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Similar or the Same? Why Biosimilars are not the Solution

Published online by Cambridge University Press:  01 January 2021

Lisa Diependaele ,
Julian Cockbain  and
Sigrid Sterckx
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Abstract

Advancements in the field of biotechnology have accelerated the development of drugs that are manufactured from cultures of living cells, commonly referred to as “biologics.” Due to the complexity of the production process, generic biologics are unlikely to be chemically identical to the reference product, and accordingly are referred to as “biosimilars.”

Encouraging the development of biosimilars has been presented as the key solution to decrease prices and increase access to biologics, but the development and use of biosimilars continues to raise problems, none of which can easily be addressed. Developing a biosimilar requires considerable time and financial resources, and legitimate safety concerns necessitate elaborate clinical testing of biosimilars. As a consequence, the introduction of biosimilars onto the market has not resulted in significant price reductions, and concerns regarding the substitution and interchangeability of original biologics with biosimilars persist.

This article will explain how the biologics production process distorts the trade-offs that traditionally guided both patent protection and regulatory exclusivities: disclosure as a key condition for benefiting from the corresponding monopoly position. Hence, we propose establishing a mechanism of mandatory deposit of the original biologic's cell line at the stage of the regulatory approval as the most effective remedy.

Type
Independent Articles
Information
Journal of Law, Medicine & Ethics , Volume 46 , Issue 3: The Medicalization of Poverty; Perspectives of Alzheimer's Disease: Ethical, Legal, and Social Issues , Fall 2018 , pp. 776 - 790
Copyright
Copyright © American Society of Law, Medicine and Ethics 2018

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Another preliminary suggestion has been made in a blog article. See DrugBaron, “Biosimilars Are Not Similar Enough: A Proposal For True ‘Biogenerics,’” DrugBaron Blog, March 19, 2013, available at <www.drugbaron.com/biosimilars-are-not-similar-enough-a-proposal-for-true-biogenerics/> (last visited August 2, 2018); This proposal, however, is incomplete as it is suggested that the originator should license others to make identical biologics. This would allow the originator companies to retain a relatively powerful position as this implies some control over how many competitors there will be, and thus prevent sufficient price competition.+(last+visited+August+2,+2018);+This+proposal,+however,+is+incomplete+as+it+is+suggested+that+the+originator+should+license+others+to+make+identical+biologics.+This+would+allow+the+originator+companies+to+retain+a+relatively+powerful+position+as+this+implies+some+control+over+how+many+competitors+there+will+be,+and+thus+prevent+sufficient+price+competition.>Google Scholar
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See Lietzan, E., “A New Framework for Assessing Clinical Data Transparency Initiatives,” Marquette Intellectual Property Law Review 18, no 1 (2014): 33–85, at note 51. The EMA, on the other hand, has always had more discretion in deciding which information can be disclosed, although “commercially confidential information” is mostly redacted before disclosure. See Regulation (EEC) No 2309/93; Schneider, G., “A Transparency Challenge: Can Commercial Confidentiality in Clinical Trials Data Be Overcome?” European Pharmaceutical Law Review 2, no. 1 (2018): 3-18.Google Scholar
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See Epstein, R., “The Constitutional Protection of Trade Secrets and Patents under the Biologics Price Competition and Innovation Act of 2009,” Food and Drug Law Journal 66, no. 3 (2011): 285-328, at 304. Were cell line deposits to be required for already approved biologics, it would seem that any “taking” would be of the regulatory approval.Google Scholar
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As an essential component of this exchange, the disclosure of the invention requires “enablement,” meaning that a “person skilled in the art” can, based on the information disclosed in the patent, make and use the patented invention.Google Scholar
It has been argued that, absent a cell line to allow the enablement of a patented biologic, a biologics patent cannot be valid. See Mandel, G.N., “The Generic Biologics Debate: Industry's Unintended Admission that Biotech Patents Fail Enablement,” Virginia Journal of Law & Technology 11, no. 8 (2006): 1-25, at 21-24; Ouellette, L.L., “Access to Bio-Knowledge: From Gene Patents to Biomedical Materials,” Stanford Technology Law Review, N1 (2010): at para 100-103; However, in this context the problem of patent invalidity is also redundant, as the biologic that is actually put onto the market will rarely be identical to the biologic that would be produced by the cell line deposited at the time of the patent application. The patent deposit is required in order to enable the skilled reader to produce a biologic with the required properties, not necessarily the biologic that the patentee subsequently markets.Google Scholar
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SPCs can be applied for, to lengthen patent rights for a maximum of five years after patent expiry, as a compensation for the time needed to obtain regulatory approval for medicinal products.Google Scholar
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For inventive new uses of a cell line or new indications an originator can apply for secondary patents, and in some cases enjoy an extension of the data exclusivity term. However, even when a secondary patent prevents the approval of a biosimilar for a new indication, “off-label” use is still possible, although cautiousness is generally advocated in absence of sufficient proof there are no clinically meaningful differences for that particular indication. See Li, E. and Lobaina, E., “Application of the FDA Biosimilar Extrapolation Framework to Make Off-Label Determinations,” Journal of Managed Care & Specialty Pharmacy 23, no. 12 (2017): 1227–1232; Zhao, S., Nair, J.R., and Moots, R.J., “Biosimilars: From Extrapolation into Off Label Use,” Current Pharmaceutical Design 23, no. 44 (2018): 6746–6751; For biogenerics, greater levels of certainty regarding functional equivalence with the original product may result in increased off label use, thereby placing originators in a situation similar to the situation for most small molecule drugs today. Without denying that the difficulty to enforce second use patents can be a legitimate concern for originators, the need to address this does not trump the potential benefits of our proposal. Other measures, such as adapting prescription and substitution policies and statutory and contractually limiting the purposes for which the deposited cell line (and resulting biologic product) may be used, can address some concerns in this regard. See infra Section 4.5.Google Scholar
See Yeh, B.T., “Protection of Trade Secrets: Overview of Current Law and Legislation,” Congressional Research Service (CRS) Report Prepared for Members and Committees of Congress, April 22, 2016.Google Scholar
In the paradigm case, trade secrecy ends the moment a secret is disclosed, for example in a patent application.Google Scholar
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One of the most prominent cases in the context of biotechnology is the United States Supreme Court ruling on Mayo Collaborative Services v. Prometheus Laboratories in 2012, reaffirming the law-of-nature exception to patentability. See Almeling, D.S., “Seven Reasons Why Trade Secrets Are Increasingly Important,” Berkeley Technology Law Journal 27, no. 2 (2012): 1091-1117, at 1114.Google Scholar
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In addition, originator companies can apply for patent protection in all the relevant global markets.Google Scholar
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