance goals which provides an incentive to the

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    many of the FDA's performance goals were reached, thereby dispelling the notion that the United States experienced a lag in drug approvals as com- pared to other countries.46

    Notwithstanding PDUFA's initial accomplishments, the FDA neverthe- less continued to constantly defend itself against its detractors, including conservative think tanks such as the Washington Legal Foundation (WLF)47 and the Competitive Enterprise Institute (CEI),48 which vehe- mently spoke out against the agency's slow drug approval process. When PDUFA was considered for reinstatement in 1997, Congress decided that additional FDA reform was necessary.49

    FDA reform legislation was first introduced in 1995 by Senator Nancy Kassebaum (R-Kan.), but her bill, S.1477,50 contained some provisions that

    FDA to meet or surpass performance goals. 21 U.S.C. 379g (stating requirements of an- nual reports).

    46. bee David A. Kessler, M.D., Remarks by the Commissioner oj rood and Drugs, 5 1 Food & Drug L.J. 207, 209-15 (1996) (remarking on report to Congress reviewing the pro- cess of PDUFA). But see Julie DeFalco, The FDA vs. Reform, Investors Business Daily, (June 7, 1996) [hereinafter DeFalco] (stating that Dr. Kessler' s statements regarding drug lag may be inaccurate). Apparently, the FDA only referred to data that would support its claim that the United States made drugs available as soon as other countries made them available. Id. For example, the FDA did not include in its report to Congress data regarding drugs first introduced in Europe in the late 1980s that were not submitted to the United States for approval until the 1990s. Id. Also, the FDA did not mention drugs submitted in the 1980s that are still not approved. Id. In addition, Dr. Kessler conceded that more drugs are available in Great Britain, but stated that the FDA found that only a few of those drugs were "priority drugs." Kessler, supra, at 21 1. This judgment may exemplify the agency's "paternalistic mindset" because, according to Joe DiMasi of the Tufts University Center for Drug Development, "[i]t is only the FDA's judgement that other drugs are not that important." DeFalco, supra.

    47. See Shenk, supra note 27, at 17 (noting that Washington Legal Foundation (WLF) was running negative ads in major newspapers stating, "[i]f a murderer kills you, its homi- cide . . . If the FDA kills you, it's merely being cautious").

    48. See Krauss, supra note 1 1 (finding that CEI suggests removing FDA's monopoly over drug approvals by allowing unapproved drugs to enter market). The drugs would be accompanied with clear warnings of their "unapproved status" as well as medical supervi- sion. Id. Under the CEI's proposal, the FDA would only evaluate drugs rather than veto a drug's release into the market. Id. Interestingly enough, both the CEI and the WLF receive generous donations from the medical device and pharmaceutical industry and tobacco com- panies that were weary of the FDA's proposal to regulate cigarette marketing to children. See Shenk, supra note 27, at 17-18.

    49. See 143 Cong. Rec. S12,241, S12,245 (statement of Sen. Barbara Mikulski) ("But while PDUFA made a huge difference, it became clear that PDUFA was not enough. More staff operating in an outdated regulatory framework, without a clear legislative framework, was deficient."). But see Editorial, The FDA Saga Continues, Wash. Post, Sept. 10, 1997, at A20 (commenting that Congress should have introduced a bill that was limited to renew- ing PDUFA; however, Senate saw this as opportunity to take authority away from FDA).

    50. S. 1477, 104th Cong. (1995). The bill provided that all Class I and II medical de-

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    sparked substantial debate in Congress because they were thought to im- pede public health.51 Eventually, Congress believed that it was able to strike an effective balance between expedited drug approval and public health,52 and passed FDAMA on November 9, 1997.53 President Clinton signed FDAMA into law on November 21, 1997.54

    vices were eligible for third party review; additionally, even some Class III devices would receive third-party review if the FDA thought it was appropriate. Id.

