Strategies for Maximizing Successful Drug Substance Technology Transfer Using Engineering, Shake-Down, and Wet Test Runs.

The technology transfer of biological products is a complex process requiring control of multiple unit operations and parameters to ensure product quality and process performance. To achieve product commercialization, the technology transfer sending unit must successfully transfer knowledge about both the product and the process to the receiving unit. A key strategy for maximizing successful scale-up and transfer efforts is the effective use of engineering and shake-down runs to confirm operational performance and product quality prior to embarking on good manufacturing practice runs such as process performance qualification runs.

Overview of Best Practices for Biopharmaceutical Technology Transfers.

Technology transfer is a key foundational component in product commercialization. It is more than just the transfer of documents; it relates to all aspects of the transfer of knowledge and experience to the commercial manufacturing unit to ensure consistent, safe, and high-quality product. This is the first in a series of articles from the BioPhorum Operations Group (BPOG) member companies discussing best practices and benchmarking of biopharmaceutical technology transfer.

The inhibitory effects of squalene-derived triterpenes on protein phosphatase PP2A.

This paper reports testing 15 polyether triterpenes with a squalene carbon skeleton for inhibitory effects on type 2A protein phosphatase. Two compounds, 16-hydroxydehydrothyrsiferol 10 and thyrsenol B 14, exhibited significant inhibitory action at a concentration of 10 microM. Comparison with thyrsiferyl-23-acetate 1 showed that a similar spatial disposition for the hydroxy group around C-15 or C-16 was the structural feature shared by these metabolites.

Characterization of F-actin depolymerization as a major toxic event induced by pectenotoxin-6 in neuroblastoma cells.

Pectenotoxins are a group of marine toxins produced by dinoflagellates and formerly included within the group of diarrhetic shellfish poison or toxins (DSP or DST) because of their physico-chemical properties. However, toxicological data on pectenotoxins are still very scarce and its mechanism of action is largely unknown, but toxicity in laboratory animals has been demonstrated by intraperitoneal injection. In this report, we present results of in vitro toxicological assessment of pectenotoxin-6, a derivative of the parental toxin pectenotoxin-2 first isolated from toxic scallops.

Azaspiracid-1, a potent, nonapoptotic new phycotoxin with several cell targets.

This paper reports on potential cellular targets of azaspiracid-1 (AZ-1), a new phycotoxin that causes diarrhoeic and neurotoxic symptoms and whose mechanism of action is unknown. In excitable neuroblastoma cells, the systems studied were membrane potential, F-actin levels and mitochondrial membrane potential. AZ-1 does not modify mitochondrial activity but decreases F-actin concentration.

PCR technique for identification of mussel species.

Random amplified polymorphic DNA (RAPD) analysis has been applied to the identification of four mussels species: Mytilus edulis, Mytilus chilensis, Mytilus galloprovincialis, and Perna canaliculus. Amplifications of DNA from mussel were carried out using random primers. The most distinctive bands were then isolated, cloned, and sequenced to design specific primers.