The US Biosimilars Act
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Ever since the signing of the US healthcare reform legislation, the Patient Protection and Affordable Care Act (PPAC), speculation as to what a US FDA biosimilar programme might look like has been rife. Now the FDA has published guidance documents on biosimilar product development, which has been described by Dr Janet Woodcock, MD, Director of the FDA’s Center for Drug Evaluation and Research, as “an innovative approach to supporting the development of biosimilars at every step of the process.” Nevertheless, these initial guidelines are rather general in nature, so the looming question remains as to what extent the US biosimilar pathway will represent a viable route to market.
The pathway for resolution of inevitable patent disputes is long and torturous and it seems that it will inevitably result in delays and litigation; the impact and implications of this represents a key consideration in the choice of the regulatory pathway. Thus, if there are no benefits in terms of reduced data requirement, a more rapid route to market and benefits to market access with the biosimilar route, then one really would have to question the value of this route.
As far as whether the biosimilar pathway will offer reduced data requirements, the jury is still out. Initial indications suggest that the FDA review divisions might initially take a more conservative stand, but one might expect that, as policy becomes more transparent and with the publication of the guidelines, a more pragmatic position might emerge.
One of the most controversial concepts raised by the Biologics Price Competition and Innovation Act of 2009 (BPCI) is that of interchangeability between the innovator and the biosimilar product. This presents a very high bar and in many instances may simply not be achievable or financially viable. Yet, without interchangeable status, a biosimilar will be no different to any other biological approved through a standalone route and, inevitably, an extensive marketing effort would be required to achieve any meaningful market penetration. On the other hand, a standalone application may not offer a viable alternative either, as this would require a more conventional and graduated development programme with the need for extensive non-clinical and phase II data. Furthermore, the inability to extrapolate between indications would require large comparative trials for each indication.
Biosimilars are an essential and inevitable part of enhancing patient access to life-saving medications, and if nations want to maximize the value of healthcare spend, bringing health and well-being to their citizens, biosimilars are a necessity and their exclusion an unaffordable luxury. Thus, one would anticipate that, inevitably, despite the debate, the BPCI will spawn an attractive US biosimilar approval pathway. Certainly, there are many sponsors of biosimilar products banking on just that and the recently published guidelines suggest that the FDA will ultimately apply sound scientific principles, which is, undoubtedly, the optimal way forward.
KeywordsFilgrastim Reference Product Draft Guideline Neupogen Biosimilar Product
The author would like to acknowledge the support and insight provided by Dr Bruce Babbitt, Principle Consultant at PAREXEL Consulting. The author has no conflicts of interest that are relevant to the content of this article. No sources of funding were used in the preparation of this article.
- 1.Behrman R, FDA news release [online]. Available from URL: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm291232.htm [Accessed 2012 Feb 9]
- 2.U.S. Department of Health and Human Services Food and Drug Administration. Guidance for industry: scientific considerations in demonstrating biosimilarity to a reference product [online]. Available from URL: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291128.pdf [Accessed 2012 Feb 9]
- 3.U.S. Department of Health and Human Services Food and Drug Administration. Guidance for industry: quality considerations in demonstrating biosimilarity to a reference protein product [online]. Available from URL: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291134.pdf [Accessed 2012 Feb 9]
- 4.U.S. Department of Health and Human Services Food and Drug Administration. Guidance for industry: biosimilars — questions and answers regarding implementation of the Biologics Price Competition and Innovation Act of 2009 [online]. Available from URL: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM273001.pdf [Accessed 2012 Feb 9]
- 5.CHMP. Guideline on similar biological medicinal products. CHMP/437/04 [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003517.pdf [Accessed 2012 April 2]
- 6.Behrman R. BioCentury interview [online]. Available from URL: http://www.biocenturytv.com/fullplayer.aspx#/BioCentury+05.01.11+%2D+%5B1%5D+The+Pathway/924495749001 [Accessed 2012 May 1]
- 7.Patient Protection and Affordable Care Act HR3590/Pub.L. No. 111–148, 124 Stat. 128; sections 7001 — 7003 (2010 Mar 23)Google Scholar
- 8.CHMP. Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: quality issues. EMEA/CHMP/BWP/49348/2005 [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003953.pdf [Accessed 2066 Feb 22]
- 10.CHMP draft guideline. Similar biological medicinal products containing monoclonal antibodies. EMA/CHMP/BMWP/403543/2010 [online]. Available from URL: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/11/WC500099361.pdf [Accessed 2010 Nov 18]
- 11.Hospira Inc. Press release. Hospira announces positive result from phase 1 U.S. Clinical Trial Of Biosimilar Erythropoietin in Renal Patients [online]. Available from URL: http://phx.corporate-ir.net/phoenix.zhtml?c=175550&p=irol-newsArticle&ID=1603932&highlight= [Accessed 2011 Sep]
- 12.US National Institute of Health. A phase 3 study comparing the effects of intravenous epoetin Hospira and epoetin alfa (Amgen) in patients with chronic renal failure requiring hemodialysis and receiving epoetin maintenance treatment. NCT01473407 [online]. Available from URL: http://clinicaltrials.gov/ct2/show/NCT01473407?term=epoetin+hospira&rank=1 [Accessed 2012 Feb]
- 13.US National Institute of Health. A phase 3 study comparing the effects of subcutaneous epoetin Hospira and epoetin alfa (Amgen) in patients with chronic renal failure requiring hemodialysis and receiving epoetin maintenance treatment. NCT01473420 [online]. Available from URL: http://clinicaltrials.gov/ct2/show/NCT01473420?term=epoetin+hospira&rank=2 [Accessed 2012 Feb 14]
- 14.Novartis. Press Release [online]. Available from URL: http://www.novartis.com/newsroom/media-releases/en/2012/1578463.shtml. [Accessed 2012 Jan 19]
- 15.US National Institute of Health. Phase III study comparing the efficacy and safety of EP2006 and filgrastim (PIONEER) [online]. Available from URL: http://clinicaltrials.gov/ct2/show/NCT01519700?term=sandoz+filgrastim&rank=1&rank=1 [Accessed 2012 Jan 24]
- 16.US National Institute of Health. Phase III study comparing the efficacy and safety of LA-EP2006 and peg-filgrastim (PROTECT2) [online]. Available from URL: http://clinicaltrials.gov/ct2/show/NCT01516736?term=sandoz+pegfilgrastim&rank=1 [Accessed 2012 Jan]
- 17.Loeb J. FDA action on Teva’s neutroval BLA causes some to question biosimilar route [online]. Available from URL: http://www.biolawgics.com/fda-approval/fda-action-on-tevas-neutroval-bla-causes-some-to-question-biosimilar-route. [Accessed 2011 Mar 29]
- 18.FDA Draft Guidance for Industry. Non inferiority clinical trials [online]. Available from URL: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM202140.pdf [Accessed 2010 Feb 20]