    51. See Pilot & Waldmann, supra note 7, at 272 (revealing that Kassebaum's reform provisions relating to third party review demonstrated that FDA should learn from progres- sive regulatory systems in other countries such as European Union). Kassebaum's bill also caused controversy because of provisions that would cause the FDA to lose jurisdiction over products if they did not meet the strict review deadlines, and it would have forced the FDA to approve products that first gained approval in Europe. See John Schwartz, Another Shot at FDA 'Modernization '; Bill to Revamp Food and Drug Agency Draws Less Controversy Than Predecessor, Wash. Post, July 22, 1997, at Al 3. The Kassebaum bill would have limited the FDA's authority to ask for safety data from device manufacturers, and that would have resulted in the FDA's inability to consider how the device could be used if the manufacturer did not include that use in the warning label. 143 Cong. Rec. S12,241, S 12,246 (statement of Senator Reed). The Secretary of the Department of Health and Hu- man Services, Donna Shalala, reportedly said on many occasions that if the third party re- view provision was not changed, she and other presidential advisers would recommend that President Clinton veto the bill. Id.

    52. Congress set forth two bills, S. 830 and H.R. 1411, which laid the groundwork for FDAMA. S. 830, 105th Cong. (1997); H.R. 1411, 105th Cong. (1997).

    53. See Lazar, supra note 45, at 20 (reporting that legislation was "ground-breaking" and would "revolutionize" the FDA's approval system).

    54. See Lazar, supra note 45, at 20. FDAMA is divided into five titles: Title I (Imrov- ing Regulation of Drugs), Title II (Improving Regulation of Devices), Title III (Improving Regulation of Food), Title IV (General Provisions), and Title V (Effective Date). See 1, Pub. L. No. 105-1 15, 1 1 1 Stat. 2296 (1997). Key provisions of FDAMA include reauthor- izing PDUFA, streamlining biological product regulation, increasing patient access to ex- perimental drugs and devices, and expanding provisions regarding the fast-track approval of therapies for serious or life-threatening conditions. FDA Consumer, Law to Reform Food, Medical Product Regulation, Mar.-Apr. 1998, at 3. FDAMA also provides for the expan- sion of distribution by manufacturers of information regarding unapproved or off-label uses of drugs and medical devices if the manufacturer commits to conducting research and filing supplemental NDAs for approval of the off-label uses. Id. Further, FDAMA calls for the expansion of a program that allows initial review of safety and efficacy by FDA-accredited outside experts for low-risk medical devices, procedures that allow the FDA to link health benefits to foods by authorizing health and nutrient content claims, and regulation of over- the-counter products under one national system. Id.

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    II. Provisions of FDAMA that Expedite the Drug Approval Process

    A. The Reinstatement ofPDUFA

    PDUFA' s renewal was arguably the incentive for the extensive FDA re- form set forth in FDAMA.55 FDAMA calls for the FDA to undertake more ambitious commitments and performance goals in accordance with the reauthorization of PDUFA.56

    FDAMA establishes the fee levels for the next five years, and the FDA expects to receive a total of $550,000,000 in user fees during this time.57 Moreover, FDAMA changes PDUFA by setting the application fees, rather than the total fee levels, at a fixed rate, which provides for both annual workload and inflation adjustments.58 Additionally, the FDA is able to keep excess funds and subtract them from the next year's fees, rather than refunding any extra fees.59

    Further, the user fees are not a substitute for general fund appropriations strictly devoted to drug approvals.60 In the first PDUFA, Congress insti- tuted two "waterline" provisions that provided certain expenditure and ap- propriations levels that must be met by the FDA in order for the agency to retain and collect user fees.61 Congress did not change these waterline pro- visions, and, therefore, the funds that the FDA receives from the govern- ment for drug approval and the funds from user fees will be expended solely on the drug approval process.62

    55. See FDA Consumer, supra note 54, at 3. 56. See H.R. Rep. No. 105-310, at 50-51 (1997) (concluding that user fees will con-

    tinue to be used to expedite drug development and review process). If a company fails to submit a user fee, the application is considered incomplete and it is rejected. See 21 U.S.C. 379h(e)(1994).

