From: Allen Heller [allen.heller.b@bayer.com]
Sent: Wednesday, September 08, 2004 5:03 PM
To: fdadockets@oc.fda.gov
Subject: Docket No. 2004N-0018






To the Division of Dockets Management:

RE:  Docket No. 2004N-0018;  Human Subject Protection; Foreign Clinical Studies
Not Conducted Under an Investigational New Drug Application


Bayer Pharmaceuticals Division welcomes the opportunity to comment on the above
referenced proposed rule issued by the Food and Drug Administration.


Bayer is in agreement with the comments provided by the Pharmaceutical Research
and Manufacturers of America (PhRMA). We would ask FDA to confirm that
conducting a study in accordance with ICH GCP and reporting and submitting the
study according to ICH E3 (clinical study reports) and M4 (common technical
document) standards and FDA's corresponding guidance documents satisfies the
requirements of the proposed revised 21 CFR 312.120. In cases where individual
requirements of section (b) deviate from the ICH standards we would request that
the agency consider modifying the requirements to conform to the ICH CSR and CTD
standards, allowing sponsors to prepare and submit IND and non-IND studies
according to a single unified standard.


Bayer submits the following additional comments for FDA's consideration:

   Non-IND studies commencing in EU member states after May 1 2004 are required
   to follow the EU Directive 2001/20/EC in conjunction with the Detailed
   Guidance on the Directive.  The Directive has been written explicitly to
   approximate the laws, regulations and administrative provisions of the EU
   Member States relating to the implementation of good clinical practice in the
   conduct of clinical trials. A visible sign that a study is conducted
   according to this Directive is the provision of the so-called EudraCT-Number
   for the study.  We recommend that the requirements in the proposed rule be
   waived for any study conducted in EU member states after May 1 2004, provided
   that the sponsor can submit a EudraCT number.


   For similar reasons we propose that the requirements in the proposed rule be
   waived for studies that have been conducted in Japan under Japanese Good
   Clinical Practices.  A statement to this effect would be included in the
   Medical Research Report.


   We are concerned with an element of the proposed rule that would require that
   the names and qualifications of the members of the IEC who reviewed the study
   be submitted.  ICH GCP requires that the investigator files include the IEC
   composition to document that the IEC is constituted in agreement with GCP.
   The current requirement under ICH GCP is that this information is available
   in sponsor files. Thus, this information would be available on request.
   Additionally, because of privacy concerns, some IECs provide only letters to
   confirm that their constitution is in agreement with GCP. We recommend as an
   alternative that FDA consider requiring the name and address of each IEC that
   approved the study.


   The requirements in part II, Section C for "a summary of the IEC's decision
   to approve or modify and approve the study, or to provide a favorable
   opinion" should be clarified. Our understanding is that it would be
   acceptable under the proposed rule to provide a general statement that the
   following IECs approved the study protocol prior to its conduct, noting any
   modifications required by the IEC (plus amendments/consent forms, etc).


   The requirements in Part II, Section C for "a description of what incentives,
   if any, were provided to subjects to participate in the study" should be
   clarified. Our understanding is that it would be acceptable under the
   proposed rule to provide a general statement in the protocol, study report,
   and sample consent that subjects were reimbursed for their time and travel
   costs or that subjects were paid for participation.


   The requirements in Part II, Section C for a "description of how
   investigators were trained to comply with GCP and to conduct the in
   accordance with the study protocol" should be clarified.  Our understanding
   is that it would be acceptable under the proposed rule to provide a general
   statement in the study report that investigators were trained at an
   investigators meeting and/or during site initiation visits.


   We are concerned with the requirement in Part II, Section C that the sponsor
   provide "copies of written commitments, if any, to comply with GCP and the
   protocol".  We believe that the proposed rule should require that these
   agreements (protocol/amendment cover pages, other investigator agreements) be
   available in the sponsor files to be provided upon request.





Allen H. Heller, M.D.
Vice President
Bayer Pharmaceuticals Corporation
400 Morgan Lane
West Haven, CT 06525
Ph: 203-812-2789
Cell: 203-430-0834
allen.heller.b@bayer.com