Control of recombinant DNA produced pharmaceuticals by a combination of process validation and final product...

Traditional methods of product release for human pharmaceutical use are designed and selected to ensure control of purity, potency, safety and identity. The selection of these tests depends upon the nature of the product. In addition to the control achieved by these methods, control of the efficiency of the manufacturing process in removing substances that cannot be tested for in the final product is achieved by "process validation". Process validation allows the use of sophisticated experimental techniques that do not lend themselves to final product testing or the use of others which, when applied to the final product, are insufficiently sensitive to be used for product release. The removal of such components as DNA and process materials can be demonstrated by these studies. Demonstrations that the manufacturing process reproducibly removes these components, eliminate the need for these tests on every batch. The essential elements of a process validation study are development of a sensitive assay technique for the component of interest and quantitation of the efficiency of individual process steps in removing that component. Even when that component is undetectable in normal process samples, the efficiency of any process step can still be determined by the addition of that component during the validation studies. The values of process validation in demonstrating the removal of DNA and in the determination of E. coli protein contamination levels during the manufacture of methionyl human growth hormone is illustrated.