    57. See 103(f)(3), 111 Stat. at 2303 (listing appropriation amounts for each of five years).

    58. See H.R. Rep. No. 105-310, at 51. PDUFA formerly accounted only for inflation because of the fixed total revenues for each year, but now the amount of total fees received will correlate with the number of applications received. Id. at 52.

    ec' o e i /'"> s'sa' iti c_a _a *'^'a jy. Ode l'JJ'l)'+), 111 O Uli. l .DKJ**.

    60. See Memorandum from Covmgton & Burling Regarding FDAMA 11 (Nov. 12, 1997) (on file with author).

    61. See2' U.S.C. 379g; see also 21 U.S.C. 379g(2) (providing that general fund appropriations must equal or exceed 1992 waterline, and that user fees must be used as an addition to appropriations dedicated to drug review process).

    62. See Covington & Burling Memorandum, supra note 60, at 11-12; see also Gil- hooley, supra note 4, at 141 (finding that drug manufacturers would be extremely dissatis- fied if user fees were used to replace government resources, which encourages FDA to maintain waterline levels). Due to budget constraints, the FDA was forced to cut back sig-

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  • 1 999] FDA MODERNIZATION ACT 1 259

    In return for the increased resources provided by user fees, the FDA, through the Center for Drug Evaluation and Research (CDER) and the Center for Biologies Evaluation and Research (CBER), set forth ambitious and promising performance goals for the next five years.63 For example, the performance goals for fiscal year 1998 included the review and action on ninety percent of standard NDAs, Product License Applica- tions/Biologic License Applications (PLAs/BLAs) filed during fiscal year 1998 within twelve months, and the review and action on ninety percent of priority original NDA and PLA/BLA submissions within six months of re- ceipt.64 By fiscal year 2002, the FDA's goal is the review and action on ninety percent of standard NDAs and PLA/BLA submissions filed that year within ten months, and the review and action on priority applications within six months.65

    The new performance goals indicate that the reinstatement of PDUFA will result in speedier reviews, but it still could take a manufacturer up to seven years to get a drug through the development phase.66 In FDAMA, Congress addressed the need for procedures and goals that will reduce the time necessary for a drug to get through the clinical testing phases.67

    The FDA established various management goals that will facilitate the

    nificantly on resources for food and other programs because it could not reduce drug re- sources. Id. As a result, other programs would not act faster on their regulatory issues be- cause they had to account for a disproportionate amount of the overall FDA cutback. Id.

    63. See Center for Drug Evaluation and Research, PDUFA Reauthorization Perform- ance Goals and Procedures (Nov. 16, 1997) [hereinafter Center for Drug Evaluation and Research]. The FDA's performance goals were set out in a letter from Secretary Shalala to the Chairs of the House Commerce Committee and Senate Labor and Human Resources Committee. See Memoran- dum from Hogan & Hartson Regarding the Impact of FDAMA on the Development and Marketing of Pharmaceutical and Biological Products 2 (Dec. 9, 1997) (on file with author). The performance goals address overall drug development and review times, and drug devel- opment times are expected to be reduced significantly. Id.

    64. See Center for Drug Evaluation and Research, supra note 63. Other goals include the review and action on 90% of standard efficacy supplements filed during fiscal year 1998 within 12 months of receipt, the review and action on 90% of priority efficacy supplements within six months of receipt, the review and action on 90% of manufacturing supplements within six months of receipt, the review and action on 90% of all resubmitted applications filed during fiscal year 1998 within six months of receipt, and the review and action on 30% of Class I resubmitted original applications within two months of receipt. See id.

    65. See id. 66. See S. Rep. No. 1 05-43, at 54 ( 1 997). 67. See id. ("PDUFA II will focus on shortening overall development time and stream-

    lining interaction with FDA required of a drug innovator during the highly regulated drug development phase and establish new performance measures and procedures for FDA . . . .").

