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EXHIBIT 10.9
FIRST AMENDMENT TO AGREEMENT
THIS FIRST AMENDMENT is made the 21st day of November 1996 to an
agreement dated 20 August 1996 ("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 XXX 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 in accordance with GMP; 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 by to amend the terms of the
Agreement as follows:
1. The following shall be added to Schedule 1:
"The Customer and Lonza may make changes to the Product Specification
by mutual agreement."
2. A new Stage 7 shall be added to Schedule 2 as follows:
"Stage 7 Product Equivalence Studies
7.1 Objectives
7.1.1 To characterize Product produced at Lonza and compare it
with a sample of Product produced by the Customer. The samples to be used are
from the following sources:
- [*] development pilot batch produced at Lonza under Stage
3 of the Services;
- 2000 litre GMP lot produced at Lonza under Stage 5 of the
Services;
- reference lot number [*] produced by the Customer.
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
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7.1.2 To investigate the formation of a [*] from a batch of
Product made at Lonza.
7.1.3 To provide reference material for release of GMP batches of
Product.
7.2 Activities
7.2.1 Analyze the three samples detailed in Stage 7.1.1 above,
using assays as described in the Specification for Product detailed in
Schedule 1 of this Agreement, namely:
[*].
7.2.2 Analyse the three samples using additional techniques,
namely:
[*].
7.2.3 Prepare reference standard material for use in subsequent
Product release from both the [*] pilot batch and the first 2000 litre GMP
batch of Product (Stage 5 of Schedule 2). Reference standard from the [*]
pilot batch (Stage 3 of Schedule 2) will be used for release of the first 2000
litre GMP batch. Reference standard from the first 2000 litre GMP batch will be
used for release of subsequent GMP lots.
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
2.
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7.2.4 Issue Report of Activities to Customer.
7.3 Timescale
Stage 7 shall be complete upon issue of the report (Stage 7.2.4)
of activities to the Customer. It is estimated that this report will be issued
[*] from commencement of activities under Stage 7."
3. A new Stage 8 shall be added to Schedule 2 as follows:
"Stage 8 Determination of Extinction Coefficient
8.1. Objective
To determine an extinction coefficient for purified Product [*].
8.2 Activities
8.2.1 Receive material from the Customer (purified batch number
[*]). [*] method.
8.2.2 [*] compared to a calibration standard.
8.2.3 Estimate the [*] from the value obtained for [*] and the
theoretical relative composition. Calculate a mean value for [*].
8.2.4 Repeat Stages 8.2.1-8.2.3 on two further occasions.
Calculate an overall mean [*].
8.2.5 Measure the [*].
8.2.6 Determine the extinction coefficient of the [*] under
Stages 8.2.4 and 8.2.5.
8.2.7 Issue a report of activities to the Customer.
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
3.
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8.3 Timescale
Stage 8 shall be complete upon issue of the report (Stage 8.2.7) of
activities to the Customer. It is estimated that this report will be issued [*]
from commencement of activities under Stage 8."
4. A new Stage 9 will be added to Schedule 2 as follows:
"Stage 9 Establishment of a [*] Assay
Background
[*].
9.1 Objectives
To establish an assay for [*].
9.2 Activities
9.2.1 Select the optimum [*].
9.2.2 Develop [*].
9.2.3 Optimize the assay for use with the Product and establish
assay performance criteria.
9.2.4 [*].
9.2.5 Issue report of activities with the GMP standard operating
procedure (SOP) for the assay procedure to the Customer.
9.3 Timescale
Stage 9 shall be complete upon issue of the report (Stage 9.2.5) of
activities to the Customer. It is estimated that this report will be issued [*]
from commencement of activities under Stage 9".
5. A new Stage 10 will be added to Schedule 2 as follows:
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
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"Stage 10 Evaluation of Retrovirus Clearance
10.1 Objective
To establish virus clearance data for [*].
10.2 Activities
10.2.1 Design a [*]. Prepare a GLP study protocol.
10.2.2 Collect samples from a manufacturing run [*].
10.2.3 Carry out the [*] for each of the [*].
10.2.4 Repeat the [*].
10.2.5 [*].
10.2.6 [*].
10.2.7 Issue a report of activities to the Customer.
10.3 Timescale
Stage 10 will be complete on issue of the report of activities (Stage
10.2.7) and it is estimated that this will be issued [*] from commencement
of Stage 10".
6. A new Stage 11 will be added to Schedule 2 as follows:
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
5.
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"Stage 11 Stability Studies on [*]
11.1 Objective
To test the stability of [*].
11.2 Activities
11.2.1 Devise protocols for the stability studies according to the
principles of GLP and supply the protocols to the Customer for review.
11.2.2 Take [*].
11.2.3 Assay [*].
11.2.4 Measure [*].
11.2.5 Deliver samples [*].
11.2.6 Issue a report of activities to the Customer.
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
6.
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11.3 Timescale
Stage 11 shall be complete on the report of activities to the Customer.
It is estimated that this report will be issued [*] from commencement of
Stage 11. Interim reports can be supplied (e.g. for IND submission) at the
Customer's request".
7. 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 (Stages 7 to 11) the Customer shall pay Lonza as follows:
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STAGE PRICE
(UK
STERLING)
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Stage 7 Product Equivalence Studies. pound sterling [*]
Stage 8 Determination of Extinction coefficient. pound sterling [*]
Stage 9 Establishment of [*] Assay. pound sterling [*]
Stage 10 Evaluation of Retrovirus Clearance. pound sterling [*]
Stage 11 Stability Study [*]. pound sterling [*]
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* Does not include Testing Laboratory charges which will be charged
in addition at the price invoiced to Lonza.
2. Payment
Payment by the Customer of the Price for Stages 7 to 11 shall be made
against Lonza's invoices as follows:
2.1 For Stage 7
50% (pound sterling [*]) upon commencement of Stage 7
50% (pound sterling [*]) upon completion of Stage 7.
2.2 For Stage 8
50% (pound sterling [*]) upon commencement of Stage 8
50% (pound sterling [*]) upon completion of Stage 8.
2.3 For Stage 9
50% (pound sterling [*]) upon commencement of Stage 9
50% (pound sterling [*]) upon completion of Stage 9.
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
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2.4 For Stage 10
pound sterling [*] upon commencement of Stage 10
pound sterling [*] upon completion of Stage 10
Testing House charges will be charged on completion of Stage 10.
2.5 For Stage 11
50% (pound sterling [*]) upon commencement of Stage 11
50% (pound sterling [*]) upon completion of Stage 11".
8. Save as expressly provided herein, the terms and conditions of the
Agreement shall continue in full force and effect.
AS WITNESS the hands of the duly authorised representatives of the
parties hereto the day and year first above written.
Signed for and on behalf of _____________________________
Lonza Biologics PLC _____________________________
Title
Signed for and on behalf of
XXXXXXX PHARMACEUTICAL INC _____________________________
_____________________________
Title
* Certain confidential information contained in this document, marked by
brackets, has been omitted and filed with the Securities and Exchange
Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
8.
