chapter  3
58 Pages

Manufacturing Overview

WithSarfaraz K. Niazi

Macromolecular (large molecules) substances (e.g., therapeutic proteins) are manufactured by a number of methods, including extraction from natural sources (as done in the past to extract erythropoietin from urine), modification of naturally occurring protein, mammalian cell culture in vitro, mammalian cell culture in vivo, production by microorganisms, and chemical syntheses. The overall regulatory scheme for biotechnology derived products is the same as for products in the same category produced by traditional manufacturing methods, with the addition of specific requirements suited to the biotechnology derived product. As an example, somatropin (human growth hormone) was approved by the FDA on July 30, 1976, derived from natural sources (Asellarcin® of Serono) and in April 1979 (Crescormon® of Genentech); both of these products have since been discontinued and replaced with recombinantly produced somatropin in 1993. The entire technical package relating to purity and characterization of somatropin remains the same for the product except there are new steps of production added.