DISTRIBUTION, MANUFACTURING, AND LICENSE AGREEMENT

This Distribution, Manufacturing, and License Agreement is entered into at the date of countersignature (the “Effective Date”) by and between Acambis Research Limited, Peterhouse Technology Park, 100 Fulbourn Road, Cambridge CB1 9PT UK (“Acambis Research”) and Baxter Healthcare SA, having offices at Hertistrasse 2, CH-8304 Wallisellen, Switzerland (“BHSA”) and Baxter Healthcare Corporation, having offices at One Baxter Parkway, Deerfield, IL 60015 (“BHC”).

Table of Contents

1.

Recitals

2.

Definitions

3.

Distributorship

3.1

Grant of Distributor Rights in the Territory

3.2

Distribution of Product Outside the Territory

3.3

Marketing Authorisations

4.

Description of Supplies and Services

4.1

Manufacture of Crude Bulk Vaccine

4.2

Purification, Formulation, Fill/Lyophilize/Finish, and Diluent

4.3

Labelling, Syringe, Kitting, Packaging ******

4.4

Bifurcated Vaccinating Needles

4.5

Distribution

5.

Payment & Payment Amount

6.

Title and Risk of Loss

7.

Export/Import Requirements

8.

License & Non-Compete

9.

Audits & Reports

10.

Security

11.

Manufacturing Standards

12.

Limitations of Liability

13.

License Status

14.

Notification Procedures for Adverse Events and Pharmacovigilance

15.

Indemnity & Insurance

16.

Confidentiality

17.

Notices

18.

Term and Termination

19.

Force Majeure

20.

Independent Organizations

21.

Intellectual Property

22.

Regulatory Support

23.

General

Attachment A – Vero Cell Know-How License between Baxter Healthcare SA (Switzerland) and Acambis Inc.( December 02)
Attachment B – Product Pricing Recommendation Table for Sales to Customers
Attachment C – Sample Indemnification Template

1.0

RECITALS

WHEREAS Acambis has developed a lyophilized smallpox vaccine manufactured in vero cells (ACAM 2000 (Acambis)) that is the subject of BB-IND # 10628 filed with the U.S. Food and Drug Administration on August 22, 2002;

WHEREAS Acambis Research intends to market and sell the ACAM 2000 (Acambis) vaccine and the ACAM 2000 (******) vaccine and related components to Governments other than the United States Government and to Non-Governmental Organizations;

WHEREAS Baxter has developed an international sales force to market and make sales to Government and Non-Government Organizations;

WHEREAS, Baxter and Acambis acknowledge that the Product (as hereinafter defined) is not licensed in the Territory. Therefore, due to regulatory and liability reasons, the Product shall not be distributed in the private market under this Agreement;

WHEREAS Baxter has the capability and capacity to manufacture crude vaccine to be processed into ACAM 2000 (Acambis) vaccine and/or ACAM 2000 (******) vaccine; and

WHEREAS Baxter Healthcare SA (BHSA) and Acambis Inc., entered into the Vero Cell Know-How License dated of December 2002 (Attachment A), that provides for the transfer of Baxter’s Vero cell technology for ACAM 2000 to Acambis, Inc.

NOW, THEREFORE, THIS AGREEMENT WITNESSETH that in consideration of the mutual agreements herein set forth and other valuable consideration, the Parties agree as follows:

2.0

DEFINITIONS

In this Agreement, the following terms shall have the following meanings:

“ACAM 2000 (Acambis)” means the vaccine manufactured and tested as described in BB-IND # 10628, as amended from time to time.

“ACAM 2000 (******)” means the vaccine consisting of the same Crude Bulk Product as used for ACAM 2000 (Acambis), but purified at Baxter’s facility ****** and/or filled and finished (wet or lyophilized) under different processes and locations than used to manufacture ACAM 2000 (Acambis).

“Agreement” means this Agreement, including all schedules, appendices, and attachments and amendments agreed to in writing by the Parties;

“Acambis” means Acambis PLC and/or any of its affiliates or subsidiaries, including but not limited to Acambis Research.

“Affiliate” means any company, partnership or other legal entity or person which directly or indirectly controls, is controlled by or is under common control with a Party.

