PDA Cell Substrate Task Force: Emerging Technologies for Virus Detection Technical Document—A Progress Report

The PDA Cell Substrate task force consists of 26 members derived from industry and regulatory bodies as well as independent consultants, all of whom are involved in the manufacturing or licensing of biological products. The aim of this task force is to consider issues that affect cell substrate safety and/or quality that have arisen as a result of scientific and technical advances over the past decade. The emphasis of the task force is to assess, using case studies as a basis, the approaches that have been taken to address cell substrate issues, both scientifically and with regard to current global regulatory guidelines.

The purpose of this presentation was to provide an overview of task force activities since its inception in 2008 with a focus on the development of a PDA technical report entitled “Emerging Methods for Virus Detection in the Manufacture of Biologics.” Based on surveys of the membership, the task force initially identified three focus areas for in-depth discussion at the 2009 PDA Cell Substrate Workshop organized by the task force. These areas included new cell lines and cell line engineering, virus testing of cell banks and unprocessed bulk drug substance, and raw materials. The proceedings of that workshop were published in the September/October 2010 issue of the PDA Journal of Pharmaceutical Science and Technology [PDA J Pharm Sci and Technol 2010, 64 (5) 373–494]. A further outcome of the 2009 workshop was that a number of topics were identified for further exploration in the form of PDA technical reports.

The task force decided to focus on drafting two technical documents: “Viral Contamination during Drug Manufacture: Detection, Response, and Prevention” and “Emerging Methods for Virus Detection in the Manufacture of Biologics.” The technical document on emerging methods for virus detection, which is currently in draft form, was discussed during the presentation. This document will begin with an introduction that will serve to place the document in the context of the current regulatory framework, highlight recent virus contamination events, and provide a rationale for how limitations of current methodologies might be aided by the use of new technologies for broad virus detection. The new technologies that will be highlighted in this document include degenerate polymerase chain reaction, PLEX-ID, massively parallel sequencing, and virus microarray. Each methodology will be described, followed by analysis of pros and cons associated with the technique and its potential application to evaluating the safety and quality of biological products. In addition, the document will contain a stand-alone chapter on assay standardization in order to highlight the importance of this critical aspect of method development. It is anticipated that this document will be available in 2012.

• © PDA, Inc. 2011