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    interaction between the FDA and drug manufacturers.68 For example, the FDA provided meeting management goals in which prompt responses to meeting requests are mandated, as well as prompt scheduling of meetings.69 Such provisions are particularly beneficial to small manufacturers who were previously unable to schedule such meetings with the FDA.70

    Moreover, the FDA set forth procedures for major dispute resolutions involving the review of human drug applications and supplements. The FDA must respond to appeals of its decisions within thirty calendar days of the receipt of the appeal.71 Additionally, the FDA now has a thirty-day deadline to reply to a drug manufacturer's response to an FDA-imposed clinical hold on trials. Previously, the agency did not have such a dead- line.72 The FDA also agreed to update its electronic information systems so that by fiscal year 2002, the FDA will be equipped to handle the paperless receipt and processing of INDs, human drug applications, and related sub- missions.73

    Finally, in another effort to expedite the development of drugs and bio- logical products, CBER and CDER will send out "information request" letters to drug sponsors whose pending applications are deficient in some way, rather than denying an application without informing the manufac-

    68. See Center for Drug Evaluation and Research, supra note 63. 69. See id. The FDA is required to respond to a meeting request, indicating the date,

    time, and place of the meeting, within 14 calendar days of receipt of the request. Id. The meeting is to be scheduled on the next available date on which all relevant Center personnel are available, and the meeting is "to be consistent with type of meeting requested." Id. Seventy percent of the meetings are to be held within this time frame by fiscal year 1999, increasing to ninety percent by fiscal year 2001. Id. There are three types of meetings: (1) type A meetings are the most urgent because development would be held up unless the meeting occurred, (2) type B meetings are less urgent meetings to review Phase II data, and (3) type C meetings are an appeal to an advisory council of an adverse determination. Lisa Raines, Genzyme Corporation, Remarks at the Federalist Society Meeting Presenting An FDA Report Card: Implementation of FDAMA (Oct. 8, 1998) [hereinafter Raines].

    70. See Raines, supra note 69 (commenting that inability to schedule meeting was a substantial obstacle to new drug's development).

    71. See Center for Drug Evaluation and Research, supra note 63. The performance goal for the major dispute resolution is that 70% of answers to appeals will be provided within 30 calendar days starting in fiscal year 1999, increasing to 90% by fiscal year 2001. Id.

    72. See id. The FDA has committed to provide 75% of responses to clinical holds within thirty calendar days of the Agency's receipt of the response starting in fiscal year 1998, and will provide 90% of its responses within 30 days starting in fiscal year 1999. Id.

    73. See id; see also Merrill, supra note 3, at 1784 (noting that before FDA began ac- cepting NDAs and data from clinical trials in electronic form, it received some NDAs that were several hundred volumes of hard copy data, sometimes delivered in a rental truck, and would take up reviewer's entire office).

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  • 1 999] FDA MODERNIZATION ACT 1 26 1

    turer of the application's deficiencies.74 Thus, the reinstatement of PDUFA is likely to expedite the application review process as well as the drug de-

    velopment process because of new management initiatives and the contin- ued acquisition of user fees.73

    B. Expediting Study and Approval of Fast Track Drugs

    FDAMA contains provisions that codify and expand the FDA's current regulations for accelerated drug approval.76 In fact, FDAMA has signifi- cantly broadened the scope of drugs that are eligible for expedited or "fast track" approval.77 FDAMA requires the Secretary of the Department of Health and Human Services (Secretary) to facilitate the development and expedite the approval of fast track drugs that are "intended for the treat- ment of a serious or life-threatening condition"78 and that demonstrate the potential to address "unmet medical needs for such a condition."79

    Under FDAMA's fast track program, a sponsor can request fast track designation for its drug at the same time as, or any time after, it submits an IND.80 Further, FDAMA allows for the rolling review of applications. If a

    74. See Center for Drug Evaluation and Research, supra note 63. 75. See Marketletter, Wall Street Notes and FDA Confirms Rapid Drug Pace, Mar. 30,

    1998, available in 1998 WL 9220982 ("[U]nder PDUFA II drug review times will be tight- ened even more, with intensive focus on shortening drug development times through FDA industry/company interactions, meetings [sic] etc.").