“Baxter” means both BHSA and BHC unless otherwise indicated.

“Control” means the ownership of more than 50% of the issued share capital or the legal power to direct or cause the direction of the Board or general management and policies of the entity in question.

“Customer” means any governmental authority (military or civilian) other than the United States Government, any third party acting on behalf of a governmental authority other than the United States Government, or a Non-Government Organization (NGO). Customer does not include a private individual, doctor, hospital, or physician supply house. The U.S. Government is not a Customer, whether purchasing the Product for its own use or for transfer to a third-party.

“Crude Bulk Vaccine” means cell harvest of vaccinia virus grown on serum free Vero cells that originates from the ACAM 1000 master virus seed and the ACAM 2000 production virus seed.

“Marketing Authorisations” means any and all authorisations required from any Regulatory Authority to officially market, distribute, or sell the Product.

“Net Sales” means the actual total amount invoiced and/or received from a Customer for the sale of any Product after deducting the following costs, provided such costs are attributable to such sale of the Product and are actually borne by the selling Party (whether Acambis Research or Baxter) and are specifically itemized in a commission statement to the non-selling party (Acambis Research or Baxter) and not otherwise incorporated into the sale to the Customer: (i) outbound transportation expenses for shipments to Customers; (ii) taxes consisting of sales, use, turnover, excise, export, import, duties or VAT, separately billed or invoiced and borne by the selling Party imposed by a government agency on such sales; (iii) credit or allowances given or made for Product returned or not accepted by Customers, provided that such credit or allowances shall not exceed the invoiced amount for such Product, (iv) insurance charges covering the Product during transportation to the Customer; (v) trade and/or cash discounts allowed and taken, for reasons such as quantity purchased and (vi) liquidated damages of any kind stipulated in the sales contract payable to a Customer in the Territory, including but not limited to the damage caused by default or delay, provided that Acambis Research has consented according to Article 3.1.4 and 3.1.5.

“Non-Government Organization” means an organization which is independent from the state and is self-governing, nonprofit/not-for-profit and established voluntarily by citizens or by legal entities other than State agencies (i.e., organizations that exercise legislative, executive, and/or judicial powers) on the basis of their individual or social interests and opinions and are associated with organizations such as the United Nations. Examples of Non-Government Organizations are the World Health Organization and the Pan American Health Organization.

“Party” means Acambis Research, BHSA or BHC.

“Parties” means Acambis Research, BHSA, and BHC together.

“Product” means either: (1) a 5,000 dose Smallpox Vaccine Kit containing (a) fifty (50), 100-dose vials of lyophilized ACAM

2000 (Acambis)-vaccine manufactured as described in the Product Specification below; (b) fifty (50) vials of diluent with each vial being sufficient to reconstituted one vial of lyophilized smallpox vaccine; (c) 5,000 bifurcated vaccinating needles; and (d) 50 syringes for transferring the diluent; (hereinafter “Smallpox Vaccine Kit”), (2) a 5,000 dose Smallpox Vaccine Kit containing (a) fifty (50), 100-dose vials of wet (liquid frozen) ACAM 2000 (******) vaccine manufactured as described in the Product Specification below and (b) 5,000 bifurcated vaccinating needles; (both (1) and (2) are hereinafter referred to as “Smallpox Vaccine Kit”) or (3) Crude Bulk Vaccine as described in the Product Specification below that has not been purified, formulated, lyophilized or placed in vials (hereinafter “Crude Bulk Product”).

“Product Specification” means partially purified vaccinia virus produced in a vero cell culture substrate with a final potency sufficient to confer immunity against smallpox as specified in IND BB-10628 as amended from time-to-time or, once US Food and Drug Administration licensure is granted, as specified in such license.

“Regulatory Authority” means any authority having jurisdiction to regulate the manufacture, sale, or distribution of the Product

“Scenario” means the split of responsibility for manufacturing the Product as between Baxter and Acambis Research as defined in Provisions 4.0.1 and 5.3

“Seller” means the Party that sells the Product to a Customer. For sales of Product for delivery to Customers within the Territory, the Seller shall be BHSA or one of its affiliated companies or subsidiaries. For sales of Product for delivery to Customers outside the Territory, the Seller shall be Acambis Research or its designated agent(s)

“Term” shall have the definition given in Section 18.0.

