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CONTRACT MANUFACTURING AGREEMENT
THIS CONTRACT MANUFACTURING AGREEMENT (the "Agreement") is made and entered into
as of March 17, 2000 ("Date of Agreement"), by and between:
Chiron S.p.A., with its registered offices at Xxx Xxxxxxxxxx 0, 00000 Xxxxx,
Xxxxx, hereafter referred to as "Chiron",
and
SynCo Bio Partners B.V., with its registered offices at Xxxxxxxxxxxxx 00, 0000
XX Xxxxxxxxx Zuidoost, The Netherlands, hereafter referred to as the "SynCo".
BACKGROUND
- Chiron has developed or is developing a broad line of novel adult and
pediatric vaccines for viral and bacterial infectious diseases;
- SynCo operates a manufacturing plant in Amsterdam, The Netherlands;
- Chiron wishes to contract with SynCo to provide services related to the
production of certain vaccines or intermediate products in the Plant, in
quantities and at times to be separately agreed upon between Parties.
SynCo is willing to use its personnel, expertise and facilities to
discharge such contract manufacturing tasks and to provide such services,
assistance, advice and consulting as Chiron may request from time to
time.
NOW, THEREFORE, in consideration of the premises, the mutual covenants, terms
and conditions hereinafter set forth, THE PARTIES AGREE AS FOLLOWS:
ARTICLE 1 - DEFINITIONS
For the purpose of this Agreement the following terms shall be defined as
follows:
1.1. "Affiliate" means: with respect to either Party, any company, entity,
joint venture or similar business arrangement which is controlled by,
controlling or under common control with such Party, and shall include without
limitation any company fifty percent or more of whose voting stock or
participating profit interest is owned or controlled, directly or indirectly, by
such Party, and any company which owns or controls, directly or indirectly,
fifty percent or more of such Party.
1.2. "BPRs" means: the batch production records and other documents providing
the manufacturing history of a batch of Product.
1.3. "Confidential Information" means: (a) all information disclosed by either
Party in writing and designated confidential, (b) all information disclosed
orally that is confirmed in writing and designated confidential within thirty
(30) days after such disclosure, (c) all information relating to Patents, (d)
all Specifications, (e) all other Technology, and (f) all other information
relating to the manufacture of the Products, whether such information is
provided to SynCo by Chiron hereunder or otherwise.
1.4. "GMP" means: European Good Manufacturing Practices for Medicinal Products
as in effect at the time of manufacture of any Product supplied to Chiron
hereunder.
1.5. "Material" means: the working cell banks and specific reagents as
required for the manufacture of the Products in accordance with the relevant
Specifications. Commercially available raw materials are excluded.
1.6. "Parties" and "Party" means: SynCo and Chiron and SynCo or Chiron,
respectively, as the context may require.
1.7. "Patents" means all Patents owned by or licensed (with a right to
sublicense) to Chiron or any of its Affiliates claiming Technology.
1.8. "Plant" means: SynCo's facility located at Xxxxxxxxxxxxx 00, 0000 XX
Xxxxxxxxx Zuidoost, The Netherlands.
1.9. "Product" or "Products means: any or all of the vaccine products or
intermediate products thereof listed on Exhibit B.
1.10. "Specifications" means: with respect to each Product, the specifications
for such Product as set forth in Exhibit C, as such specifications may be
amended by Chiron from time to time.
1.11. "Technology" means: all inventions, discoveries, procedures, processes,
methods, data, information, results, trade secrets and know-how, whether
patentable or otherwise, owned by or licensed (with a right to sublicense) to
Chiron or any of its Affiliates as of the Agreement Date or any time during the
term of this Agreement relating to the manufacture of the Products and shall
include, without limitation, the Specifications.
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ARTICLE 2 - MANUFACTURE OF PRODUCT
2.1. SynCo shall manufacture and supply to Chiron such quantities of Products
as Chiron may from time to time order in accordance with the terms of
this Agreement.
2.2. SynCo will manufacture the Products on a campaign basis, one campaign per
Product per year, with a minimum of 8 batches per campaign.