    76. See H.R. Rep. No. 1 05-3 1 0, at 54. 77. See S. Rep. No. 105-43, at 3 (discussing that before FDAMA's enactment, expe-

    dited review and approval of drugs was confined to treatments for AIDS/HIV and cancer). 78. 1 12 (a)(l), 1 1 1 Stat. 2309. Congress intends for the Secretary to use the follow-

    ing to define a "serious life-threatening condition," which indicates an intent to broaden the scope of fast track designation:

    The seriousness of a disease is a matter of judgment, but generally is based on its im- pact on such factors as survival, day to day functioning, or the likelihood that the dis- ease, if left untreated, would progress from a less serious one. Thus, AIDS, all other stages of HIV, Alzheimer's, angina pectoris, heart failure, cancer, and many other diseases are clearly serious in their full manifestations. Further, many chronic ill- nesses that are generally well managed by available therapy can have serious out- comes.

    H.R. Rep. No. 105-310, at 55. 79. Marketletter, PHRMA Proposals for Fast-Track Products, Apr. 27, 1998, available

    in 1998 WL 1 1622363 (finding that PHRMA suggests widening definition of unmet medical needs to include any "product that shows the potential to provide some meaningful thera- peutic benefit to patients over existing treatments" so that new treatments for patients who are unresponsive to current therapies could qualify for fast track designation); see also 112(a)(l), 111 Stat. at 2309.

    80. See 1 12(a)(2), 1 1 1 Stat. at 2309. It a drug meets the statutory criteria for a fast track drug, the Secretary is required to designate it as such within sixty days of receipt of the request for designation. See id.

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    drug shows signs of efficacy, its application can be reviewed even if it is not yet complete.81 Usually, in order for a drug to meet safety and efficacy standards necessary for approval, the drug must demonstrate an effect on a clinical endpoint, such as morbidity or mortality, or on a validated surro- gate endpoint, such as cholesterol levels or blood pressure.82

    FDAMA provides an additional basis for approving a fast track product, which will result in faster access to new therapies and a significant reduc- tion of the clinical trial process.83 Under FDAMA, a drug may be approved if it is found to have an effect on a "surrogate endpoint that is reasonably likely to predict clinical benefit."84 These drugs may suggest major clinical benefits, but their effects on clinical endpoints are not proven.85 Sponsors of fast track drugs are subject to further post-approval requirements, such as conducting studies to validate surrogate endpoints or to confirm effects on clinical endpoints,86 and submitting any promotional materials to the Secretary during the pre-approval and post-approval periods.87 The Secre- tary also retains the right to an expedited withdrawal of approval of a fast track drug after an informal hearing.88

    The fast track provisions of FDAMA will prove to be an extremely ef- fective way to expedite the drug approval process,89 especially in light of the rolling review of applications, the approval of drugs when only the sur- rogate endpoints are known, and the broadening of the scope of drugs that

    81. See H.R. Rep. No. 1 05-3 1 0, at 56. 82. See id. at 54. 83. See id. at 55; see also John Schwartz, FDA Approves Treatment For Advanced

    Breast Cancer: New Engineered Antibody Slows Tumors, WASH. POST, Sept. 26, 1998, at A8 (noting that FDA approved Herceptin, a drug designed to combat advanced breast can- cer, just four months after manufacturer, Genentech, Inc., applied to FDA even though its clinical endpoints are uncertain).

    84. 6 1120>m 111 Stat.at2309. 85. See H.R. Rep. No. 105-310, at 54 (explaining drug that may reduce amount of HIV

    detectable in blood of an AIDS patient will be approved even though drug's ultimate effect on health and survival requires further study).