“Territory” , as such term relates to sales to a government authority (military or civilian) or any third-party acting on behalf of a government authority, means all countries worldwide, excluding the United States (and its territorial possessions) and the United Kingdom. “Territory”, as such term relates to sales to Non-Government Organizations, shall mean all countries throughout the world.

3.0

DISTRIBUTORSHIP

3.1

Grant of Distributor Rights in the Territory

3.1.1

     Subject to the terms and conditions of this Agreement, during the Term, Acambis Research hereby appoints BHSA as Acambis’ Research’s exclusive distributor in the Territory for the sole purposes of marketing, promoting, soliciting customers for, distributing, and selling (or otherwise disposing of) the Product to Customers for delivery in the Territory and BHSA accepts such appointment. BHSA may not assign or otherwise transfer its distributorship rights, with the exception as to affiliated companies or subsidiaries. Baxter shall not actively sell or distribute the Product to any entity other than Customers within the Territory. The Parties may however agree on a case by case basis that Baxter uses a local distributor if required by local law, regulations, or Government request.

3.1.2

     Acambis Research shall not, during the Term, appoint any other person, firm, company or other entity as (a) its distributor for the marketing, promotion,or sale of the Product to Customers in the Territory; (b) its distributor for the solicitation of Customers for the Product to be delivered in the Territory; or (c) agent or reseller of the Product to Customers in the Territory.

3.1.3

     Acambis Research shall not, during the Term, market, promote or solicit Customers for, or actively sell or distribute, the Product in the Territory without the prior written consent of BHSA (such consent not be unreasonably withheld or delayed). However, this provision does not restrict Acambis Research from selling the Product in the Territory to persons who are located within the European Union, who are not solicited by Acambis Research and who approach Acambis Research on their own initiative.

3.1.4

     BHSA shall coordinate each potential Customer order with Acambis Research. Prior to signing any agreement or contract for the sale of a Product, BHSA shall inform Acambis Research (in writing and in English) of the material features of such agreement or contract, including but not limited to: customer name, price for the Product, whether the Customer is providing indemnity and the terms of such indemnity, payment terms, which Product is being ordered (Smallpox Vaccine Kits containing ACAM 2000 (Acambis) vaccine, Smallpox Vaccine Kits containing ACAM 2000 (******) vaccine, or Crude Bulk Product), proposed manufacturing and delivery schedule, contractual consequences of delivery delays, potential Marketing Authorization

requirements that are indispensable to the Customer, any regulatory requirements of the Customer or the competent Regulatory Authority(ies) any special labelling requirements, under which Scenario (as set for in Section 5.3 below) the Product will be manufactured, and, if applicable, the Scenario under which the originally delivered liquid ACAM2000 (******) Product will be replaced.

3.1.5

     Each Customer order must be approved by Acambis Research prior to Baxter or its subsidiaries signing any agreement or contract for the sale of Product, such approval shall not to be unreasonably withheld and shall be compliant with applicable laws and regulations. Acambis Research agrees to actively cooperate with Baxter and to use all commercially reasonable endeavours to pursue with such approval.

3.1.6

     BHSA shall inform each Customer in the Territory that the Product: (a) prior to licensure, is intended for emergency use only and is not a licensed product in the Territory or the United Kingdom; and (b) until such time that the Product receives licensure from the US Food and Drug Administration (“US FDA”), is not licensed in the United States.

3.1.7

     Acambis Research has provided BHSA with a recommendation with regard to Customer prices for the Product in the Territory, which is attached to this Agreement as Attachment B (the price recommendations in Attachment B reflect the prices for Customers providing Attachment C indemnity). BHSA shall however not be obliged to follow such recommendations.

