Exhibit 10.62

***Text Omitted and Filed Separately

with the Securities and Exchange Commission.

Confidential Treatment Requested

Under 17 C.F.R. Sections 200.80(b)(4)

and 240.24b-2.

COMMERCIAL SUPPLY AGREEMENT

between

SAVIENT PHARMACEUTICALS INC.

and

BIO-TECHNOLOGY GENERAL (ISRAEL) LTD.

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COMMERCIAL SUPPLY AGREEMENT

This Commercial Supply Agreement (the “Agreement”) is made and entered into as
of the 20th day of March 2007, (hereinafter the “Effective Date”), by and
between Savient Pharmaceuticals, Inc., a public company organized under the laws
of the State of Delaware having its principal place of business at One Tower
Center, 14th Floor, East Brunswick, New Jersey 08816, USA (“Savient”), and
Bio-Technology General (Israel) Ltd., a private company organized under the laws
of the State of Israel having its principal place of business at Beer Tuvia
Industrial Zone, POB 571, Kiryat Malachi 83104, Israel (“BTG”) (hereinafter,
each of Savient and BTG a “Party” and, collectively, the “Parties”).

WITNESSETH:

WHEREAS, pursuant to the Share Purchase Agreement (the “SPA”) and the Asset
Purchase Agreement (“APA”), each dated March 23, 2005 (the SPA and APA,
collectively, the “Divestiture Agreements”), Savient has, on 17 July 2005, sold
to Ferring B.V. all of the issued and outstanding share capital of BTG, and to
Ferring International Centre S.A. all of Savient’s right, title and interest in
certain drug products and drug candidates developed and/or manufactured by BTG,
but not in any case in the drug candidate known as “PEG-uricase” (or also known
as “Puricase”); and

WHEREAS, the Parties to this Agreement have entered into a development agreement
dated March 20, 2007, (the “Development Agreement”) according to which BTG
renders continued development, manufacturing and other services in relation to
Puricase.

WHEREAS, Savient wishes BTG, and BTG is willing, to supply Bulk Product for
Commercial Launch and further commercial sales.

NOW THEREFORE, in consideration of the foregoing premises, which are
incorporated into and made a part of this Agreement, and of the mutual covenants
which are recited herein, the Parties agree as follows:

ARTICLE 1

DEFINITIONS

1.01       “AE” shall mean, with respect to the Product, any adverse event
associated with the use of the Product in a patient or clinical investigation,
whether or not considered drug related, including the following: an adverse
event occurring in the course of the use of the Product in professional
practice; an adverse event occurring from drug overdose whether accidental or
intentional; an adverse event occurring from drug abuse; an adverse event
occurring from drug withdrawal; and any significant and consistent failure of
expected pharmacological action. AE shall include, without limitation, any
unfavorable and unintended sign (including, without limitation, an abnormal
laboratory finding), an exacerbation of a pre-existing condition, intercurrent
illness, drug interaction, significant worsening of a disease under
investigation or treatment, significant failure of expected pharmacological or
biological action, symptom or disease temporally associated with the use of the
Product, whether or not considered related to

 

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the Product. Notwithstanding anything foregoing to the contrary, with respect to
the Territory in which the Product is marketed, AEs shall include any experience
required to be reported to a relevant authority in any such country.

1.02       “Affiliate” shall mean any business entity which directly or
indirectly controls, is controlled by, or is under common control with any Party
to this Agreement. A business entity shall be deemed to “control” another
business entity if (i) it owns, directly or indirectly, at least fifty percent
(50%) of the issued and outstanding voting securities, capital stock, or other
comparable equity or ownership interest of such business entity, or (ii) it has
the de facto ability to control or direct the management of such business
entity. If the laws of the jurisdiction in which such entity operates prohibit
ownership by a Party of fifty percent (50%) or more, “control” shall be deemed
to exist at the maximum level of ownership allowed by such jurisdiction;
provided, however, that there is a de facto ability to direct or control its
management.

1.03       “BLA” means a regulatory application filed with a governmental agency
in a country or a group of countries (e.g. FDA or EU EMEA) for the purpose of
lawfully marketing, selling, distributing, importing, exporting, manufacturing,
developing or using a therapeutic or prophylactic product for the treatment or
prevention of a disease or physical condition; a BLA shall include, without
limitation, a Product License Application or Marketing Authorization in the
European Union, and a Biologics License Application or a New Drug Application in
the United States.

1.04       “BTG Assigned Improvements” shall mean all developments, discoveries,
inventions, improvements, designs, methods, processes, techniques, devices,
formulae and trade secrets related to the Product (including, without
limitation, its pharmaceutical utility) and/or Processing of the Bulk Product or
Product which are (i) made, created, developed or conceived, or reduced to
practice, by BTG or an Affiliate of BTG and (ii) dominated by the Savient Patent
Rights or necessary or useful in the Processing of the Bulk Product or Product.
Notwithstanding the foregoing, BTG Assigned Improvements shall not include any
innovations which are of general use in biopharmaceutical manufacturing.

1.05       “BTG Licensed Improvements” shall mean all developments, discoveries,
inventions, improvements, designs, methods, processes, techniques, devices,
formulae and trade secrets related to the Product (including, without
limitation, its pharmaceutical utility) and/or Processing of the Bulk Product or
Product which are (i) made, created, developed or conceived, or reduced to
practice, by BTG or an Affiliate of BTG, and (ii) necessary or useful in the
Processing of the Bulk Product or (iii) of general use in biopharmaceutical
manufacturing.

1.06       “BTG Indemnitee” shall mean BTG and its Affiliates, and each of their
respective directors, officers, employees and agents.

1.07       “BTG Know-How” shall mean all Know-How developed by BTG or any of its
Affiliates during the Term or by BTG prior to July 17, 2005 relating to (i) the
Bulk Product or Product (including, without limitation, its pharmaceutical
utility) or (ii) the Processing of the Bulk Product or Product , and shall
include, without limitation, all data (in any form, raw or analyzed or reported
and whether maintained in paper, electronic or other media forms) relating to

 

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formulation, analytical methods, pre-clinical and clinical trials, pharmacology,
toxicology, regulatory information, and data relating to the manufacture and use
of such Bulk Product or Product.

1.08       “Bulk Product” shall mean the bulk solution of polyethylene glycol
(PEG) conjugate of uricase ordered by Savient from BTG pursuant to this
Agreement.

1.09       “Business Day” shall mean any day other than (i) Friday, Saturday or
Sunday or (ii) a day on which banking institutions located in New York, New
York, United States of America or in Israel are permitted or required by law,
executive order or governmental decree to remain closed.

1.10       “cGMP” shall mean current good manufacturing practices as set forth
in Title 21, Parts 210 and 211 of the C.F.R. and 21 C.F.R. Part 312 (IND) and
Part 314 (NDA), and 21 C.F.R. Part 600 (Biological Products), as established and
amended by the FDA.

1.11       “Claim” shall mean all charges, complaints, actions, suits,
proceedings, hearings, investigations, claims, demands, judgments, orders,
decrees, stipulations, injunctions, damages (including all incidental and
consequential damages claimed by Third Parties), deficiencies, defaults,
assessments, dues, penalties, fines, costs, amounts paid in settlement,
liabilities, obligations, taxes, liens, losses, lost profits claimed by Third
Parties, expenses, costs and fees (including without limitation interest, court
costs, reasonable fees of attorneys, accountants and other experts or other
expenses of litigation or other proceedings or of any claim, default or
assessment), and includes all damages awardable pursuant to statute and treble
damages.

1.12       “Commercial Bulk Product Specifications” shall mean the manufacturing
and quality specifications for the Bulk Product, including, without limitation,
unit descriptions established initially in accordance with Section 3.01(ii) and
amended from time to time in accordance with Section 3.01(iii) .

1.13       “Commercial Launch” shall mean the first commercial sale of the
Product in any country of the Territory.

1.14       “Competing Product” shall mean any prescription pharmaceutical
product that (i) contains […***…] as an active ingredient or (ii) is used for
the therapeutic or prophylactic treatment of gout (in any form) or other
diseases and conditions involving hyperuricemia and/or monosodium urate
crystals.

1.15       “Current Provisional Bulk Product Specifications” shall mean those
provisional specifications set forth on Exhibit C hereto and any amended and
restated Bulk Product specifications which are agreed to by the Parties in
accordance with Section 3.01(i) .

1.16       “Development Agreement” shall mean that certain Development Agreement
by and between the Parties hereto, dated as of the date hereof.

1.17       “Dollar” shall mean the United States dollar.

 

 

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1.18       “FDA” shall mean the United States Food and Drug Administration or
its foreign equivalent as may be appropriate in any given context.

1.19       “Facility” shall mean, the BTG facility located at Be’er Tuvia
Industrial Zone, POB 571, Kiryat Malachi 83104, Israel, within which, and for
the purposes of the calculation of “Pro Rata Basis” as defined in Section 1.37
there is the:

(i)          “Purification Area” of the Facility used in the Processing of Bulk
Product and comprising the small purification line totaling […***…];

(ii)         “Fermentation Area” of the Facility used from time to time for the
Processing of Bulk Product and comprising the fermentation suite, totaling
[…***…];

(iii)        “Recovery Area” of the Facility used from time to time for the
Processing of Bulk Product and comprising the recovery suite, totaling […***…],
and;

(iv)        “Total Manufacturing Area” of the Facility comprising the portion of
the Facility dedicated to product manufacturing, excluding common areas such as
buffer preparation, totaling […***…].

1.20       “Field” shall mean human therapeutic or prophylactic or diagnostic
applications for the prevention, treatment and/or cure of diseases and physical
conditions.

1.21       “Filled Product” shall mean sterile Product that is in Process and
has been filled into its final primary packaging for further labeling or
packaging activities.

1.22       “Genetic Material” shall mean the master cell bank of the E. coli
strain expressing the […***…] used in the Processing of the Bulk Product.

1.23       “IND” shall mean an Investigational New Drug application, as defined
in 21 C.F.R. 312.3, and filed with the FDA or any equivalent foreign Regulatory
Agency.

1.24       “Joint Inventions” shall mean (i) all patentable inventions jointly
invented (as determined in accordance with United States patent law) by Savient
(or its Affiliates) and BTG (or its Affiliates) pursuant to their activities
relating to this Agreement during the Term, and (ii) all Know-How that Savient
(or its Affiliates) and BTG (or its Affiliates) jointly make, create, develop,
discover, conceive or reduce to practice pursuant to their activities relating
to this Agreement during the Term other than those inventions described in the
preceding clause (i).

1.25       “Know-How” shall mean all technical information, data (including,
without limitation, regulatory data) patentable and unpatentable inventions,
developments, discoveries, methods and processes that are, in each case, not
disclosed in a published patent application or patent or otherwise publicly
available, and includes, without limitation, BTG Know-How.

1.26       “Legal Requirements” shall mean (i) any present and future national,
state, local or similar laws (whether under statute, rule, regulation or
otherwise), (ii) requirements under permits, orders, decrees, judgments or
directives, and requirements of applicable Regulatory Agencies (including,
without limitation, cGMP) and (iii) regulations pertaining to commercially

 

 

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available biologic pharmaceutical products or to maintaining a BLA (with respect
to each of the foregoing, as amended or revised from time to time).

1.27       “Negligence” shall mean an act or omission implying either a failure
to exercise the care which a reasonable or prudent person would do in the
circumstances, or taking action which such a reasonable person would not; as
used herein, a reasonable or prudent person shall be considered to have such
expertise as would be required in order to allow such party to perform the
obligations of the parties hereunder with the level of skill and competence
which prevail in the pharmaceutical industry.

1.28       “Non-Conforming Bulk Product” shall mean any Bulk Product which, at
the time of delivery in accordance with ARTICLE 7, does not meet the Commercial
Bulk Product Specifications.

1.29       “OCS” shall mean Office of Chief Scientist, The Ministry of Industry
and Trade, State of Israel.

1.30       “OCS Requirements” shall mean the requirements of OCS which apply to
the Product, including, without limitation, as specified pursuant to The
Encouragement of Research and Development in Industry Law of 1984, as amended,
and in the agreements by and among Savient, BTG and the OCS.

1.31       “Person” shall mean any individual, partnership, corporation, limited
liability company, unincorporated organization or association, any trust or any
other business entity.

1.32       “Process” or “Processing” shall mean the act of purification,
preparation, filling, testing and any other pharmaceutical manufacturing
procedures, or any part thereof (including, but not limited to, product or
process specifications, testing or test methods, raw material specifications or
suppliers, equipment, etc.), relating to, as applicable, the Bulk Product and
Product.

1.33       “Product” shall mean pharmaceutical products containing Bulk Product
ordered by Savient pursuant to this Agreement.

1.34       “Product Liability Claim” shall mean a Claim of a Third Party (other
than a Claim arising out of use of the Product in a clinical trial) that (i)
arises as a result of the use of the Product during the Term that results in
personal injury or death or (ii) is in anticipation of or intended to prevent or
forestall personal injury or death as a result of the use of the Product during
the Term.

1.35       “Product Technology” shall mean the (i) Savient Patent Rights, (ii)
Savient Know-How, (iii) BTG Assigned Improvements, (iv) BTG Licensed
Improvements, (v) BTG Know-How, (vi) any developments, discoveries, inventions,
improvements, designs, methods, processes, techniques, devices, formulae, and
trade secrets which are or may be (A) developed, acquired or conceived by
Savient and/or BTG and are derived from the Development Plan performed under the
terms of the Development Agreement, developed by BTG prior to July 17, 2005 and
related to the Bulk Product or used in the Processing of Bulk Product, or are
derived from the manufacture and supply of Bulk Product, or (B) used in the
Processing of Bulk Product.

 

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1.36       “Product Specifications” shall mean the manufacturing and quality
specifications for the Product as attached hereto as Exhibit G as they may be
modified from time to time.

1.37       “Pro-Rata Basis” shall mean when Facility changes will be implemented
pursuant to the provisions of Section 6.03(ii)(B) and:

(i)          such Facility changes will impact the totality of the Total
Manufacturing Area and/or the common and technical areas related to
manufacturing, the cost of the changes multiplied by a percentage, where such
percentage equals

[…***…]

(ii)         when such Facility changes will impact only the Fermentation Area,
[…***…]

(iii)        when such Facility changes will impact only the Recovery Area,
[…***…]

1.38       “Quality Agreement” shall mean that certain Quality Agreement by and
between the Parties hereto, dated as of the date hereof and attached to this
Agreement as Exhibit D.

1.39       “Regulatory Agency” shall mean with respect to the United States, the
FDA, or, in the case of a country in the Territory other than the United States,
such other appropriate regulatory agency with similar responsibilities.

1.40       “Residual Rights Agreement” shall mean that certain Amended and
Restated Residual Rights Agreement by and between Savient and BTG, effective as
of July 17, 2005, and attached hereto as Exhibit F.

1.41       “SAE” shall mean, with respect to the Product, any serious adverse
event occurring during clinical trials of the drug at any dose that results in
any of the following outcomes: death, a life-threatening adverse drug
experience, inpatient hospitalization or prolongation of existing
hospitalization, a persistent or significant disability/incapacity, or a
congenital anomaly/birth defect. Important medical events that may not result in
death, be life-threatening or require hospitalization may be considered a
serious adverse drug experience when, based upon appropriate medical judgment,
they may jeopardize the patient or subject and may require medical or surgical
intervention to prevent one of the outcomes listed in this definition. Examples
of such medical events include allergic bronchospasm requiring intensive
treatment in an emergency room or at home, blood dyscrasias or convulsions that
do not result in patient hospitalization, or the development of drug dependency
or drug abuse.

1.42       “Savient Improvements” shall mean all inventions related to the Bulk
Product or Product (including, without limitation, its pharmaceutical utility)
and/or Processing of the Bulk Product or Product which are made, created,
developed or conceived, or reduced to practice or come to be owned, by Savient
or an Affiliate of Savient and are dominated by the Savient Patent Rights.

 

 

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1.43       “Savient Indemnitee” shall mean Savient and its Affiliates, and each
of their respective directors, officers, employees and agents.

1.44       “Savient Know-How” shall mean all Know-How developed by Savient or
any of its Affiliates during the Term relating to (i) the Bulk Product or
Product (including, without limitation, its pharmaceutical utility) or (ii) the
Processing of the Bulk Product or Product, and shall include, without
limitation, all data relating to formulation, analytical methods, pre-clinical
and clinical trials, pharmacology, toxicology, regulatory information, and data
relating to the manufacture and use of such Bulk Product or Product.

1.45       “Savient Patent Rights” shall mean all valid patent claims contained
in (i) the patent(s) and patent applications listed on Exhibit A; (ii) all
converted provisionals, divisions, continuations, continuations-in-part,
reissues, reexaminations or extensions thereof; (iii) any corresponding foreign
counterparts and equivalents thereof; and (iv) any patents or patent
applications filed after July 17, 2005.

1.46       “Sublicensee” shall mean any Third Party or Affiliate to whom a
sublicense has been granted pursuant to Section 2.05.

1.47       “Term” shall have the meaning set forth in Section 11.01.

1.48       “Territory” shall mean, collectively, each country in the world.

1.49       “Third Party” shall mean any Person who is not a Party or an
Affiliate under this Agreement.

1.50       “Time” shall mean for the purposes of the calculation of Pro Rata
Basis, as defined in Section 1.37, the percentage based on […***…]

1.51       “United States” shall mean the fifty states of the United States of
America, the District of Columbia and all territories and possessions of the
United States of America and any other location where the FDA has jurisdiction
over medicinal products intended for human use.

