669at the top of the label. With a pharmacogenomics section in new labels, FDA is plan-
ning ahead to reserve a spot in the label that is specifi cally intended for pharmacoge-
nomic information that comes out of drug development or that comes out of
post-marketing studies. In the past, genomics information was part of a drug’s phar-
macokinetic and pharmacodynamic profi le and appeared in the pharmacology sec-
tion, lost within the lengthy and text-heavy product labels. FDA wants to improve on
the location of clinically relevant genetic information in the label. Examples of
genetic information labels for some drugs are shown in Table 22.1.
FDA Guidelines for Pharmacogenomics-Based Dosing
According to a draft report entitled “Realizing the Promise of Pharmacogenomics:
Opportunities and Challenges”, issued by the Department of Health and Human
Services (HHS) in 2007, the FDA must issue guidelines to help physicians use phar-
macogenomics tests for drug-dosing before the clinical community can adopt them
fully. Despite approval of Roche’s AmpliChip and including genetic information in
the label for Pfi zer’s colorectal cancer drug Camptosar, the FDA has not clarifi ed
how physicians should use the tests. Apart from FDA’s role as market gatekeeper
for pharmacogenomics products, FDA requirements and actions or the lack thereof,
infl uence the ways in which marketed pharmacogenomic diagnostic technologies
are used in clinical practice. For example, FDA approval of a pharmacogenomic test
does not necessarily result in dosing guidelines for accompanying therapy.
Pharmacogenomic-based testing can identify patients who are likely to respond dif-
ferently to particular drugs and indicate the need for customized dosing, but that
testing does not necessarily translate into dosing instructions. As such, patients will
have to be monitored and have their dosing adjusted empirically.
FDA and Validation of Biomarkers
The FDA has recognized pharmacogenomics as an opportunity to identify new bio-
markers that may expedite the drug development process. FDA guidance also makes
a distinction between pharmacogenomic tests that may be considered either proba-
ble or known valid biomarkers, which may be appropriate for regulatory decision
making, and other less well-developed tests that are either observational or explor-
atory biomarkers that, alone, are insuffi cient for making regulatory decisions.
A pharmacogenomic test result may be considered a valid biomarker if it is mea-
sured in an analytical test system with well-established performance characteristics
and there is an established scientifi c framework or body of evidence that elucidates
the physiologic, pharmacologic, toxicologic, or clinical signifi cance of the test
results. For example, the effects of genetic variation in the human enzymes CYP2D6
and thiopurine methyltransferase on drug metabolism are well recognized scientifi -
cally and are included in some approved drug labels. The results of genetic tests that
FDA and Personalized Medicine