The Case for Disclosure of Biologics Manufacturing Information

Yaniv Heled

doi:10.1177/1073110519898043

The Case for Disclosure of Biologics Manufacturing Information

Published online by Cambridge University Press: 01 January 2021

Yaniv Heled

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Abstract

Ten years after the enactment of the Biologics Price Competition and Innovation Act (BPCIA), competition in biologics markets remains scant and far from sufficient for lowering prices of biologics to the level of 80-90% price drops seen in generic drug markets. This reality is not a result of one or two cardinal reasons, but many. If lowering the price of biologics is the goal and competition is the means by which we seek to achieve that goal, then there does not seem to be a quick fix to address all of the many impediments to competition that plague biologics markets. Yet, certain changes to how the Food and Drug Administration (FDA) evaluates and approves biologics may go a long way toward the creation of meaningful competition in biologics markets. One such change would be making original biologics' manufacturing information available to follow-on manufacturers.

As recognized by several commentators, access to biologics manufacturing information is key to increasing competition in biologics markets. Without access to such information, making follow-on biologics is difficult and expensive, if not outright impossible. This is expected to be especially true for the highly anticipated class of interchangeable biologics, none of which has been approved by the FDA to date. Yet, it has long been the position of the brand-name pharmaceutical industry (Industry) that biologics manufacturing information is proprietary and, thus, may not be shared. Congress has subscribed to the Industry's position, prohibiting the FDA from disclosing regulatory filings submitted by developers of original biologics, including manufacturing information, to third parties. That prohibition not only undermines competition in biologics markets, but is also wasteful, potentially unethical, and poses unnecessary risks to the health and safety of patients.

This article makes the case for FDA sharing of original biologics manufacturing information with follow-on biologics developers. It is informed by the similar legal and commercial circumstances in the area of pesticides and the regulatory regime established by Congress in the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), which is administered by the Environmental Protection Agency (EPA). The article reviews the FIFRA regime, including its upholding as constitutional by the United States Supreme Court, and then examines its applicability to the area of biologics. The article concludes with a proposal for a similar regime to be incorporated into the pathway for approval of follow-on biologics as a means of increasing competition in biologics markets.

Type: Symposium Articles
Information: Journal of Law, Medicine & Ethics , Volume 47 , Issue S4: Current Topics in Health Law: Papers from the 2019 ASLME Health Law Professors Conference , Winter 2019 , pp. 54 - 78

DOI: https://doi.org/10.1177/1073110519898043 [Opens in a new window]
Copyright: Copyright © American Society of Law, Medicine and Ethics 2019

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By “truly competitive” and “competitively robust” biologics markets I mean levels of competition sufficient to drive down the cost of biologics (and follow-on versions thereof) significantly for payors and patient-consumers, well beyond the 15-30% price drops currently typical of biologics markets subsequent to the entry of follow-on products. See, e.g., Price, W. N. II, “Regulating Secrecy,” Washington Law Review 91(2016): 1769, 1798 (discussing the high costs of developing biosimilars and that “biologics are expected to remain much more expensive, with drops of only 20–30 percent in price once competitive biosimilars enter the market”); Rockoff, J. D., “Knockoffs of Biotech Drugs Bring Paltry Savings,” Wall Street Journal, May 5, 2016, available at <http://www.wsj.com/articles/knockoffsof-biotech-drugs-bring-paltry-savings-1462458209> (last visited November 11, 2019) (Both Zarxio and Inflectra are sold at a 15% discount from the biologic price.”); Carrier, M. A. and Minniti, C. J. III, “Biologics: The New Antitrust Frontier,” University of Illinois Law Review 2018 (2018): 1, at 10 (“But while the entry of multiple small-molecule generics results in significant price erosion (50% with 2 generics and 75% with at least 6), we predict that the reductions may be more modest given attempts to recoup biosimilar development costs, which greatly exceed those incurred by generics.”). For comparison, in the context of small-molecule drugs, significant price drops of more than 70% are typical subsequent to the entry of five or more generic products into a specific drug market. See Food & Drug Admin., “Generic Competition and Drug Prices,” available at <https://www.fda.gov/aboutfda/centersoffices/officeof-medicalproductsandtobacco/cder/ucm129385.htm> (last visited November 11, 2019).Google Scholar

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The brand-name pharmaceutical industry (Industry or Pharmaceutical Industry, for short) includes the brand-name pharmaceutical and biopharmaceutical industries, their various, numerous official and unofficial lobbying arms under the leadership of the Pharmaceutical Research and Manufacturers of America (PhRMA) and the Biotechnology Innovation Organization (BIO), industry-funded patient groups, researchers, research institutions, medical salespersons, and more. Notably, when it comes to biologics the traditional lines between brand-name and follow-on/generic parts of the industry are not as clear as they are in the small-molecule context. Still, with a few notable exceptions, it is possible to speak of efforts led by and on behalf of the brand-name biopharmaceutical industry, which are opposed to the interests of those parts of the industry that are focused on bringing follow-on biologics to market.Google Scholar

Like in my previous article, while this article focuses on the Industry's efforts in the United States, it is important to recognize that these efforts are not limited to this country alone and that local efforts are part of larger, well-coordinated strategies aimed at limiting follow-on biologics as a regulatory and commercial phenomenon worldwide. See Heled, supra note 4, at 113 n.7.Google Scholar

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Under BPCIA, original biologics developers benefit from a twelve-year market exclusivity period during which the FDA may not approve applications for follow-on products seeking to imitate the original biologic. 42 U.S.C. § 262(k)(7)(A). In addition, BPCIA creates a four-year data exclusivity period during which the FDA is not allowed to receive applications for follow on products that seek to imitate the original biologics. Both these market and data exclusivity periods may then be supplemented by an additional period of six months of exclusivity for putting the original biologic through additional clinical studies in pediatric populations, bringing the market and data exclusivity period to a total of 12.5 and 4.5 years respectively. 42 U.S.C. § 262(m)(2)(A). For further discussion of these and other exclusivities available in original biologics, see also discussion infra notes 168-171 and accompanying text.Google Scholar

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The hallmark of generic pharmaceutical products is their fungibility with the product they seek to imitate. This quality, once recognized by the FDA, allows for replacement of the original product with its follow-on version at the pharmacy level and often — depending on state substitution laws — without involvement of the prescribing physician. Follow-on biologics that are not approved by the FDA as interchangeable, however, cannot be similarly replaced by pharmacists, and so the competitive challenge they pose to original biologics is more akin to the kind of competition posed by “me-too” drugs, namely standalone pharmaceutical products that are indicated for the same disease or condition but are not clinically fungible. Examples of me-too drugs include the numerous cholesterol-lowering drugs that followed lovastatin (atorvastatin, fluvastatin, pitavastatin, simvastatin, pravastatin, and rosuvastatin) and hypertension drugs that followed captopril (benazepril, zofenopril, perindopril, trandolapril, enalapril, lisinopril, and ramipril). Pharmaceutical companies typically develop “me-too” drugs where the potential market for a certain condition is sufficiently lucrative to support more than one product. Google Scholar

See infra note 59.Google Scholar

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See Federal Trade Commission, Emerging Health Care Issues: Follow-On Biologic Drug Competition (2009): at iii (estimating the product development costs for small-molecule generic drugs is $1-5 million) [FTC 2009 Report], available at <https://www.ftc.gov/sites/default/files/documents/reports/emerging-health-care-issues-follow-biologic-drug-competition-federal-trade-commission-report/p083901biologicsre-port.pdf> (last visited November 11, 2019).+(last+visited+November+11,+2019).>Google Scholar