ARTICLE 2

INTELLECTUAL PROPERTY LICENSES

2.01       Grant of Licenses; Assignment.

(i)          No restriction of license rights under the Residual Rights
Agreement. The parties are agreed that the following provisions shall not in any
way remove or restrict the rights pertaining to the grant of licenses to either
party (“RRA License Rights”) as they exist pursuant to the Residual Rights
Agreement. In the event of a conflict between this Agreement

 

 

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and the Residual Rights Agreement with respect to the RRA License Rights, the
relevant provisions of the Residual Rights Agreement shall take precedence.

(ii)         Grant by Savient. Savient hereby grants to BTG, and, if applicable,
shall cause its Affiliates to grant to BTG, a fully paid-up, royalty-free,
non-exclusive license within the State of Israel (“BTG Territory”) to
manufacture, have manufactured, produce, have produced, develop, have developed,
use, have used, offer for sale, have offered for sale, sell, have sold, export,
and have exported Bulk Product under the Savient Patent Rights, the Savient
Know-How, and the rights to the Savient Improvements for supply exclusively to
Savient.

(iii)        Grant by BTG. BTG hereby grants to Savient and, if applicable,
shall cause its Affiliates to grant to Savient, a fully paid-up, royalty-free,
non-exclusive license in the Territory to manufacture, have
manufactured,“***Confidential Treatment Requested” produce, have produced,
develop, have developed, use, have used, offer for sale, have offered for sale,
sell, have sold, export, and have exported Bulk Product under the BTG Licensed
Improvements and BTG Know-How.

(iv)        Assignment by BTG. BTG shall promptly assign (and, if applicable,
shall cause its Affiliates to assign) to Savient all right title and interest in
and to any invention or discovery which may be claimed as a BTG Assigned
Improvement. BTG shall execute (and, if applicable, shall cause its Affiliates
to execute) such documents as may be necessary to obtain, perfect or maintain
any patent rights arising out of the BTG Assigned Improvements, and shall
cooperate with Savient so far as reasonably necessary with respect to furnishing
all information and data in its possession which is reasonably necessary or
useful to obtain and maintain such patent rights.

2.02       Notice of Improvements & Joint Inventions. BTG shall give Notice to
Savient of all BTG Assigned Improvements, BTG Licensed Improvements and Joint
Inventions promptly within due course of the discovery or creation thereof, but
in any event at least thirty (30) days prior to any proposed publication thereof
by BTG, its Affiliates or Sublicensees. Savient shall give Notice to BTG of all
Savient Improvements and Joint Inventions promptly within due course of the
discovery or creation thereof, but in any event at least thirty (30) days prior
to any proposed publication thereof by Savient, its Affiliates or Sublicensees.
The Parties shall, in any event, notify each other no less than annually, of
whether they have made any BTG Assigned Improvements, BTG Licensed Improvements,
Savient Improvements or Joint Inventions, as the case may be.

2.03       Disclosure of Know-How. BTG shall disclose, and shall cause its
Affiliates to disclose, as soon as reasonably practicable, to Savient all BTG
Know-How acquired, developed or which comes to be possessed by the BTG or any of
its Affiliates after the date hereof (and upon reasonable request by Savient,
shall make such disclosure in writing).

2.04       Use of Joint Inventions.

(i)          Subject to subsections (ii) and (iii) hereof, each Party shall have
the right to practice under the Joint Invention rights without any duty of
accounting to the other Party.

(ii)         BTG agrees that, except as otherwise agreed by the Parties in
writing, it shall not (and shall, if applicable, ensure that its Affiliates
shall not) (A) grant any license under the

 

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Joint Invention Rights to any other Person to manufacture, have manufactured,
produce, have produced, develop, have developed, use, have used, market, have
marketed, import, have imported, export, have exported, sell or have sold any
Competing Product, or (B) practice any Claim under the Joint Inventions rights
to manufacture, have manufactured, produce, have produced, develop, have
developed, use, have used, market, have marketed, import, have imported, export,
have exported, sell or have sold any Competing Product.

(iii)        Each Party agrees that it shall (and shall, if applicable, ensure
that its Affiliates shall) notify the other Party before granting any license to
any other Person to manufacture, have manufactured, produce, have produced,
develop, have developed, use, have used, import, have imported, export, have
exported, offer for sale, have offered for sale, sell or have sold any product
outside the Field under the Joint Invention rights; provided, however, that
neither Party shall grant or purport to grant any license under the Joint
Invention rights that is exclusive as to the other Party or its assignees or
Sublicensees without the prior written consent of such other Party.

2.05       Sublicensing. Savient shall have the right to grant sublicenses of
licenses granted to it in Section 2.01 of this Agreement to its Affiliates and
to any Third Party; provided, however, that Savient, to the extent applicable,
(i) ensures that each such Sublicensee and Third Party shall consent to be bound
by the terms of this Agreement as a Sublicensee or Third Party and to the same
extent as Savient with respect to such Sublicenses or Third Party’s activities,
(ii) informs BTG, in confidence, of each sublicense granted, and any
modification or termination thereof, within sixty (60) days after the
modification, or termination of a sublicense and (iii) guarantees to BTG the
performance of any of its obligations which it fulfills through sublicensing and
remains primarily liable for the performance of such obligations.

2.06       OCS Requirements. BTG shall not without prior written approval of
Savient (and, if applicable, shall ensure that its Affiliates shall not) take
any action (including, without limitation, Processing the Bulk Product outside
the State of Israel) which would (i) cause either Party (or any of their
Affiliates) to violate any of the OCS Requirements or (ii) result in any
increase of royalties due to OCS. Additionally, upon request by Savient, BTG
shall cooperate and collaborate with Savient in applying to the OCS for Savient
to carry out the manufacture of the Bulk Product through a Third Party outside
the State of Israel. The Parties acknowledge the rights and obligations of each
Party under Section 5 of the Residual Rights Agreement and each Party shall
honor such rights and obligations set forth therein.

ARTICLE 3

SPECIFICATIONS; ONGOING REGULATORY ASSISTANCE

3.01       Specifications.

(i)          Current Provisional Bulk Product Specifications. The Current
Provisional Bulk Product Specifications are attached as Exhibit C. The Parties
are agreed that the Current Provisional Bulk Product Specifications may still be
subject to modification based on the outcome of the Validation, as defined and
performed pursuant to the Development

 

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Agreement, and subject to the mutual agreement of the parties, such agreement
not to be unreasonably conditioned, delayed or withheld.

(ii)    Initial Commercial Bulk Product Specifications. The initial Commercial
Bulk Product Specifications shall be agreed upon in writing by the Parties, as
soon as reasonably practicable after the conclusion of the Validation, as
defined and performed pursuant to the Development Agreement, but in no event
later than ninety (90) days from the conclusion of the Validation, unless the
Parties shall mutually agree to extend such time period (hereinafter the
“Commercial Bulk Product Specifications”). The Commercial Bulk Product
Specifications shall be incorporated into this Agreement by formal amendment as
Exhibit C-1 and shall be the controlling standards for the manufacture of Bulk
Product pursuant to this Agreement unless and until they are changed by written
agreement between the parties. In determining the Commercial Bulk Product
Specifications, the Parties shall take into consideration particularly (i) the
results of the subsequent development activity of BTG under the Development
Agreement and (ii) the results of the Validation as defined and performed
pursuant to the Development Agreement.

(iii)    Amendment of Commercial Bulk Product Specifications. Subject to the
provisions of Section 6.02 and 6.03 (including the cost reimbursements
provisions thereof), Savient shall have the right to amend the Commercial Bulk
Product Specifications from time to time; provided, however, that (i) Savient
shall use commercially reasonable efforts to minimize the frequency of such
changes and shall provide BTG with reasonable advanced Notice of any changes to
the Commercial Bulk Product Specifications (but, in any event, at least ninety
(90) days advance notice) and (ii) the Parties have agreed in writing upon the
implications and costs related to any contemplated changes pursuant to this
Section 3.01, which agreement shall not be unreasonably conditioned, withheld or
delayed. Without in any way limiting the foregoing, any modifications to the
Commercial Bulk Product Specifications required by any Regulatory Agency with
jurisdiction to require such modifications shall be made in accordance
therewith.

3.02    Ongoing Assistance by BTG for Initial and Subsequent Filings or
Applications.

(i)    Upon the expiration or earlier termination of the Development Agreement,
BTG hereby agrees to provide, in respect to any jurisdiction within the
Territory (A) all information and assistance which is reasonably necessary for
or useful in the preparation of (i) comprehensive and complete INDs and BLAs,
including, without limitation, the Chemistry Manufacturing and Controls (CMC)
section of the BLAs for the Product, (ii) any amendments and supplements to such
filings and applications, (iii) subsequent filings and applications for
secondary indications or additional marketing, sale, importing, exporting
authorizations, or (iv) similar filings and applications and (B) access to the
Facility and pertinent information to FDA inspectors conducting the pre-approval
inspection. All documents to be supplied by BTG pursuant to this Section 3.02 or
any other provision of this Agreement shall be translated by BTG into the
English language as may be necessary. Any labor costs of BTG employees and/or
Third Party expenses incurred by BTG related to this assistance shall be
reimbursed by Savient in the manner and at the rates set forth on Exhibit B
hereto.

 

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(ii)    Ownership. The Parties agree that all INDs and BLAs arising under this
Agreement, including any and all modifications and supplements thereto, will be
owned by and held in the name of Savient and will list BTG in accordance with
its role as contemplated under this Agreement and in compliance with the Legal
Requirements. BTG shall have no rights in or to the IND or BLA and any and all
modifications and supplements thereto, other than any rights specifically
granted pursuant to this Agreement.

3.03    Record and Files. Upon the expiration or earlier termination of the
Development Agreement, BTG shall maintain those documents required by the
applicable Legal Requirements during the Term and for any period required by
such Legal Requirements. BTG shall maintain those records specified in 21 C.F.R.
§ 600.12(e) for cases of divided manufacturing responsibility for biologics and
shall provide the records as specified therein to any Third Party fillers or
manufacturers designated by Savient.

ARTICLE 4

SUPPLY OF INGREDIENTS AND MATERIALS

4.01    Procurement of Ingredients and Materials.

(i)    Ordinary and Safety Stocks. Ingredients and materials necessary for the
Processing of Bulk Product shall be purchased and stored by BTG in accordance
with the terms of the Quality Agreement and in commercially reasonable and
prudent production and safety stock quantities necessary to meet the Bulk
Product Forecast (as defined in Section 5.03) giving due regard to the potential
for production and batch failures, Bulk Product loss until delivery to Savient
and the amendment of the Bulk Product Forecast in accordance with Section 5.06.

(ii)    PEG Purchases from NOF. The foregoing notwithstanding, Savient, in its
sole and absolute discretion, shall have the right, but not the obligation, to
directly contract with NOF Corporation for m-PEG-NPC (mono-methoxy polyethylene
glycol nitro-phenyl carbonate) (hereinafter the “PEG”) necessary for BTG to
Process the Bulk Product, provided, however, in the event Savient elects to do
so, then (i) Savient shall use best efforts to ensure that adequate stock,
including safety stock quantities, of PEG, in amounts to be agreed upon between
the Parties, are delivered to BTG in a timely manner in order to enable BTG to
fulfill its obligations to Process Bulk Product to meet the requirements of all
Purchase Orders placed by Savient pursuant to Section 5.05; (ii) BTG agrees that
it will, in accordance with the terms of the Quality Agreement, store and test,
as applicable, such stock of PEG delivered by NOF; (iii) BTG shall reimburse
Savient for the cost of any PEG utilized in the Processing of Bulk Product that
is determined to be (a) Non-Conforming Bulk Product, or (b) a failed batch; (iv)
that such agreement between Savient and NOF shall not materially interfere with
the terms of this Agreement or unduly interfere with BTG’s ability to carry out
its work; and (v) the inability of BTG to perform under the terms of this
Agreement, where such failure is due to the failure of Savient to ensure the
timely delivery to BTG of adequate stock of PEG shall not be deemed to be a
breach by BTG of its obligations under this Agreement.

 

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4.02       Maintenance of Genetic Material. From the Effective Date, BTG shall
(or shall procure one of its Affiliates to) maintain such quantity of Genetic
Material to meet Purchase Orders placed and the Bulk Product Forecast provided
by Savient pursuant to ARTICLE 5. In the event of the expiration or termination
of this Agreement, BTG shall, within thirty (30) days of the effective date of
such expiration or termination, transfer to Savient or its designee any and all
remaining quantities of Genetic Material. Any labor costs of BTG employees
and/or Third Party expenses incurred by BTG related to transfer of Genetic
Material shall be reimbursed by Savient in the manner and at the rates set forth
on Exhibit B hereto.

4.03       Reference Materials. BTG shall provide Savient with any physical,
chemical or biological material that is otherwise unavailable, which is to be
used as a reference standard in the testing of Bulk Product, ingredients or raw
materials. Such physical, chemical or biological material shall be provided to
Savient at […***…]. Payments due by Savient under this Section 4.03 shall be
payable by Savient no later than […***…] days after the invoice date.

ARTICLE 5

BTG FACILITY CAPACITY, FORECASTING, PURCHASE ORDERS

AND ORDER CONFIRMATIONS

5.01       BTG Facility Bulk Product Processing Capacity and Capacity
Reservation Fee.

(i)          Existing Facility Capacity. Savient and BTG acknowledge that based
on the (A) Purification Area used in the Processing of Bulk Product, (B) the
Fermentation Area and the Recovery Area used from time to time for the
Processing of Bulk Product, (C) methods, processes and procedures currently
utilized in the Processing of Bulk Material as of the Effective Date, and (D)
[…***…] in the Facility as of the Effective Date (hereinafter the “Capacity
Parameters”), the BTG Facility has the projected capacity to Process up to
[…***…] batches of Bulk Product per calendar year in the absence of other
products manufactured in the areas specified above. Additionally, Savient and
BTG acknowledge that this capacity could be increased, upon appropriate advance
notice, if additional shift operations were implemented and/or certain Facility
changes were made.

(ii)         Subject to the terms set forth in this Section 5.01(ii), in order
to reserve capacity at BTG for the Processing of Bulk Product, for all Bulk
Product forecasted by Savient to be Processed by BTG and purchased by Savient
prior to the Commercial Launch of the Product and through […***…] (hereinafter
the “Reservation Fee Period”), Savient shall remit to BTG a Processing Capacity
Reservation Fee in the amounts and manner set forth below:

(A)        Within ten (10) Business Days of the provision of the Preliminary
Bulk Product Forecast pursuant to Section 5.02, Savient shall remit to BTG a
Processing Capacity Reservation Fee of […***…] ($[…***…]).

 

 

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(B)        Within ten (10) Business Days of the provision of the Bulk Product
Launch Forecast pursuant to Section 5.03, Savient shall remit to BTG a
Processing Capacity Reservation Fee equal to the amount required to bring
Savient’s Processing Capacity Reservation Fee, when added to the amount remitted
under Section 5.01(ii)(A), to […***…] percent ([…***…]%) of the applicable
Price, as defined in Section 8.01, of the number of batches of Bulk Product
reflected on such Bulk Product Launch Forecast, provided, however, if the amount
calculated under this Section 5.01(ii)(B) is less than the Processing Capacity
Reservation Fee remitted under Section 5.01(ii)(A) the Processing Capacity
Reservation Fee shall remain at such higher amount. In the event that the
initial Bulk Product Launch Forecast pursuant to section 5.03 is not provided by
September 30, 2007, then Savient shall remit monthly to BTG an additional
Processing Capacity Reservation Fee of $[…***…] for each additional month that
passes until the provision of the initial Bulk Product Launch Forecast.

(C)        Within ten (10) Business Days of the provision of any Bulk Product
Forecast pursuant to Section 5.03 or any Amended Bulk Product Forecast provided
by Savient pursuant to Section 5.06 provided by Savient on or before July 1,
2009, Savient shall remit to BTG a Processing Capacity Reservation Fee equal to
the amount required to bring Savient’s Processing Capacity Reservation Fee, when
added to the amount remitted under Sections 5.01(ii)(A) and 5.01(ii)(B), to
[…***…] percent ([…***…]%) of the applicable Price, as defined in Section 8.01,
of the number of batches of Bulk Product reflected on such Bulk Product Forecast
or Amended Bulk Product Forecast that are projected for purchase during the
Reservation Fee Period, provided, however, if the amount calculated under this
Section 5.01(ii)(C) is less than the aggregate of the Processing Capacity
Reservation Fee remitted under Sections 5.01(ii)(A) and 5.01(B) the Processing
Capacity Reservation Fee shall remain at such higher amount.

(D)         All Processing Capacity Reservation Fee amounts remitted by Savient
to BTG under this Section 5.01(ii) shall:

(1) earn interest at the […***…] with the interest earned thereon inuring to the
sole benefit of Savient;

(2) be credited, inclusive of interest, by BTG on a per batch basis by providing
a […***…]% discount on the value of each batch at the time of invoicing for Bulk
Product purchased by Savient during the Reservation Fee Period until it is fully
utilized, provided however, except as otherwise provided in Sections
5.01(ii)(F), 5.01(ii)(G) and 5.01(ii)(H), any uncredited Processing Capacity
Reservation Fee, inclusive of interest, remaining at the end of the Reservation
Fee Period due to a failure by Savient to take delivery of Bulk Product which
conforms to the Commercial Bulk Product Specifications and which is ordered
pursuant to a Bulk Product Forecast provided pursuant to Section 5.03 or an
Amended Bulk Product Forecast provided pursuant to Section 5.06 and which is
otherwise properly amended pursuant to Section 5.05 shall be forfeited by
Savient to BTG. For purposes of clarity, the credit of the Processing

 

 

***Confidential Treatment Requested

 

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Capacity Reservation Fee shall accrue upon the delivery of the Bulk Product by
BTG to Savient and shall be reflected on the invoice which relates to the Bulk
Product shipment in question; and

(3) BTG shall provide to Savient a quarterly statement within […***…] Business
Days of the end of each calendar quarter of the then current balance of the
Processing Capacity Reservation Fee, inclusive of interest, available for credit
to the purchase of Bulk Product by Savient.

