Bilateral Supplemental Agreement

Subcontract Number: 200-2002-00012(CBL) (PO 28890)

Modification Number: 0003

Effective Date: This Subcontract modification is effective as of the last signed date below.

Subcontractor:

Chesapeake Biological Laboratories, Inc.

1111 S. Paca Street

Baltimore, MD 21230-2591

Authority for, and type of, modification: Bilateral Supplemental Agreement

Description of Modification:

Clause B.1

Increases the “Firm Fixed Price” and the “Total Amount” to account for a supplemental payment for third fills under Item 0001A

Clause B.2

Changes “Quantity” from ten months to the “period of performance” of Item 0002

Table 1

Adds ******* supplemental payment for each third fill under Item 0001A product

Clauses B.4, B.5,

Clarifies that the “Estimated Quantity” is stated in vials

and B.6

Clause B.8

Adds provision for the General Release and invoicing for such release

Clause E.1

Clarifies the acceptance procedure for filled vials (paragraphs (c) and (d))

Clause F.1(b)

Clarifies the timing of the Item 0001B change-over and modifies the Item 0004B

delivery date  

Clause F.2

Modifies the period of performance for Items 0001A, 0001B, 0002, 0003A,

0003B, 0004A, and 0004B

Clause G.1

Deletes reference to general safety and microbial limits test and adds a reference to paragraph H.3.1 in paragraph (xiii) (paragraph (2)), clarifies acceptance procedures (paragraph (3)) and adds a Government/Buyer Property provision (paragraph (4)).

Clause G.2(f)

Modifies the ordering periods for Items 0003A, 0003B, 0004A, and 0004B.

Clause H.3

Modifies missed fill provision and deletes “partial fill” underutilization fee

Clause H.3.1

Adds provision relating performing scheduled fills (Item 0001A three per week, two per week thereafter (exclusive of make-ups)) and potential extensions to the filling period

Clause H.4

Modifies guaranteed payment and advance payment provisions

Clause H.5

Modifies planned schedule and notification of bulk vaccine shipment provisions

Modification 0003

Clause H.6

Replaces Validation of Consistency of Manufacture provision

Clause H.6.1

Adds provision *******

Clause H.17

Modifies property provision to cover Buyer-furnished property

Section J

Modifies Attachments to include new planned vaccine schedule, Buyer-Furnished

Property, Modification 0003 general release, and Statement of Work Modification

0001

Total Change to Subcontract Amount:

Item 0001A

*******

*******

Item 0002

*******

*******

Item 0008

*******

*******

Changes to Subcontract:

See attached Pages 1 - 19

ACAMBIS, INC.

CHESAPEAKE BIOLOGICAL LABORATORIES, INC

__________________________

__________________________

*******

*******

*******

*******

December 31, 2002

December 30, 2002

Section B

1.

Delete Items 0001A, 0002, 004A, 005A, 006

Substitute:

B.1

SUBCONTRACT LINE ITEM 0001A

Vaccine for Use as an Investigational New Drug (“IND”)

US Government ACAM 2000 Program

Estimated

Description

Firm Fixed Price

Quantity

Total Amount

Fill, Lyophilize,

See Table 1

1,550,000

*******

Finish and Perform

for per vial

vials

+

Specified Quality Control

charge and

*******

Tests For Vaccinia (ACAM2000)

Supplemental

IND Vaccine as Described

Payment for 3rd

In the Vaccine Statement of Work

Fills

SUBCONTRACT LINE ITEM 0001B

Change-over of Manufacturing Facilities

Description

Firm Fixed Price

Quantity

Perform All Activities

*NSP

1

Required to Clean Up

Facility After Filling

ACAM 2000

* The change-over fee for Item 0001B is included in the “per vial” price for    Item 0001A.

