1
EXHIBIT 10.15
SUPPLY AGREEMENT
BETWEEN
ADVANCED CORNEAL SYSTEMS, INC.
AND
BIOZYME LABORATORIES, LTD.
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TABLE OF CONTENTS
PAGE
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ARTICLE 1 - DEFINITIONS..........................................................................1
1.1 "Act".............................................................................1
1.2 "ACS Vitrase(TM)Product"..........................................................1
1.3 "ACS Corneaplasty(TM)Product".....................................................1
1.4 "Equipment".......................................................................1
1.5 "Facility"........................................................................1
1.6 "FDA".............................................................................2
1.7 "GMP Grade".......................................................................2
1.8 "Good Manufacturing Practices"....................................................2
1.9 "Ophthalmic Applications".........................................................2
1.10 "Product".........................................................................2
1.11 "Specifications"..................................................................2
1.12 "Unit"............................................................................2
ARTICLE 2 - CERTIFICATION AND APPROVAL...........................................................2
2.1 Certification.....................................................................2
2.2 Milestone Payments................................................................3
2.3 ACS Equipment.....................................................................3
ARTICLE 3 - SUPPLY...............................................................................4
3.1 Product Supply....................................................................4
3.2 Forecasts.........................................................................4
3.3 Orders............................................................................5
3.4 Form of Order.....................................................................5
3.5 Annual Purchase Requirements......................................................6
3.6 Pricing...........................................................................6
3.7 Payment...........................................................................7
3.8 Delivery..........................................................................7
3.9 Shipping Requirements.............................................................7
3.10 Title and Risk of Loss............................................................7
ARTICLE 4 - REPRESENTATIONS AND WARRANTIES.......................................................7
4.1 Product Warranties................................................................7
4.2 Testing Warranties................................................................8
ARTICLE 5 - QUALITY ASSURANCE REQUIREMENTS.......................................................9
5.1 Release Testing...................................................................9
5.2 Stability Testing.................................................................9
5.3 Retains...........................................................................9
5.4 Maintenance of Records............................................................9
5.5 Inspection of Manufacturing Facility and Manufacturing Data.......................9
5.6 FDA Inspection of Facility.......................................................10
5.7 Subcontracting...................................................................10
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TABLE OF CONTENTS
{CONTINUED)
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5.8 Reprocessing......................................................................9
ARTICLE 6 - ACCEPTANCE OF PRODUCT...............................................................10
6.1 Review of Results of Release Testing.............................................10
6.2 Rejection of Product.............................................................10
6.3 Results of Regulatory Authority Inspections......................................10
ARTICLE 7 - SHORTAGE OF SUPPLY..................................................................11
7.1 Notification.....................................................................11
7.2 Priority Allocation..............................................................11
7.3 Other Remedies...................................................................11
ARTICLE 8 - INDEMNIFICATION.....................................................................
8.1 Indemnity by ACS.................................................................
8.2 Indemnity by Biozyme.............................................................
8.3 Defense of Indemnification Claims................................................
ARTICLE 9 - CONFIDENTIALITY.....................................................................11
9.1 Confidential Information.........................................................11
ARTICLE 10 - TERM...............................................................................12
10.1 Term.............................................................................12
10.2 Termination for Cause............................................................10
10.3 Termination with Notice..........................................................13
10.4 Effect of Expiration or Termination on Agreement.................................13
10.5 Survival.........................................................................13
ARTICLE 11 - MISCELLANEOUS......................................................................13
11.1 Suppliers........................................................................13
11.2 Force Majeure....................................................................13
11.3 Relationship of the Parties......................................................14
11.4 Assignment.......................................................................14
11.5 Entire Agreement.................................................................14
11.6 Severability.....................................................................14
11.7 Headings.........................................................................14
11.8 Notices..........................................................................15
11.9 Public Disclosure................................................................15
11.10 Amendment; No Waiver.............................................................15
11.11 No Conflict......................................................................16
11.12 Governing Law....................................................................16
11.13 No Strict Construction...........................................................16
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TABLE OF CONTENTS
{CONTINUED)
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11.14 Counterparts.... ................................................................16
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SUPPLY AGREEMENT
This Supply Agreement (the "Agreement") is entered into as of the 23rd
day of September 1999 (the "Effective Date") by and between Biozyme
Laboratories, Ltd., a company incorporated in England and Wales under number
1034731 whose registered office is at Xxxx 0, Xxxxxxxxx Xxxxxx Xxxxxx,
Xxxxxxxxx, Xxxxx, XX0 0XX, Xxxxxx Xxxxxxx ("Biozyme") and Advanced Corneal
Systems, Inc., a California corporation ("ACS").
RECITALS
A. Biozyme has expertise in the production of particular animal sourced
hyaluronidase.
B. ACS has developed products which utilize such particular animal
sourced hyaluronidase for use in ophthalmic applications.
C. Biozyme wishes to supply to ACS, and ACS wishes to purchase from
Biozyme, quantities of the Product for use in its products and sale worldwide on
the terms and conditions set forth below.
