Exhibit 4.31
Confidential treatment
has been requested for certain portions of this exhibit. The copy
filed herewith omits the information subject to the confidential
treatment request. Omissions are designated as
“[*****]” or “*******”. A complete version
of this exhibit has been filed separately with the Commission
pursuant to an application for confidential treatment under Rule
24b-2 promulgated under the Securities Exchange Act of 1934, as
amended.
ACAMBIS
SUBCONTRACT MODIFICATION 0003
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Subcontract No.:
200-2002-00010(BXTR)
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Modification No.:
0003
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Effective Date: December
20, 2002
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Subcontractors:
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Baxter Healthcare
SA
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Baxter Healthcare
Corporation
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Hertistrasse 2
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One Baxter
Parkway
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CH-8304 Wallisellen,
Switzerland
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Deerfield, IL
60015
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Description of
Modification:
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(1)
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Allows for orders up to
3.0 million kits (300,000,000 doses),
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(2)
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Extends the ordering
period to December 31, 2003,
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****
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Increases the
******** and transportation temperature for vaccine from
********
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(3)
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Changes the size of the
case of bifurcated vaccinating needles from 5,600 per case to 5,000
per case.
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Authority
for, and type of, modification: Bilateral Supplemental
Agreement
Total
Subcontract value change: $0.00 Changes to Subcontract:
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Deletes
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Subcontract Sections A.1,
A.2, B, C (Items 0001 and 0003), and G.8
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Adds
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The attached modified
Subcontract Sections A.1, A.2, B, C (Items 0001 and 0003), and
G.8.
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RELEASE OF
CLAIMS
In
consideration of the modifications made above, this Modification is
in full settlement of any Subcontractors right to equitable
adjustment as the result of the changes made herein. Except to the
extent modified herein, the subcontract terms and conditions remain
unchanged. This supplemental agreement constitutes the full
agreement of the parties and supercedes any prior agreements with
respect to the changes made herein.
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For: ACAMBIS,
INC.
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For: BAXTER HEALTHCARE
S.A. and BAXTER HEALTHCARE CORPORATION
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********
********
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********
********
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********
********
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********
********
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Execution Date December
20, 2002
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Execution Date December
20, 2002
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Modification
0003
2
Modification
0003
Section A
– Introduction
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A.1
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BACKGROUND
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The United States
Government has recognized the need to maintain a stockpile of
smallpox vaccine to deal with the consequences if smallpox virus
were used as a terrorist weapon against the civilian population.
The Department of Health and Human Services (DHHS), Centers for
Disease Control and Prevention (CDC), National Center for
Infectious Diseases (NCID), has awarded Acambis Inc. a contract to
develop, license, manufacture, and create a stockpile of vaccine,
in quantities as may be ordered by the Government, within the
shortest time possible, but for the initial order not later than
December 31, 2002 and for subsequent orders within a time to be
negotiated at the time of order.
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A.2
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PURPOSE
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The purpose of this
Subcontract is for Contractor to purchase crude bulk vaccine from
the 1 st Subcontractor sufficient to produce an
estimated 155 million doses of such vaccine (with a maximum total
quantity of 300 million doses), as an investigational new drug
(“IND”). After Contractor processes the crude bulk
vaccine, the Contractor shall provide to 2 nd
Subcontractor finished lyophilized vaccine, diluent, and certain
materials (“components”) necessary for the 2
nd Subcontractor to assemble various components into
100-dose kits ********
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3
Modification
0003
Section B –
Schedule of Subcontract ITEMs/Prices
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ITEM
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Description
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Estimated
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Unit
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Estimated
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Quantity
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Price
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Total
Amount
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0001 –
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Bulk Vaccine/Partial Kit
Assembly
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-Preliminary kit
(IND)(initial order)**
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0001A Crude Bulk
Vaccine
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155,000,000
doses
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********
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********
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0001B Partial Kit
Assembly
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1,550,000
Kits*
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********
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********
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0002 –
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Bulk Vaccine/Partial Kit
Assembly
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-Preliminary kit
(IND)**
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0002A Crude Bulk
Vaccine
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********
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********
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********
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0002B Partial Kit
Assembly
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********
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********
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********
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*Orders for ITEMs 0001
and 0002 combined shall not exceed 3.0 million kits or 300 million
doses.
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** Unit Price/Kit under
ITEMs 0001 and 0002 consists of two parts: (1) the selling price of
the bulk vaccine delivered to Contractor for further processing by
the Contractor into lyophilized 100-dose vials to be used as a
component of the kits to be assembled under this Subcontract and
(2) the charges for kit components not furnished by Contractor and
partial kit assembly. For ITEM 0001A, the bulk vaccine-selling
price is ******* at ******** doses ******** kits). For ITEM 0002A,
additional orders shall be at ********) up to a total of ********
doses ordered, in the aggregate, for ITEMs 0001A and 0002A; and
******** for total doses ordered in the aggregate exceeding
******** doses. The charges for kit components not furnished by
Contractor and partial kit assembly under ITEMs 0001B and 0002B is
********
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Title, Risk of Loss and
Invoices for Crude Bulk Vaccine
1. The
******** shall, with at least ten (10) working days advance notice
to the Contractor, ship crude bulk vaccine conforming to the
Subcontract requirements from ********to ******** Each lot of crude
bulk vaccine shipped to Contractor shall be accompanied with a
Certificate of Conformance (Section J, Attachment B) to the effect
that shipped crude bulk vaccine conforms to Subcontract
requirements.
