From: Peters, Jenny [jepeters@amgen.com]
Sent: Thursday, April 20, 2006 8:31 PM
To: Dockets, FDA
Subject: Amgen Inc's Comments re 2005D-0011 - Warnings and Precautions,
C ontraindications, and Boxed Warning Sections of Labeling for Human
Prescr iption Drug and Biological Products--Content and Format

Please find Amgen's comments regarding subject docket and guidance.  Do not
hesitate to contact Jenny Peters at 805-447-8840 with any questions.  Kind
regards, Jenny

____________________
Line 169:  A discussion of how to treat, or otherwise manage, an adverse
reaction that has occurred.
Comment:  Presumably above is limited to providing information regarding
unusual treatments and/or management, as opposed to general medical
practice.  Please clarify this intent in the text.

Line 176:  A discussion of the mechanism of the adverse reaction.
Suggested revision:  A discussion of the mechanism of the adverse reaction,
where known.

Line 316-351 Boxed Warning (§ 201.57(c)(1))
Comment re Appropriate Stratification of Risk Information:  The current
guidance offered by FDA for Boxed Warnings states that the adverse reaction
in question should be so serious in proportion to the potential benefit that
it must be emphasized in assessing the use of the drug.  If there is no
additional context added to a Boxed Warning of a potential, theoretical
adverse reaction that enables the reader to predict or manage their approach
to the drug, then the reader is left with a completely unbalanced risk
statement.  The current draft guidance only states that the adverse reaction
in question must be very serious in proportion to potential benefit.  There
is nothing stated regarding the strength of evidence needed for the adverse
reaction in question.  The assumption by at least some physicians could be
that the adverse event in question is based on firm evidence.

Minimally, FDA should include some broad guidance for a measure of the
evidence required to establish that the event in question is an adverse
reaction that requires emphasis. By not including some guidance on what
evidence is sufficient to stratify an adverse reaction as requiring
emphasis, FDA creates a situation where physicians and patients could be
misinformed regarding risk to the extent that they would not utilize
therapies of known benefit simply because of concern regarding theoretical,
potential risk.

Specific Revision: Beyond the broad guidance requested above, we also
suggest the following text be added at the end of Line 351,  "A boxed
warning may not be appropriate for a suspected adverse reaction for which
the only evidence regarding causality is biological plausibility."


Jenny Peters
Amgen Regulatory Affairs
805-447-8840