NOW, THEREFORE, the parties agree as follows:
ARTICLE 1 - DEFINITIONS
1.1 "Act" means the United States Food, Drug and Cosmetics Act, as
amended from time to time and the regulations promulgated thereunder.
1.2 "ACS Vitrase(R) Product" means a product containing hyaluronidase as
an active ingredient used to treat various diseases of the human eye.
1.3 "ACS Corneaplasty(TM) Product" means a product system, containing
hyaluronidase as an active ingredient used to correct refractive vision errors
of the human eye.
1.4 "Equipment" shall have the meaning set forth in Article 2.3.
1.5 "Facility" means the facility at Biozyme Laboratories, Ltd.,
Blaenavon Gwent, South Wales, United Kingdom.
1.6 "FDA" means the United States Food and Drug Administration.
1.7 "GMP Grade" means Product that has been produced in accordance
with applicable Good Manufacturing Practices with respect to active
pharmaceutical ingredients.
1.8 ."Good Manufacturing Practices" means the current good manufacturing
practices for manufacturing active pharmaceutical ingredients as set forth in 21
CFR Parts 210 and
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211 and the Rules Governing Medical Products in the European Community as set
forth in Volume IV; Guide to Good Manufacturing Practice for the Manufacturing
of Active Pharmaceutical Ingredients.
1.9 "Ophthalmic Applications" means any application, whether research
or commercial, of the Product for administration to the human or animal eye.
1.10 "Product" means animal sourced hyaluronidase manufactured in
accordance with the Specifications.
1.11 "Specifications" means the manufacturing, quality control,
packaging, labeling, shipping and storage specifications for the Product, as set
forth in Exhibit A hereto or as otherwise mutually agreed in writing by ACS and
Biozyme from time to time.
1.12 "Unit" means that amount of enzyme causing the same turbidity
reduction as the 'International Unit' (I.U.) as compared with the International
Standard meeting the applicable Specifications.
ARTICLE 2 - CERTIFICATION AND APPROVAL
2.1 Certification. Promptly upon execution of this Agreement, but in
no event later than Xxxxx 00, 0000, Xxxxxxx will use best efforts to obtain
third party certification ("GMP Certification"), by an auditor acceptable to
both Biozyme and ACS, that the manufacture of Product by Biozyme at the Facility
is in compliance with GMP requirements. ACS shall bear the reasonable costs
associated with the third party audit and inspection of the Facility as
requested by ACS. ACS shall also bear the costs of outside laboratory testing
for the new water system and cleaning validations as required to obtain GMP
certification. Biozyme shall bear the costs in connection with the modification
or improvement of the Facility including certain improvements to Xxxx 00, cold
rooms 1 and 2 and laboratory 3 as required in order to obtain certification of
compliance with GMP requirements.
2.2 Milestone Payments. Upon receipt of GMP certification pursuant to
Article 2.1 above, ACS shall pay to Biozyme Pound Sterling40,000 (British
Pounds). In addition, ACS shall pay to Biozyme, Pound Sterling20,000 (British
Pounds) immediately upon the occurrence of each of: (i) FDA approval of a New
Drug Application ("NDA") for the ACS Vitrase(R) product; and (ii) FDA approval
of an NDA for the ACS Corneaplasty(TM) product system.
2.3 ACS Equipment.
2.3.1 ACS shall acquire, in a timely manner and at its own
expense, and install or have installed at the Facility, the equipment listed in
Exhibit B attached hereto ("Equipment"). Biozyme shall not utilize the Equipment
for any use other than for the manufacture of the Product for ACS. The Equipment
shall, at all times, remain the sole and exclusive property of ACS.
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2.3.2 Biozyme, at its expense, shall make all necessary site
preparations and cause the Equipment to be operated in accordance with any
applicable operating manuals, manufacturer's instructions and GMP requirements.
Biozyme shall effect and bear the reasonable expense of all necessary repair,
maintenance and operation of the Equipment. Replacements required to be made to
maintain the Equipment in good condition, reasonable wear and tear excepted, and
to comply with all applicable laws to which the use and operation of the
Equipment may be or become subject shall be subject to the prior written
approval of ACS, the cost of which shall be the responsibility of ACS. All
replacement Equipment and parts furnished in connection with such maintenance or
repair shall immediately become the property of ACS and part of the Equipment
for all purposes hereof. All such maintenance and repair services shall be
immediately paid for and discharged by Biozyme with the result that no lien
under any applicable laws will attach to the Equipment as a result of the
performance of such services or the provision of any such material.
2.3.3 Biozyme shall obtain and maintain for the term of this
Agreement, at its own expense, (a) "all risk" insurance against loss or damage
to the Equipment, (b) commercial general liability insurance (including
contractual liability, products liability and completed operations coverage)
reasonably satisfactory to ACS.