Attached as Exhibit D is Chiron's firm order for Products to be
(delivered) in 2000. SynCo hereby accepts such order. Subsequent orders
shall be by firm written purchase order submitted nine months in advance
of the requested shipping date.
2.3. SynCo shall promptly notify Chiron by phone and by facsimile if any firm
purchase order submitted by Chiron cannot be filled within 15 days of the
requested shipping date. In such a case, SynCo will discuss with Chiron
the means for promptly eliminating the back order.
2.5. SynCo shall ship in accordance with Chiron's shipping instructions, at
Chiron's expense. Title and risk of loss with respect to each shipment
shall pass to Chiron upon delivery of the Product to a common carrier at
the Plant.
ARTICLE 3 - TRANSFER OF TECHNOLOGY AND MATERIAL.
3.1. Chiron hereby grants to SynCo a non-exclusive, royalty free license under
the Patents and to use the Technology to manufacture Product solely for
Chiron in accordance with the terms and conditions of this Agreement.
3.2. Chiron shall provide SynCo with the Specifications and all other relevant
Technology for the purpose of enabling SynCo to perform its obligations
under this Agreement.
3.3. Chiron will furnish SynCo, free of charge, with the Material in
sufficient quantities for the purpose of enabling SynCo to perform its
obligations under this Agreement. The Material will remain the exclusive
property of Chiron. SynCo will not transfer the Material to any third
party. The Material will be released by the QA officer of Chiron. SynCo
will maintain records of usage of the Material, and will inform Chiron of
needs for additional quantities in a timely manner, and return to Chiron
any unused quantities of the Material upon request.
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ARTICLE 4 - REGULATORY AFFAIRS AND QUALITY ASSURANCE
4.1. SynCo shall manufacture all Products supplied to Chiron hereunder in the
Plant and shall not transfer Technology to, or manufacture Product at,
any other location without the prior written consent of Chiron.
4.2. SynCo shall and maintain adequate equipment, knowledge and experience and
competent personnel to carry out satisfactorily its obligations under
this Agreement.
4.3. SynCo shall exercise all reasonable skill, care and diligence in the
performance of its duties under this Agreement and shall carry out all
responsibilities with recognized professional standards and the
requirements of GMP. SynCo shall obtain and maintain all legally required
permits in order to manufacture the Products in the Plant. SynCo shall
inform Chiron of all permits filed and their status with respect to
approval.
4.4. SynCo shall not subcontract any part of its obligations under this
Agreement to a third party without prior written approval by Chiron.
4.5. Chiron will provide to SynCo the release tests to be performed on the
Products and SynCo will perform such release testing in accordance with
Chiron's written instructions.
4.6. SynCo shall write and maintain all BPRs and all documentation relating to
the manufacture of Product supplied hereunder in the English language.
4.7. Subject to reasonable prior notice, Chiron's designated representatives
may inspect those portions of the Plant used in the production of the
Products for the purpose of determining compliance with GMP and the terms
of this Agreement at reasonable times during the production campaign of
the Products. SynCo will provide full cooperation for these inspections.
4.8. SynCo's Quality Assurance unit shall review and approve all BPRs and
shall investigate all deviations on such BPRs. This unit shall also
ensure that the Plant and manufacturing operations are in compliance with
GMP and with any other applicable law or regulation in effect during the
time of manufacture of the Product. Within sixty days of completion of
manufacture of each batch of Product, SynCo will supply Chiron with a
"Certification of Compliance" for such batch stating that the BPRs and
related documentation have been reviewed and found to be in GMP
compliance.
4.9. Chiron will have final responsibility for the release of each batch of
Product manufactured by SynCo.
4.10. SynCo will notify Chiron at least six (6) months in advance of any
proposed modifications to the Plant, utilities, equipment or any other
aspect of the manufacturing process for the Products. SynCo shall not
make any such change without the prior written consent of Chiron, which
consent Chiron may withhold in its reasonable discretion if the change
have any impact on Chiron's Marketing Authorizations for any or all of
the Products.