(E)        Subject to the last sentence of this Section 5.01(ii)(E), Savient and
BTG acknowledge and agree that by the conclusion of the Reservation Fee Period
the demand for Savient’s Product will be sufficiently capable of reliable
forecasting as to negate the need for a Processing Capacity Reservation Fee and
that such will not be required for Bulk Product forecasted for purchase beyond
the expiration of the Reservation Fee Period. On that basis, the final
Processing Capacity Reservation Fee shall be due based on […***…] percent
([…***…]%) of the applicable Price, as defined in Section 8.01, of the number of
batches of Bulk Product reflected on the Bulk Product Forecast or Amended Bulk
Product Forecast that is submitted for the period […***…]. If there is a delay
in the commercial launch of the Product beyond […***…] or any other factor
reasonably preventing a reliable Bulk Product forecasting by the conclusion of
the Reservation Fee Period, then the Parties will meet in good faith and discuss
whether a further capacity reservation fee is necessary or appropriate and, if
it is agreed necessary, for what duration and amount, if any.

(F)        Anything to the contrary notwithstanding, in the event that any
amount of the Processing Capacity Reservation Fee, inclusive of interest,
remains unused or unapplied at the end of the Reservation Fee Period due to a
failure by BTG for any reason, including Force Majeure conditions affecting BTG
or the import, export or transportation of the Bulk Product which is beyond the
reasonable control of BTG or Savient, to timely deliver any number of batches of
Bulk Product properly ordered and accepted in accordance with the terms of this
Agreement, then any amount of the Processing Capacity Reservation Fee, inclusive
of interest, which would have been used for or applied to the purchase of Bulk
Product but for the non-delivery or untimely delivery thereof, shall be refunded
to Savient by wire transfer within […***…] Business Days of the end of the
Reservation Fee Period. For purposes of determining timely delivery pursuant to
this section, the delivery dates identified in a Purchase Order submitted and
accepted in accordance with Section 5.05 herein shall be considered binding,
except in the event of a Force Majeure condition affecting BTG or the import,
export or transportation of the Bulk Product which is beyond the reasonable
control of BTG or Savient, in which case the Parties shall agree upon a
reasonable extension of the delivery date in accordance with Section 14.14
hereof.

(G)        In the event this Agreement is terminated by Savient pursuant to
Sections 11.02 (ii) (for Force Majeure conditions affecting BTG), 11.02 (iii)
(Material Breach by BTG), or 11.02 (v) (for insolvency of BTG) hereof, any
amount of the Processing Capacity Reservation Fee and accrued interest thereon
which has not been applied to payments for Bulk Product actually purchased by
and delivered to Savient, shall be

 

 

***Confidential Treatment Requested

 

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returned to Savient via wire transfer within […***…] days of the effective date
of termination of this Agreement. In the event this Agreement is terminated with
the mutual consent of both Parties, then, as part of such mutual consent, the
Parties shall discuss in good faith and reach resolution with regard to the
disposition of the then-existing Capacity Reservation Fee, including any
interest thereon, having due regard for the reasons and basis that lead the
Parties to terminate this Agreement by mutual consent.

(H)        Savient and BTG further acknowledge and agree that in the event the
BLA for Savient’s Product is not filed with the FDA on or before December 31,
2008 then the Processing Capacity Reservation Fee previously paid by Savient to
BTG and accrued interest thereon relating to Bulk Product Forecasts provided by
Savient before December 31, 2008 shall be refundable to Savient only in the
event and to the extent that BTG is able, with the use of best efforts, to
mitigate its losses by scheduling into the Processing Capacity reserved for
Savient during such period production of a product or products on behalf of BTG,
an Affiliate, or a third party, or any combination thereof.

5.02       Preliminary Bulk Product Forecast. As soon as reasonably practicable,
but in no event later than thirty (30) days from the date of full execution of
this Agreement, Savient shall provide BTG a preliminary, non-binding projection
of its first eighteen month rolling forecast that sets forth Savient’s then best
estimate of the date for the delivery of the first commercial quantity of Bulk
Product and the total quantity of Bulk Product for commercial supply that
Savient expects to order from BTG within the eighteen (18) month period
following delivery of such first commercial quantity (“Preliminary Bulk Product
Forecast”). In the Preliminary Bulk Product Forecast, Savient shall:

(i)          set forth the assumptions it is utilizing for the establishment of
the date for the delivery of the first commercial quantity of Bulk Product;

(ii)         include a breakdown of the total quantity of Bulk Product by month
for the eighteen months following the delivery of the first commercial order;
and

(iii)        identify the variables, Process and regulatory questions and issues
and logistical considerations that could impact the date for the delivery of the
first commercial quantity of Bulk Product.

Within thirty (30) days of the issuance of the Preliminary Bulk Product
Forecast, Savient and BTG shall meet to commence good faith discussions and
agree on the methodology and timeline for bringing to resolution and conclusion
any and all Process and regulatory questions, issues and logistical
considerations outlined in the Preliminary Bulk Product Forecast. Savient and
BTG shall use their mutual best efforts to conclude these discussions and reach
final resolution as soon as reasonably practicable, but in no event later than
July 30, 2007, unless the parties mutually agree that additional time is
required.

5.03       Bulk Product Launch Forecast and Bulk Product Forecast. Commencing at
least twelve (12) months prior to the delivery date of the first Firm Order,
Savient shall submit to BTG its final initial launch Bulk Product forecast which
shall set forth month by month an eighteen (18) month rolling forecast that sets
forth the total quantity of Bulk Product for commercial supply

 

 

***Confidential Treatment Requested

 

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that Savient either has ordered, desires to order, or expects to order from BTG
within the eighteen (18) month period following delivery of such first
commercial quantity (“Bulk Product Launch Forecast”). Thereafter, Savient shall
provide on a monthly basis on or before the first Business Day of each calendar
month an updated Bulk Product forecast for the next ensuing eighteen (18) month
rolling period (“Bulk Product Forecast”). In the Bulk Product Forecast, Savient
shall:

(i)          include a breakdown of the total quantity of Bulk Product by month
for the following eighteen (18) month rolling period; and

(ii)         in respect of the monthly breakdown under (i) above, identify the
relevant set of Bulk Product Specifications.

As used herein, the term “Forecast” shall mean, as applicable, the Bulk Product
Launch Forecast or Bulk Product Forecast, as may be amended from time to time
pursuant to Section 5.06 hereof.

5.04       Firm Orders and Firm Forecasts. The Bulk Product Forecast submitted
monthly by Savient shall breakdown by month of the next ensuing eighteen (18)
months of the Bulk Product Forecast and shall consist of:

i.            a rolling firm irrevocable order for the first two (2) quarters
(i.e. quarters 1 and 2) of the Bulk Product Forecast (“Firm Order”), which shall
each be the subject of a Purchase Order delivered and confirmed in accordance
with Section 5.05;

ii.           a rolling two (2) quarter forecast for the second two (2) quarters
(i.e. quarters 3 and 4) of the Bulk Product Forecast (each a quarterly “Firm
Forecast”); and

iii.          a rolling two (2) quarter estimate for the third two (2) quarters
(i.e. quarters 5 and 6) of the Bulk Forecast (each a quarterly “Estimated
Forecast”).

5.05       Purchase Orders and Order Confirmations. Savient will accompany its
monthly update of the Bulk Product Forecast with a written purchase order
(“Purchase Order”) for each new Firm Order that was only a Firm Forecast in the
previous month’s Bulk Product Forecast. Each Purchase Order shall specify the
Bulk Product ordered and the time, manner and address of delivery, all of which
shall be subject to this ARTICLE 5. BTG shall confirm each Purchase Order in a
written order confirmation within seven (7) Business Days after receipt of the
Purchase Order.

5.06       Amending Forecasts. Any Bulk Product Forecast that is not a Firm
Order is to be considered a forecast or estimate to be used for planning
purposes, and shall not be construed as a firm commitment by Savient to BTG and
thus can be increased or reduced by Savient from time to time. Savient shall be
entitled at any time up until and including the time that a Firm Forecast or
Estimated Forecast becomes a Firm Order, to increase or decrease such monthly
Firm Forecast or Estimated Forecast for Bulk Product, provided, however, such
increases or decreases on a monthly basis shall not be greater than twenty-five
percent (25%) of the originally forecasted quantity for such month and each
month may not be increased and decreased more than one time. As a request by
Savient to increase the quantity of Bulk Product in a Firm Forecast prior to its
becoming a Firm Order may require longer lead times for delivery than

 

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requested by Savient, both Parties shall agree jointly on a new delivery date as
close as possible to the requested date having due regard for BTG’s commercial
commitments to Third Parties and its own production needs, such agreement to not
be unreasonably withheld, conditioned or delayed. Once a Firm Forecast becomes a
Firm Order, Savient may not reduce it, but may request that BTG increase the
quantity of Bulk Product subject to a Firm Order and BTG shall use commercially
reasonable efforts to fill the increased order.

5.07       Fulfillment of Purchase Orders; Review of Forecasts.

(i)          BTG shall satisfy, in accordance with their terms, Savient’s
Purchase Orders, provided and confirmed in accordance with Section 5.05. BTG
shall promptly notify Savient if it becomes aware or believes that it will not
be able to satisfy such Purchase Orders on time, in full, or at all, which
Notice shall include an explanation in reasonable detail of the reason for BTG’s
failure to comply with a confirmed Purchase Order and its proposed course of
action for remedying such failure. Savient shall be entitled to request BTG to
produce evidence to support its Notice, BTG’s response to such request shall not
be unreasonably denied or delayed.

(ii)         Within ten (10) Business Days of its receipt of the Bulk Product
Launch Forecast or a Bulk Product Forecast or any amendment thereto, BTG shall
review such Forecast and in the event that BTG believes that it will not be able
to satisfy the quantity, time or manner for delivery of any portion of the order
for any amount of Bulk Product identified in any portion therein (i.e.: in the
Firm Order, Firm Forecast or Estimated Forecast portions), BTG shall notify
Savient of the same, provide a reasonable explanation of the cause of its
inability to do so and provide alternatives for the delivery of the quantity
and/or scheduling or manner of delivery to satisfy the requirements of Savient.

(iii)        Unless BTG has indicated, in accordance with Section 5.07(ii), an
inability to satisfy the identified quantities of Bulk Product in the Bulk
Product Launch Forecast, any Bulk Product Forecast, or any amendment thereto,
BTG may not refuse to accept a Purchase Order which does not deviate from the
previously provided Bulk Product Launch Forecast, Bulk Product Forecast or
amended forecast, as the case may be when, on a rolling basis, months contained
in a Firm Forecast or Estimated Forecast period becomes a Firm Order.

(iv)        In the event that BTG notifies Savient of its inability to supply
any subject quantity of Bulk Product identified in the Bulk Product Launch
Forecast, any Bulk Product Forecast or amended forecast, the parties agree to
work together in good faith to expeditiously resolve the discrepancy between the
subject forecast and BTG’s inability to supply Bulk Product in accordance
therewith.

5.08       Effect of Supply Failure. In the event of a Supply Failure (as
defined herein), no forecast or estimate shall be considered a Firm Order until
such time as BTG proves to Savient’s reasonable satisfaction that the cause of
such Supply Failure has been corrected. “Supply Failure” shall mean BTG has
experienced […***…] failed batches of Bulk Product within a calendar quarter, or
[…***…] failed batches of Bulk Product aggregated over the course of two
consecutive quarters, or […***…] failed batches of Bulk Product aggregated over
the course of a calendar year. For purposes of this definition, any Bulk Product
that is discovered and notified by Savient in accordance with Section 6.04 (iv)
to be Non-Conforming Bulk Product after

 

 

***Confidential Treatment Requested

 

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delivery shall be considered a failed batch. In the event of a Supply Failure
during the Reservation Fee Period, the period covered by the Reservation Fee
Period shall be extended by the quarterly or other period of such Supply
Failure.

5.09       Preferential Right of Supply. BTG shall schedule its own products or
those of an Affiliate for processing at the Facility and shall not accept from a
customer that is a Third Party any orders for product processed at the Facility
to the extent the fulfillment of such scheduling or order could, at the time of
BTG’s scheduling or acceptance of such Third Party order, reasonably be expected
to impede BTG’s ability to fulfill Savient’s Bulk Product Requirements as
reflected on the then current monthly Firm Orders, Firm Forecast and Estimated
Forecast submitted by Savient pursuant to Section 5.04 and acted upon by the
Parties pursuant to Sections 5.05, 5.06, and 5.07 supra.

5.10       Alternative Supplier. Savient shall have the right to establish an
alternative supplier for Bulk Product for up to twenty percent (20%) of its
annual world-wide Bulk Product requirements; provided, however,

(i)         in the event of a Supply Failure under Section 5.08 above, Savient
shall have the right to purchase all of its Bulk Product requirements from an
alternative supplier upon reasonable prior written notice to BTG until BTG
demonstrates to Savient’s reasonable satisfaction that BTG has fully remedied
such Supply Failure, and

(ii)        if despite the good faith efforts of BTG to modify its Capacity
Parameters to meet the needs of Savient, or, as applicable, the Parties good
faith efforts to agree on cooperative methods to modify the BTG Capacity
Parameters, Savient’s Forecasts for orders of Bulk Product up to the OCS
Requirements are reasonably anticipated to exceed BTG’s available capacity for
the Processing of Bulk Product, then Savient shall have the right to purchase
any and all of its requirements of Bulk Product that Savient reasonably
determines in good faith may exceed BTG’s available capacity from Savient’s
alternate supplier.

BTG acknowledges its obligation to assist Savient with Technology Transfer to an
alternative contract manufacturing organization in accordance with the terms and
conditions of Section 5.02 of the Development Agreement.

5.11       Effect of Termination on Purchase Order. Unless otherwise agreed to
in writing by the Parties, the termination of this Agreement shall automatically
terminate all then existing Purchase Orders, except when the termination of this
Agreement is pursuant to Sections 11.02 (i) (Elective) and 11.02(iv) (Material
Breach by Savient), provided such material breach by Savient is not based on the
non-payment of non-disputed amounts for Bulk Product deliveries, in which case
BTG shall honor and fulfill any then existing Purchase Order and Savient shall
pay BTG for any Purchase Order so honored and fulfilled by BTG pursuant to the
terms of this Agreement.

 

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ARTICLE 6

PRODUCTION

6.01       Obligation to Supply and Purchase. BTG shall manufacture and supply
all Bulk Product quantities ordered by Savient and confirmed by BTG in
accordance with the provisions of this Agreement. The Parties acknowledge and
agree that, pursuant to the OCS Requirements and subject to the terms of this
Agreement, Savient is obligated to order at least 80% of its annual world-wide
Bulk Product requirements from BTG (“OCS Annual Requirements”) and BTG is
obligated to provide such OCS Annual Requirements. BTG shall bear all risk of
loss associated with production and batch failures or loss of Bulk Product until
delivery to Savient, in accordance with the provisions of Section 7.01.

6.02       Process Changes.

(i)          Prior Approval of Savient Required. Except as set forth in this
Section 6.02, BTG shall not make any change to the Process for the Bulk Product
that would have an impact on the Bulk Product or Product, result in a change to
the Commercial Bulk Product Specifications or the Product Specifications or
require submissions to or approvals from any Regulatory Agency, except by prior
written approval of Savient for such change, which approval shall not be
unreasonably conditioned, withheld or delayed.

(ii)         Changes Based on Applicable Legal Requirements. BTG shall make such
changes to the Process for the Bulk Product as may be required pursuant to
applicable Legal Requirements; provided that BTG shall have notified Savient in
advance of any required change and shall have obtained the prior written
approval of Savient for such change, which approval shall not be unreasonably
conditioned, withheld or delayed. Costs incurred by BTG in connection with
changes to the Process for the Bulk Product that are required pursuant to Legal
Requirements applicable solely to the Process for the Bulk Product, including
but not limited to the purchase of equipment, shall be paid by Savient in
advance, or on such other basis as the parties may agree at such time, of the
incurrence of such charges at (x) […***…] percent ([…***…]%) of cost […***…];
(y) […***…], if applicable, as per Exhibit B; (z) […***…] at […***…] percent
([…***…]%) of cost; provided, however, that Savient shall have explicitly
approved in writing any contemplated changes pursuant to this Section 6.02(ii)
prior to BTG implementing any such changes. To the extent that the cost of any
purchase of equipment is fully allocated to Savient, title to such equipment
shall vest in Savient and Savient shall have the right, but not the obligation,
to remove such equipment at its sole cost and expense upon the expiration or
termination of this Agreement.