2.3.4 If any items of Equipment shall become lost, stolen,
destroyed, or damaged beyond repair for any reason, or in the event of
condemnation, confiscation, seizure or requisition of title to or use of such
items (collectively, an "Event of Loss"), Biozyme shall promptly pay to ACS the
fair market value of the Equipment subject to the Event of Loss as determined by
an objective third party evaluator agreeable to both parties. Upon payment of
such amount by Biozyme, ACS will transfer to Biozyme, "AS IS, WHERE IS, WITHOUT
RECOURSE, REPRESENTATION OR WARRANTY," all of ACS's right, title and interest,
if any, in such items of Equipment.
2.3.5 (a) ACS and Biozyme confirm their intent that title to the
Equipment shall remain in ACS (or its successors and assigns) exclusively. If
requested by ACS, Biozyme, at ACS's cost, will affix plates or markings on the
Equipment and on any operating manuals and manufacturer's instructions
indicating the interests of ACS and its assigns therein, and Biozyme will not
allow any other indicia of ownership or other interest in the Equipment to be
placed on the Equipment. Biozyme shall not sell, assign, grant a security
interest in, sublet, pledge, hypothecate or otherwise encumber or suffer a lien
upon or against the Equipment.
(b) Location. Biozyme may move such Equipment from the
Facility only if Biozyme gives at least thirty (30) days prior written notice of
the relocation or such other documentation as ACS reasonably requests to protect
its interest in the Equipment.
(c) Biozyme shall keep copies of all operating manuals and
manufacturer's instructions with respect to the Equipment in good condition at
the Facility.
2.3.6 In the event ACS should decide to sell or otherwise dispose
of any or all of the Equipment, Biozyme shall have the right of first refusal to
purchase such Equipment at ACS' good faith determination of the Equipment's fair
market value. If Biozyme elects not to
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purchase the Equipment under this Article 2.3.6, Biozyme shall, at ACS's
expense, return the Equipment to ACS in the same condition as delivered, normal
wear and tear expected, at such location as ACS shall designate.
ARTICLE 3 - SUPPLY
3.1 Product Supply. Subject to the terms and conditions of this
Agreement, Biozyme shall supply ACS with ACS's requirements for Product, which
shall not be less than the minimum quantities of the Product set forth in
Article 3.5, during the term of this Agreement. Biozyme agrees that it shall not
manufacture Product for any third party for use in Ophthalmic Applications, and
shall not authorize any third party to manufacture or produce the Product for
third parties for use in Ophthalmic Applications.
3.2 Forecasts. During the term of this Agreement, at least sixty (60)
days prior to the start of each calendar quarter ("Q1"), ACS shall provide
Biozyme with a rolling written forecast of the quantities of Product estimated
to be required on a quarterly basis during Q1 and the next three (3) quarters
("Q2" through "Q4").
3.3 Orders. ACS shall place orders with Biozyme at any time for
delivery of the Product specifying the amount of Product ordered and required
delivery date(s). Biozyme shall accept such orders from ACS, subject to the
terms and conditions of this Agreement, provided that Biozyme shall not be
obligated to accept orders for any given quarter to the extent the quantity
ordered exceeds 120% of the quantity forecast in the forecast provided under
Article 3.2 above for the immediately preceding calendar quarter, but shall use
good faith efforts to fill orders for such quantities from available supplies.
Upon acceptance by Biozyme, each ACS order shall be final and not subject to
modification without the consent of Biozyme.
3.4 Form of Order. ACS's orders shall be made pursuant to a written
purchase order, and shall provide for shipment in accordance with reasonable
delivery schedules as may be agreed upon from time to time in writing by Biozyme
and ACS.
3.4.1 All sales of the Product pursuant to this Agreement shall
be subject to the standard terms and conditions of sale of Biozyme from
time to time set out in Biozyme Laboratories Ltd. catalogue, except to
the extent that any provision of those terms and conditions of sale is
inconsistent with any provisions of this Agreement in which event the
latter shall prevail; or
3.4.2 Biozyme and ACS agree in writing to vary those terms and
conditions of sale.
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3.5 Annual Purchase Requirements. ACS shall be required to order the
following minimum quantities of Product during the initial five (5) calendar
years following the Effective Date. ACS orders for non-GMP Product during
calendar year 1999 shall be applied to the Annual Purchase Requirements for 1999
as defined below.
1999 250 million Units
2000 350 million Units
2001 500 million Units
2002 1,200 million Units
2003 1,500 million Units
3.6 Pricing.
3.6.1 Prices for commercial supply of the Product shall be as
follows:
(a) For orders providing for shipments of less than 100
million Units, $451 United States Dollars per million Units:
(b) For orders providing for shipments of 101 to 200
million Units, $428 United States Dollars per million Units: or
(c) For orders providing for shipments of more than 201
million Units, $410 United States Dollars per million Units:
3.6.2 Any increase in the pricing for Product after the initial
two years of the agreement shall be presented to ACS by Biozyme not later than
ninety (90) days prior to the proposed effective date of the pricing change and
shall provide justification for the pricing increase. In no event shall such
pricing increase (i) be applicable to purchase orders accepted by Biozyme prior
to the effective date of the pricing change and (ii) in no event shall exceed
five percent (5%) per annum, unless such increase is due to a documented
increase in Biozyme's cost for the purchase of ovine raw material.
