[ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDED.
EXHIBIT 10.19
GTX INC.
[ * ]
INQUIRY NO. [ * ]
AUGUST 8, 2003
EAGLEPICHER
PHARMACEUTICAL SERVICES
CONFIDENTIAL AND RESTRICTED
This contract contains confidential and proprietary information of GTx, Inc. The
contents of this contract will be restricted to those XXXX personal with a need
to know the contents hereof.
TABLE OF CONTENTS
(CONTINUED)
PAGE
I. Introduction................................................. 4
II. Proposed Services............................................ 4
III. Deliverables................................................ 10
IV. Project Budget.............................................. 10
V. Timelines................................................... 10
VI. Assumptions................................................. 10
VII. Designated Representatives.................................. 12
VIII. Standard Terms and Conditions............................... 12
IX. Insurance................................................... 12
X. Project Authorization....................................... 13
I. INTRODUCTION
GTx Inc. has requested a quotation for [ * ] prepared under current good
manufacturing practices (cGMP). Eagle Picher Pharmaceutical Services
(XXXX) has extensive experience with [ * ] and we are excited to utilize
this knowledge to assist GTx in the development and manufacturing of [ *
]. Our customer focus and commitment to delivering the right product at
the right time and at the right price is unmatched by our competition.
II. PROPOSED SERVICES
SCOPE OF WORK SUMMARY
XXXX will manufacture [ * ] of [ * ] in our API plant equipment. This will
involve scaling up the current manufacturing process [ * ] into our plant
equipment ([ * ]). XXXX will make every effort to manufacture [ * ] with
the same target purity as previous kilo lab campaigns.
A [ * ] process is used to manufacture [ * ]. The [ * ] are outlined in
the `Detailed Scope of Work' section of this proposal. To limit the risk
as larger production batches are manufactured and to continue the
development of the process XXXX will execute the following activities:
Phase I- Analytical Method Transfer & Validation
-Demonstrate and incorporate assay methods for [ * ].
-Validate and incorporate [ * ].
-Transfer [ * ] assay methods from [ * ] to be used to assay the
[ * ] and [ * ].
-Perform analytical method validations for key intermediate [ * ].
-Perform abbreviated analytical method validations for each of the
[ * ] intermediates.
-Incorporate in-process monitoring assays for [ * ].
-Characterize a working standard for the [ * ].
-Set specifications for the release of the [ * ]. A lab batch will
be performed to generate [ * ]. Specifications will be proposed
based upon the analysis of these [ * ] of the [ * ].
-Validate analytical methods for release testing of [ * ] ([ * ]).
Phase II- GMP Set-up Activities for Pilot Plant Production of [ * ]
[ * ] batch records for plant equipment and processing.
[ * ] validation studies to develop [ * ] plant equipment.
-Project process training for [ * ].
Phase III- cGMP production of [ * ]
-[ * ] (assuming no [ * ] are removed)
-Certificate of Analysis for cGMP Batch
4
-Production Report
DETAILED SCOPE OF WORK
XXXX will manufacture [ * ] of [ * ] in our API Plant equipment. The
manufacture of [ * ] is a [ * ] process and is outlined below. Prior to
manufacture of each step in the plant equipment the analytical method
transfer/validation and GMP set-up activities for that step will be
completed. All XXXX analytical support for this project will be conducted
at the [ * ] facility.
[ * ]
PHASE I- ANALYTICAL METHOD TRANSFER & VALIDATION
[ * ]
XXXX will validate the [ * ] from [ * ]. A validation protocol will be
submitted to GTx for approval prior to execution. The validation protocol
will follow the [ * ], and the method will be validated for the following:
o Specificity ([ * ]),
o Accuracy,
o Precision,
o Linearity,
o Quantitation Limit,
o Detection Limit,
o Robustness, and
o Range.
The validated procedure will be converted into XXXX'x [ * ]. NOTE: A
specification for [ * ] that includes an acceptable level of [ * ] will be
defined before the validation protocol can be approved. The analytical
method validation report will be provided to GTx as a deliverable. The
[ * ] method will meet the validation parameters or GTx will be notified.
An assay method for [ * ] will be obtained from the vendor and used for
the release testing. An STM will be written for use in the release testing
of this raw material. The current standard test specifications (STS) for
[ * ] will be updated to add this assay to the current specifications.
Vendor specifications will be used for the STS.