(iii)       Changes Made at the Request of Savient. From time to time, Savient
may request that BTG make certain changes (other than those required by Legal
Requirements) to the Processing of the Bulk Product; provided, however, that (A)
Savient shall seek to minimize such changes, (B) Savient shall enter into good
faith negotiations with BTG regarding the implementation of any such change to
the Processing of the Bulk Product, with BTG’s consent to such change not being
unreasonably withheld, conditioned, delayed or denied and (C) after the Parties
have agreed upon the implications and costs related to a change to the
Processing

 

 

***Confidential Treatment Requested

 

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of the Bulk Product, BTG shall implement such change. Costs incurred by BTG in
connection with such changes shall be reimbursed by Savient at (x) […***…]
percent ([…***…]%) of cost excluding […***…]; (y) […***…], if applicable, as per
Exhibit B; (z) […***…] at […***…] percent ([…***…]%) of cost. To the extent that
the contemplated changes requested by Savient necessitate the purchase of
equipment and the cost of such purchase of equipment is fully allocated to
Savient, title to such equipment shall vest in Savient and Savient shall have
the right, but not the obligation, to remove such equipment at its sole cost and
expense upon the expiration or termination of this Agreement.

(iv)       Improvements by BTG. If BTG identifies a potential improvement that
would (A) require changes to the Process, (B) have an impact on the Product or
Bulk Product or (C) require submissions to or approvals from any Regulatory
Agency, then BTG shall notify Savient of such improvement and the Parties shall,
in good faith, discuss implementation of such improvement. Such improvement
shall not be made unless the Parties reach agreement including, without
limitation, agreement on allocation of cost, which agreement shall be at the
sole discretion of the Parties. To the extent that the contemplated changes
necessitate the purchase of equipment and the cost of such purchase of equipment
is fully allocated to Savient, […***…].

(v)         Price Adjustment. In the event of any changes to the Process,
pursuant to this Section 6.02, the Parties will meet and discuss the impact such
Process changes have on the cost of Processing Bulk Product, either negative or
positive, and will negotiate the resulting adjustment to the Price, as defined
in Section 8.01, such adjustment to appropriately reflect the investment made by
each Party in such Process changes relative to the manner in which such changes
impact the cost of Processing the Bulk Product. To effectuate this Section
6.02(v), both parties shall exchange appropriately detailed documentation and
analysis required to adequately assess the negative or positive impact such
Process changes have on the cost of Processing Bulk Product.

6.03       Facility Changes.

(i)          Facility Changes by BTG. From time to time, BTG may desire to make
certain changes or modifications to its Facility (other than those required by
Legal Requirements) (“Facility Changes”) which Facility Changes impact, directly
or indirectly, the Processing of the Bulk Product. BTG shall be entitled to make
Facility Changes which impact, directly or indirectly, the Processing of the
Bulk Product without the prior approval of Savient, provided, however:

(A)       prior to the approval of the BLA for Savient’s Product, BTG shall (x)
use its best efforts to minimize Facility Changes which impact, directly or
indirectly, the Processing of the Bulk Product, and (y) not implement any
Facility Changes that will inhibit BTG’s ability to meet its obligations to
supply Savient’s requirements under this Agreement or require the approval of a
Supplement to the BLA for Savient’s Product, unless such change is unavoidable;

 

 

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(B)         after the approval of the BLA for Savient’s Product, BTG shall not
implement any Facility Changes that will inhibit BTG’s ability to meet its
obligations to supply Savient’s requirement under this Agreement unless and
until the Parties have agreed to a plan for inventory stockpiling to satisfy
Savient’s requirements, and;

(C)        BTG shall promptly provide Savient notice of its Facility Changes
which may impact, directly or indirectly, the Processing of the Bulk Product
prior to the anticipated commencement of such Facility Changes and shall enter
into good faith negotiations with Savient regarding the implementation of any
such Facility Change and the satisfaction of Savient’s requirements for the
stockpiling of safety stocks on Bulk Product in order that Savient can meet the
clinical and market demands of its Product.

Under no circumstances shall BTG implement a Facility Change which may endanger
the quality of the Bulk Product. Costs incurred by BTG in connection with such
Facility Changes shall be borne by BTG. As used in this Section 6.03(i),
“promptly” shall mean, given the nature and substance of the Facility Change,
that period of time commercially reasonably necessary to complete the
discussions and negotiations envisaged herein.

(ii)         Facility Changes Based on Applicable Legal Requirements. BTG shall
make such changes to the Facility as may be required pursuant to applicable
Legal Requirements; provided that BTG shall promptly notify Savient in advance
of such planned Facility Change; provided, however, that such notice from BTG
shall be provided not later than ten (10) Business Days following BTG’s being
notified of the necessity of changes to the Facility pursuant to Legal
Requirements. Costs incurred by BTG in connection with such changes shall be
reimbursed by Savient as follows:

(A)        Changes Specific to Savient’s Bulk Product. To the extent that
changes to the Facility, including but not limited to the purchase of equipment,
are required pursuant to Legal Requirements applicable solely to the Bulk
Product, costs incurred for such changes shall be paid by Savient in advance of
the incurrence of such charges, or on such other basis as the parties may agree
at such time, at (x) […***…] percent ([…***…]%) of cost […***…]; (y) […***…], if
applicable, as per Exhibit B, and; (z) […***…] at […***…] percent ([…***…]%) of
cost; provided, however, that the Parties shall have agreed to a plan for the
satisfaction of Savient’s requirements for safety stock of the Bulk Product to
meet the clinical and market demands of its Product. To the extent that the cost
of any purchase of equipment is fully allocated to Savient, title to such
equipment shall vest in Savient and Savient shall have the right, but not the
obligation, to remove such equipment at its sole cost and expense upon the
expiration or termination of this Agreement.

(B)        Changes Not Specific to Savient’s Bulk Product. To the extent that
changes to the Facility are required pursuant to Legal Requirements applicable
to biopharmaceutical manufacturing in general, costs incurred for such changes
shall be reimbursed by Savient […***…].

(C)        Changes in Connection With Another Product. If changes to the
Facility are required pursuant to Legal Requirements applicable solely to other
activities or the

 

 

***Confidential Treatment Requested

 

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manufacture of other products in the Facility (even if such changes would not be
required in the absence of the Processing of the Bulk Product at the Facility or
if the Processing of the Bulk Product benefits from such changes) the costs
incurred for such changes […***…].

Provided, however, that in the event of changes to the Facility required
pursuant to applicable Legal Requirements, the Parties shall enter into good
faith negotiations regarding the implementation of any such Facility Change in a
manner intended to minimize the interruption of the supply of Bulk Product and,
in any event, shall agree on a method for the satisfaction of Savient’s
requirements for the stockpiling of safety stocks of Bulk Product in order that
Savient can meet the clinical and market demands of its Product.

(iii)        Changes Made at the Request of Savient. From time to time, Savient
may request that BTG make certain changes to the Purification Area (other than
those required by Legal Requirements); provided, however, that

(A)        Savient shall seek to minimize such changes,

(B)        Savient shall enter into good faith negotiations with BTG regarding
the implementation of any such change, with BTG’s consent to such change not
being unreasonably withheld, conditioned, delayed or denied and

(C)        after the Parties have agreed upon the implications and costs related
to the Savient requested changes, BTG shall implement such changes.

Costs incurred by BTG in connection with such changes to the Facility shall be
reimbursed by Savient at (x) […***…] percent ([…***…]%) of cost […***…]; (y)
[…***…], if applicable, as per Exhibit B, and; (z) […***…] at […***…] percent
([…***…]%) of cost. To the extent that the contemplated changes requested by
Savient necessitate the purchase of equipment and the cost of such purchase of
equipment is fully allocated to Savient, title to such equipment shall vest in
Savient and Savient shall have the right, but not the obligation, to remove such
equipment at its sole cost and expense upon the expiration or termination of
this Agreement.

(iv)          Price Adjustment. In the event of any changes to the Facility,
pursuant to this Section 6.03, the Parties will meet and discuss the impact such
Facility changes have on the cost of Processing Bulk Product, either negative or
positive, and will negotiate the resulting adjustment to the Price, as defined
in Section 8.01, such adjustment to appropriately reflect the investment made by
each Party in such Facility changes relative to the manner in which such changes
impact the cost of Processing the Bulk Product. To effectuate this Section
6.03(iv), both parties shall exchange appropriately detailed documentation and
analysis required to adequately assess the negative or positive impact such
Facility changes have on the cost of Processing Bulk Product.

(v)        Alternate Use of Purification Area. BTG shall have the right, but not
the obligation, to utilize the Purification Area for the production, handling or
storage of other

 

 

***Confidential Treatment Requested

 

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products during periods when the Purification Area is not being utilized for the
Processing of Bulk Product pursuant to the terms and conditions of Section 5.7
in the Quality Agreement.

6.04      Quality Assurance.

(i)         Testing by BTG. BTG shall perform quality testing using assays
proposed by BTG and acceptable to Savient (which acceptance shall not be
unreasonably conditioned, withheld or delayed) in order to assure that the Bulk
Product complies with the Commercial Bulk Product Specifications, and shall
retain samples of Bulk Product produced and records of the tests made on each
such batch in accordance with applicable Legal Requirements. In addition, except
as otherwise agreed by the Parties in writing, no Bulk Product shall be
delivered until such Bulk Product has been processed in accordance with the
tests, inspections and controls required under the Commercial Bulk Product
Specifications and such other tests as the Parties may mutually agree upon in
writing; provided, however, that the foregoing shall not relieve BTG of its
obligation under ARTICLE 5. BTG shall maintain records with respect to the
quality testing and shall deliver such records to Savient by facsimile or email
and overnight courier prior to shipment of the Bulk Product. Savient shall pay
for any and all costs and expenses related to the delivery of records to Savient
by overnight courier. Such records shall also be made available to Savient
during normal Israeli business hours, upon prior written request.

(ii)         Notice of Non-Conforming Bulk Product. BTG shall promptly notify
Savient of any Non-Conforming Bulk Product of which it becomes aware, whether or
not such Non-Conforming Bulk Product been delivered to Savient or its designee,
specifying the Bulk Product release testing and batch number.

(iii)       Testing by Savient. At Savient’s election, Bulk Product may be
subjected to testing by Savient at Savient’s facilities or facilities of a Third
Party designated by Savient in order to verify conformance with the Commercial
Bulk Product Specifications, using assays proposed by BTG and acceptable to
Savient (which acceptance shall not be unreasonably conditioned, withheld or
delayed). Savient shall maintain records with respect to the scope and nature of
any such testing and shall disclose such records to BTG in a timely fashion.

(iv)       Notice of Delivery of Non-Conforming Bulk Product. Savient shall
notify BTG in writing of any Non-Conforming Bulk Product within

(A)        forty-five (45) days of delivery of such Non-Conforming Bulk Product
in the event of a defect which was discovered or could have been discovered by
Savient through the use of reasonable testing methods and procedures mutually
agreed to by the Parties in writing or

(B)        ten (10) Business Days of Savient’s discovery of the Non-Conforming
status of the Bulk Product in the event of a defect not recognizable for Savient
through the use of such testing methods and procedures (hereinafter “Hidden
Defect”).

Savient’s notices of any non-conforming Bulk Product shall specify the manner in
which the Bulk Product fails to meet the Commercial Bulk Product
Specifications,. BTG shall have the

 

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right to examine and test any Bulk Product in Savient’s possession that Savient
claims is Non-Conforming. The Parties shall cooperate to determine the point at
which the Bulk Product became Non-Conforming. In the event that the Parties
cannot agree as to whether any Bulk Product was Non-Conforming at the time of
delivery, the Parties shall promptly appoint an independent specialist
(appointed by mutual agreement between the Parties, which agreement shall not be
unreasonably withheld, conditioned or delayed) who shall determine whether such
Bulk Product was Non-Conforming at the time of delivery. In the absence of
manifest error, the independent specialist’s decision shall be conclusive and
binding on the Parties.

Except as otherwise provided herein relating to Hidden Defects in the Bulk
Product, if Savient fails to notify BTG in writing of any non-conforming Bulk
Product within forty-five (45) days of delivery, then the Bulk Product delivered
by BTG to Savient shall be deemed to be in all respects in accordance with this
Agreement and Savient shall be bound to accept and pay for the same accordingly.
For the avoidance of doubt, this shall apply irrespective of whether or
not Savient has carried out quality testing in accordance with Section 6.04
(iii).

(v)         Observation by Savient. During the Term, Savient (including
Savient’s agents and consultants) shall have the right, at Savient’s sole cost
and expense, during normal business hours and upon reasonable notice, to visit
the Facility as per the Quality Agreement.

(vi)         Recalls and Voluntary Withdrawals. If either Party becomes aware of
information about distributed Product containing Bulk Product indicating that it
may be Non-Conforming with respect to the Bulk Product or that there is
potential adulteration, misbranding and/or any potential issues regarding safety
or effectiveness with respect to the Bulk Product, it shall promptly serve
Notice to that effect on the other Party. Savient will initiate an investigation
and assessment of such circumstances and shall promptly notify BTG of its
findings and any proposed course of action. The Parties shall meet to discuss
such circumstances and to consider appropriate courses of action. Savient shall
bear all costs associated with a recall of the Product unless such recall is
caused by a Hidden Defect with respect to the Bulk Product, in which case BTG
shall pay all costs associated with the recall, up to the maximum value of the
Product Price paid by Savient to BTG for the Bulk Product containing such Hidden
Defect.

(vii)         Filled Product Release Testing. The Parties acknowledge that BTG
is performing the Filled Product release testing for Savient under the terms of
this Agreement and the Development Agreement until such time as the Filled
Product release testing and methods can be transferred to Savient’s new third
party fill/finisher of Product (hereinafter “Third Party Fill/Finisher”) or
alternate Bulk Product or Product supplier. Savient will use its best efforts to
effectuate the Technology Transfer of Product Technology to enable such Filled
Product release testing to be performed by Savient’s Third Party Fill/Finisher
or its alternate Product supplier as expeditiously as commercially practicable,
and upon the approval of such amendments to this Agreement, and, if still in
effect at such time, the Development Agreement shall be entered into relieving
BTG of its obligation to perform release testing on Filled Product. It is the
express intention of the Parties to mutually use best efforts to accomplish this
Technology Transfer in adequate time to file the Product BLA with both BTG and
Savient’s Third Party Fill/Finisher as alternate parties designated to perform
the release testing of Filled Product, provided, however, the failure to succeed
in this regard shall not be deemed

 

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a breach by Savient, nor shall it relieve BTG of its obligations to perform such
release testing until such time as Savient’s Third Party Fill/Finisher is
approved to perform such release testing.

6.05       Labeling and Packaging. BTG shall label and package the Bulk Product
in accordance with Legal Requirements applicable to pharmaceutical products
shipped in bulk for further processing, labeling, or repackaging.

6.06       Stability. Stability related activities for which BTG is responsible
shall be completed in accordance with Quality Agreement. All costs incurred by
BTG related to such activities shall be reimbursed by Savient in the manner and
at the rates set forth on Exhibit B hereto.

ARTICLE 7

DELIVERY; INVOICES; WARRANTY

7.01       Shipment and Delivery. BTG shall use its best efforts to deliver Bulk
Product in accordance with the delivery dates specified in its order
confirmations or the Purchase Orders, as may be appropriate. All shipments shall
be made by BTG pursuant to Savient’s instructions FCA Ben Gurion Airport, Tel
Aviv, Israel, (Incoterms 2000) with BTG being responsible for delivering the
Bulk Product cleared for export to the freight forwarder nominated by Savient.

7.02       Certificate of Analysis. An appropriate Certificate of Analysis and
all relevant batch records shall precede the shipment of each Bulk Product batch
delivered to Savient. BTG shall, for customs purposes, upon delivery of the Bulk
Product, provide Savient with a valid declaration of origin, in a form
reasonably acceptable to Savient, in respect of all Bulk Product supplied to
Savient under this Agreement, together with such other supporting documents
relating to the origin of such Bulk Product as Savient may reasonably require.
If any of the foregoing documents are only available in a language other than
English, the Parties shall agree upon an English language template for such
document(s), and BTG shall provide to Savient an English language translation of
any deviations from the template(s); provided, however, that any documentation
required by any Regulatory Authority to be supplied for the purpose of
importing, exporting, selling, storing, transferring, or otherwise disposing of
Bulk Product, shall be provided in the English language.

7.03       Method of Invoicing. All orders under this Agreement shall be
invoiced at the price which is in effect at the time of shipment.

7.04       Warranty. BTG hereby represents and warrants to Savient that (i) the
quality (purity, physical and chemical properties) of the Bulk Product supplied
by it to Savient shall be in accordance with its Specifications, shall not be
adulterated or misbranded within the meaning of the applicable US food and/or
drug law or regulation, and shall comply with all Legal Requirements (including
cGMP) and those applicable laws, rules and regulations governing the
formulation, manufacture, testing prior to delivery, packaging, labeling
according to the Specifications for the Bulk Product and storage and delivery of
the Bulk Product and (ii) the Processing of the Bulk Product at the Facility
shall be in compliance with the CMC section of

 

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the BLA, as reviewed and attested to as accurate by BTG. This warranty is
exclusive and is in lieu of all other warranties, whether written or oral,
express, implied or statutory.

ARTICLE 8

PRICE

8.01       Price. The Parties agree that the Bulk Product shall be charged to
Savient at the price set out in Exhibit E attached hereto (the “Price”).

8.02       Remittance of Payments. Payments due by Savient under Section 8.01
shall be payable by Savient no later than […***…] days after the invoice date;
provided, however, that Bulk Product associated with such payment was actually
delivered in accordance with Section 7.01. Savient shall make payment by wire
transfer of Dollars from a single source in the United States to a bank account
designated by BTG or by such other payment method as the Parties may agree upon
from time to time. Except where any amounts payable are in dispute under this
Agreement and to the extent such dispute is resolved in favor of Savient, in the
event of late payment, interest on any past due payments shall accrue at the
rate of […***…] percent per month, or if such rate shall exceed the maximum rate
allowed by law, then at such maximum rate, and shall be payable on demand.

