The quest for generic biotechnology pharmaceuticals in the USA

Thomas J. Kowalski is a partner in the New York office of Frommer Lawrence & Haug LLP. Pamela Fekete is an associate in the New York office of Frommer Lawrence & Haug LLP. Her practice focuses on infringement studies and patent litigation, primarily relating to pharmaceutical litigation under the Hatch– Waxman Act. Anne-Marie C. Yvon is a scientific advisor in the New York office of Frommer Lawrence and Haug LLP. She is a registered patent agent whose work focuses on the prosecution of biotechnology patents. Keywords: generic biologics, biogenerics, biotechnological pharmaceuticals, follow-on biologics Thomas J. Kowalski Frommer Lawrence & Haug, LLP, 745 Fifth Avenue, New York, NY 10151, USA Tel: +1 212 588 0800 E-mail: The quest for generic biotechnology pharmaceuticals in the USA Thomas J. Kowalski, Pamela Fekete and Anne-Marie C. Yvon Date received (in revised form): 10th December, 2004 Abstract As patent protection expires on the first generation of biotechnology products, such as human growth hormone and erythropoietin, there is an impetus for the development and marketing of generic equivalents. Currently there is no statutory or regulatory framework governing generic biotechnology products. This paper explores the potential solutions that have been suggested by members of the pharmaceutical industry and government, both in the USA and internationally. In the USA, a company can bring a generic version of a certain pharmaceutical product to market either when the product loses patent protection, such as by expiration or invalidation by a court ruling, or under the Hatch– Waxman Act. The Act provides a mechanism for companies to file a New Drug Application under Section 505(b)(2), relying on safety and efficacy studies not performed by or for the applicant (referred to in this context as a ‘paper NDA’), or an Abbreviated New Drug Application (ANDA) under Section 505(j). As first generation biotechnology products are approaching the loss of patent protection, many companies are interested in marketing competitive versions of these products. There is currently no established statutory or regulatory scheme for effecting this result. While the Food and Drug Administration (FDA) has indicated that the 505(b)(2) route might be available for this purpose,1 it recently indicated in a response to several citizen petitions regarding 505(b)(2) that it will specifically address the use of 505(b)(2) for biologic-type products at some future time.2 Therefore, unlike traditional pharmaceutical products, for which a steady stream of generics have been reaching the market in a pattern that directly correlates with patent expiry, the path to ‘biogenerics’ is less straightforward. Even the terminology used to describe biotechnological and biological products is unsettled. ‘Biological products’ are regulated under the Public Health Service Act (42 USC §262) and defined as a ‘virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings.’3 This definition does not appear to include biotechnological products, such as recombinant insulin and human growth hormone. (Even if it did, however, there is no provision in the Federal Biologics Act for an abbreviated application process.) The terms ‘biogenerics’ and ‘follow-on biologics’ have been suggested for generic biotechnology products; however, recent indications from the FDA are that any official term for generic versions of biotech drugs will include the word ‘protein’.4 In this paper, we will use ‘biogenerics’, for lack of a better term. Biotechnology products currently provide treatment for some of the most debilitating diseases, including hepatitis, & HENRY STEWART PUBLICATIONS 1478-565X. J O U R N A L O F C O M M E R C I A L B I O T E C H N O L O G Y . VOL 11. NO 3. 271–274. APRIL 2005 271 Kowalski, Fekete and Yvon Legislation is needed to provide a regulatory scheme for bringing generic biotechnology products to market multiple sclerosis, anaemia in patients with chronic renal failure, and immunological deficiency resulting from cancer treatment. These critical patient populations are still waiting for legislation analogous to the Hatch–Waxman Act that will provide both an incentive to the innovators of biotechnology to keep pursuing this cutting edge technology, and a pathway for generic companies to provide low-cost equivalents. With several biotechnological products facing expiration of patent coverage before 2007, the time is ripe for legislation outlining an approval process for biogenerics. Table 1 shows the firstgeneration products are facing patent expiration according to IMS Health. At the IIR Global Generic Strategies conference in Barcelona in March-April 2004, Federico Pollano, Head of Business Development at BioGeneriX, forecast ‘[i]n 2010, nearly 50% of all new approved pharmaceuticals will be of biotechnological origin.’5 This anticipated growth, however, will not necessarily translate into the same potential for biogenerics. As Pollano noted, ‘biopharmaceuticals are defined by their production process, any change can impact safety and efficacy and therefore demands new approval.’5 The fact that it is impossible to exactly replicate a biological process poses a potential difficulty in demonstrating equivalence to the brand product. Sandoz, the generic division of Novartis AG, provides a practical example of the difficulties of gaining approval of a biogeneric drug in the USA. Sandoz filed for FDA approval of its generic recombinant human growth hormone, Omnitrope, under Section 505(b)(2).5 While the FDA notified Sandoz in September of this year that it found no deficiencies in the application, the agency stated that it was unable to approve the application due to ‘uncertainty regarding scientific and legal issues.’6 Opponents of the Section 505(b)(2) route of biogeneric approval argue that a full complement of data should be required for generic biotech products, owing to the inherent complexity of protein products. They argue that differences in manufacturing processes could result in differences in the protein product and its clinical effects, and that studies of each new product are the only way to ensure safety and effectiveness.7 On 14th and 15th September, 2004, the FDA held a workshop on the scientific considerations related to developing biogenerics. Draft guidance from the FDA on this topic is expected during the coming year.8 At the same time, the Generic Pharmaceutical Association (GPhA) is lobbying for legislation to create a process for generic biologics. GPhA representative William Schultz, of Zuckerman Spaeder, stated before the 23rd June, 2004, Senate Judiciary Committee session ‘[w]e urge Congress to direct FDA to play an active role (...truncated)