With some exceptions (e.g., human growth hormone and insulin), biologics are typically very large molecules with complex three-dimensional (and, possibly, quaternary) structures and appendages (e.g., oligosaccharide chains) that are very difficult to precisely characterize using current scientific methods. Moreover, at least some biologics consist of not a single API but a collection or mixture of structurally-related variations of a certain therapeutically-active molecule in a certain ratio between the different variations. See, e.g., Chhina, M., U.S. Food & Drug Admin., Overview of Biological Products (2013): 8, available at <https://www.fda.gov/downloads/AboutFDA/Transparency/Basics/UCM356666.pdf> (discussing how the structure of small molecules are known, yet in biological products the “[s]tructure may or may not be completely defined or known”); U.S. Food & Drug Admin., Guidance for Industry: Quality Considerations in Demonstrating Biosimilarity of a Therapeutic Protein Product to a Reference Product (2015): 7, available at <https://www.fda.gov/downloads/drugs/guidances/ucm291134.pdf> (last visited November 11, 2019) (“Using multiple, relevant, state-of-the-art methods can help define tertiary protein structure and, to varying extents, quaternary structure and can add to the body of information supporting biosimilarity. At the same time, a protein's three-dimensional conformation can often be difficult to define precisely using current physicochemical analytical technology.”).+(discussing+how+the+structure+of+small+molecules+are+known,+yet+in+biological+products+the+“[s]tructure+may+or+may+not+be+completely+defined+or+known”);+U.S.+Food+&+Drug+Admin.,+Guidance+for+Industry:+Quality+Considerations+in+Demonstrating+Biosimilarity+of+a+Therapeutic+Protein+Product+to+a+Reference+Product+(2015):+7,+available+at++(last+visited+November+11,+2019)+(“Using+multiple,+relevant,+state-of-the-art+methods+can+help+define+tertiary+protein+structure+and,+to+varying+extents,+quaternary+structure+and+can+add+to+the+body+of+information+supporting+biosimilarity.+At+the+same+time,+a+protein's+three-dimensional+conformation+can+often+be+difficult+to+define+precisely+using+current+physicochemical+analytical+technology.”).>Google Scholar

See, e.g., Dahodwala, H. and Sharfstein, S.T., Biosimilars: Imitation Games, 8 ACS Med. Chem. Lett. 690, 691 (2017).Google Scholar

This reality is evident in the fact that since the enactment of BPCIA in 2010 through the time of writing of this article — over nine years — no follow-on biologics developer has attempted to seek approval for its biosimilar product as interchangeable with an already-approved original biologic. This is not due to a legal impossibility to do so. Even in the absence of specific guidance, BPCIA has granted the FDA authority to approve follow-on biosimilar products as interchangeable with existing products and follow-on product developers were free to file their applications for such approval at least since the enactment of BPCIA, in March 2010. That no follow-on biologics developer has done so since 2010 is, at least in part, due to the fact that follow-on product developers have been unable to establish identity or near-identity of their follow-on products to the original biologics they seek to imitate, as is done in small-molecule drugs under the Hatch-Waxman Act. At least as late as May 2015, the FDA's position was that “[a]t this time, it would be difficult as a scientific matter for a prospective biosimilar applicant to establish interchangeability … given the statutory standard for interchangeability and the sequential nature of that assessment.” Food & Drug Admin., Biosimilars: Additional Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009; Guidance for Industry (May 2015): at 7, available at <https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM273001.pdf>..' href=https://scholar.google.com/scholar?q=This+reality+is+evident+in+the+fact+that+since+the+enactment+of+BPCIA+in+2010+through+the+time+of+writing+of+this+article+—+over+nine+years+—+no+follow-on+biologics+developer+has+attempted+to+seek+approval+for+its+biosimilar+product+as+interchangeable+with+an+already-approved+original+biologic.+This+is+not+due+to+a+legal+impossibility+to+do+so.+Even+in+the+absence+of+specific+guidance,+BPCIA+has+granted+the+FDA+authority+to+approve+follow-on+biosimilar+products+as+interchangeable+with+existing+products+and+follow-on+product+developers+were+free+to+file+their+applications+for+such+approval+at+least+since+the+enactment+of+BPCIA,+in+March+2010.+That+no+follow-on+biologics+developer+has+done+so+since+2010+is,+at+least+in+part,+due+to+the+fact+that+follow-on+product+developers+have+been+unable+to+establish+identity+or+near-identity+of+their+follow-on+products+to+the+original+biologics+they+seek+to+imitate,+as+is+done+in+small-molecule+drugs+under+the+Hatch-Waxman+Act.+At+least+as+late+as+May+2015,+the+FDA's+position+was+that+“[a]t+this+time,+it+would+be+difficult+as+a+scientific+matter+for+a+prospective+biosimilar+applicant+to+establish+interchangeability+…+given+the+statutory+standard+for+interchangeability+and+the+sequential+nature+of+that+assessment.”+Food+&+Drug+Admin.,+Biosimilars:+Additional+Questions+and+Answers+Regarding+Implementation+of+the+Biologics+Price+Competition+and+Innovation+Act+of+2009;+Guidance+for+Industry+(May+2015):+at+7,+available+at+.>Google Scholar

See Gitter, D. M., “Innovators and Imitators: An Analysis of Proposed Legislation Implementing an Abbreviated Approval Pathway for Follow-on Biologics in the United States,” Florida State University Law Review 35 (2008): 555, 561 n.21 (describing “the maxim that, for biopharmaceuticals, the ‘process is the product.’”); Carver, K. Hessler et al., “An Unofficial Legislative History of the Biologics Price Competition and Innovation Act of 2009,” Food & Drug Law Journal 65 (2010): 671, 708-09 (describing the Industry's position on “[w]hether the process is the product”).Google Scholar

See Price, supra note 5, at 1975 notes 134–36; see also Price, W. N. II and Rai, A. K., “Are Trade Secrets Delaying Biosimilars,” Science 348 (2015): 188, 189 (describing attempts of follow-on biologics makers to imitate original products as “rang[ing] from merely expensive to nearly impossible and creat[ing] much of the cost barrier for biosimilar entrants”); Tzeng, L., “Follow-On Biologics, Data Exclusivity, and the FDA,” Berkeley Technology Law Journal 25 (2010): 135, 138 and note 23 (emphasis added) (“The complexity of the biologic molecules, production in living organisms, and sensitivity of end-product structure to changes in the manufacturing process render exact [follow-on biologic] replication nearly impossible.”).CrossRef Google Scholar

See Gitter supra note 40, at 561 note 21.Google Scholar

21 C.F.R. § 601.2(a) (requiring “[a] full description of manufacturing methods … [and] sample(s) representative of the product for introduction or delivery for introduction into interstate commerce.Google Scholar

See infra notes 136-138 and accompanying text.Google Scholar

See, e.g., Carver et al., supra note 40, at 698–99, 698 note 218, 699 notes 218–25, 700 notes 232-37, 701 note 271 (arguing, for example, that FDA reference to biologics manufacturing information submitted in earlier products' marketing applications raises “insurmountable legal obstacles” and describing the Industry's efforts to assert and enforce that position; describing Industry's successful efforts to foreclose FDA utilization of data contained in earlier regulatory filings for the approval of follow-on biologics); Korwek, E. L., “Towards Understanding the “Generic” Debate about Biologics,” Journal of Biolaw & Business 7 (2004): 1, 5 (discussing the argument by the Bio-technology Industry Association (BIO) that the FDA's reliance on “innovator information essentially involves misappropriation of the innovator's trade secret and confidential business information, which is not permitted under the Takings Clause of the Fifth Amendment”); Letter from Robert A. Long, Jr., Partner, Covington & Burling, to Food & Drug Admin. 4–5, 8–10, 15–17 (July 13, 2005), available at <https://web.archive.org/web/20170211011252/ http://www.fda.gov/ohrms/dockets/dockets/03p0176/03p-0176-c000003-01-vol3.pdf> (last visited November 11, 2019) (Docket Nos. 2004P-0171/CP and 2003P-0176/CP) (arguing that the Trade Secrets Act prohibits a government employee from disclosing trade secrets discovered “in the course of his employment or official duties,” that the Food, Drug & Cosmetics Act (FDCA) prohibits any person from “using to [their] own advantage, or revealing … any information … concerning any method or process, which, as a trade secret, is entitled to protection,” and that the Takings Clause and FDA policies “clearly support[s] innovators' reasonable, investment-backed expectation that trade secret data submitted to FDA would not be used in follow-on approvals”).Google Scholar

