From Bench to Bedside: Development of Polymerase Chain Reaction Integrated Systems in the Regulated Markets
Martin Lee, Diane Lee and Phillip Evans
from: Molecular Diagnostics: Current Research and Applications (Edited by: Jim Huggett and Justin O'Grady). Caister Academic Press, U.K. (2014)
The evolution of the polymerase chain reaction (PCR) as a revolutionary molecular biology tool has been extremely rapid since its inception in 1983. This may be attributed, in part, to the simplicity of the process for the general molecular biologist and also because of the open licensing strategy provided for underpinning products by key stakeholders. The development of commercial products for the applied markets such as food, veterinary, and defence has been greater than for human diagnostics. This sector has been restrictive for most system developers because of the high value of upfront and running royalty licences. In addition, the human diagnostic area is highly regulated in the US (FDA) and the EU (IVDD). The core patents covering the PCR process are approaching their termination dates in key territories, largely negating the requirement for such licences. The opportunity for those developers of Nucleic Acid Tests (NAT) on highly automated laboratory devices and/or simple to use integrated point-of-use PCR devices (iNAT) to "tap into" the content developed within this broad research sector is enormous. This text is written to provide both technical and commercial advice to those involved in this technology transfer opportunity. The text is presented as a number of short key-notes in the following areas: 1) PCR formulation; 2) assay stabilisation; 3) the sample extraction reagent interface; 4) nucleic acid extraction 5) signalling and automated analysis; 6) suppliers and GMP; 7) system validation; and 8) the regulatory process. These notes are intended to provide guidance to the key issues rather than a prescriptive manual. The author will direct the reader to the appropriate authority. It will be of most use for individuals and organisations either intending to provide, or to receive, product content. It is based upon the author's experiences in developing integrated systems for the applied and diagnostics sectors over the last 15 years read more ...