676
Further, it will be helpful if the device sponsor and the therapeutic product sponsor
submit information about the proposed IVD companion diagnostic device in a pre-
IND submission. Finally, the FDA strongly encourages sponsors to request meet-
ings with both relevant device and therapeutic product review divisions as early in
development as possible.
CLSI Guidelines for RNA Controls in Gene Expression Assays
Microarray and realtime quantitative PCR (qPCR) technologies are emerging as
vital components of genomic, evidence-based medicine. Standard controls are
required to ensure reliability and quality from these assay platforms before microar-
ray and realtime-qPCR results are accepted for clinical applications. The ability to
report reliable gene expression results of known quality is key to the successful
employment of microarrays and realtime-qPCR as tools in toxicogenomics, phar-
macogenetics, pharmacogenomics, and as diagnostic devices in clinical medicine.
In response to this need, Clinical and Laboratory Standards Institute (CLSI) has
published “Use of External RNA Controls in Gene Expression Assays; Approved
Guideline (MM16-A)”, which provides a set of agreed-upon protocols supporting
the use of external RNA controls in microarray- and realtime-qPCR-based gene
expression experiments. This guideline addresses important issues associated with
the use of external RNA controls as a tool for verifi cation of technical performance.
In addition, it supports the evaluation of qualitative results for a specifi c clinical
analyte, including:
- Preparation of control transcripts
- Design of primers and amplicons
- Quality control
- Use in fi nal experimental or clinical test application
- Analysis and interpretation of data obtained
This document is intended to help ensure comparable within-platform assay per-
formance to enable comparisons of gene expression results. The protocols will
enable research and clinical laboratories, regulatory agencies, accrediting agencies,
reference laboratories, as well as test, microarray, and reagent manufacturers to
assess the performance of these expression assays. Further details can be seen at
CLSI website ( http://www.clsi.org ).
Regulation of Direct-to-Consumer Genetic Testing
Various states are beginning to tackle the problem of uncontrolled personal genetic
services. In 2008, New York State, warned 23 companies that they must have per-
mits to offer their services to New Yorkers. New York’s warning letter was a blow
not only to new companies such as Navigenics (now acquired by Life Technologies)
and 23andMe that entered into the fi eld of consumer genomics in 2007, but also to
22 Regulatory Aspects of Personalized Medicine