B.2

SUBCONTRACT LINE ITEM 0002

Manufacturing Time to Fill, Lyophilize, and Finish Vaccinia IND Vaccine(s)

Quantity

Description

Firm Fixed Price

(months)

Total Amount

Manufacturing Time

See Paragraphs

See Paragraph

As Ordered

to Fill, Lyophilize,

B.2(a) & (b)

F.2 (Period of

Finish and Perform

below

Performance)

Specified Quality Control

Tests For Vaccinia IND

Vaccine as Described

In the Vaccine Statement of Work

(a)  

For manufacturing time utilized to fill and finish ACAM 1000 vaccine under Item 0002, the price shall be ******* per vial (utilization of Item 0002 for filling and finishing ACAM 1000 vaccine is subject to Government approval).

(b)  

For manufacturing time utilized to fill and finish ACAM 2000 vaccine under Item 0002, the price shall be as set forth in Table 1 below.

(c)

See Section H.4 regarding guaranteed payment terms.

* Plus ******* supplemental payment for each ******* (applicable to Item 0001A only) (See Provision H.3.1)

B.4

SUBCONTRACT LINE ITEM 0004A (Indefinite Delivery/Indefinite Quantity) Diluent to Accompany ACAM 1000 IND Vaccine

Estimated

Estimated

Description

Firm Fixed Price

Quantity

Total Amount

Manufacture, Fill,
Finish, and Perform
Quality Control Tests
for Diluent as Described
in the Diluent Statement of Work

*******

538,500
vials

*******

(a)  

Orders under Item 0004A are subject to Government approval.

(b)

See Section G.2 for ordering provisions.

B.5

SUBCONTRACT LINE ITEM 0005A (Indefinite Delivery/Indefinite Quantity)
Approved Vaccine (after receipt of Biologics License)

Description

Firm Fixed Price

Quantity

Total Amount

Fill, Lyophilize,
Finish and Perform
Specified Quality Control
Tests For Licensed ACAM
1000 or 2000 Vaccine as
Described In Statement of
Work

*******

(Vials

as Ordered)

(As Ordered)

(a)  

The estimated quantity is ******* vials of vaccine. This is Buyer’s current best estimate of the quantities that may be ordered. The actual amounts ordered may be more or less.

(b)

See Section G.2 for ordering provisions.

B.6

SUBCONTRACT LINE ITEM 0006 (Indefinite Delivery/Indefinite Quantity)
Diluent to Accompany Approved Vaccinia Vaccine(s)
(after receipt of Biologics License)

Description

Firm Fixed Price

Quantity

Total Amount

Manufacture, Fill,
Finish, and Perform
Quality Control Tests
For Diluent as Described
in Statement of Work

*******

(Vials as
Ordered)

(As Ordered)

(a)  

Estimated Quantity - The estimated quantity is ******* vials of diluent. This is Buyer’s current best estimate, but the number ordered may be more or less.

(b)

See Section G.2 for ordering provisions.

2.

Add Item 0008

B.8

SUBCONTRACT LINE ITEM 0008
General Release (Section J, Attachment I)

Item 0008AA

Total Amount

Reservation of Manufacturing
Capacity in August
and September 2003

*******

(a)  

Buyer shall make payment for Item 0008AA within 10 calendar days of receipt of invoice or January 20, 2003, whichever is later.

Item 0008AB

Total Amount

All Other Aspects Covered by
the General Release Not Included
in Item 0008AA

*******

(a)  

Buyer must make payment for Item 0008AB within 10 calendar days of receipt of invoice or January 20, 2003, whichever is later.

1.

Delete Provision E.1

Substitute:

E.1

INSPECTION, QUALITY ASSURANCE, AND ACCEPTANCE

(a)

Inspection and acceptance of the articles, services, and documentation called for herein shall be accomplished by the Contractual Officer, or his duly authorized representative (who for the purposes of this Subcontract shall be the Program Officer) at the destination of the articles, services or documentation.

(b)

Each order tendered for acceptance shall include a Certificate of Conformance (See Section J, Attachment F), properly executed by the Manufacturer. A copy of the Certificate of Conformance shall also be included with Manufacturer’s invoice following Buyer’s inspection and acceptance of each order.

(c)

Approval of Manufacturer’s final batch records shall constitute “acceptance.”