3.1.8

     BHSA shall not make or give any promises, warranties, guarantees or representations concerning the Product other than those contained in BB-IND # 10628 and/or in Acambis Research’s product literature and shall provide the Customer with a detailed outline description of the qualities and specifications of ACAM 2000 (******) vaccine and ACAM 2000 (Acambis) vaccine. Baxter and Acambis Research shall jointly create a document that shall be provided to each Customer which outlines the differences of ACAM 2000 (Acambis) compared to ACAM 2000 (******). Baxter shall market the ACAM 2000 (Acambis) vaccine only for the indications authorised by the US FDA and, if applicable, may market the ACAM 2000 (******) vaccine only for those indications as authorized by the competent Regulatory Authority(ies) in the Customer’s territory. Baxter shall market the ACAM 2000 (Acambis) vaccine as Acambis vaccine and not represent or otherwise give the appearance to a Customer that the ACAM 2000 (Acambis) vaccine is a Baxter vaccine.

3.1.9

     If Acambis Research believes that BHSA is not using all reasonable endeavours to market and promote the Product in a country of the Territory or is not otherwise complying with its obligations under this Agreement in a country in the Territory (the “Neglected Country”), Acambis Research may provide written notice thereof to BHSA, specifying the basis of its belief and any additional commercial activities Baxter should reasonably undertake. Within 30 days of such notification, the Parties shall meet and discuss in good faith the steps Baxter is taking to market and promote the Product and any such additional activities BHSA should commercially reasonably undertake. In the event that the parties are unable to agree on such additional activities or if BHSA does not undertake agreed upon remedial steps to remedy any default within 60 days of notice, Acambis Research may terminate the assignment of BHSA being the exclusive distributor as set forth in Art 3.1.1 of this Agreement in the Neglected Country and such Country shall be excluded from the Territory.

3.1.10

     Provided that Acambis Research has consented according to Article 3.1.4 and 3.1.5, BHSA may offer to Customers who have been provided with liquid frozen Product the subsequent delivery of lyophilised Product at no charge. After the free delivery of the lyophilised Product, BHSA shall be responsible for it’s disposal. BHSA may not resell such liquid frozen Product.

3.1.11

     BHSA shall not promote, make sales or otherwise engage in negotiations related to the Product to any country, identified as acting contrary to the foreign policy and national security goals of the U.S., restricted under internal policy or in contravention of any international conventions established by the United Nations, including but not limited to the list of countries that the US Secretary of State has made a determination (that remains in effect) that such country has repeatedly provided support for acts of international terrorism. At the time of signing this Agreement, that list is: Iran, Iraq, Libya, Syria, Cuba, North Korea, and Sudan.

3.1.12

     Should during the term of this Agreement or thereafter Acambis decide to market the Product to private individuals or entities outside the United States or its territories, or the United Kingdom, then the Parties shall enter into good faith discussions as to whether it might be agreeable to use Baxter as a potential distributor.

3.2

Distribution of Product Outside the Territory

3.2.1

     BHSA shall not, during the Term, market, promote or solicit persons for, or actively sell or distribute, the Product outside the Territory without the prior written consent of Acambis Research (such consent not be unreasonably withheld or delayed).

However, this provision does not restrict BHSA from selling the Product outside the Territory to Customers who are located within the European Union, who are not solicited by Baxter and who approach Baxter on their own initiative. Such sales will be subject to the same payment obligations as sales within the Territory as set out in Section 5 below. Baxter may cooperate with or provide sales assistance to Acambis to promote the Product to Customers outside the Territory, however, absent written agreement to the contrary, Baxter shall not receive payment for such cooperation or sales assistance in addition to the split of Net Sales addressed in provision 5.3 below.

3.3

Marketing Authorisations

3.3.1

ACAM 2000 (Acambis)  

3.3.1.1

     Acambis shall initially have the right to file for any Marketing Authorization(s) with respect to ACAM 2000 (Acambis). Should Acambis decide, in its sole discretion, to apply for and obtain a Marketing Authorization in a country or region, then Acambis will be responsible for filing and maintaining the Marketing Authorization(s) for ACAM 2000 (Acambis) and shall bear all related costs. If (1) Acambis decides to not apply for or obtain a Marketing Authorization in a specific country or region or (2) Baxter or any Baxter affiliate is required by law or government request to apply for a Marketing Authorization in any country, then Acambis and BHSA shall consult to jointly decide if a Marketing Authorization in this particular country is commercially justified from a business perspective. Acambis shall not unreasonably refuse to file and maintain the Marketing Authorization(s) for ACAM 2000 (Acambis) nor shall it unreasonably refuse to allow Baxter or any Baxter affiliate to file for a Marketing Authorization under the circumstances of (2) above.

