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THIS FOURTH AMENDMENT is made the 17th day of September, 1997 to an Agreement
dated 20 August 1996, and amended 18th November 1996 and 1997
("the Agreement")
BETWEEN
XXXXXXX PHARMACEUTICAL INC. of 000, Xxxxxxxxxx Xxxxxx, Xxxxx 000, Xxxx Xxxx, XX
00000, XXX ("the Customer")
AND
LONZA BIOLOGICS PLC of 000 Xxxx Xxxx, Xxxxxx, Xxxxxxxxx, XX0 0XX, Xxxxxxx
("Lonza").
WHEREAS:
A. The parties entered into the Agreement pursuant to which Lonza agreed to
provide Services to the Customer to develop a Process for production of
Product; and
B. Customer now wishes Lonza to perform certain additional Services in
association with the above mentioned development and manufacture of
Product; and
C. Lonza is prepared to provide such additional Services on the terms and
conditions set out herein.
NOW THEREFORE it is hereby agreed to amend the terms of the Agreement as
follows:
[*] Confidential treatment requested pursuant to a request for confidential
treatment filed with the Securities and Exchange Commission. Omitted
portions have been filed separately with the Commission.
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1. A new Stage 15 shall be added to Schedule 2 as follows:
"Stage 15 - Validation of [*].
15.1 Objectives
15.1.1 To obtain [*] data for [*] model [*] across the Process used in
the purification of bulk Product. The study will be designed to
be included in a Biologics Licence Application.
15.1.2 To review in the study report the appropriateness, or otherwise,
of any of the Process steps as a [*] step.
15.2 Activities
15.2.1 Design a scaled-down process for the [*] steps. This will mimic
as closely as possible the manufacturing scale Process. Agree a
GMP study protocol with the Customer. Agree which Testing
Laboratory to use with the Customer.
15.2.2 Collect samples from a [*] scale manufacturing batch of Product.
Samples will be collected at appropriate points prior to the [*]
steps and the [*].
15.2.3 Validate the scaled-down process for each of the [*] steps
without a [*]. Compare the [*] profile, Product yield and
purity with the full manufacturing Process.
15.2.4 Repeat the scaled-down process for each of the [*] steps, each
spiked separately with the [*] as agreed in the study protocol.
The [*] will be prepared and assayed by personnel at the
Testing Laboratory. The [*] experiments will be carried out by
Lonza personnel in the Testing Laboratory's facility.
15.2.5 Assay [*] recovered in Product-containing fractions (to allow
calculation of [*]) and selected unbound and wash fractions to
determine where possible where [*] is removed and hence
identify critical steps in the Process.
15.2.6 Evaluate the extent of [*] on [*].
15.2.7 Evaluate the [*] effects of Process materials and/or
interference with [*]. Evaluate the inactivation of selected [*]
by the [*] for the [*] and the column regeneration conditions
for the [*].
15.2.8 Calculate [*] factors for each step by dividing total [*]
applied to each [*] to that recovered with Product.
[*] Confidential treatment requested pursuant to a request for confidential
treatment filed with the Securities and Exchange Commission. Omitted
portions have been filed separately with the Commission.
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15.2.9 Issue a final study report to the Customer, copies of data
generated under Stage 15 if requested by the Customer and
deviations and amendments to the protocol agreed under 15.2.1.
Twice during the course of this Stage 15 if requested by the
Customer (and more frequently if agreed between the parties)
Lonza will issue to the Customer unaudited interim data
summaries provided such requests from the Customer are
reasonable in nature.
15.3 Timescale
Stage 15 will be complete on issue of the final report under activity
15.2.9. It is estimated that this final report will be issued [*]
from commencement of State 15."
[*] Confidential treatment requested pursuant to a request for confidential
treatment filed with the Securities and Exchange Commission. Omitted
portions have been filed separately with the Commission.
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2. The following shall be added to Clauses 1 and 2 of Schedule 3:
"1. Price
In consideration for Lonza carrying out the Services as detailed in
Schedule 2 (Stage 15) the Customer shall pay Lonza as follows:
Stage Price (UK Sterling)
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Stage 15 -- Evaluation of [*] [*]
(1) The Price for this Stage does not include Testing Laboratory charges
which will be passed on directly to the Customer.
2. Payment
Payment by the Customer of the Price for Stage 15 shall be made against
Lonza's invoices as follows:
2.1 For Stage 15
[*] upon commencement of Stage 15
[*] upon completion of Stage 15
Testing Laboratory charges will be
invoiced to the Customer on completion of Stage 15."
3. Save as expressly provided herein, the terms and conditions of
the Agreement shall remain in full force and effect.
AS WITNESS the hands of the duly authorized representatives of the parties
hereto the day and year first above written.
Signed for and on behalf of /s/ XXXXX XXXXXX
LONZA BIOLOGICS PLC ----------------------------------------
CEO
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Signed for and on behalf of /s/ XXXXXXX X. XXXXXX
XXXXXXX PHARMACEUTICAL INC. ----------------------------------------
Vice President and CFO
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[*] Confidential treatment requested pursuant to a request for confidential
treatment filed with the Securities and Exchange Commission. Omitted
portions have been filed separately with the Commission.
