email: <FDADockets@oc.fda.gov>

Docket No. 2000N-1484

October 9, 2003; Comments by Public Citizen's Health Research Group on
Proposed Rule: Safety Reporting Requirements for Human Drug and
Biological Products

Comments are referenced to [Federal Register]{.underline}, v68, #50,
Friday, Mar 14, 2003.

Overall comments on proposed regulations for 21 CFR 310.305, 21 CFR
314.80, and 21 CFR 314.98:

The original proposed rule amending drug postmarketing safety reporting
regulations was published almost 10 years ago in 1994; a final rule on
the topic was published in 1997. The present proposed rules on drug
postmarketing safety reporting are being published in 2003. It is hoped
the respective final rules are finalized and published more
expeditiously

The submission of individual, postmarketing, suspected adverse drug
reaction reports, as per the proposed rule, is quite complex - -
differing timeframes and what is expected to be contained in the
individual report and when. Whatever rule is finalized for individual
postmarketing suspected adverse drug reaction (SADR) reports needs to be
presented also as a Flow Diagram. The Flow Diagram would start with
postmarketing SADR information coming into contact with the
applicant/manufacturer. Decision nodes would be shown in the diagram,
noting the questions, actions, and timeframes, necessary for properly
classifying and completing the individual report for its subsequent
submission to FDA, both individually and as part of an aggregate
submission (eg, periodic report). Such a flow diagram would aid both
applicants/manufacturers and those in FDA responsible for the evaluation
of the safety reports and enforcement of the respective regulations.

p 12418, 1^st^ full ¶, on "over-reporting" of study reports:

The danger is in underreporting not overreporting. Given this kind of
loophole, the drug industry will come up with excuses not to report
postmarketing SADRs that now are automatic. This is a terrible idea.

p 12419, 2^nd^ full ¶: regarding whether FDA should consider prohibiting
use of postmarketing SADR reports it receives in product liability
actions:

The "disclaimers" are quite sufficient; there is no reason to add more
action on this.

p 12420, 1^st^ column, III.A.5.:

What information makes a patient "identifiable" and to whom? What
information makes a reporter "identifiable" and to whom? Applicants and
other prescription drug manufacturers should not be allowed to define
"identifiable," since they could use definitions that would allow them
to report fewer postmarketing SADR reports to FDA. FDA should define
"identifiable" in a de minimis manner, so if there is a question as to
whether the patient or reporter is "identifiable," the company shall
submit the postmarketing SADR report to FDA.

p 12420, 2^nd^ column, 1^st^ full ¶: regarding studies, when should the
code be broken:

We assume this simply means there is no reason for making a SADR report
to the FDA on an individual patient unless it is known whether the
patient was, for example, using a placebo or the drug. This should not
preclude the requirement for submission to the FDA of interim analyses,
disaggregated by group, that might suggest increased overall dangers to
those getting the drug. These are the kinds of data now submitted in
many cases to the Data Safety Monitoring Boards (DSMBs), but the context
of such results might be better understood by the FDA and possibly used
as a basis for placing a clinical hold on the study.

p 12421, IIIA7:

What is the definition of a "class action lawsuit"? Is it a certain
number of reports all from the same law firm? Or does the initial
reporter have to state to the applicant/manufacturer that the report is
part of a class action lawsuit?

p 12421, 2^nd^ column, last ¶ and p 12435, 3^rd^ column, III.D.11. Class
Action Lawsuits:

Under the proposed regulations, class action lawsuit postmarketing SADR
reports are to be considered as neither spontaneous nor study, because
FDA believes the information contained therein is duplicative and not
complete and would be submitted to FDA from other sources prior to the
lawsuit. FDA does not present any data to support this viewpoint.
Instead of not having the applicant/manufacturer submit any such
individual class-action lawsuit reports, FDA should, especially for
expedited reports, have the applicant/manufacturer submit one expedited
report for each unique combination of SADR and drug and note in the
report submitted to FDA that the report represents "X" number of class
action lawsuit reports (however class action lawsuit is eventually
defined). This would help the public who have to depend on the public,
CD-ROM AERS database (consisting of individual postmarketing SADR
reports) distributed through NTIS to have access to this information,
rather than having to go through FOI to get the information via one of
the types of periodic reports, not knowing when the periodic report came
in to FDA.

p 12422, 2^nd^ column, definition of "drug substance":

Whose classification would be required in naming and listing the drug
substance? - - International Nonproprietary Name (INN)? This should be
standardized, otherwise FDA will have to construct another computerized
dictionary to link the various names for the same drug substance.

p 12427, 3^rd^ column, last sentence:

Since FDA talks about future capabilities, why is there no mention of a
companion compliance program being written for the FDA field inspectors
and CDER Compliance? Very detailed regulations, which the proposed
regulations are, do not protect public health if they are not enforced.

We are examining the timeliness and completeness of recent,
postmarketing, expedited reports submitted by applicants to FDA; an
initial review shows notable, serious deficiencies. When the assessment
is completed, we will forward it to you.

p 12435, 2^nd^ column, 1st full ¶, "...contractors are typically
considered agents of the manufacturer or applicant."

If FDA views contractors in this manner, then any clock starting a
required FDA reporting timeframe should start when the information
becomes known to the contractor if the contractor and not the
applicant/manufacturer is the first to receive the postmarketing SADR
information.

p 12480, 1^st^ column, "(vii) *The 15-day followup report*."

How does FDA want to handle an initial report that is classified as
"expedited" but on followup is found not to be? Does it continue to
treated as expedited or not? We recommend the default should be to keep
it as expedited unless there is clear evidence, which there probably is
not in most cases, it should no longer be treated as expedited.

p 12486, "(e) *Patient privacy*."

The 1^st^ sentence should be changed to read: "...the applicant and its
contractors shall assign a unique code to each initial report,
preferably not more than eight characters in length. Letters and numbers
shall not be mixed in the same code. Any followup(s) to the initial
report shall have the same code as the initial report."

Not having mixed letters and numbers will prevent confusion, eg, when
searching on the unique code as to whether the character is a zero or
the letter "O". FDA does not want a followup to have a different code
from its initial report; again, having the same code for initial and any
followup report(s) facilitates searching and grouping of reports.