    86. See 1 12(b)(2)(A), 1 1 1 Stat. at 2309. 87. See 112(b)(2)(B), 111 Stat. at 2309 (noting that promotional materials must be

    sent to Secretary at least thirty days prior to dissemination of information). 88. See 112(b)(3), 111 Stat. at 2310. The Secretary can withdraw a drug if: (1) the

    sponsor failed to conduct post-approval studies with due diligence; (2) a post-approval study failed to verify a clinical benefit; (3) other evidence demonstrates that the drug is not safe or effective; and (4) the sponsor disseminates false or misleading promotional materials. See 1 12(b)(3)(A)-(D), 1 1 1 Stat. at 2310.

    89. See David Brown, AIDS Death Rate in '97 Down 47%: New Drug Treatments Credited; Overall U.S. Mortality Fell 3%, Wash. Post, Oct. 8, 1998, at Al (stating that de- cline in AIDS deaths is largely due to new drug breakthroughs and FDA's ability to make drugs available to infected persons).

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  • 1 999] FDA MODERNIZATION ACT 1 263

    are eligible for fast track status.90

    C. International Harmonization

    The drug approval process has been adversely affected by discrepancies between the various regulatory requirements of agencies that approve drugs for worldwide sale.91 As a result, in 1990, drug regulators and representa- tives of the pharmaceutical industry from the United States, Europe, and Japan92 joined forces to sponsor an International Conference on Harmoni- zation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).93

    In addition to the formation of ICH, the United States negotiated a pharmaceutical Mutual Recognition Agreement (MRA) with the European Community (EC), designed to facilitate international commerce by pro- moting trade and eliminating regulatory barriers.94

    FDAMA expressly gives the FDA the authority to enter into regulatory agreements with other countries, and encourages routine meetings with these countries to discuss ways to harmonize regulatory requirements.95

    90. See Raines, supra note 69. The FDA must issue guidance documents on the poli- cies and procedures applicable to fast track drugs no later than November 21, 1998. See Hogan & Hartson Memorandum, supra note 63, at 18.

    91. See Paul M. Booth, Ph.D., FDA Implementation of Standards Developed by the International Conference on Harmonisation, 52 FOOD & Drug L.J. 203 (1997) (describing how drug must go through each regulatory agency's approval process, thereby increasing costs to drug manufacturers).

    92. 1 he regulators and representatives include the Commission of the European Com- munities, the FDA, the Japanese Ministry of Health and Welfare, the European Federation of Pharmaceutical Industry Associations, the United States Pharmaceutical Manufacturer's Association, and the Japanese Pharmaceutical Manufacturers Association. See Ileana Dominguez-Urban, Harmonization in the Regulation of Pharmaceutical Research and Hu- man Rights: The Need to Think Globally, 30 CORNELL Int'l L.J. 245, 252 (1997).

    93. See id. at 252 (finding that purpose of ICH is to eliminate duphcative technical re- quirements for approving new drugs in three regions in order to provide patients earlier ac- cess to new drugs); see also Booth, supra note 91, at 203 (clarifying that fundamental goals of ICH are to reduce costs associated with gaining regulatory approval and to streamline approval process).

    94. See Richard A. Merrill, FDA and Mutual Recognition Agreements: Five Models of Harmonization, 53 Food & Drug L.J. 133 (1998) (noting that no general statutory provi- sions gave FDA authority to enter into agreement relating to regulatory responsibilities).

    95. 410, 1 1 1 Stat. at 2372-73. The Secretary is directed to support the Office of the U.S. Trade Representative in meetings with foreign representatives to discuss methods and approaches to reduce the burden of regulation and to harmonize requirements "if the Secre- tary determines that such harmonization continues consumer protections consistent with this Act." Id. 410(c)(l). Within 180 days of enactment, the Secretary must "make public a plan that establishes a framework for achieving mutual recognition of good manufacturing practices inspections." Id. 410(c)(4).