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4.11. SynCo will retain manufacturing data, test records, and raw material
samples as required to satisfy GMP. SynCo will provide Chiron, free of
charge, with copies of all manufacturing data and test records, as well
as copies of other documents resulting from work under this Agreement,
required by Chiron for regulatory purposes. In the event of termination
of the Agreement, all original manufacturing data, test records, samples
and other materials required to satisfy GMP for the production of the
Products will be delivered to Chiron promptly upon its request.
4.12. SynCo will permit the Regulatory Authorities to conduct inspections
relating to the manufacture of the Products and will cooperate fully in
connection with such inspections. SynCo will notify Chiron promptly of
any of such inspections and shall promptly inform Chiron of the results
of such inspections.
ARTICLE 5 - WARRANTIES AND LIABILITY
5.1. SynCo warrants that:
a) the Products will be manufactured, packed, stored and delivered in
compliance with this Agreement and all applicable laws,
regulations, and orders, including GMP; without limiting the
generality of the foregoing, SynCo will obtain and maintain in
effect all required governmental permits, licenses, and approvals
applicable to the manufacture of the Products and shall produce
the Products in accordance with all such permits, licenses,
orders, applications and approvals;
b) the Material will be received and stored in accordance with all
applicable laws, regulations and orders and in accordance with the
relevant specifications;
c) on the date of delivery thereof, the Products will conform to the
Specifications; and
d) it will not carry on activities in the Plant which could
reasonably prevent the Products from being manufactured in
accordance with all applicable laws, regulations, and orders,
including GMP.
EXCEPT AS OTHERWISE EXPRESSLY PROVIDED HEREIN, SYNCO MAKES NO WARRANTIES EXPRESS
OR IMPLIED AND EXPRESSLY DISCLAIMS WARRANTIES OF FITNESS FOR A PARTICULAR
PURPOSE OR MERCHANTABILITY, AND SYNCO SHALL NOT BE LIABLE FOR INCIDENTAL OR
CONSEQUENTIAL DAMAGES IN ANY CASE OF NONCONFORMITY. NEITHER PARTY SHALL BE
LIABLE TO THE OTHER PARTY FOR INCIDENTAL OR CONSEQUENTIAL DAMAGES ARISING FROM
ANY ALLEGED OR ACTUAL BREACH OF THIS AGREEMENT.
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5.2. SynCo shall promptly replace, free of charge, any defective or
non-conforming Product supplied to Chiron, provided Chiron notifies SynCo
in writing upon discovery of such defect or non-conformity within a
period of sixty days after SynCo's Quality Assurance has approved the
Product pursuant to paragraph 4.8, and provided Chiron allows SynCo to
evaluate the claim and to test the said quantity of Product within a
reasonable period of time, but not to exceed sixty days. Replacement of
the Product by Synco pursuant to this paragraph 5.2 shall be the sole
remedy of Chiron against SynCo for defective or non-conforming Product.
5.3. If the Parties disagree whether such Product is defective or
non-conforming, then the Product in dispute will be tested and further
analyzed by a qualified independent testing laboratory reasonably
acceptable to both Parties. Such laboratory's testing will determine,
using representative samples, whether the quantity of the Product is
defective or non-conforming with the Specifications. The resulting
determination of the laboratory will be final and binding on SynCo and
Chiron. SynCo will bear the cost of such testing if the testing
demonstrates that the Product is defective or non-conforming and Chiron
will bear the cost if the testing demonstrates the Product is neither
defective nor non-conforming.
5.4. Except to the extent subject to indemnification by Chiron pursuant to
paragraph 5.5., SYNCO will indemnify, defend and hold harmless Chiron and
its Affiliates from and against any and all losses, claims, damages or
liabilities (including but not limited to reasonable attorney's fees)
arising from or relating to (a) any breach by SynCo of its
representations, warranties or covenants under this Agreement; or (b) any
negligence or intentional wrongdoing of SynCo.
5.5. Except to the extent subject to indemnification by SynCo pursuant to
Section 5.4., Chiron will indemnify, defend and hold harmless SynCo and
its Affiliates from and against any and all losses, claims, damages or
liabilities (including but not limited to reasonable attorney's fees),
arising from or relating to (a) any use, including clinical trials, or
sale by Chiron or any third party of any Product supplied by Synco
hereunder; (b) any allegation by any third party of infringement of its
intellectual property rights by or the manufacture, use or sale of
Products by Chiron or any of its Affiliates; (c) any breach by Chiron of
its representations, warranties or covenants under this Agreement; or (d)
any negligence or intentional wrongdoing of Chiron.