(d)

Buyer will accept delivered filled vials that conform to Subcontract requirements. A filled vial shall be considered to conform to Subcontract requirements if its manufacture conforms to good manufacturing practices and does not materially deviate from the approved Master Batch Records or standard operating procedures. A “material deviation” is one that causes the product to fail to meet the Buyer’s release criteria.

(e)

On site inspections of the physical plant may be conducted by the Buyer, the Government and/or their duly authorized representatives and other designated technical experts. Plant inspection, at a minimum, will include Device Master Records, document control procedures, facilities, personnel training records, equipment process procedures, and Quality Assurance Program reviews. Further, the on site representative(s), if designated, will perform the inspection and acceptance of articles, services and documentation contained in (a) above.

(f)

In addition to the inspections discussed above, Buyer may conduct one full-scale GMP audit per year. Buyer may conduct additional full-scale GMP audits if the parties mutually agree or in the instance of a product failure, deviations from acceptable production practices, or any other occurrence that calls the product’s quality or integrity into question.

(g)

Manufacturer agrees to provide and maintain a quality control system acceptable to Buyer and the Government and to provide access to Manufacturer’s facilities at all reasonable times for surveillance periodically by Buyer and authorized representatives of the Government. Manufacturer agrees to include, and to require its subcontractors to include, the substance of this paragraph, including this sentence, in each of its subcontracts under this Subcontract.

1.

Delete Provision F.1(b)

Substitute:

(b)

The Manufacturer shall deliver, within the time frames specified, the Items set forth below.

No.

Description

Delivery Date

1

Vials of IND ACAM 2000 per Subcontract Item 0001A

As scheduled in accordance with provision H.5

2

Change-over per Subcontract Item 0001B

At the completion of filling ACAM 2000

3

Vials of IND ACAM 1000 and/or ACAM 2000 per Subcontract Item 0002

As scheduled in accordance with provision H.5

4

Change-over(s) per Subcontract Item 0003A and/or 0003B

At end of each Item 0002 product campaign(s)

5

Vials of IND Diluent to accompany ACAM 1000 vaccine per Subcontract Item 0004A

Concurrent with delivery of Item 0002 ACAM 1000 vaccine to which the diluent relates or, if no related vaccine, as mutually agreed between Buyer and Manufacturer prior to Issuance of the Delivery Order.

6

Vials of IND Diluent to accompany ACAM 2000 vaccine per Subcontract Item 0004B

Concurrent with delivery of Item 0002 ACAM 2000 vaccine to which the diluent relates or, if no related vaccine, as mutually agreed between Buyer and Manufacturer prior to issuance of the Delivery Order.

7

Vials of ACAM 1000 or 2000 per Subcontract Item 0005A

As agreed upon between Buyer and Manufacturer prior to Issuance of the Delivery Order.

8

Change-over(s) per Subcontract Item 0005B

At end of Item 0005A product campaign(s)

9

Vials of Diluent per Subcontract Item 0006

As agreed upon between Buyer and Manufacturer prior to Issuance of the Delivery Order.

2.

Delete Provision F.2

Substitute :

F.2

PERIOD OF PERFORMANCE

(a)

The period of performance for this Subcontract will be from Subcontract Award until January 31, 2007.

(b)

The period of performance for:

(i)     Item 0001A is from April 11, 2002 until delivery of 1,550,000 vials of lyophilized ACAM 2000 that qualify for final product release by the Buyer or September 1, 2003 (as extended by any fills to be made up by the Manufacturer under H.3.1), whichever is earlier (the completion date for Item 0001A);

(ii)    Item 0002 is from the completion date for Item 0001A to September 1, 2003, as extended in accordance with H.3.1 (the completion date for Item 0002); and

(iii)   Item 0004A and 0004B is from April 11, 2002 to October 1, 2004.

(c)

The period of performance for Items 0001B, 0003A, and 0003B facility change-overs will not exceed 30 calendar days after completion of prior vaccine campaign fill with the last of such change overs being completed no later than thirty days after the completion date for Item 0001A or Item 0002, whichever is later.

(d)

The period of performance for Items 0005A, 0005B, and 0006 will be negotiated with the Manufacturer prior to award of the delivery order(s).

(e)

The actual period of performance for delivery orders may extend beyond the Subcontract period of performance.