See also Carver et al., supra note 40, at 699 and notes 219–25 (discussing how the Industry's assertion of its position that regulatory submissions made in connection with BLAs are proprietary and confidential successfully dissuaded the FDA from attempting to develop a regulatory pathway for the approval of generic biologics based on its existing authorities under FDCA and the Public Health Service Act).Google Scholar

As mentioned earlier, a few exceptions to this general rule exist in relatively small and well characterized biologics such as human growth hormone and insulin.Google Scholar

See 42 U.S.C. § 262(k)(2)(A)(I)(aa) (requiring that applications for marketing approval of follow-on biologics include “analytical studies that demonstrate that the [follow-on] product is highly similar to the reference product notwithstanding minor differences in clinically inactive components”.). See also Price supra note 5, at 1796-1797.Google Scholar

See 42 U.S.C. § 262(k)(2)(A)(I)(bb)-(cc) (requiring that applications for marketing approval of follow-on biologics include animal studies and “a clinical study or studies … that are sufficient to demonstrate safety, purity, and potency in 1 or more appropriate conditions of use for which the [original] product is licensed and intended to be used”).Google Scholar

According to the FDA Interchangeability Guidance, a “switching study” is a clinical study or studies used to determine the impact of alternating or switching between a proposed interchangeable biologic and the original product it seeks to imitate. See FDA Interchangeability Guidance supra note 6 at 5, note 12 and 9-14.Google Scholar

42 U.S.C. § 262(k)(4).Google Scholar

See Food & Drug Admin., Scientific Considerations in Demonstrating Biosimilarity with a Reference Product; Guidance for Industry (April 2017): 7, 10-12 (discussing a case-by-case approach wherein the sponsor of a follow-on biologic uses a “stepwise approach to developing the data and information needed to support a demonstration of biosimilarity,” yet also arguing that the first step should be to compare structural and functional characterization, before beginning in-vitro and animal studies); FDA Interchangeability Guidance supra note 6; Koyfman, H., “Biosimilarity and Interchangeability in the Biologics Price Competition and Innovation Act of 2009 and FDA's 2012 Draft Guidance for Industry,” Biotechnology Law Report 32 (2013): 238, 246 (stating FDA's stepwise approach does not describe what differences in structure would require heightened animal or clinical studies, and further proposing a step-by-step approach using scientific literature to determine what amount of structural difference might affect the biologic); Building a Wall Against Biosimilars, supra note 22, at 264.Google Scholar

See also Dahodwala and Sharfstein, supra note 38, at 692 (describing the development of follow-on biologics as a game).Google Scholar

See Price and Rai, supra note 41, at 189.Google Scholar

See, e.g., FTC 2009 Report supra note 36, at iii; Blackstone, E. A. et al., “The Economics of Biosimilars,” American Health & Drug Benefits 6 (2013): 469, 471.Google Scholar

Id. Interestingly, the estimated development time of follow-on biologics is not much shorter than the time it takes to develop an original biologic. See Beall, R. F. et al., Nature Biotechnology 37 (2019): 708, 709 (finding that the median total pre-market development time for new biologics approved by the FDA between 2007 and 2016 was 10.6 or 12.4 years).Google Scholar

See, e.g., Scientific Considerations in Demonstrating Biosimilarity, supra note 52, at 7, 10–12 (discussing FDA's guidance on the “stepwise approach”); see also Paradise, J., “The Legal and Regulatory Status of Biosimilars: How Product Naming and State Substitution Laws May Impact the United States Healthcare System,” American Journal of Law & Medicine 41, no. 1 (2015): 49, 68 (describing the task of determining that two biologic products are similar and the regulatory process thereof as complicated and uncertain).CrossRef Google Scholar

See supra discussion following note 8. To illustrate, the protracted legal battle surrounding the approval and launch of the first biosimilar approved in the United States, Zarxio (Filgrastim-sndz), has been ongoing at least since October 2014 and included, thus far, at least six rounds of litigation, including three before the Court of Appeals for the Federal Circuit and one before the United States Supreme Court, and raised numerous novel legal questions, e.g., whether BPCIA's patent dispute resolution scheme (a.k.a. “patent dance”) is mandatory or optional, the preemption of state causes of action in light of BPCIA, as well as more mundane issues like patent claim construction, patent infringement, and more. See Amgen, Inc. v. Sandoz, Inc., No. 14-cv-04741, 2015 WL 1264756 (N.D. Cal. Mar. 19, 2015); Amgen, Inc. v. Sandoz, Inc., 794 F.3d 1347 (Fed. Cir. 2015) (affirming in part, vacating in part, remanding); Sandoz, Inc. v. Amgen, Inc., 137 S.Ct. 1664 (2017) (reversing in part, vacating in part); Amgen, Inc. v. Sandoz, Inc., 877 F.3d 1315 (Fed. Cir. 2017) (on remand, affirming); Amgen Inc. v. Sandoz Inc., 295 F. Supp. 3d 1062 (N.D. Cal. 2017) (granting Sandoz's motion for summary judgment of noninfringement of U.S. Patent No. 8,940,878); and Amgen Inc. v. Sandoz Inc., 923 F.3d 1023 (Fed. Cir. 2019) (affirming), in which, most recently, on June 7, 2019, Amgen filed a Petition for En Banc Rehearing that may result in yet another round of litigation.Google Scholar

See, e.g., FTC 2009 Report at v; Megerlin, F. et al., “Biosimi-lars and the European Experience: Implications for the United States,” Health affairs 32 (2013): 1083. See also Sarpatwari, A. et al., “Competition and Price among Brand-Name Drugs in the Same Class: A Systematic Review of the Evidence,” PLoS Medicine 16 (2019): e1002872, available at <https://doi.org/10.1371/journal.pmed.1002872> (last visited November 11, 2019) (finding that brand-brand competition — the kind that takes place when non-interchangeable biosimilars enters the market — does not result in lower drug prices absent additional structural reforms). CrossRef Google Scholar

See also Bone, R. G., “A New Look at Trade Secret Law: Doctrine in Search of Justification,” California Law Rev. 86 (1998): 241, 266-70 (discussing the inefficiencies and waste created by trade secrecy in general); Price and Rai, supra note 41, at 1048-49 (also discussing the additional negative implications of non-disclosure to innovation).Google Scholar

See also Frapaise, F.-X., “The End of Phase 3 Clinical Trials in Biosimilars Development?” BioDrugs 32 (2018): 319 (proposing a more resource-conservative approach to comparing follow-on biologics with original products which “may be more appropriate than 600-to 1000-patient, phase 3 trials in assessing biosimilarity and therapeutic equivalence”).CrossRef Google Scholar

See, e.g., Webster, C. J. and Woollett, G. R., “Comment on ‘The End of Phase 3 Clinical Trials in Biosimilars Development?’” BioDrugs 32 (2018): 519 (arguing that clinical studies in humans done for the mere purpose of comparing clinical safety and efficacy of a biosimilar with an original biologic are unethical); see also discussion infra notes 123-125 and accompanying text.CrossRef Google Scholar

See also Price, supra note 5, at 1770, 1777, 1784–1793 (making the observation that, despite BPCIA, biologics are “wildly expensive and look to stay that way” and concluding that the lack of competition in biologics markets is attributable to the combination of trade secrecy and FDA regulation).Google Scholar

See, e.g., Letter from John C. Yoo, Professor, University of California to Senator Orrin G. Hatch, Chairman, Committee on the Judiciary, Oct. 21, 2004, available at <https://www.regulations.gov/document?D=FDA-2003-P-0003-0027> (last visited November 11, 2019) (arguing, prior to the enactment of BPCIA, that FDA use of regulatory filings does not constitute a taking under the Fifth Amendment and that FDA may do so with respect to past filings made in connection with BLAs); Letter from Robert A. Long, Jr., Partner, Covington & Burling to Food and Drug Administration, Division of Docekts Management (HFA-305), July 13, 2005, available at <https://www.regulations.gov/document?D=FDA-2012-P-0317-0001> (last visited November 11, 2019) (Exhibit 44) (arguing that FDA use of regulatory filings made in connection with applications for approval of biological products would constitute a taking under the Fifth Amendment); Epstein, R. A., “The Constitutional Protection of Trade Secrets and Patents Under the Biologics Price Competition and Innovation Act of 2009,” Food & Drug Law Journal 66 (2011): 285 (making a similar argument to that of Long's Letter post BPCIA). See also Carver et al., supra note 40, at 698 note 218 (“The threshold question whether FDA could lawfully approve a biosimilar product on the basis of trade secrets and confidential commercial information owned and submitted by another applicant were explored in submissions to FDA as well as Congress, and discussed in a hearing before the Senate Judiciary Committee. The question was never resolved.”).Google Scholar

