BRUSSELS, Belgium - Concern that changes in manufacturing processes could alter the consistency of biotechnology-derived products is pushing European drug authorities toward new rules.
The European Union's Committee for Proprietary Medicinal Products (CPMP), the senior scientific advisory group to the European Medicines Evaluation Agency, in London, is planning a concept paper on the demonstration of comparability of biotechnology-derived products.
The CPMP's biotechnology working party (BWP) is to oversee the drafting of a new guideline over the next few weeks, with a view toward releasing a public consultation document by the end of 1998.
The move springs from repeated questions raised within the CPMP and the BWP when biotech products have had to be reassessed following changes in production process during development or after delivery of marketing authorization. The problem also arises when recombinant proteins from the same molecular group are produced by different manufacturers.
Companies have been seeking advice in advance from the CPMP.
Even the FDA's 1996 “Guidance Concerning Demonstration of Comparability of Human Biological Products, including Therapeutic Biotechnology-Derived Products“ addressed only changes introduced in a production process for a given product from an identified manufacturer, but did not cover the more general question of how to compare two biopharmaceutical products from different manufacturers, the CPMP said.
The proposed guideline should deal solely with biotechnology-derived recombinant proteins, representing a homogenous class of products in terms of production and purification, the CPMP said, and should look at physico-chemical and biological tests required to demonstrate structural equivalence of the two products.
It should also cover identification and assessment of the potential impact of production changes on drug quality, with special attention to factors such as pilot production vs. full scale production; implementation of a new production site; and alteration of the production process (particularly in cell substrate or culture media), purification scheme and equipment.
In addition, the guideline should outline to what extent quality testing (including characterization, physico-chemical tests and biological assays) is sufficient to demonstrate the comparability of two recombinant proteins; and to what extent there is a need for clinical and toxicological studies (including tolerance data, in particular in relation to the neo-antigenicity of the new product).
Where possible, the CPMP said decision trees should be set up or proposed so as to guide the producer in proper analytical, preclinical and clinical development. *