1

Delete Provision G.1

Substitute :

G.1

INVOICE/VOUCHER SUBMISSION

(1)

The Manufacturer shall submit an original and four (4) copies of contract invoices to the following address:

Acambis, Inc.
(Attn: Accounts Payable)
38 Sidney Street
Cambridge, MA. 02139

(2)

The Manufacturer shall include the following information with each invoice:

i.

Manufacturer’s Name & Address;

ii.

Manufacturer’s Tax Identification Number (TIN);

iii.

Subcontract and Purchase Order Number;

iv.

Invoice Number;

v.

Invoice Date;

vi.

Contract Line Item Number (per Section B) and Delivery Order Number Shown on each Delivery Order;

vii.

Quantity, including (if applicable) specifying the number of vials of vaccine and diluent actually filled and delivered;

viii.

Unit Price & Extended Amount for each line item, including the Fixed Price Billed based upon the actual number of vaccine and/or diluent vials filled and delivered;

ix.

Total Amount of Invoice;

x.

Name, title and telephone number of person to be notified in the event of a defective invoice;

xi.

Payment address, if different from the information in (2)i. Above;

xii.

A copy of the Certificate of Conformance (See Section J, Attachment G) signed by the Manufacturer for each batch of vaccine and/or diluent tendered for acceptance or for change over of manufacturing facility; and

xiii.

If the invoice includes an amount due under Clauses H.3, H.3.1, H.4, or H.6 a description and a calculation for such amount.

(Any invoice submitted without required Certifications shall be considered defective and returned to Manufacturer without payment.)

(3)

Manufacturer may invoice twice monthly for delivered and accepted products and related services. For this purpose, products and related services are “delivered” if the Manufacturer has completed the certificate of analysis and the certificate of conformance and the filled vaccine and/or diluent vials are available for pick up by Buyer’s designee. Acceptance shall be evidenced by Buyer’s approval of the final batch records.

(4)

Together with Manufacturer’s final invoice for Subcontract Items,

Manufacturer shall submit a list of all property supplied to Manufacturer as Buyer-furnished property and a certification that all Buyer-furnished property has either been consumed as an expendable materials in performance of the Subcontract or returned to the Buyer.

2.

Delete Provision G.2(f)

Substitute :

(f)

Ordering Periods

(i)    Items 0003A and 0003B – From Contract Award until 30 days after the completion date of Item 0001A or Item 0002, whichever is later.

(ii)   Items 0004A and 0004B –  From Contract Award until October 1, 2006.

(iii)  Items 0005A and 0005B and 0006 – From Receipt of BLA until January 31, 2007.

3.

Delete Provision G.7

Substitute:

G.7

BUYER’S OBLIGATION TO PAY

Buyer agrees to make timely payment on the payment dates set forth in this Agreement. In addition, unless the Subcontract specifies otherwise, Buyer agrees to make payment within thirty (30) calendar days of receipt of a properly submitted invoice or voucher.

Timely payment is essential to this Agreement. Should Buyer fail to pay a proper invoice (including batch records that are accepted, approved, and not disputed by the Buyer) within 30 days of receiving such invoice, Manufacture shall provide notice of such non-payment to Buyer. Buyer’s repeated failure to cure non-payments within 15 days of receiving notice from the Buyer will be a material breach of the Agreement.

Section H

1.

Delete Provision H.3

Substitute:

H.3

MISSED FILL FEES (ITEM 0001A IND ACAM 2000 VACCINE)

(a)

Buyer shall provide the Manufacturer with sufficient bulk vaccine product to perform the number of fills per week during the Item 0001A period as shown in Section J, Attachment G.

(b)

Buyer will pay Manufacturer a “missed fill” fee of ******* whenever Buyer fails to provide sufficient bulk vaccine product to Manufacturer, or fails to make available sufficient Baxter personnel as required under Section H.6.2, in order for Manufacturer to perform three fills per week for any week scheduled for three fills (Section J, Attachment G) from the date of the first signature on Modification 0003 to the completion date of Item 0001A.