3.3.1.2

     If obtaining a Marketing Authorization for a certain country or region is not commercially justified from a business perspective and Acambis elects not to file for such Authorization, Baxter may apply for and obtain such Marketing Authorization(s) and shall bear all related costs.

3.3.1.3

     Baxter shall provide all documents to Acambis (either in English or German) required for Acambis to apply for and obtain such Marketing Authorization(s). Baxter shall not be required to provide any document or information that is not in its possession or that Baxter is not entitled to disclose to Acambis.

3.3.2

ACAM 2000 (******)

3.3.2.1

     If (1) Baxter or any Baxter affiliate is required by law or government request to apply for and obtain a Marketing Authorization for ACAM 2000 (******) or (2) Baxter determines that it wants to apply for and obtain a Marketing Authorization for ACAM 2000 (******), Baxter may do so. Should Baxter decide to apply for and obtain a Marketing Authorization for ACAM 2000 (******), Baxter shall bear all related costs.

3.3.2.2

     If, in the first instance discussed in Provision 3.3.2.1 above, Baxter decides not to apply for and obtain a Marketing Authorization, then Acambis and BHSA shall consult to jointly decide if a Marketing Authorization in this particular country is commercially justified from a business perspective.

3.3.2.3

     Acambis shall provide all documents to Baxter (in English) required for Baxter to apply for and obtain such Marketing Authorization(s). Acambis shall not be required to provide any document or information that is not in its possession or that Acambis is not entitled to disclose to Baxter.

3.3.3

     At the conclusion or termination of this Agreement, BHSA shall transfer all ACAM 2000 (Acambis) Marketing Authorizations acquired under this Article and all materials obtained from Acambis Research hereunder to Acambis Research. Such transfer shall be at no charge to Acambis Research other than Acambis Research shall reasonably compensate BHSA for it’s transfer activities relating to transferring the Marketing Authorization(s) from BHSA’s name to Acambis’ name.

4.0

DESCRIPTION OF SUPPLIES AND SERVICES

4.0.1

     The division of manufacturing responsibilities described in Provisions 4.1 through 4.5 below shall be divided between Baxter and Acambis Research as indicated in the Scenarios set forth in provision 5.3 below. Baxter and Acambis Research shall agree on which Scenario will be utilized for each sale of the Product prior to either Party executing any agreement with a Customer. If the division of manufacturing responsibilities proposed by the Seller is not included in the provision 5.3 Scenarios, Baxter and Acambis Research shall negotiate in good faith to reach a reasonable split of the Net Sales based on their relative contributions to

manufacturing the Product.

4.0.2

     The cost for performing the manufacturing responsibilities as detailed in the various Scenarios shall be borne by the Party having the responsibility for performing such responsibilities.

4.0.3

     Baxter and Acambis agree that they will use the highest diligence reasonable in performing their respective responsibilities under this Agreement.

4.0.4

     BHSA agrees to inform Acambis within fifteen (15) calendar days of the result of any regulatory development or material change to the Vero Cell Master File. BHSA shall be responsible for all costs related to the creation and maintenance of the Vero Cell Master File.

4.0.5

     Acambis, as the IND (and later product license) holder for the ACAM 2000 (Acambis) vaccine in the United States, shall be responsible for reporting any biological Product deviations to the US FDA under 21 CFR 600.14 and shall bear all costs related to licensure of ACAM 2000 (Acambis) vaccine in the United States. Baxter agrees to inform Acambis of any deviations that might be reportable under 21 CFR 600.14 within ten (10) calendar days of obtaining such information.

4.0.6

     The Party who is the Marketing Authorization holder for ACAM 2000 (Acambis) vaccine or ACAM 2000 (******) vaccine for the Marketing Authorization in a country other than the United States shall be responsible for all reports required by the relevant Regulatory Authority(ies) arising out of product deviations. The non-Marketing Authorization holding Party agrees to inform the Marketing Authorization holding party of any reportable deviations within ten (10) calendar days of obtaining such information.