Federal Pesticide Act of 1978, Pub. L. No. 95-396, 92 Stat. 819 (codified at 7 U.S.C. §§ 136–136w-8).Google Scholar

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See Ruckelshaus v. Monsanto Co., 467 U.S. 986, 1006–07 (1984) (holding that EPA's consideration or disclosure of data submitted by an original product developer to the agency did not constitute an unconstitutional taking regardless of whether such data included trade secrets so long as parties submitting such data were on notice that the agency might disclose the data so prior to submitting its data); Union Car-bide Agric. Prods. Co. v. Costle, 632 F.2d 1014, 1017 (2d Cir. 1980) (reversing a temporary restraining order against the implementation of FPA).Google Scholar

Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), ch. 125, 61 Stat. 163 (1947) (codified as amended at 7 U.S.C. §§ 136–136w-8 (2012)).Google Scholar

7 U.S.C. § 136a(a).Google Scholar

Id. In the context of FIFRA, the safety and benefits of a product are considered under the title of “unreasonable adverse effects on the environment,” which is defined as “(1) any unreasonable risk to man or the environment, taking into account the economic, social, and environmental costs and benefits of the use of any pesticide, or (2) a human dietary risk from residues that result from a use of a pesticide in or on any food…. [including] the risks and benefits of public health pesticides separate from the risks and benefits of other pesticides. In weighing any regulatory action concerning a public health pesticide under this subchapter, the Administrator shall weigh any risks of the pesticide against the health risks such as the diseases transmitted by the vector to be controlled by the pesticide.” 7 U.S.C. § 136(bb).Google Scholar

7 U.S.C. § 136a(c)(1)(F)(i). See also Envtl. Prot. Agency Office of Pesticide Programs, Questions and Answers–Exclusive Use Data Protection for Minor Use Registrations 2 (2014), available at <http://www.epa.gov/pesticides/minoruse/exclusive-use-questions.pdf, archived at <http://perma.cc/BXM9-UMSM> (last visited December 16, 2019).+(last+visited+December+16,+2019).+In+1998,+Congress+added+to+FIFRA+an+option+to+extend+the+ten-year+data+exclusivity+period+by+one+year+for+every+three+new+“minor+uses”+approved+by+the+EPA+for+the+original+pesticide+product.+7+U.S.C.+§+136a(c)(1)(F)(ii).+Notably,+such+extension+is+only+available+up+to+three+times+in+each+pesticide+product+(up+to+a+total+of+thirteen+years+of+data+exclusivity)+and+cannot+be+granted+for+“minor+uses”+registered+more+than+seven+years+after+the+onset+of+the+ten-year+data+exclusivity+period.+Id.+To+prevent+abuse+of+such+extensions,+FIFRA+instructs+the+EPA+to+grant+one-year+extensions+only+after+consulting+with+the+Secretary+of+Agriculture+and+subject+to+a+determination+that+certain+public+policy+considerations+are+applicable.+See+7+U.S.C.+§+136a(c)(1)(F)(ii)(I)–(IV).+These+considerations+are:+“(I)+there+are+insufficient+efficacious+alternative+registered+pesticides+available+for+the+use+[in+a+particular+crop];+(II)+the+alternatives+to+the+minor+use+pesticide+pose+greater+risks+to+the+environment+or+human+health;+(III)+the+minor+use+pesticide+plays+or+will+play+a+significant+part+in+managing+pest+resistance;+or+(IV)+the+minor+use+pesticide+plays+or+will+play+a+significant+part+in+an+integrated+pest+management+program.”.+Id.>Google Scholar

7 U.S.C. § 136a(c)(1)(F)(iii). This subsection further creates an elaborate scheme for resolution of disputes regarding the amount of the compensation, including a mandatory arbitration between the parties in case of a dispute. Id. Notably, disagreement between the parties regarding the compensation will not delay registration by the EPA. Id.Google Scholar

Id.Google Scholar

FIFRA §§ 10(d)(1)(A)–(C); 7 U.S.C. §§ 136a(c)(1)(F) (iv), 136h(d).Google Scholar

7 U.S.C. § 136h(d)(1).Google Scholar

7 U.S.C. § 136h(g).Google Scholar

7 U.S.C. § 136a(c)(1)(F)(iii).Google Scholar

See Union Carbide, 632 F.2d at 1016 (“As enacted in 1947, FIFRA did not specifically prohibit the USDA from publicly disclosing submitted data or from using data supplied by one applicant to determine whether to register a pesticide offered subsequently by another.”).Google Scholar

See Federal Pesticide Control Act of 1971: Hearings Before the H. Comm. on Agric., supra note 66 at 170 (Statement of W.B. Ennis, Jr., Chief of Crops Protection Research Breachdd, U.S. Dep't of Agric.) (“Since 1940 we have witnessed agricultural changes…. This has come about primarily because of … control of damaging weeds, diseases, insects, and other pests and parasites.”).Google Scholar

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Federal Environmental Pesticide Control Act of 1972, Pub. L. No. 92-516, §§ 3(c)(5)(C)–(D), 86. Stat. 973, 980–81.Google Scholar

See Union Carbide, 632 F.2d at 1016 (“This costly research and lengthy development process produce data that define the peculiar characteristics of the pesticide submitted for registration … [and] must be submitted to obtain registration.”).Google Scholar

Id.; Federal Pesticide Control Act of 1971: Hearings Before the H. Comm. on Agric. supra note 66 at 331 (statement of Richard H. Wellman, Vice President, Process Chems. Div. of Unio Carbide Corp.) (arguing that newer and higher regulatory barriers were being placed before the original pesticide product developers and that the cost of developing the necessary data in support of product marketing applications was heavy).Google Scholar

See Union Carbide, 632 F.2d at 1016 (“[I]t appears that the USDA made no public disclosures of data but did make use of data on hand in evaluating later applications.”).Google Scholar

See, e.g., H.R. Rep. No. 95-663, at 41–42, 58 (1977) (describing the dispute surrounding the definition of proprietary information).Google Scholar

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Id.; see also H.R. Rep. No. 95-663, at 41–42, 58.Google Scholar

See H.R. Rep. No. 95-663, at 41 (reasoning provided by Rep. Thone for his proposal of a ten-year period of data exclusivity).Google Scholar

See H.R. Rep. No. 92-511, at 69, 72 (1971) (remarks of Reps. Foley & Dow); S. Rep. No. 92-970 at 12–13 (1972) (letter from the Attorney General); H.R. Rep. No. 95-663, at 41, 53–54 (1977) (reasoning provided by Rep. Fithian for his proposal to provide appropriate compensation in lieu of data exclusivity; letter from the EPA expressing preference for compensation of product developers for use of their data over exclusivity in such data).Google Scholar

See, e.g., H.R. Rep. No. 95-663, at 41–43, 58.Google Scholar

Id.Google Scholar

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Id.; see also Union Carbide, 632 F.2d at 1017.Google Scholar

Ruckelshaus, 467 U.S. at 987. The Supreme Court held that the data submitted between October 22, 1972 and September 30, 1978 was subject to another set of amendments to FIFRA that were in force prior to the enactment of FPA and that allowed a data submitter to protect its trade secrets from internal use by EPA by designating relevant data as trade secrets at the time of submission, provided that the EPA agreed with the designation. Id., at 1010-11. The Ruckelshaus Court viewed these arrangements as creating an explicit guarantee of “an extensive measure of confidentiality and exclusive use … [which] formed the basis of a reasonable investment-backed expectation.” Id., at 1011.Google Scholar