(c)

If the Buyer fails to provide the Manufacturer sufficient bulk vaccine product to enable the Manufacturer to fill either or both of the other two fills scheduled for any week, Buyer will pay the Manufacturer ******* for each of those two fills missed.

(d)

Manufacturer may invoice for the “missed fill” fee (paragraphs (b) and (c)above) at the conclusion of each one-week period (Monday through Sunday) during the Item 0001A period of performance.

2.

Add Provision H.3.1

H.3.1

MANUFACTURER’S COMMITMENT TO PERFORM SCHEDULED FILLS

(a)

Missed Fills (Items 0001A and 0002)

If Manufacturer misses any fill scheduled during a week (See Section J, Attachment G) and Manufacturer has product to perform that fill, that missed fill shall be made up by either (1) performing five fills within any two week period during the Item 0002 period of performance, or (2) extending the Item 0002 period of performance to make up the missed fills not yet made up. However, the Item 0002 period of performance shall not be extended in the event the missed fill is caused by Buyer’s failure to provide sufficient bulk vaccine product.

(b)

Supplemental Payment for Three Fills in a Week (Item 0001A)

(i)     Manufacturer shall perform three fills of bulk vaccine product each week (Monday through Sunday) from January 6, 2003 to the completion date for Item 0001A (the “Three Fill Period”), as illustrated in the attached Subcontract Schedule (Section J, Attachment G). Buyer shall pay Manufacturer ******* each time the Manufacturer performs three fills in a one week period during the Three Fill Period.

(ii)     The Manufacturer has the right to miss a third fill during any given week by performing only two fills in that week. For each week during the Three Fill Period that Manufacturer elects to perform only two fills, Manufacturer shall make up the missed third fill as specified in subparagraph (a) above. Buyer shall pay Manufacturer ******* each time Manufacturer performs a make-up third fill. During the Three Fill Period, Manufacturer shall not miss more than six third fills when Buyer has provided Manufacturer with vaccine product to fill.

(iii)      Manufacturer may invoice for the supplemental ******* payment under subparagraphs (a) and (b) above at the conclusion of each week during which a third fill is performed.

3.

Delete Provision H.4

Substitute:

H.4

GUARANTEED PAYMENT AND ADVANCE PAYMENTS (ITEM 0002   IND ACAM 1000 VACCINE AND/OR IND ACAM 2000 VACCINE)

(a)      Guaranteed Payment. Buyer shall make payments totaling at least the guaranteed minimum total payment of $5,000,000 for vaccinia vaccine fills under Item 0002. If, through Buyer’s failure to provide bulk vaccine, Manufacturer is unable to fill sufficient vaccinia vaccine to generate a revenue of at least $5,000,000 under Item 0002, Manufacturer is entitled to a payment measured by the difference between $5,000,000 and the total amount Manufacturer was paid for vaccine filled under Item 0002.

(b)      Nonrefundable Advance Payments.

(i)     Manufacturer may invoice Buyer ******* after January 15, 2003 as a nonrefundable advance payment of a portion of the minimum total payment guaranteed under Section H.5(a).

Modification 0003

(ii)     If Buyer fails to provide sufficient vaccinia vaccine to generate payments of at least ******* for each period from the 1st to the 15th day and the 16th to the last day of each month, from May 1, 2003 to September 1, 2003 ******* for vaccine filled under Item 0002 and change-overs under Items 0003A or 0003B, Manufacturer will be entitled to an advance payment. Such advance payment will be equal to the difference between ******* and payments made to the Manufacturer under Items 0002, 0003A and/or 0003B for that half-month period. Manufacturer may invoice for these advance payments on the 15th and the last day of each month from May 2003 through and including August 2003 until Manufacturer’s total amount paid under Item 0002 equals the minimum payment guaranteed under Item 0002 of $5,000,000.

(iii)      Advance payments made under paragraphs (i) and (ii) above shall be applied against future invoices as a credit to the Buyer.

(iv)     Once payments made under Item 0002 equal or exceed $5,000,000, Manufacturer shall not be entitled to further advance payments under this Section H.4(b) and the then-current amount of advanced payments made shall continue to be credited to the Buyer on future invoices, as described above.