ARTICLE 9

REPORTING OF EVENTS

9.01       Exchange of Drug Safety Information. The Parties shall have the
rights and responsibilities pertaining to AEs, SAEs and biologic product
deviations in accordance with the provisions of the Quality Agreement attached
hereto as Exhibit D.

9.02       Events Affecting Integrity or Reputation. During the Term, the
Parties shall notify each other immediately of any circumstances of which they
are or become aware of whereby the integrity and reputation of the Product or of
the Parties are threatened by the unlawful activity of any Third Party in
relation to the Product. In any such circumstances, the Parties shall cooperate
to limit any damage to the Parties and/or to the Product.

9.03       Governmental Inspection. Each Party shall advise the other of any
governmental communication, inspection or report which addresses or affects the
Bulk Product promptly after becoming aware of it. Savient shall have the right
to observe any such governmental inspection; provided, however that such
governmental inspection is specifically related to the Bulk Product.

 

 

***Confidential Treatment Requested

 

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ARTICLE 10

NON-COMPETITION AND NON-SOLICITATION

10.01    Non-Competition. During the Term of this Agreement, and for a period of
thirty (30) months after the termination thereof, BTG agrees not to, and shall
cause its Affiliates not to, use the Product Technology to manufacture, promote,
market or sell any Competing Product in the Territory, nor will BTG acquire
directly or indirectly any rights or interest in or to a Competing Product which
is being manufactured, promoted, marketed or sold in the Territory. The Parties
agree that an acquisition by BTG’s Affiliates of any rights or interest in or to
a Competing Product which is being manufactured, promoted, marketed or sold in
the Territory shall not be deemed to be an indirect acquisition by BTG, provided
BTG has not participated in the acquisition process of its Affiliate.

10.02    Non-Solicitation. During the Term and for a period of thirty (30)
months after the termination of this Agreement, the Parties agree that neither
Party shall solicit any employee of the other Party or any of its Affiliates,
with whom it has come in contact or interacted for the purposes of the
performance of this Agreement, to leave the employment of the other Party or its
Affiliate and accept employment or work as a consultant with the first Party,
except in the event the other Party has approved such solicitation in writing.
Notwithstanding the foregoing, nothing herein shall restrict or preclude either
Party’s right to make generalized searches for employees by the issue of
advertisement in the media (including trade media) or by engaging search firms
to engage in searches that are not targeted or focused on an employee or
employees of the other Party.

ARTICLE 11

TERM & TERMINATION

11.01    Term. This Agreement shall be in effect from the Effective Date and
shall continue in effect until terminated pursuant to a Notice served by either
Party in accordance with Section (the “Term”).

11.02    Termination. This Agreement may be terminated in accordance with the
following sections:

(i)          Elective. Either Party may terminate this Agreement by giving at
least three (3) years’ advance Notice (“Elective Termination Notice”) to the
other Party, which Elective Termination Notice may not be given prior to the
seventh (7th) anniversary of the first delivery of Bulk Product by BTG under
this Agreement but may be given at any time thereafter. Upon the third (3rd)
anniversary of the Elective Termination Notice, this Agreement shall terminate,
unless extended by mutual agreement of the Parties.

(ii)         Force Majeure. In the event a Party (“Affected Party”) continues to
experience a Force Majeure condition for a period of at least six (6) months
after Notice of the Force Majeure was given pursuant to Section 14.04, the other
Party shall be entitled to terminate this Agreement by giving a Notice of
termination to Affected Party at any time while such Force

 

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Majeure persists thereafter with the termination becoming effective on the date
specified in the Notice of termination.

(iii)        Material Breach by BTG. Savient shall be entitled to terminate this
Agreement, in the event that BTG commits a material breach of this Agreement
(including, without limitation, in the event of a Supply Failure pursuant to
Section 5.08 that is not due to an event of Force Majeure or a failure on the
part of Savient to supply critical raw materials which it is obligated to supply
pursuant to the terms of this Agreement) and BTG fails to cure such breach
within sixty (60) days of receiving a Notice of default from Savient (or such
longer period as Savient may reasonably agree if said breach is incapable of
cure within such sixty (60) days) (“BTG’s Cure Period”), by giving a Notice of
Termination to BTG (after expiration of BTG’s Cure Period, if applicable), with
the termination to take effect on the date specified therein, provided, however,
that if BTG experiences a second Supply Failure within any twelve (12) month
period then BTG’s Cure Period shall be zero (0) days unless otherwise specified
in the Notice of Termination provided by Savient in its sole discretion.

(iv)        Material Breach by Savient. BTG shall be entitled to terminate this
Agreement, in the event that Savient commits a material breach of this Agreement
and Savient fails to cure such breach within sixty (60) days of receiving a
Notice of default from BTG (or such longer period as BTG may reasonably agree if
said breach is incapable of cure within such sixty (60) days) (“Savient’s Cure
Period”), by giving a Notice of termination to Savient (after expiration of the
Savient Cure Period, if applicable), with the termination to take effect on the
date specified therein. For purposes of this Section only, any amount of the
Processing Capacity Reservation Fee and accrued interest thereon which has not
been applied to payments for Bulk Product actually purchased by and delivered to
Savient shall be forfeited by Savient to BTG as of the effective date of
termination of this Agreement.

(v)        Insolvency. Either Party shall be entitled to terminate this
Agreement, by giving Notice to the other Party (“Insolvent Party”), in the event
of an Insolvency Event occurring in relation to the Insolvent Party, such
termination to take effect upon delivery of the Notice of termination to the
Insolvent Party. “Insolvency Event” for the purpose of this Clause shall mean
any commencement – whether voluntarily or involuntarily – of any action seeking
any relief by liquidation, reorganization (other than for corporate
reorganization), dissolution or similar act under any bankruptcy, insolvency or
similar law or otherwise any action seeking any arrangement between or with its
creditors or any commencement of a proceeding or receipt of an order, judgment
or decree seeking the liquidation, reorganization or dissolution of a Party or
any other relief under any bankruptcy, insolvency or similar law or an
arrangement is made with respect to such Party’s debts or business by its
creditors with or without the consent of that Party.

11.03     Savient’s Rights Upon Termination. In the event Savient terminates
this Agreement pursuant to Sections 11.02 (i) (Elective), 11.02 (ii) (for Force
Majeure conditions affecting BTG), 11.02 (iii) (Material Breach by BTG), or
11.02 (v) (for insolvency of BTG) or in the event BTG terminates this Agreement
pursuant to Section 11.02 (i), BTG shall promptly, upon request by Savient,
convey to Savient all Know-How, BTG Licensed Improvements and other information
related to the Processing of the Product and/or Bulk Product sufficient to
enable Savient or any other Persons engaged by Savient to manufacture, produce
or provide the Product

 

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and/or Bulk Product and BTG shall provide all other assistance that Savient may
reasonably request, at no cost to Savient. Such Know-How, BTG Licensed
Improvements and other information shall include, without limitation, all
records and reports related to (i) the development of the Bulk Product, Product
and/or Process, (ii) the Processing of the Bulk Product and Product, (iii)
testing for compliance with the Specifications, and (iv) batch records. Unless
this Agreement is terminated pursuant to Section 11.02 (iii), Savient shall be
responsible for the reasonable labor costs and expenses incurred by BTG in
conveying such Know-How, BTG Licensed Improvements and other information and
providing such assistance. Such labor costs of BTG employees and/or Third Party
expenses shall be reimbursed by Savient in the manner and at the rates set forth
on Exhibit B hereto.

11.04     BTG’s Rights Upon Termination. In the event that BTG terminates this
Agreement pursuant to Sections 11.02(i) (Elective), 11.02(ii) (for Force Majeure
conditions affecting Savient), 11.02(iv) (Material Breach by Savient) or
11.02(v) (for insolvency of Savient), any and all outstanding non-disputed
payments due from Savient pursuant to this Agreement shall become immediately
due and payable. Anything to the contrary notwithstanding, upon termination by
BTG, BTG shall promptly, upon request by Savient and at Savient’s cost, convey
to Savient, all Know-How, BTG Licensed Improvements and other information
related to the Processing of the Bulk Product and/or Product sufficient to
enable Savient or any other Persons engaged by Savient to manufacture, product
or provide the Bulk Product and/or Product and BTG shall provide all other
assistance that Savient may reasonably request, at Savient’s sole cost.

11.05     Effect of Termination. Termination of this Agreement for any reason is
without prejudice to the Parties’ accrued rights and shall not be construed to
release either Party of any obligation matured prior to the effective date of
such termination.

11.06     Survival. The following provisions shall survive the expiration or
termination of this Agreement: 2.01(iii), 2.01(iv), 2.04, 3.02, 3.03, 4.01 (ii),
5.11, 6.04 (i), 6.04(ii), 6.04 (iv), 6.04 (vi), 6.04 (vii), 6.06, ARTICLE 7,
ARTICLE 8, ARTICLE 9, Section 10.01 (except in the event of a termination by BTG
pursuant to Section 11.02 (iv) (Material Breach by Savient)), 10.02, 11.03,
11.04, 11.05, 11.06, ARTICLE 12, ARTICLE 13, ARTICLE 14. The survival of
Sections 3.02, 3.03, 6.04 (vii) and 6.06 shall be subject to BTG being
compensated for any actions on their part under these provisions post expiration
or termination on the basis of the principles set forth in this Agreement. The
Parties expressly understand and agree that Section 2.01 (ii) shall not survive
the expiration or termination of this Agreement. For the avoidance of doubt,
even after the termination of this Commercial Agreement pursuant to either
Section 11.02 (iii) or Section 11.02 (iv), each Party’s rights under the
Residual Rights Agreement shall subsist in full and irrespective of the grounds
for such termination, except Savient may not compel BTG to perform any
additional manufacturing services as may be required by the Residual Rights
Agreement.

 

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ARTICLE 12

REMEDIES

12.01    Remedies for Non-Conforming Bulk Product. In the event BTG delivers to
Savient Bulk Product that does not meet the Commercial Bulk Product
Specifications, Savient shall, at its option, be entitled to (A) the replacement
of such Non-Conforming Bulk Product with corresponding Bulk Product meeting the
Bulk Product Specifications and with the cost of the PEG material supplied by
Savient and the cost of shipment for such replacement Bulk Product being borne
by BTG; or (B) a refund of (x) any price paid by Savient for such Non-Conforming
Bulk Product, (y) the cost of the PEG material supplied by Savient for such
Non-Conforming Bulk Product, and (z) the shipment costs associated with such
Non-Conforming Bulk Product, provided, however, that Savient has notified BTG in
writing of the non-conforming Bulk Product in accordance with Section 6.04 (iv).
In addition, Savient shall, at BTG’s option and cost, either destroy or return
to BTG at its Facility any Non-Conforming Bulk Product.

12.02    Indemnity by BTG.

(i)        BTG shall defend, indemnify and hold harmless each Savient Indemnitee
from and against (i) all Claims of Third Parties that arise as a result of a
material breach of any covenant, agreement, warranty or representation made by
BTG under this Agreement, and (ii) all Product Liability Claims, or such portion
of Product Liability Claims, as are allocated to BTG pursuant to Section 12.04.

(ii)        BTG shall not be obligated under this Section 12.02 to the extent it
is shown that the Claim was the direct result of a material breach of any
covenant, warranty or representation made by Savient under this Agreement.

(iii)        BTG shall have no obligation under this Section 12.02 unless

(A)         Savient gives BTG prompt written notice of any Claim for which it
seeks to be indemnified under this Agreement,

(B)         BTG is granted full authority and control over the defense against
such Claim, and

(C)         Savient cooperates fully with BTG in defense of the Claim (all
reasonable out-of-pocket expenses of such cooperation to be borne by BTG).

Savient shall have the right to participate in the defense of any such Claim
utilizing attorneys of its choice, at its own expense; provided, however, that
BTG shall have full authority and control to handle any such Claim, including
without limitation any settlement or other disposition thereof, for which
Savient seeks indemnification under this Section 12.02; provided, however,
further that any settlement that includes an admission of fault, culpability or
liability on the part of Savient shall not be concluded without Savient’s
consent, which consent shall not be unreasonably conditioned, withheld, delayed
or denied.

 

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(iv)        BTG shall indemnify and hold Savient harmless for any income tax or
other taxes which Savient may be required by current or future Legal
Requirements to pay on behalf of BTG with respect to any monies payable to BTG
under this Agreement, including without limitation, any associated penalties,
fines and interest (hereinafter, a “Tax Claim”); provided, however, that if
Savient becomes aware of any Legal Requirements according to which Savient is
required to pay any taxes on behalf of BTG or to withhold any amounts with
respect to any such Tax Claim, then Savient shall act in strict compliance with
such Legal Requirements and shall promptly serve written notice to that effect
on BTG. Furthermore, upon learning of the existence of a Tax Claim, Savient
shall provide prompt written notice to BTG where such notice shall include
copies of all materials received by Savient which pertain to the Tax Claim.
Additionally, upon request by BTG, Savient shall provide reasonable assistance
to BTG to enable BTG to defend any such Tax Claim and/or support a claim for a
refund or a foreign tax credit with respect to any such Tax Claim; provided that
BTG shall reimburse Savient for any out-of-pocket expenses which Savient incurs
in rendering any assistance to BTG pursuant to this provision within thirty (30)
days of receipt of a reasonably specific demand for reimbursement with
accompanying documentation demonstrating such amounts claimed. Savient shall
obtain the approval of BTG for any individual out-of-pocket expense in excess
of […***…] Dollars ($[…***…]), such approval not to be unreasonably withheld,
delayed or conditioned. BTG shall have the sole right to handle any such Tax
Claim utilizing attorneys of its choice, at its own expense; provided, however,
that any settlement that includes an admission of fault, culpability, penalty
fine or any other liability on the part of Savient shall not be concluded
without Savient’s consent, which consent shall not be unreasonably conditioned,
withheld, delayed or denied.

12.03    Indemnity by Savient.

(i)         Savient shall defend, indemnify and hold harmless each BTG
Indemnitee from and against all Claims of Third Parties that arise as a result
of (A) a material breach of any covenant, agreement, warranty or representation
made by Savient under this Agreement, and (B) patent infringement involving the
manufacture, use, importation, sale or marketing of the Bulk Product or Product,
and (C) all Product Liability Claims, or such portion of Product Liability
Claims, as are allocated to Savient pursuant to Section 12.04.

(ii)         Savient shall not be obligated under this Section 12.03 to the
extent it is shown that the Claim was the direct result of a material breach of
any covenant, warranty or representation made by BTG under this Agreement.

(iii)         Savient shall not be obligated under this Section 12.03 unless

(A)         BTG provides Savient with prompt written Notice of any Claim for
which it seeks to be indemnified under this Agreement,

(B)         Savient is granted full authority and control over the defense
against such Claim, and

 

 

***Confidential Treatment Requested

 

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(C)         BTG cooperates fully with Savient in defense of the Claim (all
reasonable out-of-pocket expenses of such cooperation to be borne by Savient).

BTG shall have the right to participate in the defense of any such Claim
utilizing attorneys of its choice, at its own expense; provided, however, that
Savient shall have full authority and control to handle any such Claim,
including without limitation any settlement or other disposition thereof, for
which BTG seeks indemnification under this Section12.03; provided, however,
further that any settlement that includes an admission of fault, culpability or
liability on the part of BTG shall not be concluded without BTG’s consent, which
consent shall not be unreasonably conditioned, withheld, delayed or denied.

12.04    Product Liability Claims. Notwithstanding the foregoing Sections 12.02
and 12.03, the Parties’ responsibilities with respect to Product Liability
Claims shall be governed by this Section12.04.

(i)          BTG shall be solely responsible for all Product Liability Claims
that arise out of Non-Conforming Bulk Product, provided, however, that the
following conditions are cumulatively satisfied: (A) such nonconformance existed
at the time the Bulk Product was delivered by BTG and (B) such nonconformance
was the result of BTG’s failure to manufacture the Bulk Product in strict
adherence with the Process and (C) such Non-Conformance was the result of a
Hidden Defect. Savient shall be solely responsible for all Product Liability
Claims that arise out of Non-Conforming Bulk Product in each of the following
cases: (A) such non-conformance occurred after the Bulk Product was delivered to
Savient or (B) the Non-Conforming Bulk Product was manufactured by BTG in strict
adherence with the Process or (C) such Non-Conformance was not the result of a
Hidden Defect.

(ii)          Each Party shall give the other prompt written notice of any
Product Liability Claim, but the omission of such notice shall not relieve
either Party from its obligations under this Section 12.04, except to the extent
the other Party can establish actual prejudice and direct damages as a result
thereof. With respect to each Product Liability Claim, Savient shall have the
first right to defend and settle such Product Liability Claim. In the event that
Savient does not assume the defense of such Product Liability Claim within
ninety (90) days following Savient’s receipt of notice of the commencement or
assertion of such Product Liability Claim, BTG may notify Savient of BTG’s
desire to take the lead role in the defense of such Product Liability Claim. If,
within ten (10) days after BTG notifies Savient of such desire, Savient does not
assume the defense of such Product Liability Claim, then BTG may take the lead
role in the defense of such Product Liability Claim.