3.6.3 Pricing for Product as defined in Article 3.6.1 above shall
be applicable to GMP Grade Product. Pricing for non-GMP Grade Product shall be
$410 USD per million units.
3.6.4 Notwithstanding Article 3.6.2, Biozyme shall be entitled to
increase the price of the Product to cover extra expenses which are a
direct result of changes to the Specifications requested by ACS.
3.7 Payment. Upon shipment of the Product, Biozyme will generate and
deliver to ACS an invoice for the quantities delivered. ACS shall remit payment
to Biozyme within thirty-five (35) days of such invoice date.
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3.8 Delivery. Biozyme shall provide delivery of the Product, subject to
the provisions in Article 3.3 as follows:
(a) ACS orders for shipments of Product less than 60
million units: within forty-five (45) days of receipt of ACS order.
(b) ACS orders for shipments of Product more than 60
million units: within ninety (90) days of receipt of ACS order.
3.9 Shipping Requirements. Biozyme shall be responsible for arranging
for shipment of Product in accordance with shipping instructions which ACS shall
provide to Biozyme reasonably in advance of any such shipment (including,
without limitation, destination point and courier). Prior to delivering Product
to the courier, Biozyme shall package the material in accordance with good
commercial practice with respect to protection of the Product during
transportation and to comply with any applicable regulations and government
requirements. ACS shall be responsible for (i) obtaining all governmental
permits, consents and approvals which are required in order to export Product
from the United Kingdom and import the Product into the country of destination,
and (ii) making any notifications or other filings (whether before or after
shipment) which are required in connection with the exportation of Product from
the United Kingdom or importation of Product into the country of destination.
All out-of-pocket costs associated with freight insurance and custom duties, as
well as any special packaging expenses shall be paid by ACS.
3.10 Title and Risk of Loss. Title and risk of loss or damage shall
pass to ACS upon delivery of Product to the courier approved by ACS. In all
cases, delivery of Product shall be FOB point of shipment.
ARTICLE 4 - REPRESENTATIONS AND WARRANTIES
4.1 Product Warranties. Biozyme represents and warrants for the
period of this Agreement and for the twelve months immediately following
termination that (i) each shipment of Product will conform to the
Specifications, and all Product produced under this Agreement shall be GMP Grade
following completion of the GMP certification as specified in Article 2.1, (ii)
its standard manufacturing procedures conform to the applicable requirements of
all applicable Specifications at the time it is shipped hereunder, and (iii) to
the best of Biozyme's knowledge, the Product does not infringe the intellectual
property rights of any third party.
4.2 Testing Warranties. Biozyme represents and warrants for the
period of this Agreement and for the twelve months immediately following
termination that it shall use due care in conducting the testing specified in
Article 5 hereof and shall perform all such testing in accordance with the terms
of this Agreement and generally prevailing industry standards.
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ARTICLE 5 - QUALITY ASSURANCE REQUIREMENTS
5.1 Release Testing. Biozyme shall be responsible for all quality
control testing and analysis of Product outlined in Exhibit C to ensure that it
conforms to the Specifications and the warranties set forth in Article 4.1
hereof (the "Release Testing"). Biozyme shall provide ACS, at the time the
Product is shipped, with the results of all Release Testing, together with a
Certificate of Analysis relating to such testing, in order to enable ACS to
review such data in accordance with the provisions of Article 5 hereof.
5.2 Stability Testing. Biozyme shall be responsible for conducting
stability testing of the Product in accordance with the provisions of Exhibit D
hereto. Product required for Stability Testing pursuant to Exhibit D will be
provided by ACS to Biozyme at no cost from Product purchased under this
Agreement.
5.3 Retains. Biozyme shall retain a sufficient quantity of each
production run of Product to enable the performance of the tests required by
this Article 5 at least twice. Such samples shall be retained during such period
as is required by the Specifications, GMP requirements and all applicable
regulatory requirements.
5.4 Maintenance of Records. Biozyme shall keep, for a period of seven
(7) years following the end of the relevant calendar quarter, or such longer
period as shall be required by the Act or the applicable regulatory authorities
in any jurisdiction in which the Product is sold, exact, true and complete
records of all operations involved in the manufacture, testing, storage and
shipping of Product produced in such calendar quarter.
