Development of Lyophilization Processes for Large Scale Production of Pharmaceutical Products
Development of Lyophilization Processes for Large Scale Production of Pharmaceutical Products
July/August 2004
Ivette Novoa, Alida L?pez, Alex Guti?rrez, Orestes Mayo, Ph.D. (National Center of Bioproducts, Cuba) and Louis Rey, Ph.D. (International Consultant, Switzerland)
A yophilization process for two recombinant pharmaceutical products such as, the Streptokinase and the human *2b Interferon, was initially designed by trial and error. Very extensive cycles for both products were obtained by this method. The application of the DTA technique, combined with the determination of the electric impedance, showed that it was possible to decrease the total processing time in 41.6% for Streptokinase and in 44.4% for Interferon, obtaining a quantity of approved units higher than 99% and offering satisfactory results in the physical and biological analyses required for the delivery of each product.
1. Introduction
The National Center of Bioproducts offers, among other services, the development of medium and large scale lyophilization processes. Two of the most important products designed for human use and introduced at production quantities are recombinant Streptokinase and recombinant *2b Interferon. The development of the lyophilization processes of these products was initially based on the trial and error method which resulted in very long processes. In the case of recombinant *2b Interferon, a major portion of each batch showed a cosmetic problem: a collapsed cake which was rejected during the inspection stage and resulted in accepted product reduction.
The design of the lyophilization process is commonly successful when it is based on the study of the behavior of the formulations of the product during the freezing and heating stages. Such a study
will define important properties and identify the most important thermal events.
The main purpose of this paper is to establish a methodology for the design of the lyophilization process for both products in order to increase the yield to more than 95% and to decrease the total process time in more than 20%.
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