Meeting the regulatory requirements for pharmaceutical production of recombinant DNA derived products

Genetic engineering provides the opportunity for the synthesis of human proteins and derivatives thereof which are of significant value for replacement therapy. However, in addition to genetic engineering an extensive process development has to be carried out in order to establish an economic production process and to guarantee consistently high product quality from batch to batch. This includes the characterization of the production host cell vector construct, the validation of the fermentation and the protein purification process as well as the lyophilization and the reconstitution of the final product. A number of in-process and final product controls have to be established and limits for the specification have to be elaborated to provide consistent product quality. Real time stability data have to be supplied because data from accelerated conditions do not allow extrapolation of the shelf life of proteins. Data obtained from process development and validation of the production process contributes to the preparation of the chemical pharmaceutical dossier and the expert report to be submitted to the regulatory authorities.