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5.6. Any person seeking indemnity pursuant to this section (the "Indemnified
Party") shall notify the Party from whom indemnification is sought (the
"Indemnifying Party") in writing promptly upon becoming aware of any
claim, threatened claim, damage, loss, suit, proceeding or liability
("Claim") to which such indemnification may apply. Failure to provide
such notice shall constitute a waiver of the Indemnifying Party's
indemnity obligations hereunder if and to the extent the Indemnifying
Party is materially damaged thereby. The Indemnifying Party shall have
the right to assume and control the defense of the Claim at its own
expense. If the right to assume and control the defense is exercised, the
Indemnified Party shall have the right to participate in, but not
control, such defense at its own expense and the Indemnify Party's
indemnity obligations shall be deemed not to include attorneys' fees and
litigation expenses incurred by the Indemnified Party after the
assumption of the defense by the Indemnifying Party. If the Indemnifying
Party does not assume the defense of the Claim, the Indemnified Party may
defend the Claim; provided, that the Indemnified Party will not settle or
compromise the Claim without consent of Indemnifying Party, which consent
will not be unreasonably withheld. The Indemnified Party shall cooperate
with Indemnifying Party and will make available to Indemnifying Party all
pertinent information under the control of the Indemnified Party.
ARTICLE 6 - CONSIDERATIONS AND PAYMENTS
6.1. As payment in full for Product supplied hereunder, Chiron shall pay to
SynCo the fully burdened, fairly allocated cost to SynCo of manufacturing
such Product, determined in accordance with the accounting methodologies
to be agreed by the Parties promptly after the date of this Agreement and
attached as an exhibit hereto. The Parties agree that the cost for dried
purified meningitis C polysaccharides supplied hereunder during 2000 and
2001 shall be as set forth in Exhibit A.
6.2. SynCo shall invoice Chiron in Netherlands Guilders or Euro's. Payment
terms to SynCo shall be thirty (30) days net from the date of invoice.
ARTICLE 7 - CONFIDENTIALITY AND INTELLECTUAL PROPERTY
A Party receiving Confidential Information from the other Party or developing
Confidential Information hereunder shall not disclose such Confidential
Information to any third party or otherwise for a period extending ten (10)
years following expiration or earlier termination of this Agreement, except as
follows:
(a) to the extent such information is or becomes general public knowledge
through no fault of the recipient Party; or
(b) to the extent such information can be shown by contemporaneous
documentation of the recipient Party to have been in its possession prior
to receipt thereof hereunder; or
(c) to the extent such information is received by the recipient Party from a
third party without any breach of an obligation to the disclosing Party;
or
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(d) to the extent required by law, by local authorities for regulatory
purposes or is necessary to perform its obligations under this
Agreement, in which case, the recipient Party may disclose the
information if the recipient Party gives the other Party prior notice of
such disclosure and an opportunity to comment upon the content of the
disclosure. However, SynCo shall have the right, at all times and
without the obligation to give notice to Chiron, to use information
related to its Plant for its own business purposes and Chiron shall
have the right, at all times and without the obligation to give notice
to SynCo, to use the information related to the Vaccines for its own
business purposes.
For the avoidance of doubt: It is understood that SynCo purchased the Plant and
certain related equipment, including computers and other information technology
systems, from an Affiliate of Chiron, and that prior to such purchase the Plant
and equipment were utilized by Chiron and its Affiliates for the manufacture of
Products. It is further understood that certain employees of SynCo formerly
were employees of an Affiliate of Chiron and were engaged directly or indirectly
in the manufacture of Products. Notwithstanding anything to the contrary
contained herein, and in particularly notwithstanding paragraph (b) above, all
information relating the Specifications, Technology or manufacture of the
Products which exists as of the date of this Agreement shall be owned solely and
exclusively by Chiron and shall not be disclosed by SynCo at any time during the
term of this Agreement or for a period of ten years following the expiration or
earlier termination of this Agreement.
