(9)
Robert A. Moe, PhD. - Executive
Vice-President
George Clay, PhD. - Group
Leader, CNS Pharmacology
Robert Bost, PhD. - Director
of Food Products,
Regulatory Affairs
Holly Ru Probst - Director,
Corporation Information
Management Group.
Dave Britton - Director
Corporation Information
Department
William Merino, PhD. -
Director, Domestic Pharmaceutical
Products
Richard Viktora - Attorney
James Phelps - Vice-President,
General Counsel
Elwood H. Ensor, PhD. -
Vice-President
Paul Klimstra, PhD. - Vice-President
Pre-Clinical
Research and Development
Roger Thies - Attorney
During the course of our
investigation one or more of the
following Searle personnel
were present in the Conference Room
which we used for our data
review.
Richard Viktora - Attorney
Roger Thies - Attorney
George Clay, PhD. - Group
Leader, CNS Pharmacology
Robert Bost, PhD. - Director
of Food Products
Regulatory affairs
Don Cook, PhD. - Associate
Director, Department of
Bio Research
Dick Aspinol, PhD. - I.
I. D. Group Leader
Bill Jenkins, PhD. - Director,
Product Affairs
Fred McIlreath, PhD. -
Director, Regulatory Affairs
Paul Landefeld, - Attorney
Most of the time one attorney
(R. Viktora or R. Thies) and
one scientist were present.
During our initial meeting with
Searle personnel, James
Phelps stated that a Searle monitor
must be with us at all
times during our data review in order
to "protect the data".
During the course of our
investigation, various individuals
were interviewed in an
attempt to obtain all available raw
data and reconstruct the
manner in which the study was con-
ducted, as accurately as
possible. Since many employees
involved in the study or
support areas are no longer employed
at Searle, others were
interviewed who had general knowledge
of such parameters as statistics
and chemistry.
(10)
Significant interviews
are attached as Exhibits, as referenced.
Individuals interviewed
were as follows:
1. Donna Helms - Administrative
Assistant to Dr. McConnell on 5-18-77,
6-30-77 and 7/1/77 (Exh.
#46).
2. Judith Beauchamp - Hematology
Lab Supervisor on 6-2-77 (Exh. #47).
3. Barbara Bickford (Nee
Ross) - Technician, Department of Analytical
Research on 6-1-77 and
6-2-77 (Exh. #48).
4. Clifford J. Suel - Supervisor,
Department of Analytical Research and
Development on 6-2-77 (Exh.
#49).
5. Bartolome R. Tangonan
- Research Technician, Pathology Toxicology
Department on 6-1-77 (Exh.
#50).
6. Tony Martinez - Research
Assistant and Toxicology Lab Supervisor on
5-19-77, 6-3-77, 7-7-77,
7-20-77 and
8-2-77 (Exh. #51).
7. Ted Reichert - Supervisory
Systems Analyst on 5-24-77 (Exh. #52).
8. Phil Polli - Systems
Analyst on 5-24-77 (Exh. #53).
9. Judith Schmal - Clinical
Chemistry Section Supervisor on 6-2-77 and
6-7-77 (Exh. #54).
10. Jane Drury - Analytical
Chemist, Bioanalytical Dept. 6-7-77.
11. Alan Mitchell - Teratologist
on 7-20-77 (Exh. #56).
12. Raymond G. Schroeder
- Former Searle Teratologist on 7-18-77 (Exh.
#57).
13. Dr. Rudolph Stejskal
- Pathologist on 6-23-77.
14. Patricia Erdenberger
- Research Assistant and Histopathology Lab
Supervisor on various dates
(Exh. #58).
Dr. Robert McConnell, Pathology-Toxicology
Advisor at the time of this
study, was not directly
involved with daily procedures. He is no longer
employed at Searle.
An attempt was made to
interview Dr. K. S. Rao, Monitor of Study P.
T.
#988S73 on 7-25-77. We
were referred to Dr. Rao's attorney, who refused
permission for an interview
(see Jerome Bressler's memo dated 7-27-77,
Exh. #33).
(11)
PURPOSE OF STUDY PT 988S73
(E-77/78)
SC-19192: 115 Week Oral
Tumorigenicity Study in the Rat
According to the submission
to FDA, this study was intended to evaluate
the safety and tumorigenic
potential of SC-19192, diketopiperazine
(5-benzyl-3, 6-dioxo-2-piperazine-acetic
acid), which is a conversion
product of aspartame, and
to induce and define such adverse effects as
might occur only at prodigious
multiples of the estimated daily human
intake. The commercial
grade of aspartame (SC-18862) may contain up
to 2
percent of the conversion
product (DKP), according to Searle's
specifications.
DATES
Study e-77/78 (PT #988S73)
was initiated on November 8, l971. The study
was to be terminated at
104 weeks, but was extended to 115 weeks. The
reason for extending the
study was stated as follows in protocol amendment
#3 dated September 6, l973:
"it was decided to extend or continue the
study until the mortality
of either sex reduced the control group to 20
animals per sex, provided
the survival in the treated groups is not less
than 10 animals/sex/treated
group prior to that period. This approach is
consistent with current
FDA desires." A copy of the study protocol
is
attached as exhibit #11.
Initiation of treatment
was staggered over a two week period as follows:
HOUSING DATE PLACED SCHEDULED
DAYS ON
GROUP ON STUDY SACRIFICE
STUDY
A - Male 11/8/71 1/21/74
805
B - Female 11/9/71 1/22/74
805
C - Male 11/9/71 1/22/74
805
D - Female 11/10/71 1/23/74
805
E - Male 11/11/71 1/24/74
805
F - Female 11/12/71 1/25/74
805
G - Male 11/15/71 1/28/74
805
H - Female 11/16/71 1/29/74
805
J - Male 11/17/71 1/30/74
805
K - Female 11/17/71 1/30/74
805
L - Male 11/18/71 1/31/74
805
M - Female 11/19/71 2/1/74
805
