The Leahy-Smith America Invents Act (AIA) and the Biologics Price Competition and Innovation Act (BPCIA) are dramatically reshaping business strategies designed to protect intellectual property and regulatory exclusivity rights granted by the United States Patent and Trademark Office (PTO) and the Federal Drug Administration (FDA) to the sponsors of new and follow-on versions of many biopharmaceutical products. The AIA alters many provisions in the U.S. patent statutes, most notably long-standing policies and practices relating to the conditions for patentability of an invention, particularly 35 USC §§ 102 and 103 relating to novelty and non-obviousness, respectively, and introduces new provisions relating to post-grant review proceedings and prioritized examination that will affect the business plans of academic and corporate institutions seeking to discover and develop health care products that serve unmet medical needs or provide consumers with safe sources of drug products at a low cost. The BPCIA implements many new provisions relating to the abbreviated review and approval of follow-on biopharmaceutical products. Important aspects of the BPCIA, particularly issues identified in draft guidance documents that were released by the FDA in February 2012 concerning the characterization, comparison, and evaluation of reference and follow-on macromolecules, will be discussed in this article. Political issues that may jeopardize the BPCIA, economic considerations faced by drug product sponsors, and public reaction to the guidance documents are also discussed in this final article of a three-part series describing key provisions of the AIA and the BPCIA that affect intellectual property and regulatory exclusivity rights of institutions having an interest in developing novel or follow-on versions of biopharmaceutical drug products…
Tag: <span>biosimilars</span>
Biosimilars, and related biopharmaceutical biobetters and biogenerics, are still relatively new, but are already starting to impact worldwide biopharmaceutical markets. Most discussions of biosimilars center on developed regions where markets are mature and manufacturing capabilities allow for the cost-efficient manufacture of these complex molecules. This article covers the development of these products outside the United States (US), European Union (EU), and other developed, generally rather affluent and high-technology economy-based countries. To start, we first offer some definitions…
Low sialic acid erythropoietin (Neuro-EPO) is a nonerythropoietic molecule that shows neuroprotective activity in some rodent models for brain ischemia. One reason for poor absorption may be the rapid removal of the drug from the site of absorption by mucociliary clearance. For that reason, bioadhesive polymers are used to increase the residence time of the drug in the nasal cavity. The objective of the current study was to evaluate different bioadhesive polymers to identify Neuro-EPO formulations with characteristics suitable for nasal delivery. For this purpose, four different polymers: (1) hydroxypropyl methylcellulose (HPMC) F4M; (2) HPMC K4M; (3) Carbopol 974P; and (4) dextran 70 were assessed to define the appropriate concentration. The physicochemical evaluation of placebo formulations showed reductions in apparent viscosity, except with dextran 70. With dextran 70, the bioadhesive polymers interacted with other excipients such as buffers, isotonic agents, and antimicrobial preservatives. The decrease of apparent viscosity was observed significantly in the formulation with Carbopol 974P, which also showed the presence of instability. Formulations with Neuro-EPO and HPMC showed adequate physicochemical properties with the pH, isotonicity, and concentrations of protein by reverse-phase (RP) high-pressure liquid chromatography (HPLC), as expected. However, the formulation with dextran 70 showed chemical incompatibility, as evidenced by the reduction of protein concentration and purity. In the permanent unilateral ischemia model, a higher survival percentage was observed with formulations of HPMC F4M and HPMC K4M, evidenced by the analysis of neurology parameters. Both formulations were significantly different from their vehicle…
The global demand for new biologics and vaccines, combined with the growing emergence of biosimiliars, is challenging drugmakers to re-evaluate their processes and seek ways to make them more flexible, reliable, and cost-effective. Increasingly, manufacturers are turning to closed, single-use processing systems to meet aggressive campaign turnaround times, reduce risks, and control costs. Innovative single-use technologies provide biopharmaceutical manufacturers greater flexibility for replacing traditional stainless piping, valves, equipment, or even entire process suites with polymer-based solutions. The benefits of converting to pre-sterilized, single-use systems have been documented in numerous articles and case studies, and these benefits would be lost if manufacturers could not safely and securely connect a variety of systems and components together to create a complete aseptic process. Connectology may appear to be a small part of an overall system design; however, connection and disconnection of tubing for process fluid transfer is a critical aspect of single-use processing. Manufacturers must carefully consider the available options because the right connector not only affects the operator’s convenience, but can be the deciding factor in maintaining process sterility and product quality…