An [ * ] test will be used to monitor the completion of the reaction in
[ * ]. The proposed test will use the assay method supplied by [ * ]. The
method will work to measure the [ * ] or GTx will be notified.
The [ * ] will be tested for release using the [ * ] assay method. A
working standard of [ * ] will be characterized. The working standard of
[ * ] (approximately [ * ]) will be characterized by [ * ]. The method to
measure the assay [ * ] will have an abbreviated
5
validation performed using the following tests on one sample: Accuracy,
Precision, Linearity, Quantitation Unit, and Stability [ * ]. The method
will not be validated at this time. The method will be shown to be
validatable by performing these tests on [ * ]. The method will perform
adequately on the [ * ] or GTx will be notified. A report will be written
summarizing the results.
Samples of [ * ] from previous work at XXXX will be tested by [ * ] to
determine an [ * ] profile. The information obtained from this analysis
will be used to establish release specifications for [ * ]. The standard
test specification (STS) for [ * ] will be modified accordingly.
[ * ]
[ * ] will be tested using the manufacturer's method for assay. A Standard
Test Method will be written for this raw material. The current STS for
[ * ] will be updated to add an assay to the current specifications.
Vendor specifications will be used for the STS.
The [ * ] is not isolated in the current process. However, the reaction to
form [ * ] should be monitored for completion using an [ * ] test. XXXX
will use [ * ] assay method for the in-process monitoring of [ * ]. The
method will work to measure the disappearance of starting materials and/or
appearance of the product in the reaction or GTx will be notified.
A working standard of [ * ] ([ * ]) will be characterized. The working
standard will be characterized by [ * ]. The assay method for [ * ] will
have an abbreviated validation performed using the following tests on one
sample: Accuracy, Precision, Linearity, Quantitation Limit and Stability
[ * ]. The method will not be validated at this time. The method will be
shown to be validatable by performing these tests on one sample of
intermediate. The method will perform adequately on the intermediate or
GTx will be notified. A report will be written summarizing the results.
Samples of [ * ] from previous work at XXXX will be used to determine an
impurity profile for this intermediate. This profile will be used to
establish the standard test specifications (STS) for [ * ]. The STS will
be modified to include an assay.
[ * ] is combined with [ * ] in the manufacturing process. The [ * ]
method for [ * ] will be validated. A validation protocol will be
submitted to GTx for approval prior to execution. The validation protocol
will follow the [ * ], and the method will be validated for the following:
o Specificity,
o Accuracy,
o Precision,
o Linearity,
o Quantitation Limit,
o Detection Limit,
6
o Robustness, and
o Range.
The assay method will perform adequately or GTx will be notified. A
validation report will be issued for this work.
A working standard of [ * ] will be prepared. The material will be
characterized by [ * ]. Because [ * ] may be stored for longer periods of
time, some stress studies will be performed to assess how labile the
compound is under certain conditions. Forced degradation studies will
examine [ * ].
Samples of [ * ] from previous work at XXXX will be used to determine the
impurity profile of this material. This profile will be used in
establishing the standard test specifications (STS) for [ * ]. The STS
will be modified to include an assay in the specification.
[ * ]
[ * ] will be tested for release using the manufacturer's method for
assay. A STM will be written for this raw material. The current STS for
[ * ] will be updated to add an assay to the current release tests. Vendor
specifications will be used for the STS.
An assay method for [ * ] will be obtained from the vendor and used for
the release testing. A STM will be written to use for this raw material.
The current STS for [ * ] will be updated to add an assay to the current
specifications. Vendor specifications will be used for the STS.
In-process monitoring of [ * ] will use the assay method supplied by
[ * ]. The method will work to measure the [ * ] or GTx will be notified.
The [ * ] will be tested for release using the [ * ] assay method. The
scope for this [ * ] is similar to the scope of work proposed for [ * ]. A
working standard of [ * ] will be characterized, The working standard
([ * ]) will be characterized by [ * ]. The [ * ] assay method for [ * ]
will have an abbreviated validation performed using the following tests on
one sample: Accuracy, Precision, Linearity, Quantitation Limit, and
Stability per [ * ]. The method will not be validated at this time. The
method will be shown to be validatable by performing these tests on one
sample of [ * ]. The method will perform adequately on the [ * ] or GTx
will be notified. A report will be written summarizing the results.
Samples of [ * ] from previous work at XXXX will be used to determine an
[ * ]. This profile will be used in the determination of the standard
specifications of [ * ]. The STS sheet will be modified to include a [ * ]
assay.