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    Since the authorization of FDAMA, the United States and EC concluded negotiations of the MRA.96 Both entities agreed that each region would recognize each other's inspections of manufacturing facilities.97 This agreement, if approved and implemented, will ultimately eliminate the du- plication of inspections and prevent delays in drug availability.98

    Although the international harmonization provisions may not provide immediate results, the provisions facilitate the FDA's participation in de- creasing regulatory burden, which will eventually result in expeditious ap- proval of new drugs.99

    III. Potential Public Health Consequences Related to Expedited Drug Review

    The FDA is faced with the difficult task of protecting the public from drugs that can be dangerous without delaying the availability of useful treatments.100 Before FDAMA was enacted, a reviewer who approved an unsafe drug would suffer tremendous consequences, while a reviewer who delayed or denied drug approval would be overlooked.101 Congress was confident that FDAMA's provisions would not cause public health con- cerns;102 however, since FDAMA's enactment, the FDA appears to focus on marketing drugs as quickly as possible, which may be detrimental to the FDA's duty to protect public health.103

    Ultimately, the drug reviewer must reconcile the tension between speedy drug review and safety, and it appears that, as a consequence of FDAMA's ambitious performance goals, a reviewer's productivity is linked to the

    96. See Mutual Recognition of the Food and Drug Administration and European Community Member State Conformity Assessment Procedures (MRA), 63 Fed. Reg. 17,744, 17,744 (1998) (codified as amended at 21 C.F.R. pt. 26 (1999)) (proposed Apr. 10, 1998) (observing that negotiations of MRA were concluded on June 20, 1997).

    y/. eeid. 98. See id. at 17,746. 99. See Hogan & Hartson Memorandum, supra note 63, at 87.

    100. See Shenk, supra note 27, at 18; see also Rutherford, supra note 22, at 214 (noting that drug reviewer can make two errors: (1) approving a drug with serious adverse effects, and (2) rejecting or delaying approval of a beneficial drug).

    101. See Rutherford, supra note 22, at 214 (finding that reviewer who approved danger- ous drug would undergo congressional examination, professional criticism, and may lose his or her employment).

    102 See generally 143 CONG. REC. S 12,24 1-42 (emphasizing that FDAMA would prove to be beneficial to consumers, FDA, and manufacturers).

    103. See Robert I. Misbin, A Possible Drug Fix?, WASH. POST, Aug. 24, 1998, at A 18. Misbin, an FDA drug reviewer, described unethical experimental testing of new drugs that required patients to discontinue standard, effective drug therapy in order to determine the effect of a new drug. See id. He also noted that these experiments were conducted at major universities with the approval of the FDA. See id.

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  • 1 999] FDA MODERNIZATION ACT 1 265

    number of drugs approved.104 Reviewers are under tremendous pressure to approve drugs from drug manufacturers, physicians, and Wall Street.105 In fact, the FDA appears to be working too closely with drug manufacturers during the review process.106 Such a relationship could result in a conflict of interest leading to fatal approval errors.107 In fact, the FDA removed a record number of recently-approved drugs in 1998 that proved to be harm- ful.108

    The FDA can combat threats to public health by encouraging drug manufacturers to use their resources and scientific experts to focus on the quality of drugs they are developing, not just the quantity.109 Moreover, the FDA should be encouraged to utilize outside experts to assist in reviewing applications so that FDAMA's performance goals will be met and the risk of haphazard review will be reduced.110 The current system of testing new

    104. See id. ("The more new drugs approved, the more productive the FDA appears, even if the new drugs are not as good as what is available already.").

    15. See Stephen Fried, The mil of the nil; Inside the tUA, Fressure to Approve New Drugs Can Clash With Safety, Wash. POST, May 31, 1998, at Cl (concluding that decision to approve or not to approve is $231 million question, and any decision other than "yes" will be second-guessed).