The Party assuming the defense of any Product Liability Claim as permitted under
this Section 12.04 (the “Controlling Party”) shall consult with the other Party
on all material aspects of the defense, including without limitation settlement,
of such Product Liability Claim, and the Parties shall cooperate fully with each
other in connection therewith. The non-defending Party shall also have the right
to participate in the defense of any Product Liability Claim utilizing attorneys
of its choice, at its own expense. In furtherance of the Parties’ cooperation,
the Controlling Party will consult with the other Party regarding strategic
decisions, including without limitation the retention of counsel and defense of
each Product Liability Claim. The Controlling Party will otherwise keep the
other Party fully informed of the status and progress of the defense and any

 

- 32 -

--------------------------------------------------------------------------------

settlement discussions concerning the Product Liability Claim. Any settlement of
a Product Liability Claim that would admit liability on the part of any Party or
its Affiliates or Agents, or that would involve any relief other than the
payment of money damages, shall be subject to the prior written approval of both
Parties, such approval not to be unreasonably withheld or delayed. All damages
and expenses (including attorney’s fees) incurred in connection with the defense
of a Product Liability Claim shall be allocated between the Parties in
accordance with Section 12.04 (i).

12.05     Limitation of Damages. Notwithstanding anything to the contrary set
forth in this Agreement, in no event shall either Party be liable to the other
Party for, and each Party shall procure that none of its Affiliates or
Sublicensees shall make any claim against the other Party (or its Affiliates and
Sublicensees) for, any lost profits, loss of business, loss of contracts,
diminished goodwill, diminished reputation, or consequential, indirect,
incidental or special damages arising under or in connection with this Agreement
or the Bulk Product.

ARTICLE 13

DISPUTE RESOLUTION AND ARBITRATION

13.01     Governing Law. This Agreement and any and all matters arising directly
or indirectly herefrom shall be governed by and construed in accordance with the
laws of the State of New York, United States of America, without giving effect
to (A) its conflict of law principles and (B) the United Nations Convention on
Contracts from the International Sale of Goods.

13.02     Arbitration. Any dispute, controversy or claim arising out of or in
relation to this contract, including the validity, invalidity, breach or
termination thereof, shall be resolved by arbitration in accordance with the
Swiss Rules of International Arbitration of the Swiss Chambers of Commerce in
force on the date when the Notice of Arbitration is submitted in accordance with
these Rules. The number of arbitrators shall be three; the seat of the
arbitration shall be Zurich, Switzerland; the arbitral proceedings shall be
conducted in English and shall take place in London, England.

ARTICLE 14

MISCELLANEOUS

14.01     Confidentiality. During the Term of this Agreement or the Commercial
Agreement, whichever expires later, and for a period of three (3) years
thereafter, each Party (the “Receiving Party”) shall keep strictly confidential
any Confidential Information disclosed by any other Party (the “Disclosing
Party”), using at least the same degree of care that it uses to protect its own
confidential or proprietary information, but in no event less than reasonable
care. The provisions of this ARTICLE 14 shall apply to all Confidential
Information, and to all proprietary information of the Disclosing Party relating
to the Product and/or the Process that is disclosed (or known) to a Receiving
Party prior to the date hereof (which shall be deemed to be Confidential
Information, subject to the exceptions in clauses (i) through (iv) below, for
purposes of this Agreement). The nature and terms of this Agreement shall be
deemed to be Confidential

 

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--------------------------------------------------------------------------------

Information of each Party, subject to the exceptions set forth in clauses (i)
through (iv) below, for purposes of this Agreement. The Receiving Party shall
use Confidential Information solely for the purposes of this Agreement and the
activities contemplated hereby and shall not disclose or disseminate any
Confidential Information to any Person at any time, except for disclosure to
those of its Affiliates, directors, officers, employees, consultants,
accountants, attorneys, advisers and agents that have a need to know such
information to permit the Receiving Party to exercise its rights or fulfill its
obligations pursuant to this Agreement, provided that such Persons are bound to
maintain the confidentiality of such Confidential Information to the same extent
as if they were parties hereto. The obligations set forth in this Section 14.01
are subject to the following exceptions:

(i)           The Receiving Party may disclose the Disclosing Party’s
Confidential Information that is required to be publicly disclosed by law or by
regulation; provided, however, that: (A) the Receiving Party shall, where
possible, seek confidential treatment for any Confidential Information of the
Disclosing Party, and shall provide the Disclosing Party with prompt advance
notice of such disclosure and reasonable opportunity to review any such
disclosure so that the Disclosing Party may, if it desires, seek a protective
order or other appropriate remedy; and (B) the Parties or their Affiliates may
disclose the terms of this Agreement in any filings with the U.S. Securities and
Exchange Commission (provided that the Parties or their Affiliates, as
applicable, use commercially reasonable efforts to seek confidential treatment
for any trade secrets, commercial terms or information, or financial terms or
information).

(ii)           Pursuant to an agreement to maintain confidentiality, any Party
may discuss, or provide a copy of, this Agreement to its accountants, its
attorneys, and its current, future or potential investors or shareholders.

(iii)           Pursuant to an agreement containing confidentiality obligations
and subject to the other Parties’ written consent, either Party may provide a
copy of this Agreement or relevant portions thereof to any Third Party
sublicensee, if required pursuant to the relevant license agreement with such
Third Party.

(iv)           Any other disclosure of the nature or terms of this Agreement
(including, without limitation, any public announcements, press releases or
similar publicity with respect to this Agreement) by any Party, must be approved
in advance in writing by Savient, in its sole discretion, as to form and content
of such disclosure; provided, however, that the contents of any public
announcement, press release or similar publicity which has been reviewed and
approved can be re-released by any Party in any form without a requirement for
re-approval.

14.02    BTG Insurance. BTG and/or its Affiliates shall obtain and maintain
during the Term and for five (5) years thereafter comprehensive general
liability insurance on a claims-made basis, with endorsements for product
liability with annual coverage limits of not less than […***…] Dollars
($[…***…]) per claim and […***…] Dollars ($[…***…]) annual aggregate. All of
BTG’s insurance policies shall be issued by “A-rated” insurers as designated by
Standard and Poor’s Corporation and/or by acceptable other means. The minimum
level of insurance set forth herein shall not be construed to create a limit on
BTG’s liability hereunder. On the Effective Date and upon the request of Savient
(provided that such request shall be made no more than

 

 

***Confidential Treatment Requested

 

- 34 -

--------------------------------------------------------------------------------

once per calendar year), BTG shall furnish to Savient a certificate of insurance
evidencing such coverage as of such date. Each such certificate of insurance, as
well as any certificates evidencing new or modified coverages of BTG, shall
include a provision whereby thirty (30) days written notice must be received by
Savient prior to coverage modification or cancellation by either BTG or the
insurer. In addition, BTG shall promptly notify Savient of any cancellation or
modification of such insurance coverage and of any new or modified coverage. In
the case of a modification or cancellation of such coverage, BTG shall promptly
provide Savient with a new certificate of insurance evidencing that BTG’s
coverage meets the requirements in the first sentence of this Section 14.02.

14.03     Savient Insurance. Savient shall obtain and maintain during the Term
and for five (5) years thereafter comprehensive general liability insurance on a
claims-made basis, with endorsements for product liability with annual coverage
limits of not less than […***…] Dollars ($[…***…]) per claim and […***…] Dollars
($[…***…]) annual aggregate. All of Savient’s insurance policies shall be issued
by “A-rated” insurers as designated by Standard and Poor’s Corporation and/or by
acceptable other means. The minimum level of insurance set forth herein shall
not be construed to create a limit on Savient’s liability hereunder. On the
Effective Date and upon the request of BTG (provided that such request shall be
made no more than once per calendar year), Savient shall furnish to BTG a
certificate of insurance evidencing such coverage as of such date. Each such
certificate of insurance, as well as any certificates evidencing new or modified
coverages of Savient, shall include a provision whereby thirty (30) days written
notice must be received by BTG prior to coverage modification or cancellation by
either Savient or the insurer. In addition, Savient shall promptly notify BTG of
any cancellation or modification of such insurance coverage and of any new or
modified coverage. In the case of a modification or cancellation of such
coverage, Savient shall promptly provide BTG with a new certificate of insurance
evidencing that Savient’s coverage meets the requirements in the first sentence
of this Section 14.03.

14.04     Notices. All notices, requests, demands, claims and other
communications hereunder (each, a “Notice”) shall be in writing. Any notice,
request, demand, claim or other communication hereunder shall be deemed duly
delivered four (4) Business Days after it is sent by registered or certified
mail, return receipt requested, postage prepaid, or one (1) Business Day after
it is sent by overnight delivery via a reputable national courier service, in
each case to the intended recipient as set forth below:

If to Savient, to:

Savient Pharmaceuticals Inc.

One Tower Center, 14th Floor

East Brunswick, New Jersey 08816, USA

Telecopy: +1-732-418-9065

Attention: Philip K. Yachmetz, EVP & CBO

 

 

***Confidential Treatment Requested

 

- 35 -

--------------------------------------------------------------------------------

with copies, which shall not constitute notice hereunder, sent to:

 

Savient Pharmaceuticals, Inc.

One Tower Center, 14th Floor

East Brunswick, NJ 08816 U.S.A.

Attention: John Petrolino

   and   

Wilmer Cutler Pickering Hale and Dorr LLP

60 State Street

Boston, MA 02109

Telecopy: +1-617-526-5000

Attention: David E. Redlick, Esq.

If to BTG, to:

Bio-Technology General (Israel) Ltd.

Beer Tuvia Industrial Zone

POB 571

Kiryat Malachi 83104, Israel

Telecopy: +972-8-8612288

Attention: General Manager

with copies, which shall not constitute notice hereunder, sent to:

 

Ferring International Center SA

 

Chemin de la Vergognausaz 50

CH-1162 Saint-Prex

Switzerland

Attention: General Counsel

  

and

  

Ferring International Center SA

 

Chemin de la Vergognausaz 50

CH-1162 Saint-Prex

Switzerland

Attention: EVP, Technical Operations

Any Party may give any notice, request, demand, claim, or other communication
hereunder using any other means (including personal delivery, expedited courier,
messenger service, telecopy, telex, ordinary mail, or electronic mail), but no
such notice, request, demand, claim or other communication shall be deemed to
have been duly given unless and until it actually is received by the Party for
whom it is intended. Any Party may change the address to which notices,
requests, demands, claims and other communications hereunder are not be
delivered by giving the other Party notice in the manner herein set forth.

14.05    Entire Agreement. This Agreement and all attachments, including the
exhibits hereto, constitutes the entire agreement between Savient and BTG with
respect to the subject matter hereof, and supersedes any prior agreements or
understandings, both written and oral, between Savient and BTG with respect to
such matters, other than the Divestiture Agreements and the Residual Rights
Agreement, which shall be read together with this Agreement.

14.06    Order of Precedence. In the event of a conflict or inconsistency that
relates to the subject matter hereof between any of the terms of the following
documents, the following order of precedence shall control:

 

- 36 -

--------------------------------------------------------------------------------

  (i)

this Commercial Supply Agreement between the Parties, and Exhibits hereto

 

  (ii)

the Development Agreement between the Parties, and Exhibits thereto

 

  (iii)

the Residual Rights Agreement, and Exhibits thereto

Without limiting the generality of the foregoing, and for the avoidance of any
doubt, the following sections of the Residual Rights Agreement are hereby
superseded by this Agreement as far as the subject matter hereof is concerned:
(A) Section 3 - Research & Development; Regulatory Services; Manufacturing
Services; (B) Section 4 - Technology Transfer; (C) Section 9 - Indemnification;
(D) Section 13 – Governing Law and Dispute Resolution; (E) Annex C (Development
and Regulatory Work-Puricase); (F) Annex D (Term Sheet Manufacturing Services);
and (G) Annex E (Term Sheet for Technology Transfer). In resolving any such
conflicts, these documents shall be read as a whole and in a manner most likely
to accomplish their purposes. Any amendments to these documents on which the
Parties may agree to in accordance with the terms of each document shall take
precedence over any conflicting terms in the prior release of each document.
Each Party shall promptly report to the other in writing any inconsistencies in
these documents, even if the inconsistency is resolvable using the above order
of precedence.

14.07    Covenant of Further Assurances. The Parties covenant and agree that,
subsequent to the execution and delivery of this Agreement and without any
additional consideration, each of the Parties shall execute and deliver any
further legal instruments and perform such acts which are or may become
reasonably necessary to effectuate the purposes of this Agreement.

14.08    Waivers; Amendments. The failure of either Party to insist, in any one
or more instances, upon the performance of any of the terms, covenants or
conditions of this Agreement or to exercise any right hereunder, shall not be
construed as a waiver or relinquishment of the future performance of any such
term, covenant or conditions or the future exercise of such right, and the
obligation of the other Party with respect to such future performance shall
continue in full force and effect. Savient and BTG may (A) mutually amend or
waive any provision of this Agreement at any time and (B), from time to time
after the date hereof, modify and/or replace any of the exhibits hereto, which
modified or replaced exhibits shall automatically constitute part of this
Agreement; provided, however, that no amendment or waiver of any provision of
this Agreement and no modification and/or replacement of any exhibits hereto
shall be valid unless the same shall be in writing and duly signed by both of
the Parties.

14.09    Relationship. BTG is an independent contractor engaged by Savient for
the provision of the Bulk Product and certain services as set forth in this
Agreement. Nothing in this Agreement shall constitute BTG as an employee, agent
or general representative of Savient. This Agreement shall not constitute either
Party as the legal representative or agent of the other, nor shall either Party
have the right or authority to assume, create or incur any liability or any
obligation of any kind, express or implied, against, or in the name of or on
behalf of, the other Party. This Agreement shall not constitute, create or in
any way be interpreted as a joint venture, partnership or formal business
organization of any kind.

 

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14.10    Publicity. Except as otherwise required by Legal Requirements, neither
Party shall use the other’s name or refer to it directly or indirectly in an
advertisement, news release or release to any professional or trade publication
or issue any news release relating to this Agreement, without the prior written
approval from such Party for such use or release. The Parties agree that a news
release with respect to the consummation of this transaction and the details
thereof will be made, the content and form of which shall be reasonably agreed
between the Parties. In addition, the Parties agree that Savient shall be
permitted to disclose this Agreement and the transactions contemplated hereby in
filings made with the U.S. Securities and Exchange Commission or other
regulatory authorities in accordance with Section 14.01.

14.11    Severability. If any term of other provision of this Agreement is
invalid, illegal or incapable of being enforced by any rule of law or public
policy, all other conditions and provisions of this Agreement shall nevertheless
remain in full force and effect so long as the economic and legal substance of
the underlying transaction in any country in the Territory is not affected in
any manner materially adverse to either Party. Upon such determination that (i)
any term of other provision is invalid, illegal or incapable of being enforced
and (ii) the economic or legal substance of the underlying transaction in any
country in the Territory is affected in a manner materially adverse to either
Party, the Parties shall modify this Agreement, with respect to such country in
the Territory, so as to effect the original intent of the Parties as closely as
possible in a mutually acceptable manner to the fullest extent permitted by
Legal Requirements in such country in the Territory in order that the underlying
transaction be completed as originally contemplated to the fullest extent
possible.

14.12    No Assignment. Neither this Agreement nor any of the rights, interests,
or obligations hereunder may be assigned by either Party without the prior
written consent of the other Party hereto, except that Savient may assign its
rights, interests, or obligations hereunder to any Third Party acquiring rights
to the Product and either Party may assign its rights hereunder to any
Affiliates or any entity that acquires all or substantially all of such Party’s
business or assets (provided that no such assignment shall relieve the assigning
Party of its obligations hereunder, and the assigning Party shall remain
primarily liable for such obligations). Subject to the foregoing, this Agreement
shall be binding upon and inure to the benefit of the Parties and their
respective successors and permitted assigns.

14.13    Headings. The headings used in this Agreement are included for
convenience only and are not to be used in construing or interpreting this
Agreement.

14.14    Force Majeure. If either of the Parties is impeded in fulfilling its
undertakings in accordance with this Agreement by circumstances beyond its
reasonable control, such as, but not limited to, labor conflict, lightening
striking, acts of God, fire, war, mobilization or unforeseen military call-up of
a large magnitude, requisition, confiscation, commandeering, public decrees,
riots, insurrections, general shortage of transport, goods or energy and faults
or delays in deliveries from subcontractor or suppliers caused by any
circumstances referred to in this Section 14.14, the impediment shall be
considered a Force Majeure condition and the Party shall be exempted from
liability for delays due to such reasons; provided, however, that it notifies
the other Party thereof without undue delay after such a circumstance has
occurred. Upon such notification, the Parties shall agree upon a reasonable
extension of the time for performance, not to exceed an extension equal to the
period the Force Majeure condition continues to exist.

 

- 38 -

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14.15    Counterparts. This Agreement may be executed in any number of
counterparts, each of which will be deemed an original, but all of which
together will constitute one and same instrument.

IN WITNESS WHEREOF, the Parties hereto have caused this Agreement to be executed
by their respective officers hereunto duly authorized as of the Effective Date.

 

SAVIENT PHARMACEUTICALS, INC.     BIO-TECHNOLOGY GENERAL (ISRAEL) LTD. By:  

    /s/ Philip K. Yachmetz

    By:  

    /s/ Dov Kanner

      Name: Philip K. Yachmetz           Name: Dov Kanner       Title: EVP & CBO
          Title: Managing Director

 

- 39 -

--------------------------------------------------------------------------------

Exhibit A

Savient Patent Rights

--------------------------------------------------------------------------------

[…***…] TITLE    COUNTRY          SERIAL NO            PATENT NO     
    STATUS      

[…***…]

  

[…***…]

  

[…***…]

  

[…***…]

  

[…***…]

Confidential Materials omitted and filed separately with the Securities and
Exchange Commission pursuant to a request for confidential treatment. A total of
five pages were omitted.