5.5 Inspection of Manufacturing Facility and Manufacturing Data.
Biozyme will permit ACS representatives or its designates to visit the Facility,
during normal working hours and with reasonable prior written notice, to observe
the performance of the manufacturing, handling, storage and shipping of Product
hereunder, discuss such activities with appropriate officials of Biozyme,
inspect (and if reasonably necessary copy) all records and data required to be
maintained pursuant to this Article 5, and analyze any tangible material
relevant thereto which is then within Biozyme's control and which is reasonably
available for such testing. Biozyme will cooperate with ACS and any governmental
authority in evaluating any complaint or claim by such governmental authority,
or adverse drug reaction report, related to the Product, and shall provide
information and take such other steps as may be necessary or appropriate to
comply with all requirements imposed by any regulatory authority in any
jurisdiction in which the Product is sold with respect to the Product. ACS shall
be entitled to exercise its rights pursuant to this Article 5.5 until the
expiration of the record retention period described in Article 5.4.
5.6 FDA Inspection of Facility. Biozyme shall promptly provide ACS
with any correspondence and other documentation received from or provided to
FDA, United Kingdom or European regulatory authorities in connection with
inspection of the Facility, including without limitation any post-inspection
reports and any Establishment Inspection Reports.
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5.7 Subcontracting. It is understood that in fulfilling its obligations
hereunder, Biozyme may subcontract such obligations for the testing pursuant to
Articles 5.1 - 5.2; provided that Biozyme shall at all times be responsible to
ACS for the performance of such subcontractors.
5.8 Reprocessing. Reprocessing of the Product at any stage of its
manufacture will not be permitted unless so authorized in writing by ACS.
ARTICLE 6 - ACCEPTANCE OF PRODUCT
6.1 Review of Results of Release Testing. ACS shall promptly accept
all Units of Product supplied to it in accordance with this Agreement, but shall
have the right to reject any Product which does not meet the Specifications
according to the manufacturing records and results of the Release Testing
relating to such Product. ACS agrees to review such data and records and
indicate to Biozyme in writing within thirty (30) calendar days after receipt
thereof whether it accepts the applicable Product or rejects such Product for
failure to meet the Specifications or, if both Biozyme and ACS agree in writing
to delay its response for a mutually agreed upon period of time. In the event
that ACS shall not have so rejected Product in writing within the thirty-day
time period described above, ACS shall be deemed to have accepted such Product.
It is understood and agreed that ACS's review of data or its acceptance (or
deemed acceptance) of Product pursuant to the provisions of this Article 6.1
shall in no way modify or diminish Biozyme's obligation hereunder.
6.2 Rejection of Product. If ACS rejects any Product, then it shall
provide Biozyme with a reasonably detailed description of the basis for such
rejection. Within thirty (30) business days of receiving ACS's notice of
rejection, Biozyme shall notify ACS as to whether it agrees with such rejection.
6.3 Results of Regulatory Authority Inspections. In no event shall
ACS be required to accept any Product in the event that the results of any FDA,
United Kingdom or European regulatory authority inspection of the Facility
indicate that the Facility was not being operated at the time the Product was
produced, or the Product is not being manufactured, handled, stored, packaged or
shipped, in accordance with the applicable regulatory standards.
ARTICLE 7 - SHORTAGE OF SUPPLY
7.1 Notification. If at any time Biozyme becomes unable to supply
requirements for the Product, or becomes aware that it will be unable to supply,
Biozyme shall promptly notify ACS in writing. In such event, representatives
from ACS and Biozyme shall, at their own expense and at their earliest
opportunity, convene to address the problem, including locating alternative
suppliers and/or facilities to increase production and any other actions
necessary to resolve the problem.
7.2 Priority Allocation. During the term of the Agreement, and in
accordance with Article 3, Biozyme shall provide ACS with a priority allocation
of ovine raw materials used to
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manufacture the product and shall not allocate ovine raw materials to other
manufacturing operations until ACS requirements pursuant to Article 3.3 are
satisfied.
7.3 Other Remedies. In the event that Biozyme fails to supply to ACS
quantities of Product that Biozyme is otherwise obligated to supply under this
Agreement, and such failure is the result of Biozyme's willful breach of its
obligations hereunder or its gross negligence, the remedies in Articles 7 and 9
shall not be exclusive and ACS shall be entitled to damages and/or other
remedies legally available. In the event that ACS fails to purchase the minimum
quantities of Product set forth in Article 3.5, Biozyme shall be entitled to
terminate the Agreement forthwith and shall be entitled to damages in line with
outstanding minimum purchases; provided however, that ACS may fulfill its
obligations to Biozyme under Article 3.5 by rendering to Biozyme a payment in
the amount equal to that which would be paid to Biozyme for such minimum
purchases.
ARTICLE 8 - CONFIDENTIALITY
8.1 Confidential Information.
8.1.1 Confidentiality. All information submitted by one party to
the other in connection with this Agreement identified as confidential at the
time of disclosure shall be considered as confidential ("Confidential
Information") and shall be utilized only pursuant to the purposes set forth
hereunder. During the term of this Agreement and for a period of five (5) years
thereafter, neither party shall disclose to any third party any Confidential
Information received from the other party without the specific written consent
of such party. The foregoing shall not apply where such information: a) was or
becomes public through no fault of the receiving party, b) was, at the time of
receipt, already in the possession of receiving party as evidenced by its prior
written records, c) was obtained from a third party legally entitled to use and
disclose the same, d) is independently developed by the receiving party without
use of any Confidential Information of the disclosing party, or e) is required
by law to be disclosed to a court or governmental agency.