Each Party shall use Confidential Information received from the other Party
solely for the purposes of this Agreement and for no other purpose whatsoever.
ARTICLE 8. - TERM OF AGREEMENT
The term of this Agreement shall commence as of the Date of Agreement, and will
continue until JANUARY 1, 2002 or terminated by any party upon six (6) months
prior written notice to the other party. Termination of this agreement will not
relieve Chiron of its obligations to pay SynCo for Product previously supplied
hereunder and for commitments which arise directly out of firm purchase orders
for Products and which cannot reasonably be canceled or otherwise put to use.
ARTICLE 9 - ADDITIONAL TERMS
9.1. FORCE MAJEURE. A Party shall not be held liable to the other for any
delay in performance or non performance of that Party directly or
indirectly caused by reason of force majeure including, but not limited
to, industrial disputes, strike, lockouts, riots, mobs, fires, floods,
or other natural disasters, wars declared or undeclared, civil strife,
embargo, lack or failure of transport facilities, currency restrictions,
or events caused by reason of laws, regulations or orders by any
government, governmental agency or instrumentality or by any other
supervening circumstances beyond the control of either Party. Provided,
however, that the Party affected shall: give prompt written notice to the
other Party of the date of commencement of the force majeure, the nature
thereof, and expected duration; and shall use its best efforts to avoid
or remove the force majeure to the extent it is able to do so; and shall
make up, continue on and complete performance when such cause is removed
to the extent it is able to do so. Either Party has the right to
terminate the Agreement with immediate effect and without any liability,
upon written notice to the other Party, should the force majeure continue
after three months (3) following the first notification.
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9.2. NON-WAIVER. The failure by any Party at any time to enforce any of the
terms or provisions or conditions of this Agreement or exercise any
right hereunder shall not constitute a waiver of the same or affect the
validity of this Agreement or any part hereof, or that Party's rights
thereafter to enforce or exercise the same. No waiver by a Party shall
be valid or binding, except if in writing and signed by a duly
authorized representative of the waiving Party.
9.3. SEVERABILITY. In case one or more of the provisions contained in this
Agreement shall, for any reason, be held invalid, illegal or
unenforceable in any respect, such holding shall not affect any other
provisions of this Agreement, but this Agreement shall be construed by
limiting such provision to such extent as would nearly as possible
reflect the intent, purpose and economic effect of such provision, or,
if such is not possible, by deleting such provision from this Agreement,
provided that the remaining provisions reflect the intent of the
Parties, as evidenced by this Agreement as a whole.
9.4. CAPTIONS. All titles and captions in this Agreement are for convenience
only and shall not affect its interpretation.
9.5. LAW AND ARBITRATION. This Agreement shall be governed, construed and
interpreted by the law of the Netherlands. The Parties agree that all
disputes between them arising out of or relating to this Agreement shall
be settled by arbitration in accordance with the Rules of Conciliation
and Arbitration of the International Chamber of Commerce by three
arbitrators appointed in accordance with such Rules. The arbitration
proceedings shall take place in Amsterdam, The Netherlands if initiated
by Chiron and in Milan, Italy if initiated by SynCo and shall be
conducted in the English language. Judgment on the award may be issued
by and enforced by any court of competent jurisdiction.
9.6. ENTIRE UNDERSTANDING. This Agreement (including appendices) is the
entire understanding and agreement between the Parties relating to the
subject matter hereof and supersedes (except as provided herein) any and
all prior arrangements, understandings, and agreements between the
Parties whether written or oral relating thereto. No amendments,
changes, or modifications of the terms of this Agreement shall be valid
or binding unless made in writing and signed by the duly authorized
representatives of each Party.
9.7. INDEPENDENT STATUS OF PARTIES. Each Party is an independent party acting
in its own name and for its own account. Neither Party has any authority
to act as an agent or representative of the other, or to contract in the
name of, or create or assume any obligation against, or otherwise
legally bind, the other Party in any way for any purpose, unless agreed
separately in writing. All costs and expenses connected with each
Party's activities and performance under this Agreement unless otherwise
separately agreed or provided for in this Agreement are to be borne
solely by the Party incurring such costs and expenses.