 

 

***Confidential Treatment Requested

 

A-1

--------------------------------------------------------------------------------

Exhibit B

Compensation for Services and Reimbursement of Expenses

BTG shall submit invoices to Savient on a quarterly basis in arrears, which
invoices shall provide an account of (i) detailed descriptions of the services
performed, (ii) the number of hours such services were performed, (iii) the
levels of the individuals performing such services and (iv) detailed
descriptions of any Third Party expenses incurred (documentation of such
expenses shall be provided to Savient upon request).

Payment to BTG shall be due within forty-five (45) days of the date of the
invoice (provided that the invoice is received by Savient within three (3)
Business Days of the date thereof) or within forty-five (45) days of Savient’s
receipt of the invoice (if received by Savient four (4) or more Business Days
after the date thereof).

Compensation Rates:

 

   Level

 

 

 

Daily Rate

(eight (8) hour day)

 

 

Vice President or Senior Director

  $ […***…]

Department Head or Director

  $[…***…]

Unit Head

  $[…***…]

Exempt Non-Management Employee, Group Leader & others

  $[…***…]

Beginning on January 1, 2008, and on each successive January 1st thereafter, the
above rates shall increase by an amount equal to the average increase in the
United States Consumer Pricing Index (CPI) over the immediately preceding twelve
(12) month period.

            Third Party Expenses:

Savient shall reimburse BTG for documented expenses paid to a Third Party;
provided that, other than BTG’s travel expenses for travel at the request of
Savient, expenses for raw materials, expenses for subcontractors/consultants,
BTG shall be required to obtain Savient’s pre-approval in writing for any
expenses to be incurred in excess of […***…] Dollars ($[…***…]).

 

 

***Confidential Treatment Requested

--------------------------------------------------------------------------------

Exhibit C

Current Provisional Bulk Product Specifications

--------------------------------------------------------------------------------

SPECIFICATION PEG-URICASE API

 

Parameter

   Test    Specification

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]      […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

 

 

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]    […***…]    […***…]   
[…***…]    […***…]    […***…]    […***…]    […***…]

 

 

***Confidential Treatment Requested

 

C-1

--------------------------------------------------------------------------------

Exhibit D

Quality Agreement

--------------------------------------------------------------------------------

QUALITY ASSURANCE RESPONSIBILITY AGREEMENT

BETWEEN

SAVIENT PHARMACEUTICALS, INC.

AND

BIO-TECHNOLOGY GENERAL (ISRAEL) LTD.

(COMMERCIAL PHASE)

 

D-2

--------------------------------------------------------------------------------

Table of Contents

 

  

1

  

Purpose & Scope:

     1         

2

  

Definitions:

     1         

3

  

Notification of Process Deviations and Documentation Changes:

     3         

4

  

Materials:

     4         

5

  

Manufacturing:

     6         

6

  

Release and Shipment of Products(s):

     8         

7

  

Deviations in Process or Product:

     8         

8

  

Storage of Products(s):

     9         

9

  

Traceability of Products(s):

     9         

10

  

Conflict of Terms:

     9         

11

  

Compliance with Laws:

     9         

12

  

Inspections:

     9         

13

  

Observations by SAVIENT:

     10         

14

  

Adverse Events:

     10         

15

  

Stability:

     11         

16

  

Regulatory Action:

     11         

17

  

Annual Report to FDA:

     11         

18

  

APPENDIX I:

     13         

19

  

APPENDIX II:

     14         

20

  

APPENDIX III:

     17      

 

D-3

--------------------------------------------------------------------------------

ARTICLE 1

PURPOSE AND SCOPE:

1.01       Savient Pharmaceuticals, Inc. (“SAVIENT”) and Bio-Technology General
(Israel) Ltd. (“BTG”) have entered into a Supply Agreement of (event date)
herewith (the “Supply Agreement”).

This document (the “Quality Agreement”) defines the quality assurance
responsibilities between SAVIENT and BTG. This Quality Agreement applies only to
the manufacture and supply by BTG to SAVIENT of the Product (as defined in the
Supply Agreement).

ARTICLE 2

DEFINITIONS:

2.01       Capitalized terms used but not otherwise defined in this Quality
Agreement will have the meanings ascribed thereto in the Supply Agreement. For
ease of reference, the following definitions from the Supply Agreement which are
used in this Quality Agreement are copied in full below, amended where
appropriate for the purposes of this Quality Agreement:

 

  (i) “BLA” means a Biologics License Application filed with the FDA and/or any
other application required for the purpose of marketing or selling or using a
therapeutic or prophylactic product to be filed with a governmental agency in a
non-U.S. country or group of countries, including, without limitation, a Product
License Application or Marketing Authorization in the European Union.

 

  (ii) “Bulk Product” shall mean the bulk solution of polyethylene glycol (PEG)
conjugate of uricase ordered by Savient from BTG pursuant to the Supply
Agreement.

 

  (iii) “Bulk Product Specifications” shall mean the manufacturing and quality
specifications for the Bulk Product, including, without limitation, unit
descriptions established from time to time in accordance with section 3.01 of
the Supply Agreement.

 

  (iv) “Business Day” shall mean any day other than (i) Friday, Saturday or
Sunday or (ii) a day on which banking institutions located in New York, New
York, United States of America or in Israel are permitted or required by law,
executive order or governmental decree to remain closed.

 

  (v) “cGMP” shall mean current good manufacturing practices as set forth in
Title 21, Parts 210 and 211 of the C.F.R. and 21 C.F.R. Part 312 (IND) and Part
314 (NDA), and 21 C.F.R. Part 600 (Biological Products), as established and
amended by the FDA.

 

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  (vi) “FDA” shall mean the United States Food and Drug Administration or, where
applicable, its regulatory equivalent in a foreign jurisdiction.

 

  (vii) “Facility” shall mean, as applicable, the Be’er Tuvia manufacturing
facility located at Beer Tuvia Industrial Zone, POB 571, Kiryat Malachi 83104,
Israel

 

  (viii) “IND” shall mean an Investigational New Drug application, as defined in
21 C.F.R. 312.3, and filed with the FDA or any equivalent foreign Regulatory
Agency.

 

  (ix) “Legal Requirements” shall mean (i) any present and future national,
state, local or similar laws (whether under statute, rule, regulation or
otherwise), (ii) requirements under permits, orders, decrees, judgements or
directives, and requirements of applicable Regulatory Agencies (including,
without limitation, cGMP) and (iii) regulations pertaining to BLAs (with respect
to each of the foregoing, as amended or revised from time to time).

 

  (x) “Process” or “Processing” shall mean the act of purification, preparation,
filling, testing and any other pharmaceutical manufacturing procedures, or any
part thereof (including, but not limited to, product or process specifications,
testing or test methods, raw material specifications or suppliers, equipment,
etc.), relating to, as applicable, Bulk Product and Product.

 

  (xi) “Product” shall mean pharmaceutical products containing Bulk Product
ordered by Savient pursuant to the Supply Agreement.

 

  (xii) “Regulatory Agency” shall mean with respect to the United States, the
FDA, or, in the case of a country in the Territory other than the United States,
such other appropriate regulatory agency with similar responsibilities.

2.03        In addition, the following definitions apply to this Quality
Agreement:

(i)      “Bulk Product” shall mean bulk solution of polyethylene glycol (PEG)
conjugate of uricase in its final formulation which is in Process, and has been
produced for sterilization, filling or other finishing activities.

(ii)      “Filled Product” shall mean sterile Product that is in Process and has
been filled into its final primary packaging for further labelling or packaging
activities.

(iii)      “Final Product” shall mean finished Product in its final packaged and
labeled form which is ready for distribution to the marketplace or third party
distributors for sale or clinical use.

(iv)      “Release” shall mean control, approval and authorization of shipment.

 

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ARTICLE 3

NOTIFICATION OF PROCESS DEVIATIONS AND DOCUMENTATION OF

CHANGES:

3.01      BTG shall provide to SAVIENT, within two Business Days of BTG’s
discovery of its occurrence, written notification of (i) any deviation from the
Process as set forth in the Bulk Product Specifications and the BLA and any
deviation from cGMP requirements, regulations and standards, and any event that
represents an unexpected or unforeseeable event that may affect safety, purity
or potency of Bulk Product; and (ii) any deviation in the quality (purity,
physical and chemical properties) of the Bulk Product from the Bulk Product
Specifications. Appendix I sets forth a list of examples of deviations from the
Process, for purposes of illustration only, and is not intended to be
comprehensive or definitive.

(i)          BTG shall not conduct any retesting or reprocessing as the result
of deviations described above without prior written authorization from SAVIENT
Quality Assurance unless a delay of retesting or reprocessing would result in
increased risk to the safety, purity or potency of the Bulk Product or Product.

3.02       Any changes to be made to this Quality Agreement in accordance with
the provisions set out in this section 3 must be documented as an addendum to
this Quality Agreement, and must be signed by authorized representatives from
each of the BTG QA department and the SAVIENT QA department, in addition to
authorized representatives from any other departments as may be specified in
relation to the matters set forth in section 3.3 below. This Quality Agreement
will be reviewed by BTG and SAVIENT on a periodic basis (approximately once per
year) and revised as appropriate.

3.03       Change Control

(i)          Specifications that control the Process for the manufacture,
including packaging, holding, and test of Bulk Product and Product, must be
signed by authorized representatives from BTG and SAVIENT Quality Assurance,
SAVIENT Regulatory Affairs, and SAVIENT Manufacturing. Such documents include,
but are not limited to Bulk Product Specifications (including specifications for
intermediate), Product Specifications (including specifications for product,
component and packaging). Changes to such documents must be signed by authorized
representatives from SAVIENT Quality Assurance, SAVIENT Manufacturing and
SAVIENT Regulatory Affairs.

(ii)         Changes to additional documents that control the Process for the
manufacture of Bulk Product and Product (including test methods, manufacturing
procedures and batch records) must be assessed according to the BTG change
control process described in section 3.4. Any change that would have an impact
on the Process, Bulk Product or Product, or require submissions to or approvals
from any Regulatory Agency must receive prior written approval by authorized
representatives from SAVIENT Quality Assurance, SAVIENT Manufacturing and
SAVIENT Regulatory Affairs. If there is no such impact, BTG may proceed with the
change, but must notify SAVIENT Quality

 

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Assurance no later than 5 days from the initiation of the BTG change control
process. If SAVIENT does not agree with BTG’s assessment of impact, SAVIENT must
respond to BTG no later than within 5 days of receipt of notification.

(iii)          The stability protocol as well as any changes to the stability
protocol must be approved by SAVIENT QA and SAVIENT Regulatory Affairs.

(iv)          Critical Raw Materials. The current specifications for Critical
Raw Materials are attached as Appendix III. The Parties acknowledge and agree
that these specifications may be amended from time to time by the supplier of
the material. With respect to such amendments:

BTG shall notify SAVIENT as soon as reasonable practicable, but no later than
within 5 days of receipt of notification by BTG.

The Parties will meet and agree as to suitability of the material produced
according to the amended specification for manufacture of the Bulk Product.

3.04       BTG will utilize a documented system of written procedures for the
control of changes to documents relating to raw materials, packaging materials,
labeling, suppliers, equipment, manufacturing methods, batch size, product,
intermediates and raw materials specifications, sampling, analytical test
methods and Release requirements and any other Processing by BTG, relating to
the Bulk Product.

3.05       Any changes to any matter relating to the manufacture and supply of
Bulk Product by BTG shall be governed by the procedures set out in the Supply
Agreement at Article 3 in relation to changes to the Bulk Product
Specifications, and Article 6 in relation to changes to the Process.

3.06       SAVIENT Regulatory Affairs will have responsibility for determining
the regulatory impact of any proposed change. SAVIENT Regulatory Affairs will
determine the classification and requirements for notification to, or approval
by FDA. SAVIENT is responsible for communication of any changes to FDA. SAVIENT
Regulatory Affairs will have responsibility to advise BTG of any changes to the
BLA prior to submission.

BTG will ensure that changes are evaluated and qualified in accordance with all
applicable ICH (International Conference on Harmonization) requirements in
addition to all Legal Requirements, including but not limited to:

ICH Guideline Q5E Comparability of Biotechnological/Biological Products Subject
to Changes in Their Manufacturing Process.

 

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ARTICLE 4

MATERIALS:

4.01       Procurement of Components

BTG will procure all the components described in the Bulk Product Specifications
in such quantities as may be necessary to meet Purchase Orders placed by SAVIENT
pursuant to the Supply Agreement, and store the components in appropriate
storage conditions under quarantine until tested.

4.02       Inspection and Testing of Materials

Upon receipt, BTG shall sample in accordance with acceptable statistical
methods, inspect and test containers of all materials to be used in the Process
or in connection with the supply and manufacture of Bulk Product on a
batch-by-batch basis, in accordance with the Bulk Product Specifications.

4.03       Bulk Product

BTG will be responsible for ensuring that Bulk Product is manufactured, tested
and stored in compliance with all applicable ICH guidance documents (including,
without limitation, the guidance contained therein for master and working cell
banks) in addition to all Legal Requirements. ICH Guidance includes, but is not
limited to:

Q5D Quality of Biotechnological Products: Derivation and Characterization of
Cell Substrates Used for Production of Biotechnological/Biological Products.

Q7A, Good Manufacturing Practices Guidance for Active Pharmaceutical Ingredients

4.04        Retention, Storage and Handling of Materials and Product Samples

BTG shall sample and retain such amounts of Bulk Product and of all materials to
be used in the Process or in connection with the supply and manufacture of Bulk
Product (“Retains”) except water, compressed gasses and any highly volatile
compounds as set forth in Appendix II or as otherwise required in accordance
with applicable Legal Requirements. BTG will store for five years, or such
longer period as may be required in accordance with Appendix II or by Legal
Requirement, sample Product and Retains for each batch or lot of intermediates
and raw materials. Reasonably prior to the expiry of such retention period, or
upon termination of this Quality Agreement, BTG shall offer all such materials
to SAVIENT. Any labor costs of BTG employees and/or Third Party expenses
incurred by BTG related to the transfer of such materials shall be reimbursed by
SAVIENT in the manner and at the rates set forth on Exhibit B to the Supply
Agreement.

A schedule of specific Retains, storage conditions and retention periods for
Puricase® is listed in Appendix II.

4.05       Transmissible Spongiform Encephalopathy (TSE)

BTG will provide a written TSE declaration that all materials (including
non-dedicated equipment) used in the manufacturing process are free from animal
derived material. In addition, BTG must have available, on site, written TSE
declarations from the supplier, where appropriate, of raw material used in the
manufacturing process verifying exclusion

 

D-8

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of animal derived material. If BTG is unable to provide the above declarations,
BTG will comply with applicable TSE laws and regulations and will obtain all
associated TSE documentation as requested by SAVIENT. This documentation may
include a TSE Certificate of Suitability in accordance with European directive
75/318/EEC as amended by directive 1999/82/EEC, the note for guidance
EMEA/410/01 rev2 as amended and AP-CSP(99)4, Appendix 2, as amended.

 

4.06       Supplier Audits

BTG and SAVIENT will provide each other with copies of supplier audit reports
for materials used in the Process or manufacture of the Product.

ARTICLE 5

MANUFACTURING, PACKAGING, INSPECTION AND TEST:

5.01       The Processing, packaging, and labeling of Bulk Product will be
performed and documented by BTG. BTG will not subcontract any of the Processing,
packaging, and labeling functions except as may be permitted in accordance with
the Bulk Product Specifications, and if so permitted, in accordance with the
provision set forth in Section 2.05 of the Supply Agreement.

5.02       BTG shall not Process or store Bulk Product in the same building in
which BTG manufactures, stores or processes potentially hazardous substances
(including, without limitation, certain antibiotics such as beta-lactam and
cephalosporins, cytotoxic compounds, toxins or poisons such as pesticides or
herbicides, (collectively, “Potential Contaminants”) unless the Potential
Contaminants are stored or manufactured in contained environments and in
compliance with all Legal Requirements and the Bulk Product is Processed and
stored in compliance with building, cleaning, validation and changeover
requirements of all cGMPs and all Legal Requirements. BTG shall promptly notify
SAVIENT if any of the Potential Contaminants are manufactured, processed or
stored in any portion of the Facility which may result in the introduction of
Potential Contaminants into the areas of such facilities where the Bulk Product
is Processed. Savient is aware that other products are processed in the
Facility, the nature of those other products existing today and that certain
equipment (multi-use equipment) is used in the processing of both the Bulk
Product and these other existing products. Savient has also had the opportunity
to assess the risk to the Processing of Bulk Product of the use of such certain
multi-use equipment with respect to the other existing products. However, in the
instance where BTG intends to introduce a new product or substance to its
Facility which is out of the matrix of existing products and use such multi-use
equipment in the processing or handling of such new product or substance,
Savient will need to reassess the risks to the Processing of Bulk Product with
this new product or substance utilizing the multi-use equipment. Therefore,
whenever BTG plans to introduce a new product or molecular entity which is out
of the matrix of existing products to equipment shared with Puricase production,
BTG will provide no less than 30 days prior notice of its intent, and will
contemporaneously make supporting cleaning validation data/rationale available
to Savient. Savient will make its assessment of the risk potential for
adulteration of its own product through examination of cleaning validation

 

D-9

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documentation prior to any further Puricase production and will respond to BTG
within 5 days of its receipt of cleaning validation data/rationale as to its
conclusion(s) about the introduction.

5.03       BTG will provide to SAVIENT: a copy of all master batch record
documents and production and control records, a Certificate of Analysis
(PEG-uricase API and uricase), executed batch records and associated batch
documentation, which shall include, without limitation: formulation records,
label records, manufacturing records, environmental monitoring data,
microbiological data, in-process and final analytical data, including lab
control results, sterility data, deviations/out-of-specification reports and
cleaning records for any critical product contact equipment (for example,
fermentors or any other non-dedicated product contact equipment).