8.1.2 Permitted Use and Disclosures. Notwithstanding Article
8.1.1 above, each party hereto may use or disclose information disclosed to it
by the other party to the extent such use or disclosure is reasonably necessary
in filing or prosecuting patent applications, prosecuting or defending
litigation, complying with applicable governmental regulations or otherwise
submitting information to tax or other governmental authorities, conducting
clinical trials, making a permitted sublicense or otherwise exercising its
rights hereunder, provided that if a party is required to make any such
disclosure of another party's confidential information, other than pursuant to a
confidentiality agreement, it will give reasonable advance notice to the latter
party of such disclosure and, save to the extent inappropriate in the case of
patent applications, will use its best efforts to secure confidential treatment
of such information prior to its disclosure (whether through protective orders
or otherwise).
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8.1.3 Confidential Terms. Except as expressly provided herein,
each party agrees not to disclose any terms of this Agreement to any third party
without the consent of the other party; provided, disclosures may be made as
required by securities or other applicable laws, or London Stock Exchange
requirements, or to actual or prospective investors or corporate partners, or to
a party's accountants, lenders, attorneys and other professional advisors.
ARTICLE 9 - TERM
9.1 Term. This Agreement shall be effective as of the Effective Date
and, unless earlier terminated in accordance with the provisions of this Article
9, shall continue in full force and effect until terminated by mutual agreement
of the parties or as provided under Article 9.2 below.
9.2 Termination for Cause.
9.2.1 At any time prior to expiration pursuant to Article 9.1,
either party may terminate this Agreement for cause upon written notice to the
other party in the event that there has been a material breach by the other
party of any of the terms of this Agreement and the other party has failed to
cure such breach within sixty (60) days after receipt of written notice thereof.
Such termination rights shall be in addition to and not in substitution for any
other remedies that may be available to the party serving such notice against
the party in default. Termination pursuant to this Article 9 shall not relieve
the party in default from liability and damages to the other party for breach.
Waiver by either party of a single default or a succession of defaults shall not
deprive such party of any right to terminate this Agreement arising by reason of
any subsequent default.
9.2.2 ACS may terminate this Agreement if third party GMP
Certification for the manufacture of the ACS Hyaluronidase is not received by
December 31, 2000.
9.2.3 ACS may terminate this Agreement if Biozyme fails to
satisfy its obligations under Article 3.
9.3 Termination with Notice. ACS may terminate the agreement upon
twelve months prior written notice to Biozyme. At the end of this twelve-month
period and following delivery of all outstanding orders, ACS shall purchase
Biozyme's remaining inventory of ovine raw material which was acquired to
fulfill ACS requirements as defined under Article 3.
9.4 Effect of Expiration or Termination on Agreement. Termination of
this Agreement shall not relieve the parties of any obligation occurring or
incurred prior to such termination, including without limitation, any obligation
of ACS to pay for Product which has been manufactured prior to termination. In
addition, and without limiting the foregoing, in the event of any termination of
this Agreement, Biozyme may elect to either terminate all obligations to supply
further Product to ACS hereunder, or to continue to supply to ACS all quantities
of Product that ACS has ordered under then outstanding orders and any quantities
that ACS would be obligated to order under Article 3.3 above.
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9.5 Survival. The rights and obligations of the parties set forth in
Articles 4, 5.3, 5.4, 5.5 and 8 shall survive and remain in full force and
effect after the expiration, cancellation or termination of this Agreement for
any reason pursuant to the period of time specified in each of these Articles.
ARTICLE 10 - MISCELLANEOUS
10.1 Suppliers. Without limiting Biozyme's responsibility under this
Agreement, Biozyme shall have the right at any time to satisfy its supply
obligations to ACS hereunder either in whole or in part through arrangements
with third parties engaged to perform services or supply facilities or goods in
connection with the manufacture, testing, and/or packaging of Product, however,
ACS shall receive prior written notice of any proposed change in the suppliers
of the raw material used to manufacture the Product.
10.2 Force Majeure. Neither party to this Agreement will be liable to
the other party for failure or delay in the performance of any of its
obligations hereunder, if such failure or delay is due to causes beyond its
reasonable control, including, but not limited to, acts of God, earthquakes,
fires, strikes, acts of war, or intervention of any governmental authority, but
any such delay or failure will be remedied by such party as soon as possible
after the removal of the cause of such failure or delay.
