Process economics of animal cell and bacterial fermentations: a case study analysis of tissue plasminogen activator

ABSTRACT One link in the complex chain of medical economics is the cost of bringing new drugs and biologicals to the market. Advances in recombinant-DNA technology permit production of

therapeutically active proteins in effectively unlimited quantities. Nevertheless, each expression system has a characteristic influence on the nature of the product produced and the process

required to obtain it. In this case study we compare experiences with recombinant-tissue plasminogen activator (rtPA) produced in Chinese hamster ovary (CHO) cells and in _Escherichia

coli_, with the aim of understanding the roles of some of the parameters that affect process economics. tPA belongs to the group of highly specific serine proteases that convert plasminogen

to plasmin, which in turn degrades several protein substrates including fibrin, thus making it an effective thrombolytic agent. The treatment of acute myocardial infarction with such

thrombolytic agents can result in early discharge of patients and decreased medical costs. However, there are major differences in the prices of the various available agents. The price of

the FDA-licensed tPA product is $2,200 per dose or $22,000 per gram. It is believed that a significant portion of this price relates to manufacturing costs. We examine by way of case study

illustration the cost breakdown for the two processes, and highlight important process, design and economic considerations that ultimately define a particular protein product. Access through

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Biotechnol._ 33: 117–138. Article  CAS  PubMed  Google Scholar  Download references AUTHOR INFORMATION Author notes * Rajiv V. Datar: Corresponding author. AUTHORS AND AFFILIATIONS * Pall

Corporation, 30 Sea Cliff Ave., Glen Cove, NY, 11542 Rajiv V. Datar * TCS Biologicals, Ltd. (formerly Tissue Culture Services). Botolph Claydon, Buckingham, MK18 2LR, UK Terence Cartwright *

Abitec AB, Villavagen 36, S-640 50, Bjornlunda, Sweden Carl-Gustaf Rosen Authors * Rajiv V. Datar View author publications You can also search for this author inPubMed Google Scholar *

Terence Cartwright View author publications You can also search for this author inPubMed Google Scholar * Carl-Gustaf Rosen View author publications You can also search for this author

inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Datar, R., Cartwright, T. & Rosen, CG. Process Economics of Animal Cell and

Bacterial Fermentations: A Case Study Analysis of Tissue Plasminogen Activator. _Nat Biotechnol_ 11, 349–357 (1993). https://doi.org/10.1038/nbt0393-349 Download citation * Issue Date: 01

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