Id., at 1001–1004.Google Scholar

Id., at 1005 (internal citation marks omitted).Google Scholar

Id., at 1005–06.Google Scholar

Id., at 1006–07.Google Scholar

Id., at 1007.Google Scholar

Id., at 1007–08.Google Scholar

See id., at 1009–14 (discussing data submitted between October 22, 1972 and September 30, 1978).Google Scholar

Id., at 1008–09. The Supreme Court recognized, however, that this was not the case with respect to data submitted between October 22, 1972 and September 30, 1978. See id., at 1013–14.Google Scholar

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Id., at 1014 (citations omitted).Google Scholar

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Id., at 1016.Google Scholar

Id., at 1016–19.Google Scholar

Id., at 1019.Google Scholar

Id., at 1020.Google Scholar

Id., at 998 (quoting the district court opinion; brackets in origin).Google Scholar

Id., at 1011.Google Scholar

Note that the data is for registrations rather than applications for new pesticide products.Google Scholar

The economic literature that analyzes the regulation of pesticides in the 1970s and 1980s focuses more on the effect that EPA regulation generally had on the pesticide industry rather than on any specific episode or event during that period. See, e.g., Ollinger, M. and Fernandez-Cornejo, J., “Innovation and Regulation in the Pesticide Industry,” Agricultural & Resource Economics Review 27 (1998) (reviewing the literature): 15, 15.CrossRef Google Scholar

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Of further note in regard to a possible connection between the decrease in pesticide product registration and FPA is the potentially “intervening” factor of EPA's imposition in 1982 of additional testing requirements that further increased regulatory stringency. See id. (Ollinger, 1995), at 5 and 7 note 8.Google Scholar

Notably, the literature does recognize the debate surrounding the sharing of data by EPA and its resolution in FPA. See id. (Ollinger, 1995), at 5.Google Scholar

See also Ollinger and Fernandez-Cornejo, supra note 117, at 17 (highlighting additional similarities of the pesticide and pharmaceutical industries).Google Scholar

See also Price, supra note 5, at 1804, note 189, 1804-1808 and Price and Rai, supra note 41, at 1053 (making a proposal to publicly disclose the Chemistry and Manufacturing Controls section of New Drug Applications (NDAs) and BLAs upon approval of original biologics; discussing the advantages of trade secret disclosure in the context of regulated industries in general).Google Scholar

See supra note 51 and accompanying text.Google Scholar

See also Price supra note 5, at 1798.Google Scholar

See also supra note 62 and accompanying text.Google Scholar

While voluntary disclosure by original biologics developers would have achieved the same goals, given the structure of incentives in the area of biologics, it cannot be expected and must, therefore, be mandated by a legislative or regulatory measure. Another possibility is disclosure only in cases where an original biologic developer is unable to meet market demand, fails to maintain quality control of its products, and/or is found to have broken the law somehow in a way that limits access to its products. See also Price, supra note 5, at 1808-10. This option, however, is also too limited as it will make instances of disclosure too rare to alleviate the competitive ills that plague most biologics markets, including ones that are not affected by original product developers' misconduct.Google Scholar

For the purpose of this proposal, “manufacturing information” includes whatever information knowledge and materials necessary to create the most accurate replica of an original biologic as approved by the FDA. For further discussion of the possible need and legal feasibility of sharing the progenitor cell line, see discussion infra Part III.D.3.Google Scholar

Federal Food, Drug, and Cosmetic Act of 1938, Pub. L. No. 75-717, 52 Stat. 1040 (1938) (codified at 21 U.S.C. § 301 et seq.).Google Scholar

Public Health Service Act of 1944, Pub. L. No. 78-410, 58 Stat. 682 (1944) (codified at 42 U.S.C. § 201 et seq.).Google Scholar

Congress has nearly unlimited discretion in determining the scope of disclosure under the statute. See Ruckelshaus, 467 U.S. at 1016 (“It is enough for us to state that the optimum amount of disclosure to the public is for Congress, not the courts, to decide, and that the statute embodies Congress' judgment on that question.”).Google Scholar

The abuse of FDA Risk Evaluation and Mitigation Strategy (REMS) policies by brand-name pharmaceutical companies refusing to sell samples of their products to follow-on developers serves as both a lesson and warning against the institution of direct, unmediated dealings between original and follow-on pharmaceutical developers. See, e.g., Food and Drug Administration, Statement from FDA Commissioner Scott Gottlieb, M.D., on New Policies to Reduce the Ability of Brand Drug Makers to Use REMS Programs as a Way to Block Timely Generic Drug Entry, Helping Promote Competition and Access (May 31, 2018), available at <https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-new-policies-reduce-ability-brand-drug-makers-use-rems> (last visited November 11, 2019).+(last+visited+November+11,+2019).>Google Scholar

42 U.S.C. § 262(l)(2)(A) (“the [follow-on product] applicant … shall provide to the [original biologic developer] … the process or processes used to manufacture the biological product”). For further discussion of the patent dance framework, see infra note 172.Google Scholar

This would be similar to FPA's grant of authority to EPA to share original pesticide manufacturing information with follow-on developers only when such disclosure “is necessary to protect against an unreasonable risk of injury to health or the environment.” See supra note 76 and accompanying text.Google Scholar

A narrow tailoring of the disclosure arrangement and its close tying to the goal of bringing price competition to biologics markets in the United States would stem challenges to the constitutionality of the measure as effectuating destruction of all economically beneficial uses of trade secrets embodied in manufacturing information disclosed to follow-on developers. See Yoo, supra note 173, at 36 (“unless government regulation completely deprives property of its entire value, courts will not find a per se taking to have occurred”). It may also address other concerns having to do with protection afforded to original biologics in foreign pharmaceutical markets as well as with potential challenges to Ruckelshaus itself. For further insight into what such a challenge might entail, see Epstein, supra note 64, at 304-313.Google Scholar

See discussion infra note 178 and accompanying text.Google Scholar

42 U.S.C. § 262(j) (“The Federal Food, Drug, and Cosmetic Act … applies to a biological product subject to regulation under this section”).Google Scholar

21 U.S.C. § 331(j).Google Scholar

See 21 C.F.R. § 60.151(f) (“The following data and information in biological product file are not available for public disclosure … (1) manufacturing methods or processes, including quality control procedures…. (3) Quantitative or semiquantitative formulas.”); 21 C.F.R. § 20.61(c) (“Data and information submitted or divulged to the Food and Drug Administration which fall within the definition of a trade secret or confidential commercial or financial information are not available for public disclosure.”).Google Scholar

42 U.S.C. § 262(a)(2)(A). (last visited November 11, 2019) [Gottlieb Statement]. The FDA's set of authorities under FDCA make the discussion in this part also applicable, mutatis mutandis, to such biologics.' href=https://scholar.google.com/scholar?q=42+U.S.C.+§+262(a)(2)(A).+Notably,+some+biologics+have+traditionally+been+regulated+and+approved+via+the+regulatory+pathway+reserved+for+small+molecule+drugs+under+FDCA.+The+FDA+is+expected+to+transition+at+least+some+of+these+products+—+e.g.,+insulin+and+human+growth+hormone+—+to+regulation+and+licensure+as+biologics+under+PHSA.+See+Statement+from+FDA+Commissioner+Scott+Gottlieb,+M.D.,+on+New+Actions+Advancing+the+Agency's+Biosimilars+Policy+Framework,+December+11,+2018,+available+at++(last+visited+November+11,+2019)+[Gottlieb+Statement].+The+FDA's+set+of+authorities+under+FDCA+make+the+discussion+in+this+part+also+applicable,+mutatis+mutandis,+to+such+biologics.>Google Scholar

42 U.S.C. § 262(k)(3)(A), & (4).Google Scholar

42 U.S.C. §§ 262(i).Google Scholar

42 U.S.C. §§ 262(a)(2)(C)(I).Google Scholar

42 U.S.C. §§ 262(i).Google Scholar

FDA Mission, available at <https://www.fda.gov/about-fda/what-we-do#mission> (last visited November 13, 2019).+(last+visited+November+13,+2019).>Google Scholar