10.3 Relationship of the Parties. For all purposes of this Agreement,
Biozyme and ACS will be deemed to be independent entities, and anything in this
Agreement to the contrary notwithstanding, nothing herein will be deemed to
constitute Biozyme and ACS as partners, joint venturers, co-owners, or any
entity separate and apart from each party itself, nor will this Agreement
constitute any party hereto an employee or agent, legal or otherwise, of the
other party for any purposes whatsoever. Neither party hereto is authorized to
make any statements or representations on behalf of the other party or in any
way obligate the other party, except as expressly authorized in writing by the
other party. Anything in this Agreement to the contrary notwithstanding, except
as expressly provided in this Agreement, no party hereto will assume nor will be
liable for any liabilities or obligations of the other party, whether past,
present or future.
10.4 Assignment. This Agreement may not be assigned by either party
without the prior written consent of the other party, except that either party
may assign this Agreement, in whole or in part, to the successor (including the
surviving company in any consolidation, reorganization or merger) or assignee of
all or substantially all of its business. This Agreement will be binding upon
any permitted assignee of either party. No assignment permitted hereunder will
have the effect of relieving any party to this Agreement of any obligations
hereunder.
10.5 Entire Agreement. This Agreement and the exhibits hereto sets
forth the entire understanding between the parties relating to the subject
matter contained herein and may not be modified, amended or discharged except as
expressly stated in this Agreement or by a written agreement signed by the
parties hereto.
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16
10.6 Severability. If any provision of this Agreement is held by a
court of competent jurisdiction to be invalid or unenforceable, it will be
modified, if possible, to the minimum extent necessary to make it valid and
enforceable or, if such modification is not possible, it will be stricken and
the remaining provisions will remain in full force and effect; provided,
however, that if a provision is stricken so as to significantly alter the
economic arrangements of this Agreement, the party adversely affected may
terminate this Agreement upon sixty (60) days' prior written notice to the other
party.
10.7 Headings. The headings set forth at the beginning of the various
sections of this Agreement are for reference and convenience and will not affect
the meanings of the provisions of this Agreement.
10.8 Notices. Any required notices under this Agreement will be in
writing and be given by either party to the other in or by facsimile
transmission or by letter sent via courier, and sent to the address or place of
business of the other party as shown below and the notice will operate and be
deemed to have been given at the earliest of either the time of delivery or at
expiration of one business day from the date of the facsimile transmission or
three business days from the date the letter is deposited with the courier
service, and proof that the fax or telegram was sent or that the letter was
properly addressed and deposited will be sufficient evidence of service.
Any such notice given to Biozyme will be addressed to:
Biozyme Laboratories, Ltd.
Xxxx 0, Xxxxxxxxx Xxxxxx Xxxxxx
Xxxxxxxxx, Xxxxx XX0 000
Xxxxx Xxxxx
Xxxxxx Xxxxxxx
Attn: Xxxx Chesham, Ph.D.
Managing Director
Any notice to be given to ACS will be addressed to:
Advanced Corneal Systems, Inc.
00000 Xxxxx Xxxx
Xxxxx 000
Xxxxxx, Xxxxxxxxxx 00000 XXX
Attn: X.X. XxxXxx
Vice President/Chief Financial Officer
10.9 Public Disclosure. Neither party will originate any publicity, news
release or public announcement, written or oral, whether to the public, the
press, public stockholders or otherwise, referring to the subject matter of this
Agreement, the performance under it, or any of its specific terms and
conditions, except such statements or announcements, as in the opinion of the
counsel for the party making such announcement, are required by law, including
United States securities laws, rules or regulations, the U.K. Companies Act
requirements and the listing rules of
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17
the London Stock Exchange, without the prior written consent of the other party.
If a party decides to make a statement or announcement it believes to be
required by law with respect to this Agreement, it will give the other party
such notice as is reasonably practicable and an opportunity to comment upon the
statement or announcement.
10.10 Amendment; No Waiver. This Agreement may be amended in a written
amendment signed by both parties hereto. Any waiver by any party hereto of a
breach of any provisions of this Agreement will not be implied and will not be
valid unless such waiver is made in a writing signed by such party. Failure of
any party to require, in one or more instances, performance by the other party
in strict accordance with the terms and conditions of this Agreement will not be
deemed a waiver of the future performance of any such terms or conditions or of
any other terms and conditions of this Agreement. A waiver by either party of
any term or condition of this Agreement will not be deemed or construed to be a
waiver of such term or condition or any other term or condition. All rights,
remedies, undertakings, obligations and agreements contained in this Agreement
will be cumulative and none of them will be a limitation of any other remedy,
right, undertaking, obligation or agreement of either party.
10.11 No Conflict. Each party represents that neither this Agreement nor
any of its obligations hereunder will conflict or result in a breach of any
arrangement or agreement between such party and any third party. Each party
represents that it has not been debarred and has not been the subject of
debarment proceedings by the FDA or any other regulatory authority. Each party
will undertake the activities to be undertaken by it pursuant to this Agreement
in compliance with applicable laws.
10.12 Governing Law. This Agreement will be governed by the laws of the
State of California, excluding any choice of law rules which may direct the
application of the laws of another jurisdiction.
10.13 No Strict Construction. This Agreement has been prepared jointly
by the parties and shall not be strictly construed against either party.