4.0.7

     For ACAM 2000 (******) vaccine distributed by Baxter under this Agreement, Acambis shall provide all reasonably necessary materials, documents and assistance (not including 3d party proprietary information) to support the technical transfer of purification and formulation activities from Acambis to Baxter. Baxter shall perform any and all pre-clinical studies and clinical trials (bridging or otherwise) required to meet any and all regulatory requirements in the Territory should the Parties decide to market such ACAM 2000 (******) vaccine in a particular country in the Territory. However, nothing in this Provision 4.0.7 shall negatively impact orders for ACAM2000 (Acambis) smallpox vaccine from the United States Government.

4.0.8

     For ACAM 2000 (Acambis) vaccine, the Marketing Authorization holder is responsible for all pre-clinical studies and clinical trials required by the relevant Regulatory Authority. For those countries where Baxter is authorized by Acambis to be the Marketing Authorization holder, Baxter shall provide information related to such non-US product Marketing Authorization, pre-clinical studies, and/or clinical trials to Acambis as required by the US FDA.

4.0.9

     Each Party agrees to provide and maintain quality systems according to cGMP and to provide the other Party access to its facilities at all reasonable times for surveillance.

4.1

Manufacture of Crude Bulk Vaccine

4.1.1

Crude Bulk Vaccine shall be manufactured either at *********

4.1.2  

     Whether manufactured by BHSA or Acambis Research, each lot of Crude Bulk Vaccine shall be manufactured:

     (a)

from cGMP compliant master and production Vero cell banks so as to be acceptable to the US FDA as licensed product;

     ********

     (d)

in compliance with current Good Manufacturing Process (cGMP).

4.1.3

     If the Customer orders Crude Bulk Product, the manufacturer of the Crude Bulk Product shall package the vaccine for shipment to the customer in accordance with commercial practice to ensure safe delivery by common carrier to the destination agreed to between the selling Party and the Customer. The bulk vaccine shall also be packaged in accordance with all applicable federal, state and local rules and regulations, and the applicable rules and regulations of the importing country. ************

4.1.4

The Manufacturer of the Crude Bulk Vaccine shall also perform quality control testing on the Crude Bulk Vaccine as required by BB-IND # 10628, any subsequent US FDA license for ACAM 2000 (all as amended from time to time), and any additional QC tests required by the US FDA.

4.1.5

Use of BHSA ACAM 2000 Lots Manufactured under the US Government Subcontract for Sales to Customers.

4.1.5.1

After BHSA has completed its contractual responsibilities under Subcontract 200-2002-00010(BXTR) from the BHSA Lots of Crude Bulk Vaccine, Baxter and Acambis shall utilize excess Crude Bulk Vaccine remaining from the Lots manufactured under the Subcontract as product “manufactured” under this Agreement unless otherwise agreed. In order to be tendered under this Agreement as manufactured product, the Crude Bulk Vaccine from such Lots must meet the requirements and specifications of both Subcontract 200-2002-00010(BXTR), as modified from time-to-time, and this Agreement.

4.1.6

Manufacture of Crude Bulk Vaccine at BHSA  

4.1.6.1

If the excess Crude Bulk Vaccine from the Baxter ACAM 2000 Lots manufactured under the US Government Subcontract are not sufficient to meet orders from Customers, Baxter and Acambis Research may agree that BHSA may manufacture additional lots of Crude Bulk Vaccine . Permission from Acambis to manufacture additional Crude Bulk Vaccine shall be granted only in writing and on a lot by lot basis.

4.1.6.2

If BHSA and Acambis Research agree to manufacture additional Crude Bulk Vaccine under provision 4.1.6.1 above, Acambis Research and BHSA shall agree on a schedule for such production. Such schedule shall be based upon the following criteria: Customer requirements, availability of Acambis’ facilities, availability of Baxter facilities, the demands of other Customers, and the demands of the U.S. Government.