But see Epstein, supra note 64, at 293-94 (in an Industry funded article, taking the opposite position that BPCIA precludes FDA consideration of information filed in original biologics regulatory filings as part of its evaluation of follow-on products marketing applications). Epstein's position, however, is based on his very narrow interpretation of Section 351(k)(3) that is not mandated by the statutory language.Google Scholar

42 U.S.C. § 262(k)(2). BPCIA lists categories of “required information” under subsection (k)(2)(i) but then gives the FDA the authority to “determine, in [its] discretion,” that some of the categories of information required under subsection (k)(2)(i) are “unnecessary.” Id.Google Scholar

42 U.S.C. § 262(k)(2)(iii)(II). Notably, BPCIA does list “publicly-available information with respect to the reference product or another biological product” as an example of such “additional information” and even requires that such information be submitted to FDA by follow-on product applicants. 42 U.S.C. § 262(k)(2)(iii)(I)-(II). However, the statutory language is open and does not preclude other kinds of information.Google Scholar

Notably, Professor John Yoo has taken a similar position with respect to FDA's authority to create a pathway for approval of generic biologics even before the enactment of BPCIA. See generally Yoo supra note 173, and especially at 41-43 (arguing that FDCA Section 301(j) does not preclude FDA's broad authority to create a pathway for approval of generic biologics and that “FDA's decisions in this area should be based purely on policy considerations, and should not be deterred by Fifth Amendment concerns.”).Google Scholar

See, e.g., Mello, M. M., “What Makes Ensuring Access to Affordable Prescription Drugs the Hardest Problem in Health Policy?” Minnesota Law Review 102 (2018): 2273, 2301 (citing to Ctr. For Responsive Pols. Top Industries), available at <https://www.opensecrets.org/lobby/top.php?showYear=2019&indexType=i> (last visited November 12, 2019) (acknowledging that the pharmaceutical industry alone has already spent over $155 million on lobbying this year and spent $283 million on lobbying in 2018, which was far in excess of any other lobbying group and was worth almost twice as much as the insurance industry lobbying group in second place).Google Scholar

See, e.g., Sekerka, L.E. and Benishek, L., “Thick as Thieves? Big Pharma Wields Its Power With the Help of Government Regulation,” Emory Corporate Governance and Accountability Review 5 (2018): 113, 124-25; McGreal, C., “How Big Pharma's Money – and Its Politicians – Feed the US Opioid Crisis,” The Guardian, October 19, 2017, available at <https://www.theguardian.com/us-news/2017/oct/19/big-pharma-money-lobbying-us-opioid-crisis> (last visited November 13, 2019) (discussing how the vast majority of politicians on the federal level have received donations from pharmaceutical companies and how Industry money influences Congress's legislative agenda); Heled, supra note 4, at 116-119 (discussing the highly Industry-favorable lean of BPCIA).Google Scholar

E.g., affordable Health Care for America Act, H.R. 3962, 111th Cong. §§ 2575–77 (2009); Promoting Innovation and Access to Life-Saving Medicine Act, H.R. 1427, 111th Cong. (2009); Pathway for Biosimilars Act, H.R. 1548, 111th Cong.; Pathway for Biosimilars Act, H.R. 5629, 110th Cong. (2008); Access to Life-Saving Medicine Act, H.R. 1038, 110th Cong. (2007); Biologics Price Competition and Innovation Act of 2007, S. 1695, 110th Cong. (2007); Patient Protection and Innovation Biologic Medicines Act of 2007, H.R. 1956, 110th Cong. (2007).Google Scholar

See Sanders Amendment supra note 62. The Sanders Amendment does not mention manufacturing information.Google Scholar

For example, House Judiciary Chairman Jerrold Nadler (D-NY) and Subcommittee on Antitrust, Commercial, and Administrative Law Chairman David N. Cicilline (D-RI) released a joint statement about addressing the “bully tactics” adopted by large brand prescription drug companies, while House Judiciary Ranking Member Doug Collins (R-GA) and Subcommittee on Antitrust, Commercial, and Administrative Law Ranking Member Jim Sensenbrenner (R-WI) released a joint statement thanking Chairman Nadler and Subcommittee Chairman Cicilline and reaffirming their interest in continuing to “work[] together to promote competition and decrease pharmaceutical costs.” Press Release, Congressman Jerry Nadler, House Judiciary Unanimously Passes Bipartisan Bills to Lower Prescription Drug Prices (April 30, 2019), available at <https://nadler.house.gov/news/documentsingle.aspx?DocumentID=393903> (last visited November 13, 2019). Senator Chuck Grassley (R-IA), Chairman of the Senate Finance Committee, has also sought to address concerns regarding rising prescription drug costs through hearings and bipartisan proposals. News Release, Sen. Chuck Grassley, Grassley Op-ed: Pharma execs should stop grandstanding and work to lower prescription prices (February 26, 2019), available at <https://www.grassley.senate.gov/news/news-releases/grassley-op-ed-pharma-execs-should-stop-grandstandingand-work-lower-prescription> (last visited November 13, 2019).+(last+visited+November+13,+2019).+Senator+Chuck+Grassley+(R-IA),+Chairman+of+the+Senate+Finance+Committee,+has+also+sought+to+address+concerns+regarding+rising+prescription+drug+costs+through+hearings+and+bipartisan+proposals.+News+Release,+Sen.+Chuck+Grassley,+Grassley+Op-ed:+Pharma+execs+should+stop+grandstanding+and+work+to+lower+prescription+prices+(February+26,+2019),+available+at++(last+visited+November+13,+2019).>Google Scholar

See, e.g., We PAID (Protect American Investment in Drugs) Act of 2019, S. 2387, 116th Cong. (2019) (establishing a process for calculating a “reasonable” drug price); Efficiency and Transparency in Petitions Act, S. 660, 116th Cong. (2019) (amending requirements in the citizen petition process to prevent abuse by brand-name drug manufacturers); Accelerated Drug Approval for Prescription Therapies (ADAPT) Act, S. 658, 116th Cong. (2019) (creating an accelerated approval pathway for drugs that are legally approved in other countries); Creating and Restoring Equal Access to Equivalent Samples (CREATES) Act, S. 340, 116th Cong. (2019) (aimed at preventing abuse of risk evaluation and mitigation strategies (REMS) by creating a pathway for follow-on product manufacturers to purchase original product samples); Prescription Drug Price Relief Act, S. 102, 116th Cong. (2019) (terminating government-granted monopolies for drug manufacturers that charge excessive drug prices exceeding the median price in other countries); Prescription Drug Price Transparency Act, H.R. 1035, 116th Cong. (2019) (adding pharmacy benefits manager standards for the Medicare prescription drug program and the Medicare Advantage program to increase transparency of payment methods to pharmacies); and Bringing Low-Cost Options and Competition while Keeping incentives for New Generics (BLOCKING) Act of 2019, H.R. 938, 116th Cong. (2019) (seeking to prevent abuse of the Hatch-Waxman Act's 180-day generic exclusivity period).Google Scholar

See discussion infra Part III.E.2.Google Scholar

See, e.g., Letter from John. C. Yoo, supra note 64, at 2 and note 1. See also generally Carver (describing FDA hesitancy as one of the leading causes for the delay in the institution of a regulatory pathway for approval of follow-on biologics).Google Scholar

See supra notes 13-16 and accompanying text.Google Scholar

See, e.g., Lemley, M.A., “Intellectual Property Rights and Standard-Setting Organizations,” California Law Review 90 (2002) (“while IP rights sometimes promote innovation, at other times they can actually impede it. This is particularly true in industries where innovation is cumulative, because granting strong IP rights to initial innovators restricts the options available to improvers.”); White v. Samsung Elecs. Am., Inc., 989 F.2d 1512, 1513 (9th Cir. 1992) (Kozinski, J., dissenting) (“Overprotecting intellectual property is as harmful as underprotecting it … Overprotection stifles the very creative forces it's supposed to nurture.”).CrossRef Google Scholar