10.14 Counterparts. This Agreement may be executed in two counterparts,
both of which, taken together, shall constitute the full agreement of the
parties.
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18
IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be
executed in duplicate as of the date and year first above written by their
respective duly authorized representatives.
BIOZYME LABORATORIES, LTD. ADVANCED CORNEAL SYSTEMS, INC.
By: /s/ [ILLEGIBLE] By: /s/ [ILLEGIBLE]
------------------------------ -----------------------------
Title: Managing Director Title: Vice President
----------------------------- -----------------------------
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19
Exhibit A - Specifications
Exhibit B - Equipment
Exhibit C - Testing Specifications
Exhibit D - Stability Testing
20
EXHIBIT A
Specifications
GENERAL:
White fluffy powder with no less than 7,000 I.U./mg hyaluronidase activity
sourced from ovine testes. Other product specifications as per Release Testing
Specifications as contained in EXHIBIT C.
PACKAGING AND STORAGE:
Package in airtight polycarbonate containers and store frozen (<-15(degrees)C).
LABELING:
Primary package must be labeled with ACS name, full product name, product code
#, lot #, weight, contents, storage condition, and retest date.
SHIPPING:
Insure primary package is well insolated. Seal insolated container in a sturdy
corrugated box. Ship by commercial air courier only. Enclose certificate of
analysis with shipment.
D-1
21
EXHIBIT B
Equipment
Estimated Cost
Description (in British Pounds)
----------- -------------------
15 Liter Ion Exchange Column 2,600 Pound Sterling
Ion Exchange Resin for 15 Liter Column 2,900 Pound Sterling
Freeze Drying Apparatus (Lyophilizer) 11,500 Pound Sterling
Plastic Xxxx, (buckets, bins, etc.), Beakers 1,400 Pound Sterling
Millipore Purified Water System
Equipment/Installation Not to Exceed 17,300 Pound Sterling
Total Organic Carbon Analyzer Not to Exceed 9,998 Pound Sterling
300L Ion Exchange Column 27,500 Pound Sterling
Ion Exchange Resin for 300 Liter Column 6,000 Pound Sterling
UF Membranes 1,900 Pound Sterling
Lyophilization Flasks 1,200 Pound Sterling
Dry Box with balance 5,000 Pound Sterling
Glassware, bins Not to Exceed 1,000 Pound Sterling
D-2
22
EXHIBIT C
Testing Specifications
In Process Testing Specification*
--------------------------------------------------------------------------------
In-Process Test Specification
--------------------------------------------------------------------------------
I.U./E280 of Combined "A" Fraction No less than 10,000
--------------------------------------------------------------------------------
*Additional in-process specification as applied to HY06 process; all other
in-process specification will apply.
Release Testing Specifications
----------------------------------------------------------------------------------------
Release Test Specification
----------------------------------------------------------------------------------------
Assay (hyaluronidase activity) No less than 7,000 I.U./mg
Physical Appearance White fluffy powder
Solubility and Appearance of Solution Dissolves readily at 5 mg/mL in
0.02M sodium phosphate/0.45%
sodium chloride/0.01% bovine serum
albumin, pH 6.9, to give a clear
colorless solution.
pH (30 mg in 10mL water) 4.5 to 7.5
Loss on Drying, or Water by Xxxx Xxxxxxx To be determined following process
development
Bacterial Endotoxins No more than 0.2 I.U. endotoxin per I.U.
hyaluronidase
Microbial Limit Tests No E. coli, S. aureus, P. aeruginosa, or
Salmonella contamination. Total
microbial contamination less than 1000
organisms per gram hyaluronidase.
SDS-PAGE To be determined following process
development work using newly
received ovine testes.
----------------------------------------------------------------------------------------
X-0
00
XXXXXXX X
Stability Testing
Stability testing must be conducted on all validation batches, the first three
batches produced post regulatory approval and on a minimum of one batch per year
following regulatory approval.
The containers to be used in stability evaluations should be the same as the
actual packaging used for storage and distribution.
STABILITY TESTING TEMPERATURES AND DURATIONS:
Test all stability batches at freezer (between -25 degrees C and -10 degrees C)
and refrigerated (between 2 degrees C and 8 degrees C) conditions. Freezer and
refrigerated samples should be tested for a minimum of 3 years.
STABILITY TESTING INTERVALS:
Test stability batch samples every 3 months over the first year, every 6 months
over the second year, and then annually.
Stability Testing Specifications
--------------------------------------------------------------------------------
Release Test Specification
--------------------------------------------------------------------------------
Assay (hyaluronidase activity) No less than 7,000 I.U./mg
Physical Appearance White fluffy powder
Solubility and Appearance of Solution Dissolves readily at 5 mg/mL in
0.02M sodium phosphate/0.45%
sodium chloride/0.01% bovine serum
albumin, pH 6.9, to give a clear
colorless solution.
pH (30 mg in 10mL water) 4.5 to 7.5
--------------------------------------------------------------------------------
D-4
