Author Archives: Ronald A. Rader

corporate-background-with-mechanical-gears_GJ73Uys__L

Future Manufacturing Strategies for Biosimilars

Biosimilars are a relatively new subset of biopharmaceuticals, with the biotechnology industry finally maturing such that off-patent generic-type products increasingly will be entering major markets (1–3). So far, more than 20 biosimilars for a limited number of reference products have been approved in major markets, primarily the European Union. Only two products have been formally approved as biosimilars in the United States. For this rapidly growing industry sector, little consensus or authoritative information is available yet regarding how and where…

Lonza-opener

Bioprocessing Challenges of Antibody–Drug Conjugates

Development of highly potent active pharmaceutical ingredients (HPAPIs) is clearly a pharmaceutical industry trend. Highly potent drug products involve active agents and APIs that are so potent therapeutically (or simply just outright toxic) even in small dose that special precautions are required during their manufacture — particularly when handling the active agents. Such requirements include maximal containment and isolation of the process stream. Worker exposure and environmental release clearly pose problems. The necessity and intensity of containment efforts with HPAPIs…

Incubator holding 800–1,000 seeded trays
can produce ~1 kg crude protein overnight

A Novel Solid-Media E. coli Platform: Comparison with Standard Fermentation Processes

MicroProtein Technologies Inc. has developed the MPTxpress high-yield, low‑cost, recombinant Escherichia coli manufacturing platform. Rather than using liquid culture media within stirred bioreactors, the system uses trays filled with semisolid (gelled) culture media overlaid with or without a permeable membrane on which the E. coli is cultured. Compared with conventional liquid fermentation platforms, the MPTxpress system reduces the number of steps in up- and downstream processing and required infrastructure, significantly improves yields, and lowers costs. It provides simplicity for mixing…

Powders and Bulk Liquids

    The two major bioprocess fluids — culture media for upstream production and buffers for downstream processing — are classic single-use products. They are used once and then disposed of. The two basic options for both differ by physical state: powdered media and buffers (“powders” for in-house preparation of liquids by end users) and bulk liquid culture media and buffers, which are fully prepared by their suppliers (“liquids”). We conducted market research studies comparing the benefits and risks (value…

Bioprocess Advances Drive Vaccine Manufacturing in Developing Countries

Advances in bioprocessing technology hardware and genetic engineering are expanding the geographic options for biologics manufacturing to include developing and emerging economies. Such advances are beginning to permit biopharmaceutical production in regions that previously lacked the technical expertise or quality processes to permit complex operations, monitoring, record-keeping, and oversight. Global demand by countries for in-country production of biological vaccines is increasing, so those products tend to be leading the way in terms of adoption of modern bioprocessing in developing countries.…

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…

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…

Upstream Single-Use Bioprocessing Systems

Single-use bioprocessing equipment has become well-accepted technology in a relatively short time. Disposable devices and components have created market niches and new segments that continue to evolve. In this dynamic environment, it is difficult to measure acceptance or assess market growth. Here we project the world market for cell culture single-use systems (SUS) as well as problems affecting that market, including adoption for commercial manufacture. This is based on our 10-year analysis of the industry, with data from our eighth…

Nomenclature of New Biosimilars Will Be Highly Controversial

Biopharmaceuticals, including products approved as biosimilars, must be clearly defined, identified, and named to ensure accuracy in writing and filling prescriptions (1,2,3,4). The US biosimilars law enacted last year enables the Food and Drug Administration (FDA) to approve abbreviated biosimilar biologics license applications (bBLAs) or 351(k) filings based largely on their sponsors proving structural, composition, and clinical similarities with an approved biologic (reference product), much like generic drug approvals (5). The agency has yet to disclose how it will implement…