See, e.g., Heled supra note 4, at 129-130 (describing the case of Amgen's twenty-three years of monopoly in its filgrastim product, Neupogen).Google Scholar

See, e.g., Gottlieb Statement supra note 139 (“the life science industry realizes one of the highest rates of investment in research and development – almost 19 percent of revenues, on average.”); Atteberry et al., supra note 23 (discussing the profitability of biologics; bringing Humira as an example).Google Scholar

Estimates range from several hundreds of millions of dollars to $2.6 billion per product. See, e.g., DiMasi, J.A. and Grabowski, H.G., “The Cost of Biopharmaceutical R&D: Is Biotech Different,” Managerial and Decision Economics 28 (2007): 469, 469 (estimating the cost of development of a new biologic at $559 million); Avorn, J., “The $2.6 Billion Pill - Methodologic and Policy Considerations,” New England Journal of Medicine 372, no. 20 (2015): 1877, 1877-78 (challenging the estimates by the Tufts Center for the Study of Drug Development by noting that the Tufts estimates did not account for large public subsidies provided to pharmaceutical companies or development costs incurred by the public, did not disclose the compounds being studied, and assumed that capital costs amounted to half of the total drug development costs); Ho, C. M., “Drugged Out: How Cognitive Bias Hurts Drug Innovation,” San Diego Law Review 51 (2014): 419, 448-57 (challenging the calculation that the “average cost to develop every drug exceeds $1 billion”).CrossRef Google Scholar

See, e.g., Press Release, Tufts Ctr. for the Study of Drug. Dev., Cost to Develop and Win Marketing Approval for a New Drug is $2.6 Billion, November 18, 2014, available at <https://static1.squarespace.com/static/5a9eb0c8e2ccd1158288d8dc/t/5ac66adc758d46b001a996d6/1522952924498/pr-coststudy.pdf> (last visited November 13, 2019) (calculating $2,558 million based on an estimated $1,395 million in capital and $1,163 million in time costs). Notably, the 2014 estimate is significantly higher from an earlier estimated cost of $802 million to develop a new drug made by researchers in the same Industry funded research institute in 2000. See DiMasi, J. A. et al., “The Price of Innovation: New Estimates of Drug Development Costs,” Journal of Health Economics 22, no. 2 (2003): 155, 166.Google Scholar

Even if one were to accept the estimates of $1.2-2.6 billion as true, the sales figures of many if not most original biologics make such numbers pale in comparison. See, e.g., A. Philip-pidis, “Top 15 Best-Selling Drugs of 2018,” Genetic Engineering & Biotechnology News March 11, 2019 (reporting the sales figures of top selling original biologics as ranging between $5.908-19.936 billion annually).Google Scholar

42 U.S.C. § 262(k)(7).Google Scholar

See, e.g., Grabowski, H.C., “Follow-on Biologics: Data Exclusivity and the Balance Between Innovation and Competition,” Nature Reviews Drug Discovery 7 (2008): 479, 486 (arguing that 12.9-16.2 years of market exclusivity in original biologics are necessary to recoup the investment in an original biologic's R&D); FTC 2009 Report at v-vii (arguing against any additional exclusivity for original biologics; disputing the estimates put forward by the Industry that relied on Grabowski); Biologics and Biosimilars: Balancing Incentives for Innovation: Hearing Before the H. Subcomm. on Courts and Competition Policy of the H. Comm. on the Judiciary, 111th Cong. 17 n.3 (2009) (statement of Bruce A. Leicher); Brill, A. M., Proper Duration of Data Exclusivity for Generic Biologics: A Critique (2008): 7, 8 & 11, archived at <http://perma.cc/S825-8DVQ> (last visited November 13, 2019); Kotlikoff, L. J., Stimulating Innovation in the Biologics Industry: A Balanced Approach to Marketing Exclusivity (2008): 6, available at <https://pdfs.semanticscholar.org/ac5a/60467ecb61f49496bccd70df446d5dc825a8.pdf>, archived at <http://perma.cc/3TSM-8ZNG> (both last visited November 13, 2019).CrossRef Google Scholar

See, e.g., Grabowski, supra note 165, at 486; Safe and affordable Biotech Drugs: The Need for a Generic Pathway: Hearing Before the H. Comm. on Oversight and Gov't Reform, 110th Cong. 161–76 (2007) (statement of Henry Grabowski); Biotech Indus. Org. (BIO), A Follow-On Biologics Regime Without Strong Data Exclusivity will Stifle the Development of New Medicines 4, available at <https://www.bio.org/sites/default/files/FOBSData_exclusivity_20070926_0.pdf>, archived at <http://perma.cc/S59R-P77J> (both last visited November 13, 2019) (“[A] 14-year period of data exclusivity serves essentially as an insurance policy that provides the innovator with some certainty of protection ….”); Grabowski, H. et al., Data Exclusivity Periods for Biologics: Updating Prior Analyses and Responding to Critiques, Duke University Department of Economics, Working Paper No. 2008-10, 2008): at 4, available at <http://public.econ.duke.edu/Papers/PDF/Data_Exclusivity_Periods_for_Biologics.pdf>, archived at <http://perma.cc/C7FA-FN85> (both last visited November 13, 2019) (arguing that the purpose of the market exclusivity for original biologics developers is to provide them “with an ‘insurance policy’ against the potential failings of patent protection for biologics”); Grabowski, H. and DiMasi, J., Biosimilars, Data Exclusivity, and the Incentives for Innovation: A Critique of Kotlikoff's White Paper, Duke University Department of Economics, Working Paper No. 2009-02, 2009): at 408, available at <http://public.econ.duke.edu/Papers//PDF/FinalDraft2_5_09.pdf>, archived at <http://perma.cc/9EGXZFP9> (both last visited November 13, 2019).,+archived+at++(both+last+visited+November+13,+2019)+(“[A]+14-year+period+of+data+exclusivity+serves+essentially+as+an+insurance+policy+that+provides+the+innovator+with+some+certainty+of+protection+….”);+Grabowski,+H.+et+al.,+Data+Exclusivity+Periods+for+Biologics:+Updating+Prior+Analyses+and+Responding+to+Critiques,+Duke+University+Department+of+Economics,+Working+Paper+No.+2008-10,+2008):+at+4,+available+at+,+archived+at++(both+last+visited+November+13,+2019)+(arguing+that+the+purpose+of+the+market+exclusivity+for+original+biologics+developers+is+to+provide+them+“with+an+‘insurance+policy’+against+the+potential+failings+of+patent+protection+for+biologics”);+Grabowski,+H.+and+DiMasi,+J.,+Biosimilars,+Data+Exclusivity,+and+the+Incentives+for+Innovation:+A+Critique+of+Kotlikoff's+White+Paper,+Duke+University+Department+of+Economics,+Working+Paper+No.+2009-02,+2009):+at+408,+available+at+,+archived+at++(both+last+visited+November+13,+2019).>Google Scholar

Notably, original biologics developers' exclusivity in their products is further ensured internationally by similar extra-patent exclusivity arrangements such as the ones instituted under BPCIA as well as by foreign patents covering the original biologics. For further discussion of international implications of disclosure of original products' manufacturing information, see Price, supra note 5, at 1811.Google Scholar

42 U.S.C. § 262(k)(7)(A).Google Scholar

42 U.S.C. § 262(k)(7)(B).Google Scholar

42 U.S.C. § 262(m)(2)(A). See also discussion supra note 14.Google Scholar

Notably, patents covering original biologics and methods involved in the manufacturing of biologics are notoriously narrow and practically never disclose enough information to enable reproduction of biologics' entire manufacturing processes by competitors. See, e.g., Karshtedt, D., “Limits on Hard-to-Reproduce Inventions: Process Elements and Bio-technology's Compliance with the Enablement Requirement,” Hastings Science & Technology Law Journal 3 (2011): 135-37; Mandel, G.N., “The Generic Biologics Debate: Industry's Unintended Admission That Biotech Patents Fail Enablement,” VAJLT 11 (2006): 8; Price and Rai, supra note 41, at 1050-53 (arguing that patents are unsuitable for prompting sufficiently full disclosure of original biologics manufacturing information). Disclosure of manufacturing information to the FDA as part of an original BLA, on the other hand, is complete and includes all the details necessary to accurately recreate the full process of manufacturing an original biologic.Google Scholar