2. Legal
title to such crude bulk vaccine shall pass to the Contractor upon
shipment ******** however, due to the sensitive nature of the crude
bulk vaccine and the 1st Subcontractor’s transportation and
logistics capabilities, the ******** shall continue to be
responsible for and bear all risks of loss or damage to the crude
bulk vaccine, cost of insurance, freight and transportation until
Contractor’s receipt of such crude bulk vaccine at
Contractor’s facility ********. Upon Contractor’s
receipt of each shipment of crude bulk vaccine, Contractor shall
thereafter assume all future risks of loss or damage to such
vaccine when the vaccine is processed, returned, and received
********
3. Contractor
shall obtain, at its own risk and expense, any import license or
other official authorization and carry out, where applicable, all
customs formalities for the import of the goods. Under Paragraph
H.26, 1st Subcontractor shall assist the Contractor in obtaining
such import license or other authorizations necessary for the
import of the crude bulk vaccine.
4. The
******** shall submit an invoice for each lot of crude bulk vaccine
(exclusive of pilot lots) shipped from ******** to ******** for
manufacture of kits under Subcontract Item(s) 0001 and/or 0002.
Initially, such invoices shall be based upon the assumption that
each lot of crude bulk vaccine delivered to Contractor, shall yield
******** after down-stream processing, purification, and
lyophilization. (For example, under ITEM 0001A, ********.
Subsequent invoices for future crude bulk lots shipped for
manufacture of kits under Item(s) 0001 and/or 0002 shall be based
on anticipated actual yields as agreed to
4
Modification
0003
by the
parties. Crude bulk vaccine in excess of that required to
manufacture vaccine kits for the U.S. Government under this
Subcontract shall be processed and finished into vaccine kits for
commercial sales under the terms of a separate commercial sales
agreement between Contractor and the 1 st
Subcontractor.
5. Notwithstanding
any other provision of this Subcontract, except Section C, ITEM
0001, Paragraph A.4, payment for ITEMs 0001 and 0002 shall be made
and be due at the earlier of: (1) thirty (30) days after the US
Government makes payment to Contractor for completed kits accepted
by the Government under the terms of Contractor’s Prime
Contract (See Paragraph G.2) upon due performance by the
Subcontractors of Subcontract ITEM(s) 0001 and 0002 and
Subcontractors’ submission of proper invoices for the actual
number of kitted vaccine delivered and accepted by the Contractor;
or (2) on December 31, 2003 for the amounts invoiced for each lot
of crude bulk vaccine, as described above, ordered under Delivery
Order 0001; or (3) on December 31, 2005 for the amounts invoiced
for each lot of crude bulk vaccine, as described above, ordered
after Delivery Order 0001. In no event shall Subcontractor(s) be
paid more under this Subcontract than the Subcontract price shown
above for ITEMs 0001 and 0002 for the number of kits delivered and
accepted unless the Contractor orders additional crude bulk vaccine
for which it is obligated to make payment under Section C, ITEM
0001, Paragraph A.7. below.
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0003 –
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Kit and Component
********
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********
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********
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0004 –
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Label
Vaccine/Diluent
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********
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********
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And Re-kit
after-Licensure
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********
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0005A –
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Final Kit Assembly
and
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********
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********
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Distribution of Vaccine
and
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Diluent after
Licensure
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0005B –
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Labeling, Final Kit
Assembly,
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********
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********
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and Distribution of
IND
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Vaccine and
Diluent
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**
As ordered, ITEMs 0005A and 0005B combined shall not exceed
********
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0006 –
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Data—Not Separately
Priced
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0007-
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Payment for Additional
Services
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– Payable as
specified in Paragraph H.26.
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0007
A ********
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********
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0007
B ********
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********
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*** H.26 payment for the
initial 155M dose Government order under Contract
200-2002-00004.
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**** H.26 payment for
subsequent Government order(s) for smallpox vaccine under Section B
(Items 0002 to 0006) of Contract 200-2002-00004
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5
Modification
0003
Section C –
Description/Specification/Work Statement (References to
“TBD” shall be determined by
Mutual Agreement of the
Parties)
ITEM
0001- Manufacture of Bulk Vaccine and Partial Kit
Assembly
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1. The
1 st Subcontractor shall qualify, pursuant to mutually
agreed standards, the process for infection and harvest of ACAM2000
in the 1 st Subcontractor’s serum-free Vero cells
in preparation for current Good Manufacturing Practices
(“cGMP”) manufacture at full-scale starting in January
2002, at the facilities of Baxter ********
2. The
1 st Subcontractor shall validate its large-scale
manufacturing process during large-scale production in the ********
by producing a minimum of three (3) consecutive cGMP lots at
full-scale to show consistency of manufacture. ******** During this
period, the 1 st Subcontractor shall manufacture a
minimum of four (4) additional full-scale cGMP inspecti