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IN WITNESS WHEREOF, the Parties hereto have caused this Agreement to be executed
by their duly authorized representatives:
Chiron S.p.A. SynCo Bio Partners B.V.
/s/ Xx. Xxxxxxxx Xxxxx /s/ Dr. Mic X. Xxxxxx
Xx. Xxxxxxxx Xxxxx Dr. Mic X. Xxxxxx
Chief Executive Officer Managing Director
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EXHIBIT A
COST OF CERTAIN PRODUCT
The price per batch of dried purified MenC polysaccharides amounts to two
hundred and ninety four thousand (294,000) Dutch Guilders excluding VAT.
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EXHIBIT B
LIST OF PRODUCTS
HIB
MEN C
CRM197
MEN A
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EXHIBIT C
OPERATING PROCEDURES AND SPECIFICATIONS
BATCH PRODUCTION RECORDS
MF-BPR-MEC-2850 Preparation of Inoculum for MEC production
MF-BPR-MEC-2900 Production of MEC on 1500 liter scale; Fermentation
MF-BPR-MEC-2950 Production of MEC on 1500 liter scale; Primary Recovery
MF-BPR-MEC-3000 Extraction of MenC Polysaccharides out of CTAB Wet Paste
MF-BPR-MEC-3005 Q-Sepharose XL Ion Exchange Chromatography for the
purification of MenC Polysaccharides
MF-BPR-MEC-3010 Ultrafiltration and precipitation of Men-C polysaccharide
COMPONENT PREPARATION RECORDS (ONE-BATCH RELATED)
MF-CPR-MEN-0001 Preparation of sterile MEN base medium in shake flasks
MF-CPR-MEN-0002 Preparation of 0.2 micron filtered Fermentation Supplements
MF-CPR-MEN-0003 Materials for MEC Fermentation and Primary Recovery (1500
I scale)
MF-CPR-MEN-0004 Preparation of 0.2 Tm filtered Inoculum Supplements
MF-CPR-XXX-3940 Buffer VA; 0.4 M NaCl in 20 mM TrisHCl, pH 7.75
MF-CPR-XXX-3941 Buffer VB; 0.2 M NaCl in 38% Ethanol and 10 mM TrisHCl, pH
7.5
MF-CPR-XXX-3942 Buffer VC; 1 M NaCl in 38% Ethanol and 10 mM TrisHCl, pH
7.5
MF-CPR-XXX-3943 Buffer VD; 2 M NaCl in 38% Ethanol and 100 mM TrisHCl, pH
7.5
MF-CPR-XXX-3944 Buffer VE; 20 mM CaCl(2) in 38% Ethanol
MF-CPR-XXX-3930 2 M Calcium Chloride
MF-CPR-XXX-3959 20% (v/v) Ethanol
MF-CPR-XXX-3973 1.0 M Sodium Hydroxide
MF-CPR-XXX-3911 4.2 M Acetic Acid Solution
COMPONENT PREPARATION RECORDS (MULTIPLE-BATCH RELATED)
MF-CPR-XXX-0001 Preparation of Ultrafiltrate Yeast Extract solution (10%
w/v)
MF-CPR-XXX-2024 Sterile 50% (w/v) Glucose
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EXHIBIT C
OPERATING PROCEDURES AND SPECIFICATIONS
(CONT'D)
CLEANING CPR'S (ONE-BATCH RELATED)
MF-CPR-XPT-2030 Cleaning the 1000 I Process Tank
MF-CPR-XPT-2050 Cleaning the 4000 I Process Tank
MF-CPR-XFR-2002 Cleaning Procedure for the 1500 I Fermentation System
MF-CPR-XTL-2080 Cleaning the Transfer Loop
MF-CPR-XCT-2100 Cleaning the Recovery Skid
MF-CPR-XCT-2580 Cleaning the Westfalia CSA-8 Centrifuge
MF-CPR-XUF-2220 Cleaning and Testing of Millipore Ultrafiltration System
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