July 18, 2003

Management Dockets, N/A

Dockets Management Branch

Food and Drug Administration

HFA-305

5630 Fishers Lane, Rm 1061

Rockville, MD 20852

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| * | **NAS 0; Not Product Specific**                                   |
| * |                                                                   |
| R | **General Correspondence**                                        |
| e |                                                                   |
| : | **Medical Devices: Draft Guidance for Industry and FDA Reviewers; |
| * | Multiplex**                                                       |
| * |                                                                   |
|   | **Tests for Heritable DNA Markers, Mutations, and Expression      |
|   | Patterns; Availability.**                                         |
|   |                                                                   |
|   | **(Docket No. 03D-0120, CDRH 200316)**                            |
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Dear Sir or Madam,:

We welcome the opportunity to dialogue with the Agency regarding the
basic framework for the types of data and regulatory issues that should
be addressed in a multiplex device submission.

GlaxoSmithKline is committed to discover, develop and deliver new
medicines to address medical needs. GlaxoSmithKline is using information
gleaned from the human genome throughout the drug discovery and
development process to identify novel ways to combat disease, to predict
toxicology and to identify genetic patterns to help determine how
individual patients will respond to medicines (pharmacogenetics and
pharmacogenomics). We support development of this timely guidance. As
members of the Pharmaceutical Research and Manufacturers of America
(PhRMA), GlaxoSmithKline has actively reviewed and contributed to the
comments on this guidance submitted by PhRMA on July 11, 2003. We are in
agreement with those comments. Additionally, given our interest in the
interface between studies in clinical drug development and the use of
multiplex assays, we wish to offer additional comments. These apply both
to the guidance under current consideration and to companion documents
that may be under development
(http://www.fda.gov/bbs/topics/news/2003/beyond2002/report.html).

**Section I: Purpose**, penultimate paragraph. We commend the suggestion
that sponsors may submit "pre-IDE protocols". We suggest that when such
consultation will impact both the conduct of the IDE study and the
application of the resulting data to a drug development program, then
the model for these consultations and their documentation would be the
Pre-IND meeting guidance included in CDER guidance 2125 (Formal Meetings
with Sponsors and Applicants for PDUFA products), and CDER MAPP 4512.1
(Formal Meetings Between CDER and CDERs External Constituents). If an
alternate CDRH model or process is to be adopted, this should be
specifically stated. The consultation would lead to generation of FDA
minutes and correspondence that could be referenced by the sponsor(s)
and both Centers during future interactions.

**6. Literature and Appendix 1, point 1:** This section identifies the
use of literature to supplement or substitute for clinical performance
studies. The draft would be more instructive if the Agency were to
identify specific types of data that could potentially be supported by
literature and what type of literature might be considered relevant by
the Agency.

**IV. B. Clinical Validation and Appendix 1, points 6 & 8**: The
guidance would benefit from greater detail regarding the precise nature
and quantity of ethnicity data (as it relates to allelic frequency
variation) required in the submission. We suggest that the bridging
study approach described in International Conference on Harmonization
(ICH) guidance E5: Ethnic Factors in the Acceptability of Foreign
Clinical Data (June 1998) for extrapolating clinical data to new
geographical regions, might also be applied to allelic frequency.
Specifically the ICH guidance proposes that the authority should request
only those additional data necessary to assess the ability to
extrapolate and that the amount of data required be related to the
impact of ethnic factors.

**Need for Cross-Center agreements/processes:** It is evident that
multiplex tests will be used within the industry throughout the
discovery and development process. It is currently unclear from the
draft guidance how multiplex data will be reviewed across the Centers
and Divisions of the FDA. For example, how would
pharmacogenetic/pharmacogenomic multiplex data generated as part of an
NDA be reviewed by CDER vs. data for a disease test submitted to CDRH?
We believe that it will be important to ensure that the expectations of
all Centers are harmonized with respect to submission and review of
these data and therefore we request that comments arising on Docket No.
03D-0120 are shared with CDER/CBER as well as the CDRH authors of this
guidance.

This submission is provided in paper via duplicate copies with an
additional copy on diskette (Word 97) and an electronic copy via email
according to the instructions provided at
Http://www.accessdata.fda.gov/scripts/oc/dockets/commentdocket.cfm

Please contact me at (919) 483-4483, or my colleague Dr. Sue Hall at
(919) 483-6159, if you require clarification of any of these comments.
Thank you for your consideration.

Sincerely,

Alison Bowers

Director

Regulatory Affairs