(c)     Supplemental payments ******* per third fill) made under Provision H.3.1 for ACAM 2000 vaccine filled during the Item 0002 period shall not be included in calculating amounts under this Provision H.4.

4.

Delete Provision H.5

Substitute:

H.5

PLANNED DATES FOR VACCINE FILL, LYOPHILIZATION, FINISH, AND CHANGEOVER

(a)

For planning purposes, the anticipated dates for the fill, lyophilization, and finish of ACAM 2000 under Item 0001A from December 16, 2002 to the completion of the Item 0001A period of performance and fill of vaccinia vaccine under Item 0002 are attached. (see Section J, Attachment G).

(b)

Buyer will provide Manufacturer notice of the tentative date for shipment of bulk vaccine no later than fourteen (14) calendar days prior to shipment and the actual planned date for shipment of bulk vaccine to Manufacturer no later than seven (7) calendar days prior to the anticipated shipment date. Manufacturer shall fill all bulk vaccine as soon as reasonably practicable based on a fill schedule of at least two completed fills per week.

(c)

Buyer will provide Manufacturer at least 20 days notice prior to the initiation of any changeover under Items 0001B, 0003A, 0003B, and/or 0005B.

5.

Delete Provision H.6

Substitute:

H.6

VALIDATION OF CONSISTENCY OF MANUFACTURE

Manufacturer shall demonstrate consistency of its fill, finish and lyophilization process by manufacturing three (3) consecutive consistency lots of ACAM 2000 vaccine that conform to subcontract requirements. Acambis will notify CBL, in advance but no later than June 10, 2003, which lots are intended as consistency lots. Manufacturer shall be paid ******* for each consistency lot manufactured prior to demonstrating consistency of manufacturing. For the three successful consecutive lots that demonstrate consistency of manufacture, Manufacturer shall also be paid upon completion of the third successful lot, the difference between the above ******* and the applicable Subcontract (Item 0001A or 0002) price for the filled vaccine. Thereafter, Manufacturer shall be paid the applicable Subcontract (Item 0001A or 0002) price for filled vaccine that conforms to subcontract requirements.

6 .

Add Provision H.6.1

H.6.1

BAXTER EMPLOYEES AT CBL

******* Manufacturer has the right to review and approve the Baxter personnel assigned to Manufacturer, such approval not to be unreasonably withheld. In the event such Baxter personnel are not available during a week scheduled for 3 fills, Manufacturer shall not be obligated to perform 3 fills in that week. ******* CBL is hereby authorized to provide such Baxter employees and other Baxter representatives Acambis Proprietary Information supplied by Acambis in support of this Subcontract and protected under Clause H.16 of this Subcontract. Such disclosures shall indicate that such information is proprietary to Acambis and subject to existing confidentiality agreements between Acambis and Baxter.

Baxter employees may provide CBL with technical suggestions, but are not authorized to make decisions, agree to any action or inaction, or act in any manner on behalf of Acambis. Any technical suggestion by a Baxter employee must conform to current Subcontract requirements (i.e., not be a change to this Subcontract), and may not alter the scope of work or cause changes of such a nature as to justify an adjustment in the stated Subcontract price/cost or period of performance, or any stated limitation thereof. In the event that the Manufacturer feels that full implementation of any of these suggestions may constitute a change to the Subcontract requirements, no action shall be taken and shall notify the originator of the technical direction and the Contractual Officer in a letter separate of any required report(s). Such notification shall be given within two (2) weeks from the date on which the Manufacturer knew or should have known that the technical direction constituted a contract change. If the Manufacturer fails to provide the required notification within the above two (2) week period, it shall be deemed for purposes of this Subcontract that the technical direction was not a change to contract requirements. No technical direction, nor its fulfillment, shall alter or abrogate the rights and obligations fixed in this Subcontract.

8.

Delete Provision H.17

Substitute:

H. 17

GOVERNMENT PROPERTY/BUYER FURNISHED PROPERTY

A.

