Impact of contracted manufacturing organization protocols on operations in an aca demically based Current Good Manufacturing Practice facility

Abstract

Immunotherapy of cancer and other diseases is often dependent on adoptive transfer to patients of cellular products generated in Current Good Manufacturing Practice (cGMP) facilities. With the availability and approval of various cellular products for therapy, cell production facilities are experiencing unprecedented growth in demand for services. Increasingly, these services involve processing of externally generated cells for transfer to the bedside. The arrival of cells from external manufacturing facilities for processing and eventual infusion of cell therapy products into patients creates a new layer of responsibility and adds to an already demanding list of the existing procedures in academic cGMP facilities. Sponsors introduce their own requirements for the handling of cells that the laboratory must incorporate and follow. The challenges of creating additional access to cleanrooms, writing new standard operating procedures, expanding personnel training, altering pre-existing schedules and incorporating additional monitoring for safety of external products alter the balance of laboratory operations. Adjustments for accommodating externally manufactured products are numerous and varied, as each sponsor has requests that are product-specific. If cells produced by several different external manufacturers are handled by the same facility, the negative impact on the regular activities in this facility may be considerable. Here the authors provide a review of operational challenges that an academic-based laboratory faces and discuss solutions that could ameliorate the difficulties related to an increasing volume of industry-sponsored trials. The solution may be the development under the auspices of the Foundation for Accreditation of Cellular Therapy or the Food and Drug Administration of regulations that will guide the processing of products manufactured by external companies and make these regulations broadly applicable in all cGMP facilities.

Keywords: CMO-mandated requirements; cGMP; cell production for therapy; contracted manufacturing organization (CMO); externally manufactured cell products; transfer of cell products from CMO to the bedside.