*****If BHSA and Acambis Research agree to manufacture additional Crude Bulk Vaccine under provision 4.1.6.1 above and such bulk vaccine is to be formulated and purified at Acambis *****, BHSA shall provide the anticipated date of shipment to Acambis at least ten (10) working days prior to the shipment. Acambis shall obtain, at its own risk and expense, any import license or other official authorisation and carry out, where applicable, all customs formalities for the import of the goods. BHSA shall assist Acambis in obtaining such import license or other authorisations necessary for the import of the Crude Bulk Vaccine. Legal title to such Crude Bulk Vaccine shall pass according to Art. 6 of this Agreement. BHSA shall be responsible for the risk of loss and costs of insurance, freight, and transportation to Acambis’ facility in Canton, Massachusetts.

4.1.6.4     If BHSA ships Crude Bulk Vaccine to Acambis’ Canton facility, BHSA shall provide preliminary results of ****tests for all crude bulk lots by facsimile message within ******* of shipping Crude Bulk Vaccine to Acambis’ Canton facility and a Certificate of Analysis ***** shipping the Crude Bulk Vaccine. BHSA shall also provide finalized production batch records to Acambis within **** shipping the Crude Bulk Vaccine.

4.1.6.5     BHSA agrees to inform Acambis within ******of the result of any regulatory development or change to Crude Bulk Vaccine-specific standard operating procedures that materially affect the production of Crude Bulk Vaccine. BHSA shall notify Acambis of any required written approval from Acambis to change the master batch records and Crude Bulk Vaccine specifications prior to the production of subsequent lots of Crude Bulk Vaccine.

4.1.7

Manufacture of Crude Bulk Vaccine at Acambis’ Canton Facilities

4.1.7.1

After transferring the Vero Cell technology to its facility in Canton Massachusetts, Acambis may manufacture Crude Bulk Vaccine in accordance with the terms of the Vero Cell License Agreement and this Agreement. The Parties agree however, that Crude Bulk Vaccine manufactured at Baxter’s facilities in Orth under Acambis license shall be utilized for sales under this Agreement by the Parties to the extent feasible under import or export laws before Crude Bulk Vaccine manufactured at Acambis facilities in Canton shall be utilized.

4.2.0

Purification, Formulation, Fill/Lyophilize/Finish, and Diluent

4.2.0.1

Prior to executing an agreement or contract for the sale of Product to Customers in the Territory, Acambis Research and BHSA shall agree on a schedule for purification, formulation, fill/lyophilize or manufacture liquid frozen Product/finish, and, if applicable, provision of diluent under this Agreement. Such schedule shall be based upon the following criteria: Customer requirements, availability of Acambis’ facilities, availability of Baxter facilities, availability of bifurcated vaccinating needles, and the demands of other Customers and the U.S. Government.

4.2.1

Purification and Formulation

4.2.1.1

After manufacture of the Crude Bulk Vaccine, Acambis shall purify, formulate and perform all other required downstream processing (including quality control testing as required by BB-IND #10628 as amended from time to time and as further required by the US FDA) of the delivered Crude Bulk Vaccine such that the Crude Bulk Vaccine may be filled, lyophilized, and finished as ACAM 2000 (Acambis) vaccine.

4.2.1.2

Such purification and formulation shall be done in accordance with BB-IND # 10628 (as amended from time-to-time) and as further required by the US FDA.

4.2.2

Fill/Lyophilize/Finish

4.2.2.1

Following purification and formulation of the Crude Bulk Vaccine, Acambis shall provide for the fill, finish, and lyophilization of the Purified Bulk Vaccine. Acambis shall also provide quality control testing as required by BB-IND #10628 (as amended from time-to-time) and as further required by the US FDA.

4.2.2.2

Such fill and finish shall be done in accordance with BB-IND # 10628 (as amended from time-to-time) and cGMP.

4.2.3

Diluent

4.2.3.1

Acambis shall provide diluent in vials, each of which is sufficient to reconstitute 100 doses of lyophilized ACAM 2000 (Acambis) vaccine, in accordance with the conditions and specifications in BB-IND # 10628 (as amended from time-to-time) and cGMP.

4.2.4

Purification, Formulation, Fill/Lyophilize or manufacture liquid frozen Product/Finish, and Diluent by Baxter

4.2.4.1

To the extent Acambis licenses Baxter to purify and formulate ACAM 2000