Government Property

Manufacturer shall be responsible for the control and accountable record keeping for all Government Property under this subcontract in accordance with FAR Subpart 45.5 as supplemented by HHS Publication (OS) 74.115 entitled “Contractor’s Guide for Control of Government Property,” a copy of which will be provided upon request. Similar controls and record keeping procedures shall be used for any Buyer-furnished equipment as well.

The Chief of Material Management Branch, PGO, Centers for Disease Control and Prevention (CDC), is the Government’s Property Administrator for government property accountable under this contract. The subcontract Program Officer (or his duly authorized representative) shall be the Buyer’s Property Administrator for any Government or Buyer-furnished property under this subcontract. The Manufacturer agrees to furnish information regarding the Government property (or any Buyer-furnished property) under this contract to the respective Property Administrator, an authorized representative, or a duly designated successor(s). Any inquiry from or information proposed to be furnished to the Government Property Administrator shall be promptly reported to Buyer’s Property Administrator before furnishing information to the Government representative.

The following Government property shall be furnished to the Manufacturer under this Subcontract. Such items shall be marked as U.S. Government Property, with the Subcontract # 200-2002-00012 (CBL), the Prime Contract #200-2000-00001 (Acambis Inc, Prime Contractor) (if not already so marked when received) and shall be managed and administered while in Subcontractor’s possession in accordance with the Government Property (Fixed Price Contracts) (Dec 1989) clause, FAR 52.245.2:

* Bulk ACAM 1000 vaccine furnished under Item 0002 and the resultant filled vaccine product

The Manufacturer shall not be responsible for any loss, damage, or destruction of the above Government property (hereafter referred to as “loss”), except to the extent that such loss:

(1)

has been insured by the Manufacturer, in which case, provision H.I2 shall apply, or

(2)

such loss was the result of Manufacturer’s negligence or failure to store or manufacture such vaccine in accordance with Good Manufacturing Practices (GMP) and the applicable batch records and subcontract requirements.

B.

Buyer Furnished Property

Buyer has provided Manufacturer with the property listed in Section J, Attachment H to this Subcontract as Buyer-furnished property. Manufacturer shall manage and administer such property in accordance with the Government Property (Fixed Price Contracts) (Dec 1989) clause, FAR 52.245-2, as modified to properly reflect the parties to this Subcontract. Buyer shall either mark all Buyer-furnished property as property of Acambis Inc. provided under Subcontract 200-2002-00012(CBL) or provide labels to Manufacturer for Manufacturer to label Buyer-furnished property.

Upon Subcontract completion and prior to final payment for Subcontract Items, Manufacturer shall return such Buyer-furnished property to the Buyer with the insurance and shipment charges (external costs) pre-paid and to be reimbursed by Acambis under this Subcontract.

9.

Delete Section J, List of Attachments

Substitute:

Section J – List of Attachments

A

Vaccine and Diluent Statements of Work & Schedule A, Agreement of Technical Responsibility

B

Confidentiality Agreement

C

CBL Security Plan (when submitted and approved after award)

D

Chesapeake Biological Laboratories Inc’s Representations, Certifications and Other Statements of Offerors

E

Acambis Delivery Order (See Section G.1)

F

Certificate of Conformance (See Section G.1)

G

Item 0001A and 00002 Planned Vaccine Schedule

H

Buyer-furnished Property

I

Modification 0003 General Release

10.

Delete Section J, Attachment G  

A.             

CBL’s responsibilities as to the commercial manufacturing of the Product:

1

Prepare master batch (production) record that will be reviewed and approved by Acambis no later than one week prior to the first manufacturing run.

2

Receive API (active pharmaceutical ingredient) from Acambis, store at [**]. API to be stored under GMP conditions until manufactured by CBL. Product will be manufactured on a first in/first out basis.

3  

CBL will store at most [**] API sublots of product.

4  

Thaw product in advance of manufacturing in accordance with the master batch record and commence filling upon attainment of appropriate temperature and any other conditions as specified in the master batch record.

5  

Product will be thawed at ambient room temperature and filled at between [**] Three transport bags will each contain approximately [**] kilograms of the Product which is anticipated to result in the filling of no more than [**] vials. Each vial shall contain the volume of product as specified in the master batch record. The total of all vials produced will be designated as a lot (batch) and will be assigned a unique CBL lot number for regulatory tracking purposes.

