Biosimilars

Protein A

The number of blockbuster monoclonal antibody (MAb) drugs continues to grow. In 2008, MAbs generated revenues in excess of US$15 billion (1), making them the highest-earning category of all biotherapeutics. The world MAb market will reach $62.3 billion in 2015, with next-generation therapeutic antibody revenues reaching $2.3 billion in 2015 according to Visiongain reports published in September and November 2011 (2, 3). Biosimilar antibodies will also begin to enter established markets as regulatory authorities clear approval pathways for them. Most…

Concerns, Collaboration, and Capacity

The BPI Theater is a 50-seat venue that for seven years has been located at the heart of the BioProcess Zone on the exhibition floor of the BIO International Convention. There, BPI provides attendees with four days of live presentations focusing on the latest scientific advances and business trends in biotherapeutic development and manufacturing. On Monday afternoon, 22 April 2013, Patricia Seymour of BioProcess Technology Consultants (BPTC) moderated a roundtable discussion on biosimilar development in the BPI Theater at BIO…

Profitability in the Biosimilars Market

The biosimilars space offers significant commercial opportunity. About US$60 billion of branded biologic sales will lose patent protection over the next few years, including some of the largest-selling monoclonal antibodies (MAbs). Companies are jostling among themselves, each seeking the best position to exploit that opportunity. Regulators are creating and refining the necessary pathways to success, alliances are being forged, and companies are being acquired. Despite the significant opportunity for biosimilar MAbs, significant risks remain. Perhaps the most significant of those…

An Analysis of the US Biosimilars Development Pipeline and Likely Market Evolution

No consensus concerning biosimilar-related terminology and definitions has yet been achieved (1,2,3). Biosimilars may be defined as biopharmaceuticals slated for generic-drug–like, abbreviated, comparisons-based approvals through a formal biosimilar approval pathway in the United States, European Union, and/or other highly regulated and developed countries based on a demonstration of substantial (bio)similarity to a reference product. As required in the United States, biosimilar active agents (those involving recombinant proteins) must be identical in primary sequence with their reference products. Analytical and comparative…

In Vitro Functional Testing Methods for Monoclonal Antibody Biosimilars

The pressure to contain rising healthcare costs — combined with the number of innovator biologic drugs coming off patent (30 licensed biological drugs by 2015) — offers huge opportunities for developers of biosimilar products. In 2011, the global market size of the biosimilars industry was around US$2.5 billion. Global demand for such products — and monoclonal antibody (MAb) biosimilars, specifically — is estimated to grow at 8–17% from 2012 to 2016 (1). The advent of biosimilars should bring more affordable…

Comparability Protocols for Biotechnological Products

Comparability has become a routine exercise throughout the life cycle of biotechnological products. According to ICH Q5E, a comparability exercise should provide analytical evidence that a product has highly similar quality attributes before and after manufacturing process changes, with no adverse impact on safety or efficacy, including immunogenicity (1). Any doubt about data from such studies could translate into unforeseen pharmacological or nonclinical studies — or worse, clinical studies. Selection of analytical methods and acceptance criteria that will be applied…

Biosimilars, Oxidative Damage, and Unwanted Immunogenicity

Concerns about the economic viability of biosimilars center on their high development cost relative to small-molecule generics, along with (and partly because of) the difficulty in demonstrating bioequivalence for these complex molecules. Immunogenicity is a particular area of increasing vigilance at both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) (1, 2). Unwanted immunogenicity is an underlying cause of multiple deleterious effects for all protein-based therapeutics — including loss of efficacy, altered pharmacokinetics, and reduced…

Increasing Purity and Yield in Biosimilar Production

Current downstream processing strategies for recombinant proteins often require multiple chromatographic steps, which may lead to poor overall yields. Product purification can be especially difficult when a target protein displays reduced stability, forms isoforms or misprocessed variants, or needs to be purified from a complex mixture containing a high degree of contaminants. One technology that has been developed to tackle such limitations is based on custom-made chromatography matrices containing camelid-based single-domain antibody fragments. With a molecular weight of only 12–15…

Global Evolution of Biomanufacturing

Biomanufacturing of human therapeutics is beginning a global transformation. New technologies, improved processes, the emergence of biosimilars, and growing worldwide demand for vaccines and biologic drugs to serve local populations are driving this transformation. Over the next few years, diverse new markets will open, creating opportunities for a range of companies seeking to enter the field while putting pressure on established biomanufacturers to reassess their operating models. Many traditional barriers-to-entry in biomanufacturing are diminishing. Yet other challenges — including access…

FDA Biopharmaceutical Product Approvals and Trends in 2012

The US Food and Drug Administration (FDA) granted 18 new biopharmaceutical product approvals in 2012, covering a broad range of innovation, novelty, and healthcare and market impact. The total includes 16 full/original approvals: biologics license applications (BLAs) and new drug applications (NDAs). The other two products received supplemental approvals, both of them influenza vaccines. Among the 18 approvals were eight recombinant proteins, including two monoclonal antibodies (MAbs) and one engineered antibody-like “trap” molecule. Table 1 lists them all. Table 1: FDA…