[ * ]
7
The [ * ] will be tested using the manufacturer's method for assay. A STM
will be written for the assay of this raw material. The current STS for
[ * ] will be updated to add an assay to the current tests. Vendor
specifications will be used for the STS.
Similarly, the [ * ] will be tested using the manufacturer's method for
assay. A STM will be written for the assay of this raw material. The
current STS for [ * ] will be updated to add an assay to the current
tests. Vendor specifications will be used for the STS.
In-process [ * ] monitoring of the [ * ] reaction will use the assay
method supplied by [ * ]. The method will work to measure the [ * ] or GTx
will be notified.
The [ * ] methods ([ * ]) for release testing of [ * ] will be transferred
to XXXX and validated on [ * ]. XXXX will write a validation protocol
which will be approved by GTx prior to validation. Using [ * ], the method
will be validated for the following; Specificity ([ * ]), Accuracy,
Precision, Linearity, Quantitation Limit, Detection Limit, Robustness, and
Range. Each method will be incorporated into a STM for GMP analysis. A
validation report will be written. The methods will work properly or GTx
will be notified.
The [ * ] method for [ * ] testing of [ * ] ([ * ]) will be transferred to
XXXX and validated for [ * ]. The [ * ] methods for [ * ] will be
validated. A validation protocol will be submitted to GTx for approval
prior to execution. The validation protocol will follow the [ * ], and the
method will be validated for the following:
o Specificity ([ * ]),
o Accuracy,
o Precision,
o Linearity,
o Quantitation Limit,
o Detection Limit,
o Robustness, and
o Range.
If portions of the validation program proposed above have been performed
at [ * ] then that work will not be repeated. A validation report will be
written. The methods will work properly or GTx will be notified.
Product specific methods for [ * ] will be validated by XXXX. XXXX will
write a validation protocols and will submit these protocols to GTx for
approval prior to implementation. Using the [ * ], the method will be
validated for the following; Specificity and Accuracy. Each method will be
incorporated into a STM. A validation report will be written. The methods
will work properly or GTx will be notified.
PHASE II- GMP SET-UP ACTIVITIES FOR PILOT PLANT PRODUCTION OF [ * ]
8
A series of [ * ] are required prior to the pilot plant campaign.
o [ * ] will be rewritten for pilot plant production. The [ * ] will
be submitted to GTx for approval then issued by XXXX'x QA
department.
x XXXX and GTx will review [ * ] prior to starting plant
manufacturing.
o [ * ] will be performed to develop procedures that will be used to
1) [ * ] and 2) [ * ]. This usually entails [ * ] and [ * ] to
document the [ * ] is sufficient.
x XXXX requires operator training and a safety review of the process
before the start of manufacturing. The operators are trained on how
to handle the chemicals used in the process and their hazards.
PHASE III- CGMP PRODUCTION OF [ * ]
A cGMP batch of [ * ] will be manufactured utilizing the best technology
developed during previous [ * ]. [ * ] and [ * ] will be combined, as in
the [ * ]. Each [ * ] will be released based on the specifications
established in [ * ]. In-process reaction monitoring will be performed on
[ * ].
GTx will supply the [ * ] starting material. XXXX will provide all [ * ]
including the [ * ] and [ * ].
The [ * ] will include [ * ],
After completion of the production campaign, a production report will be
issued which will include a summary of the [ * ].
The, QC department typically provides in-process results from production
samples [ * ]. The analyses required to [ * ] typically has a [ * ] time.
Final release testing usually takes about [ * ] for [ * ] and [ * ]. If
any rush charges are incurred for rush analysis from outside vendors, the
cost will be [ * ].
The storage conditions for [ * ] and the [ * ] will be at [ * ] unless
otherwise requested by GTx. The final product will be packaged in [ * ]
inside of [ * ]. The label is in accordance with the [ * ]. The scope of
this work has incorporated [ * ].
GTx will always have the options to [ * ].
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III. DELIVERABLES
o Validation Report - [ * ]
o Summary Report - [ * ]
o Summary Report - [ * ]
o Validation Report for [ * ]
o Summary Report - [ * ]
o Validation Report for [ * ]
o Validation Report for [ * ]
o Validation Report - [ * ]
o [ * ] of [ * ] ([ * ])
o Certificate of Analysis for cGMP Batch
o Production Report
IV. PROJECT BUDGET
PHASE DESCRIPTION COST
I Analytical Method Transfer and Validation [ * ]
II GMP Set-up Activities [ * ]
III GMP Production ([ * ]) [ * ]
Raw Materials and Waste [ * ]
TOTAL [ * ]
V. TIMELINES
[ * ]
o Phase I - [ * ] from the date the proposal is signed. Phase I [ * ]
with GMP production.
o Phase II - [ * ] from the date the proposal is signed.
o Phase III - [ * ] after completion of Phase II.