6  

CBL will be responsible for performing the assembly, breakdown, cleaning, sanitisation, sterilisation and general and preventive maintenance of [***]. Acambis will provide an adequate supply, in advance, of consumables related to the [***], such that these consumables can be used with each new application of the vessel.

7  

CBL will be responsible for the calibration and general and preventive maintenance of the Flex Boy Mixer.

8  

Acambis is responsible for contracting and paying for those tests set forth in Table A as being performed at BioReliance. CBL is responsible for providing BioReliance with the appropriate number and volume of samples for analysis.

9  

At the completion of the filling operation, CBL shall remove the appropriate number and volume of samples for performance of [***] by BioReliance and retain samples [***] per Table A and the master batch record. CBL shall promptly ship the Table A samples to Acambis or BioReliance (as indicated) as soon as possible after taking such samples, not to exceed 2 business days after CBL completes sampling/inspection of the finished vials.

10

Immediately upon completion of filling, the lot of vials will be placed in a [***] lyophiliser and processed in accordance with the master batch record and the specifications set forth therein.

11

The Product lot, upon completion of lyophilization, will be capped and crimped with the CBL lot number printed on the crimp in accordance with the production batch record.

12

The lot will be 100% visually inspected in accordance with specifications contained n the master batch record and recorded in the production batch record.

13

The inspected Product will be bulk packaged in accordance with the Batch record and stored at [**] until shipping. Exact packaging/shipping parameters to be established in the master batch record as agreed between CBL, Acambis, and Acambis’s designee. The bulk package of vaccine shall be labelled.

14

All times during which product is exposed to ambient temperatures (during filling and between lyophilization and storage of final containers at [**].) will be minimised and the time intervals recorded in batch records.

15

Final filled containers will be subjected to QC tests as specified in Table B. CBL is responsible, at its cost, for performing the [***] tests set forth in Table B. CBL is also responsible for providing BioReliance and Acambis with the appropriate number and volume of samples for analysis. CBL shall promptly ship the Table B samples to Acambis or Bio Reliance (as indicated) as soon as possible after taking such samples, not to exceed 2 business days after CBL completes sampling/inspection of the finished vials.

16

CBL will be provided with validated packaging and shipping instructions specifying the manner of packaging and shipping conditions for the Product as written in the master batch record.

17

Upon successful completion of those tests performed by CBL, CBL will notify Acambis and Acambis’s designee that Product is available for pick-up.

18

Acambis or its designee will arrange for shipment of CBL-released product from CBL, with pick up from CBL at a mutually agreeable time.

19

Acambis will not request CBL to simultaneously store more than [*] completed lots of Product within its refrigerated warehouse at [**], provided, however, that the entire CBL storage area for the completed product lots is dedicated to storage of Acambis product.

20

CBL will provide a Summary of CBL Test Results that will contain results of those tests that CBL is required to perform according to Tables A and B to Acambis within two weeks of completion of each production.

21

CBL will be responsible for performing their portion of the “[***]” Acambis will pay for the samples utilised as part of the [***] protocol where Acambis performs the testing and CBL will not charge Acambis for the samples that are consumed by testing performed by CBL.

22

CBL will invoice Acambis after Product or diluent is available for pick up by Acambis or its designee and upon completion of CBL’s batch record review and approval. CBL will submit a Certificate of Conformance with the invoice.

23

The invoice amount will be in accordance with Section B of the subcontract.

B.             

Acambis’s responsibilities as to the commercial manufacturing of the Product

1

Acambis will supply API to CBL with a [***]. Reference samples will be taken and shipped as set forth in the master batch record.

2

Acambis will review and approve the master batch record that CBL uses to manufacture Acambis’s product.

3

Acambis is responsible for contracting and paying for all testing not specifically designated in Table B to CBL.

4

Acambis will specify a validated shipping method for both inbound API and outbound Product at CBL.

5

Acambis will be responsible for the final release of the Product for central storage at Acambis’s des