U.S. Const. Amend. V (“nor shall private property be taken for public use, without just compensation.”). See, e.g., Letter from Robert A. Long, supra note 45 at 2; H. Carver et al., supra note 40, at 698 (expressing the view that “approve[al of] BLAs in reliance on preclinical and clinical safety and effectiveness data submitted in other BLAs … in the view of the authors, [is] inconsistent with … the Federal Trade Secrets Act, FDCA section 301(j), and the U.S. Constitution.”); Epstein, supra note 64, at 299-300; see also supra note 45.Google Scholar

See The Law of Biologic Medicine: Hearing Before the S. Comm. on the Judiciary, S. Hrg. 108-635 at 134 (June 23, 2004) (statement of Lester M. Crawford, Acting Commissioner of Food and Drugs), available at <https://www.govinfo.gov/content/pkg/CHRG-108shrg96196/pdf/CHRG-108shrg96196.pdf> (last visited November 13, 2019) (“we do not believe such authority exists for follow-on biologics application under section 351 of the PHS Act that relies on the prior approval of the biological product or on data submitted by another sponsor.”); Carver et al., supra note 40, at 698-99. See also Yoo, J. C., “Takings Issues in the Approval of Generic Biologics,” Food & Drug Law Journal 60 (2005): 33, 34 note 10 (in an article funded by the generic industry, criticizing the FDA's reluctance to create a regulatory pathway for approval of generic biologics as unwarranted).Google Scholar

Ruckelshaus, 467 U.S. at 1002.Google Scholar

Arguably, such a change in the law would also render unreasonable any expectations that regulatory filings made subsequent to the law's going into effect would be kept confidential. See also Letter from John C. Yoo, supra note 64, at 6).Google Scholar

Ruckelshaus, 467 U.S. at 1007.Google Scholar

The Ruckelshaus Court did not consider the disclosure of regulatory filings by EPA to be per se taking and further emphasized that “this Court has generally been unable to develop any set formula for determining when justice and fairness require that economic injuries caused by public action must be deemed a compensable taking … The inquiry into whether a taking has occurred is essentially an ad hoc factual inquiry.” Ruckelshaus, 467 U.S. at 1005. See also Letter from John A. Yoo, supra note 64, at 3-4.Google Scholar

Ruckelshaus, 467 U.S. at 987 (holding that FPA's data use and disclosure provisions did not violate the Fifth Amendment with respect to data submitted prior to October 22, 1972).Google Scholar

Id., at 1005 (internal citation marks omitted); see also Penn Cent. Transp. Co. v. City of New York, 438 U.S. 104, 124, 98 S. Ct. 2646, 2659, 57 L. Ed. 2d 631 (1978) (“A ‘taking’ may more readily be found when the interference with property can be characterized as a physical invasion by government … than when interference arises from some public program adjusting the benefits and burdens of economic life to promote the common good. Government hardly could go on if to some extent values incident to property could not be diminished without paying for every such change in the general law.”).Google Scholar

See, e.g., Letter from Robert A. Long, supra note 45.Google Scholar

21 U.S.C. § 331(j).Google Scholar

See 42 U.S.C. § 262(j) (“The Federal Food, Drug, and Cosmetic Act [21 U.S.C. 301 et seq.] … applies to a biological product subject to regulation under this section”).Google Scholar

See 21 C.F.R. § 60.151(f) (“The following data and information in biological product file are not available for public disclosure … (1) manufacturing methods or processes, including quality control procedures … (3) Quantitative or semiquantitative formulas.”); 21 C.F.R. § 20.61(c) (“Data and information submitted or divulged to the Food and Drug Administration which fall within the definition of a trade secret or confidential commercial or financial information are not available for public disclosure.”).Google Scholar

See Letter from Robert A. Long, supra note 45.Google Scholar

18 U.S.C. 1905.Google Scholar

Pub. L. 114–153, 130 Stat. 376 (2016) (codified at 18 U.S.C. § 1836, et seq.).Google Scholar

Ruckelshaus, 467 U.S. at 1008.Google Scholar

Notably, Prof. John Yoo has expressed the view that PHSA Section 301(j) similarly does not provide an express enough promise, under Ruckelshaus, not to disclose trade secrets in the specific context of approval of follow-on biologics. See Letter from John C. Yoo, supra note 64, at 9. But see Epstein, supra note 64, at 293 (arguing that BPCIA's reference to “publicly available information” creates such an explicit promise).Google Scholar

See also Letter from John C. Yoo, supra note 64, at 10.Google Scholar

Id., at 1008-09.Google Scholar

Id. See also Letter from John C. Yoo, supra note 64, at 6-7 (“Statutory silence in a heavily regulated industry, the Court found … places applicants on notice that they cannot form reasonable investment-backed expectations that submitted data will not be used by the agency in the future.”).Google Scholar

See, e.g., Sharfstein, J. M. et al., “Blueprint for Transparency at the U.S. Food and Drug Administration: Recommendations to Advance the Development of Safe and Effective Medical Products,” Journal of Law, Medicine & Ethics 45, no. 2, Suppl. (2017): 7-23; Doshi, P., “FDA to Begin Releasing Clinical Study Reports in Pilot Programme,” 390 BMJ (2018): k294.CrossRef Google Scholar

Ruckelshaus, 467 U.S. at 1005.Google Scholar

Ruckelshaus, 467 U.S. at 1016-19.Google Scholar

Id., at 1016. Under the Tucker Act, “The United States Court of Federal Claims shall have jurisdiction to render judgment upon any claim against the United States founded either upon the Constitution, or any Act of Congress or any regulation of an executive department, or upon any express or implied contract with the United States, or for liquidated or unliquidated damages in cases not sounding in tort.” 28 U.S.C. § 1491.Google Scholar

See supra notes 164-166 and accompanying text.Google Scholar

See supra note 165 and accompanying text.Google Scholar

See also Epstein supra note 64 at 315 and 324 (making a similar point, viewing BPCIA's “special protections … to innovators … as the “quid pro quo” for removing at year 12 the innovator's otherwise permanent right to prevent competitors from benefitting from the government's use of those trade secrets” but disagreeing that BPCIA's scheme would allow for FDA disclosure of trade secrets to follow-on biologics developers).Google Scholar

See supra notes 37-42 and accompanying text.Google Scholar

See, e.g., Vulto, A. G. and Jacquez, O. A., “The Process Defines the Product: What Really Matters in Biosimilar Design and Production?” Rheumatology 56 (August 2017): iv14, iv23 (noting that the manufacturing complexity of biologics can have a negative impact on batch-to-batch consistency); Gonçalves, J. et al., “Biosimilar Monoclonal Antibodies: Preclinical and Clinical Development Aspects,” Clinical & Experimental Rheumatology 34, no. 4 (2016): 698, 698 (there are “unavoidable differences between even subsequent batches of the same product”); Louët, S., “Lessons from Eprex for Biogeneric Firms,” Nature Biotechnology 21 (2003): 956 (describing how small changes in the manufacturing process of the biologic Eprex caused severe immunogenic responses in patients); van Beers, M. M. C. and Bardor, M., “Minimizing Immunogenicity of Biopharmaceuticals by Controlling Critical Quality Attributes of Proteins,” Biotechnology Journal 7 (2012): 1473.Google Scholar

See Lucas v. S.C. Coastal Council, 505 U.S. 1003, 112 S. Ct. 2886, 120 L. Ed. 2d 798 (1992). The taking analysis would have changed had the purported taking pertained to real property. Id., at 1015.Google Scholar

See, e.g., 37 C.F.R. §§ 1.801 et seq. (2003) (requiring samples to be deposited with the USPTO).Google Scholar

See, e.g., 21 C.F.R. § 80.21 et seq. (2018) (requiring a request for certification by the FDA of a batch of color additives to be accompanied by a sample).Google Scholar

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The Case for Disclosure of Biologics Manufacturing Information

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