    106. See id. ("When the FDA makes an approval ... the announcements are couched in this 'See, we have found this new drug.'") (emphasis added); see also John Schwartz, Is FDA Too Quick to Clear Drugs?, Wash. POST, Mar. 23, 1999, at Al ("Consumer advo- cates, and even some of the agency's own drug reviewers, argue that the agency has become too cozy with the pharmaceutical industry and too lax, putting lives at risk.").

    107. See Rochelle Sharpe, Painkiller: How a Drug Approved by the FDA Turned Into a Lethal Failure, Wall St. J., Sept. 30, 1998, at Al. In 1997, the FDA approved the pain reliever Duract, sponsored by Wyeth-Ayerst Laboratories, even though the reviewer had some serious doubts about its safety. See id. Specialists hired by the manufacturer made persuasive arguments to the FDA that if the drug were taken properly there would be no hazard for short-term use. See id. The drug was marketed with a mild warning about the drug's potential dangers, but eleven months later, Wyeth pulled Duract off the market be- cause it caused four deaths and required eight people to receive liver transplants. See id.

    1 08. See id. (indicating that Duract was fourth drug in just twelve months that needed to be removed from market, and second major disaster for Wyeth, which also marketed Redux, an anti-obesity drug that also was taken from shelves); see also 69 American Men Taking Viagra Died From March to July, FDA Says, WASH. POST, Aug. 27, 1998, at A5 (finding that FDA reported that between late March and July 1998, 69 American men taking Viagara died, and 46% of those cases were related to cardiovascular incidents). But see New Study by FDA Finds Drugs, Devices Are as Safe as Ever, WALL St. J., May 1 1, 1999, at Bl 1 (finding that even with new swift reviews, safety standards are maintained and drugs and devices are "just as safe, if not safer, than they were in the past").

    109. See Misbin, supra note 103, at A18 (stating that money saved from dealing with "adverse events" could be used to fund medical research).

    1 10. See Gilhooley, supra note 4, at 135 (noting that outside review would supplement review process). The same or similar criteria should apply in the selection of outside ex- perts for drug review as in the selection of third party reviewers for medical devices, which

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    drugs may be too brief to detect harmful reactions that could surface after repeated use.111 Therefore, drug safety experts suggest that more follow-up studies should be conducted on drugs that have been approved rapidly.112


    FDAMA is the first major reform of the FDA in thirty years113 that has addressed the regulatory problems plaguing the drug approval process. While the future will ultimately reveal FDAMA's effectiveness, FDAMA clearly provides numerous ways to facilitate and expedite the drug approval process.

    Specifically, the provisions reinstating PDUFA and the related perform- ance goals will not only expedite the review process, but will also expedite the drug development process. The provisions relating to fast track drugs will ensure that new treatments will promptly reach people suffering from serious or life-threatening diseases. Finally, the provisions relating to in- ternational harmonization indicate a step towards decreasing regulatory burdens. Subsequently, new drugs will enter the worldwide market at a faster pace. FDAMA's promising effects on the review process, however, should not overshadow the FDA's commitment to ensure that public health is not disparaged.

    has recently been set forth by the FDA. See Implementation of Third Party Review Under the Food and Drug Administration Modernization Act of 1997, 63 Fed. Reg. 28,388, 28,388 (1998) (proposed May 22, 1998). The Notice "announces the criteria to accredit or deny accreditation to persons . . . who request to conduct premarket notification reviews of medi- cal devices consistent with the provisions of [FDAMA]." See id. These criteria reduce the risk of a conflict of interest by setting forth strict requirements for qualifications, including a requirement that accredited persons should not be involved in the design, manufacture, pro- motion, or sale of medical devices. See id. at 28,389.

    111. See Schwartz, supra note 1 06, at A 1 . 112. See id. 113. See 143 Cong. Rec. S12,241-42, (statement of Sen. Jeffords) (commenting that

    FDAMA achieves important goals and will have positive impact on millions of Americans).

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    Back Matter