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Genomics
at FDA
Frequently Asked Questions
What steps are needed to submit Voluntary Genomic
Data Submission data?
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The initial step is to contact either the Chair or Executive
Secretary of the Interdisciplinary Pharmacogenomics
Review Group (IPRG) to discuss the scope of the proposed VGDS.
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A VGDS request would then be submitted 6 to 8 weeks prior to the
proposed date for the meeting.
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The genomic data for the meeting would be submitted at least four weeks
prior to the meeting.
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Additional details of the submission steps can be found in the
MaPPs and
Best Practices for Effective and
Productive VGDS Meetings.
Can data on genomic biomarker validation be submitted as a VGDS?
Yes. This is an example of a VGDS leading to a scientific discussion
about new genomic biomarkers.
Who participates in the review of VGDS data?
Members of the IPRG. Additional resources are requested on an as needed
basis from individual reviewers (Center Experts) that are experts in
specific fields (i.e. therapeutic areas). These experts are not involved
in the review of data from required submissions that are associated with
voluntarily submitted information.
How is the scientific nature of a VGDS discussion structured?
The IPRG review of a VGDS is a scientific discussion in parallel to a
regulatory context.
How will confidentiality of the VGDS be ensured
by the Agency?
All VGDS data will be protected from disclosure to
the extent allowed by existing laws and regulations, and
consistent with our policies for disclosure of other data
submitted to INDs, new drug applications (NDAs), and biologic
license applications (BLAs). Data that are submitted to existing
INDs, NDAs, or BLAs will receive the number of their existing
application. VGDS data that are not part of an existing submission
will receive a new IND number. All VGDS data will be routed
directly to the IPRG, not the review division, and will stored on
a secured, separate server.
How will the VGDS data be distributed within the Agency?
All VGDS data will be distributed only within the IPRG, unless there is
prior agreement with the sponsor.
How will the VGDS data be stored within the Agency?
All VGDS data will be stored on a separate secure server that is
accessible to members of the IPRG only. It will not be distributed
outside the IPRG without the prior agreement of the sponsor.
What are some of the incentives to sponsors to submit VGDS?
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Provides opportunity to have informal meeting with FDA
pharmacogenomics experts
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Receive and benefit from informal peer-review feedback on
pharmacogenomics issues
and/or questions.
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Gain insight into current FDA thinking about
pharmacogenomics that may assist in reach
strategic decisions.
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Familiarize FDA with pharmacogenomics experiments, data analysis and interpretation
approaches.
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Paves the way for time- and cost-savings by familiarizing FDA with
pharmacogenomics
and avoiding future delays in review.
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Impact FDA thinking and help build consensus around
pharmacogenomics standards,
policies and guidances.
What activities does the IPRG engage in?
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Reviews and evaluates VGDSs.
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Meets with sponsors upon request before or after submitting a VGDS.
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Consults upon request with review staff on required submissions
containing genomic data.
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Integrates pharmacogenomics into the regulatory review process and helps
develop future guidance and review standards.
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Harmonizes review practices and quality review systems for genomic data
submissions.
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Coordinates among disciplines and organizations in FDA, in particular CBER, CDER, Office of Combination Products (OCP), CDRH and NCTR, to
assure the efficient, accurate, and transparent review of genomic data.
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Coordinates public discussions and agendas for advisory committee
meetings with regard to "lessons learned" from Genomic
Data Submission review
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Defines key issues to advance the use of rational pharmacogenomic
principles in drug development, in particular issues pertaining to the
regulatory review process.
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Facilitates FDA internal education regarding pharmacogenomic data,
including seminars and printed materials.
Is it correct to assume that genetic data are to be kept as long as
any other clinical data collected in a trial?
Yes.
Will the FDA be issuing specific guidances on the qualification and
use of genomic biomarkers?
Guidance on the validation and use of genomic biomarker is planned, but
not yet initiated.
What submission format should be followed for hybridization data?
No specific format is required. A summary of the results should be
discussed when the VGDS meeting is requested. Raw hybridization data,
such as .cel files, are extremely useful for VGDS review in order to
match the analytical process followed by the sponsor before the formal
VGDS meeting is scheduled.
We have genomic data related to a previous clinical submission that
was not approved. Can we submit it as a VGDS?
Yes.
We have new genomic data for a study on a drug that was previously
approved. Should we submit it through a VGDS?
If the data is a regulatory follow-up of a clinical submission, it needs
to be submitted within the original regulatory requirements. If the data
was obtained after completing or outside of the regulatory requirements,
it can be submitted as a VGDS.
A sponsor may use a test sample from a rat toxicology study to
generate data consisting of thousands of transcripts, and at that time
the biological validity of the transcriptional response of none of them
has been established. Many of the transcriptional changes may be
measured using probes consisting of sequences which have no known rat
gene sequence homology. Others may represent known rat gene sequences
but changes in transcriptional response may have no established
toxicological significance at the time of the report generation and
filing. The sponsor follows the guidance and does not submit these
"results from test systems where the validity of the biomarker is not
established." Five years later science has evolved. Certain of the
unknown sequences now have established links to known rat genes.
Furthermore, their biological significance has been validated and linked
to a toxicologic outcome. Is nondisclosure at issue here if the sponsor
does not diligently review old expression data, update old data files
with new sequence annotation information, and query against recently
publicized and validated transcriptional biomarkers? Are sponsors
required to continually monitor genomic studies that have previously
been submitted, and as understanding evolves, resubmit revised reports
with additional data and interpretations?
Nondisclosure is not an issue here because the biomarker was not a
probable valid or known valid biomarker at the time the study was run.
At the time of submission, the biomarker was an exploratory marker,
submitted with the rest of the data for which the validity in that
context had not been previously established. However, should a sponsor
become aware (either based on internal or based on external data) of new
information that affects safety (or efficacy) issues related to an
earlier submission it is expected that the sponsor informs the FDA about
these findings.
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Date created: March 22, 2005, updated June 10,
2005 |
