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**1225 Eye Street NW, Ste. 400**

**Washington, DC 20005**

September 8th, 2004

Dockets Management Branch (HFA-305)

Food and Drug Administration

5630 Fishers Lane, Room 1061

Rockville, Maryland 20852

Re: Docket No. 2004N-0018, Federal Register: June 10, 2004 (Volume 69,
Number 112, Pages 32467-32475)

Dear Sir/Madam:

The following comments are provided by the Biotechnology Industry
Organization (BIO). BIO represents more than 1,000 biotechnology
companies, academic institutions, state biotechnology centers and
related organizations in all 50 U.S. states and 33 other nations. BIO
members are involved in the research and development of healthcare,
agricultural, industrial and environmental biotechnology products. BIO
appreciates the opportunity to comment on the Food and Drug
Administration's (FDA's, the Agency's) Proposed Rule on Human Subject
Protection; Foreign Clinical Studies Not Conducted Under an
Investigational New Drug Application.

## General Comments

BIO commends FDA for requiring adherence to the principles of Good
Clinical Practice (GCP) for the conduct of clinical trials not conducted
under an Investigational New Drug Application (IND) to be accepted as
support for research and marketing applications. In 1997, FDA published
in the Federal Register the International Conference on Harmonisation
(ICH) Guidance document "Good Clinical Practice: Consolidated
Guideline." The objective of this ICH GCP Guidance is to provide a
unified standard for the European Union (EU), Japan, and the United
States to facilitate the mutual acceptance of clinical data by the
regulatory authorities in these jurisdictions.

However, BIO is concerned that there will be confusion as to the
specific GCP standard expected by FDA, as the GCP standard defined by
FDA in this Proposed Rule contains some, but not all, of the
requirements in the ICH GCP Guidance. For example, the Proposed Rule
introduces a new or slightly modified definition of an Independent
Ethics Committee (IEC) from that contained in the ICH GCP Guidance.

Because the ICH GCP Guidance already exists and has been adopted by FDA
and used as guidance for industry since 1997, we would therefore like
the following suggestions to be considered prior to finalization of the
Rule:

-   BIO recommends FDA make specific reference to the ICH GCP Guidance
    in the Final Rule and require that foreign studies not conducted
    under an IND application follow the standards of GCP as documented
    in the ICH GCP Guidance document.

-   Alternatively, we would recommend that FDA acknowledge in the Final
    Rule, and/or in subsequent guidance, that the ICH GCP Guidance
    should be taken into account as one standard that FDA finds
    acceptable, and describe in what ways the standard presented in the
    revisions to 312.120 differs from the ICH GCP Guidance.

### [Specific Comments]{.underline}

[Recommendation #1:]{.underline} BIO notes that FDA considers the GCP
standard in proposed section 312.120 to be consistent with the ICH GCP
standard. However, we believe critical elements are missing and
recommend the following requirements be included in the Final Rule:

-   Requirements for record keeping by investigators (as specified as
    Essential Documents under ICH and comparable to 312.62 under FDA IND
    regulations). 

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-   Requirement that sponsors obtain written commitments from
    investigators to comply with GCP and the study protocol.

-   We recommend the requirement in section 312.120(b) (7) of the
    Proposed Rule on documenting IEC decisions also account for
    documenting continuing review by the IEC, which is a critical
    element noted under section 312.120 (a) (1) (i) of the Proposed
    Rule.

[Recommendation #2:]{.underline} Currently section 312.120 (c) (1)
allows for the demonstration that clinical research was conducted
according to the laws and regulations in a country where such laws
provide for greater protection of human research subjects than the
principles of the Declaration of Helsinki. BIO recommends that FDA
include in the revisions to 312.120 a provision to continue to allow a
sponsor to document that a study was conducted in a country where the
laws and regulations already provide for strict adherence to the
principles of GCP, which would clearly provide for the assurance of
protection of human research subjects and the quality of clinical data.
For example, clinical trials conducted in Europe must now meet the
requirements of the EU Clinical Trial Directive and its implementing
guidance for the conduct of clinical trials under GCP.

[Recommendation #3:]{.underline} In section 312.120 (b) (6), the
Proposed Rule requires that the \"names and qualifications for the
members of the IEC that reviewed the study\" be submitted as supporting
information. BIO has two recommendations on this provision.

-   For trials conducted in Europe, confidentiality issues and
    restrictions on the transfers of data may exist due to provisions of
    EU data protection laws. BIO recommends changing this requirement to
    \"Information on the composition (preferably names and
    qualifications, but at a minimum qualifications) of the IEC that
    reviewed the study to ensure that the IEC is duly constituted\".

-   Furthermore, BIO recommends that FDA provide clarification on the
    types of information that must be provided to document the
    qualifications of IEC.

In conclusion, we appreciate the opportunity to provide our comments and
look forward to finalization of the Proposed Rule.

Sincerely,

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Sara Radcliffe

Managing Director

Science and Regulatory Affairs