VI. ASSUMPTIONS
XXXX is providing this proposal with the following assumptions. Should any
of these assumptions prove to be invalid; a revised scope of work with its
associated cost will be submitted to GTx.
1. GTx will provide [ * ] at GTx expense. All remaining raw materials
are included in this quote, including [ * ] and [ * ].
2. Any changes to this Agreement which effect cost, schedule, or alter
this Agreement materially, such as changes in processes, protocols
or additional testing or sampling,
10
shall be submitted in writing with any additional associated costs
and mutually agreed to by both parties before continuation of the
project.
3. The API manufactured at XXXX is not manufactured as a sterile API.
The customer will ensure that if a sterile product is required that
the formulated product will contain steps for terminal
sterilization.
4. This proposal does not include costs for an FDA site inspection as a
result of or in association with the manufacturing of the API named
in this proposal.
5. XXXX makes no guarantees on yield or purity until [ * ] XXXX
manufacturing runs provide adequate information for justification of
yield and purity consistency.
6. GTx bears all sales tax liability under this agreement. GTx is not
liable for taxes on XXXX income.
7. Costs outlined above do not include any shipping outside of the
scope provided in this proposal, shipping insurance, applicable
taxes or handling charges.
8. [ * ] analytical methods will be suitable and provide acceptable
performance (validatable) for use as described in the detailed scope
of work.
11
VII. DESIGNATED REPRESENTATIVES
GTX, INC
Xxxxx Xxxxxxx, Ph.D.
Director ARTA Research
Three North Xxxxxx Avenue
Van Vleet Building Third Floor
Memphis, TN 38163
901-523 -9700 ext 104
fax 000-000-0000
Xxxxxxxx@xxxxxx.xxx
EAGLEPICHER EAGLEPICHER PHARMACEUTICAL SERVICES
Xxxxx Xxxxxxx
Contracts Manager and Legal Administrator
00000 X. 00xx Xxxxxxx
Xxxxxx, Xxxxxx 00000
000-000-0000
000-000-0000
Xxxxx.xxxxxxx@xxxxxxxxxxx.xxx
VIII. STANDARD TERMS AND CONDITIONS
The terms and conditions between GTx and XXXX for this contract are
covered under the Production and Manufacturing Agreement entered into on
the 9th day of September 2002, (the "2002 Agreement"). In the event of a
conflict between the terms hereof and any provision contained in the 2002
Agreement, the terms hereof shall control; otherwise, the 2002 Agreement
shall be incorporated herein and form a put of this Agreement.
IX. INSURANCE
XXXX confirms that it has reasonable and adequate insurance in full force
and effect with qualified insurers to fully insure GTx against loss of
material or product resulting from a casualty occurring while such
material or product is in control of or on the property of XXXX. XXXX will
assume the risk of any loss to GTx material and property which is
willingly under its control or located on its property, and in the event
of a casualty, XXXX will promptly notify GTx. Pending resolution of any
resulting insurance claim, XXXX will replace any lost or damaged material.
12
X. PROJECT AUTHORIZATION
The project described above may be authorized by returning to EaglePicher
Pharmaceutical Services a signed copy of our proposal and your purchase
order. This proposal remains effective until September 08, 2003. This
proposal is subject to the attached Standard Terms and Conditions. Please
reference EaglePicher Pharmaceutical Services Inquiry [ * ] in all
correspondence. This agreement shall be interpreted and constructed in
accordance with the laws of the state of Missouri. Termination of this
agreement is subject to discussion and resolution of any outstanding
issues between the involved parties.
Sincerely, Accepted by GTx, Inc:
/s/ Xxxxx X. Xxxxxxx /s/ Xxxxx X. Xxxxxxxx Date: 8/13/03
-------------------- --------------------- -------
Xxxxx X. Xxxxxxx General Counsel
Contracts Manager and Legal Administrator Secretary
EaglePicher Technologies, LLC
EaglePicher Pharmaceutical Services looks forward to your response, and to
proceeding as soon as possible.
[ * ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS AMENDED.
13