 

   (i)

Translation: BTG will provide an English translation of all such documents,
including, without limitation, all reports, notes or comments on records that
are not part of the master batch record but if any of the foregoing documents
are only available in a language other than English, the Parties shall agree
upon an English language template for such document(s), and BTG shall provide to
Savient an English language translation of any deviations from the template(s).
When required by SAVIENT, translations shall be performed by an independent,
translation firm. Translations by a third party firm must be verified by BTG to
ensure translation of company or process specific language. Any labor costs of
BTG employees and/or Third Party expenses incurred by BTG in relation thereto
shall be reimbursed by SAVIENT in the manner and at the rates set forth on
Exhibit B to the Supply Agreement.

5.04       Upon request by SAVIENT, BTG will provide access to additional
records that are not normally part of the batch record but which bear a
reasonable relation to the Bulk Product for SAVIENT to review, which may
include, without limitation, maintenance and use records, water testing data,
training records, raw material release records, log books, receiving and
shipping records, inventory records and vendor qualification records Any labor
costs of BTG employees and/or Third Party expenses incurred by BTG in relation
thereto shall be reimbursed by SAVIENT in the manner and at the rates set forth
on Exhibit B to the Supply Agreement.

5.05       BTG will retain copies of all completed batch records for a minimum
of five years, or such longer period as may be required by Legal Requirement.
Reasonably prior to the expiry of such retention period, or upon termination of
this Quality Agreement, BTG shall offer such completed batch records to SAVIENT.
Any labor costs of BTG employees and/or Third Party expenses incurred by BTG
related to the transfer of such materials shall be reimbursed by SAVIENT in the
manner and at the rates set forth on Exhibit B to the Supply Agreement.

5.06       Use of BTG Manufacturing Space for Bulk Product

BTG has allotted an amount of manufacturing floor space at the Facility for the
Processing of Bulk Product (Purification Area in the Agreement). This space may
be used for the production of other products subject to the following
limitations:

 

D-10

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   (i) BTG may use the Purification Area for alternate product manufacturing
only during periods when the Purification Area is not used for the Processing of
Bulk Product.

   (ii) BTG adheres to all relevant cGMPs including, without limitation,
procedures for prevention of mix-ups, prevention of contamination, labeling
requirements, cleaning requirements and changeover requirements

   (iii) BTG, shall not, under any circumstances utilize any equipment dedicated
to the Processing of Bulk Product for such alternate product manufacturing

   (iv) BTG adheres to limits and procedures described in section 5.2 for
Potential Contaminants.

ARTICLE 6

RELEASE AND SHIPMENT OF PRODUCT(S):

6.01       Bulk Product shall be Released in accordance with the procedures set
forth in the Supply Agreement, together with the additional obligations
described in this section 0 of the Quality Agreement. BTG QA will review the
records described in section 5.3 above. Following review and acceptance by BTG
QA, BTG will send copies of these documents to SAVIENT QA. SAVIENT QA and
Manufacturing will then review the documentation and notify BTG whether or not
documentation is acceptable. If such documentation is not reasonably acceptable
to SAVIENT, BTG will cooperate in taking such steps as SAVIENT may reasonably
require to ensure that the documentation, and any Processing described therein
complies with the Bulk Product Specifications and all Legal Requirements.

6.02       BTG QA will be responsible for the QC testing of Filled Product until
such time as a third party laboratory has been qualified to perform such
testing. BTG will provide a Certificate of Analysis and/or stability results for
each batch that BTG tests. Savient QA will be responsible for the review of the
manufacturing batch record for Filled Product, review of the Certificate of
Analysis and Release of the Filled Product.

6.03       SAVIENT QA will be responsible for the Release of the Final Product.

6.04       Product shall be delivered in accordance with the provisions of
Article 7 of the Supply Agreement.

6.05       BTG will not ship any SAVIENT products to any destination, as
identified by SAVIENT, unless prior approval has been received from SAVIENT.

ARTICLE 7

DEVIATIONS IN PROCESS OR BULK PRODUCT:

In the event of a notification of a deviation by BTG in accordance with section
0 above, BTG shall investigate and fully document in English such deviation
within 30 days of its discovery. If BTG cannot resolve the deviation within the
30-day period, BTG will provide

 

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weekly updates of the investigation progress. At SAVIENT’s request, BTG shall
conduct such additional or more detailed investigation of the deviation as
SAVIENT may reasonably instruct. Investigation documentation will be retained by
BTG as part of the batch documentation for the batch affected. When a deviation
has occurred, SAVIENT will have the final review and decision making
responsibility as to the impact of the deviation on the Bulk Product or Product,
which will include the disposition of affected lots.

ARTICLE 8

STORAGE OF PRODUCT(S):

Bulk Product will be stored under appropriate storage conditions and in a secure
area to ensure that they comply with the Bulk Product Specifications, including
all the label requirements, quality specifications and attributes as well as
Legal Requirements.

ARTICLE 9

TRACEABILITY OF PRODUCT(S):

SAVIENT will be responsible for traceability of products to first consignee
within the US. BTG will be responsible for traceability from the finished
product lot number to raw material and component lots used in manufacture.

ARTICLE 10

CONFLICT OF TERMS:

To the extent that there exists any conflict between the terms of this Quality
Agreement and the Supply Agreement, the latter shall prevail. To the extent that
there exists any conflict between the terms of this Quality Agreement and any
Legal Requirements, the latter shall prevail.

ARTICLE 11

COMPLIANCE WITH LAWS:

BTG will ensure that all of its activities pursuant to this Agreement are
performed in accordance with all Legal Requirements (including cGMPs), the
respective Bulk Product Specifications, conditions of the BLA, and BTG’s
Standard Operating Procedures (SOPs). BTG will ensure that the Bulk Product
supplied by it to SAVIENT shall not itself cause the Final Product to be
adulterated or misbranded within the meaning of the Federal Food, Drug, and
Cosmetic Act and regulations.

 

D-12

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ARTICLE 12

INSPECTIONS:

Each party shall advise the other of any governmental communication, inspection
or report, including, without limitation, that of any appropriate regulatory
agency in any jurisdiction with responsibilities similar to those of the FDA in
respect of the United States, any environmental agency, health agency or other
governmental or administrative agency having jurisdiction over the Product or
the Processing. The notifying party shall promptly notify the other party by fax
and telephone, to the person and on the contact numbers set out below:

TO SAVIENT:

 

  

•      Contact Name:        

   Robert Lamm, Ph.D., Sr. VP of Quality and Regulatory Affairs   

•      Telephone:

   732-418-9300   

•      Fax:

   732-418-0766

TO BTG:

 

  

•      Contact Name:        

   Rivka Zaibel, VP, Quality Assurance   

•      Telephone:

   972-8-861-2007   

•      Fax:

   972-8-861-2166

 

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ARTICLE 13

OBSERVATION BY SAVIENT:

Observation by SAVIENT or its authorized representative shall be governed the
following. Observation will be limited to not more than one quality audit every
12 months. One additional quality audit may be conducted within the 12 month
period if BTG receives a communication from any regulatory authority threatening
license approval or supply of the Product due to compliance deficiencies at BTG
facilities or if BTG was found to be in material non-compliance of this
Agreement during or since the last quality audit. Person-in-Plant visits may be
conducted at the discretion of SAVIENT during the manufacture of Bulk Product at
BTG facilities. The frequency and duration of any additional visits must be
agreed to by SAVIENT and BTG.

ARTICLE 14

ADVERSE EVENTS:

14.1       BTG will provide to SAVIENT within 48 hours of becoming aware, any
information from any source that suggests an adverse event or serious adverse
event has occurred. This information will include any adverse drug experience or
reaction reports or any other information indicating that the product has any
toxicity, sensitivity reactions or is otherwise alleged to cause illness or
injury due to a possible product quality problem, adulteration or misbranding.

14.2       Quality Assurance Investigations. Upon notification to BTG that
SAVIENT has received an SAE, AE, product complaint or inquiry regarding a
Product supplied or incorporating a Bulk Product supplied, BTG shall conduct a
quality assurance investigation to determine if any process or testing
deviations or events may have contributed to the SAE, AE, product complaint or
inquiry. BTG shall provide a written report on the results of the investigation
to SAVIENT in not more than 30 days from Savient’s notification. In cases where
a more comprehensive investigation might be required, the Parties will jointly
develop an investigation plan. BTG shall reasonably cooperate with SAVIENT and
regulatory agencies regarding an investigation or inquiry that may be initiated
by a regulatory agency or otherwise required in response to a consumer or
healthcare professional. BTG shall further provide SAVIENT with all data or
other information that SAVIENT may reasonably require in connection with any
reports or correspondence that SAVIENT provides to the regulatory agency,
consumer or healthcare professional relative to any such AE, SAE or product
complaint. BTG shall make records accessible to SAVIENT for purposes of FDA or
other regulatory agency inspection.

14.3       Exchange of Drug Safety Requests. The Parties shall immediately
provide each other with copies of all drug safety requests from all governmental
and other regulatory health authorities. Proposed answers affecting the Product
will be exchanged between the Parties before submission and the Parties shall
cooperate with respect to such answers. SAVIENT shall

 

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have the ultimate decision-making authority with respect to the answers relating
to the Product. The Parties shall exchange decisions from applicable health
authorities immediately.

ARTICLE 15

STABILITY:

BTG will perform the stability testing, data interpretation, reporting and
updating of stability information to regulatory documents for the Product and
Bulk Product and for Product until such time as a third party laboratory has
been qualified to perform such testing. Stability related activities for which
BTG is responsible shall be completed in accordance with the timing specified in
stability protocols and BTG procedures.

ARTICLE 16

REGULATORY AFFAIRS:

Each Party shall advise the other Party of any regulatory action of which it is
aware which would affect the Product in any country of the Territory.

ARTICLE 17

ANNUAL REPORT TO FDA:

BTG will prepare a summary of all changes to the product, production process,
quality controls, equipment or facilities that have a potential to affect the
identity, strength, quality, purity or potency of the Product. Such data will be
prepared and sent to SAVIENT within thirty days of the end of the review period.
BTG will also ensure that the results of all stability testing performed within
the review period are sent to Savient within thirty days of the end of the
review period.

 

D-15

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Approvals

 

            

Print Name

 

  

Signature

 

  

Date

 

       

SAVIENT QA

  

Robert B. Lamm

 

  

/s/ Robert B. Lamm

  

20-Mar-07

       

 

BTG QA

 

  

 

Rivka Zaibel

  

 

/s/ Rivka Zaibel

 

  

 

20 March 2007

 

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APPENDIX I

Listing of Example Deviations

The following is a non-exclusive list of deviations requiring notification in
accordance with section 0:

 

  ●   Deviation impacting any filed regulatory document.

  ●   Use of manufacturing or testing site (finished products, intermediates,
API or excipients) other than that specified in Bulk Product and Product
Specifications and/or BLA.

  ●   Change of manufacturing scale from that specified in Bulk Product
Specifications and/or BLA.

  ●   Deviation from packaging or packaging specifications from that specified
in Bulk Product Specifications and/or BLA.

  ●   Deviation from suppliers, sources or specifications of starting and
Critical Raw Materials or supplier of any filters for Products or intermediates
set forth in Bulk Product Specifications and/or BLA.

  ●   Change in the layout, functioning or structure of the Facility, equipment
or utilities (HVAC, nitrogen, water or compressed gasses) that may affect the
quality of the Bulk Product.

  ●   Use of solvents or reagents (including volatile reagents), other than
those specified in Bulk Product Specifications and/or BLA, or change of
specifications for such solvents, reagents, or intermediates, or change in
analytical methods of solvents, reagents, or intermediates.

  ●   Deviation in amounts of solvents or reagents used from that specified in
the Process, Bulk Product Specifications and/or BLA.

  ●   Change in […***…] status of any raw material or product(s).

  ●   Any reprocessing or rework of any step of the Process.

  ●   A physical contamination, cross-contamination or other chemical
contamination.

  ●   Any manufacturing, packaging, labeling, sampling or testing deviation that
affects the quality, safety or purity of the Product.

  ●   Departures from the SOPs, IPC tests, stability SOPs, the Stability
Protocol or Batch Records outside the filed limits, excursions or any deviation
with potential registration impact.

  ●   Any unexpected results from stability testing.

  ●   Environmental monitoring results that are out-of-specification.

 

 

***Confidential Treatment Requested

 

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APPENDIX II

Schedule of Retains, Storage Conditions and Retention Periods for Puricase®

The following is a list of the reserve/retention samples that are taken during
the manufacturing processes of bulk uricase and PEG-uricase as well as from the
final bulk uricase and the final bulk PEG-uricase (Bulk Product).

The document was prepared based on the following BTG QC SOPs:

1.    SOP 04-68-1288 (v2): QC Sampling Plan for Bulk Uricase

2.    SOP 04-68-1830 (v1): QC Sampling Plan for PEG-Uricase API

3.    SOP 04-68-1861 (v1): IPC Testing of Bulk Uricase Batches

4.    SOP 04-68-1862 (v1): IPC Testing of PEG-Uricase

Table 1 details the reserve/retention samples that are taken during the
manufacturing process of bulk uricase and from the final bulk uricase.

Table 2 details the reserve/retention samples that are taken during the
manufacturing process of PEG-uricase and from the final bulk PEG-uricase (Bulk
Product).

All IPC samples (including reserve/retention samples) are to be discarded after
the Final Product is released by Savient.

Uricase retention and reserve samples will be kept for one year after
manufacturing. PEG-Uricase retention and reserve samples will be kept for six
years after manufacturing

 

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  Table 1. Reserve/Retention Samples for Bulk Uricase (IPC and Final)

 

Process Step

   Sample name    Number of Samples    Storage Temperature […***…]    […***…]   
[…***…]    […***…] […***…]    […***…]    […***…]      […***…]    […***…]   
[…***…]            […***…]      […***…]    […***…]    […***…]      […***…]   
[…***…]    […***…]      […***…]    […***…]    […***…]      […***…]    […***…]   
[…***…]      […***…]    […***…]    […***…]      […***…]    […***…]    […***…]   
  […***…]    […***…]    […***…]      […***…]    […***…]    […***…]          
[…***…]    […***…]      […***…]    […***…]    […***…]      […***…]    […***…]   
[…***…]         […***…]    […***…]      […***…]    […***…]    […***…]    […***…]
   […***…]    […***…]      […***…]    […***…]    […***…]         […***…]   
[…***…]      […***…]    […***…]    […***…]         […***…]    […***…]        
[…***…]    […***…]      […***…]    […***…]    […***…]            […***…]       
   

[…***…]

 

   […***…]           

[…***…]

 

   […***…]     

   […***…]

 

 

***Confidential Treatment Requested

 

D-19

--------------------------------------------------------------------------------

  Table 2. Reserve/Retention Samples for PEG-Uricase API (IPC and Final)

Process Step    Sample name    Number of
Samples    Storage
Temperature

[…***…]

   […***…]    […***…]    […***…]

[…***…]

  

[…***…]

  

[…***…]

  

[…***…]

  

[…***…]

  

[…***…]

     

[…***…]

  

[…***…]

  

[…***…]

  

[…***…]

  

[…***…]

  

[…***…]

  

[…***…]

  

[…***…]

     

[…***…]

  

[…***…]

     

[…***…]

  

[…***…]

     

[…***…]

  

[…***…]

        

[…***…]

  

 

[…***…]

 

  

[…***…]

 

  

 

[…***…]

  

 

[…***…]

 

  

 

 

***Confidential Treatment Requested

 

D-20

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APPENDIX III

Critical Raw Materials Used in the Production of Recombinant Uricase and
PEG-Uricase

 

 

Material

 

  

 

Manufacturer

  

 

Cat. No.

  

 

Testing

  

 

Source

  

 

Origin

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]         […***…]     

 

 

***Confidential Treatment Requested

 

D-21

--------------------------------------------------------------------------------

SPECIFICATION […***…]

 

Parameter    Test    Specification

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

 

 

***Confidential Treatment Requested

 

D-22

--------------------------------------------------------------------------------

SPECIFICATION […***…]

 

Parameter    Test    Specification

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

 

 

***Confidential Treatment Requested

 

D-23

--------------------------------------------------------------------------------

SPECIFICATION YEAST EXTRACT

 

Parameter    Specification

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

 

 

***Confidential Treatment Requested

 

D-24

--------------------------------------------------------------------------------

SPECIFICATION […***…]

 

Parameter    Specification

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

   […***…]

 

 

***Confidential Treatment Requested

 

D-25

--------------------------------------------------------------------------------

SPECIFICATION […***…]

 

Parameter    Specification

[…***…]  

    

[…***…]  

    

[…***…]  

   […***…]

[…***…]  

   […***…]

[…***…]  

    

[…***…]  

   […***…]

[…***…]  

    

[…***…]  

   […***…]

 

 

***Confidential Treatment Requested

 

D-26

--------------------------------------------------------------------------------

SPECIFICATION […***…]

 

Parameter    Specification

[…***…]  

   […***…]

[…***…]  

   […***…]

 

 

***Confidential Treatment Requested

 

D-27

--------------------------------------------------------------------------------

SPECIFICATION […***…]

 

Parameter    Test    Specification

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

 

 

***Confidential Treatment Requested

 

D-28

--------------------------------------------------------------------------------

SPECIFICATION […***…]

 

Parameter    Specification

[…***…]  

   […***…]

 

 

***Confidential Treatment Requested

 

D-29

--------------------------------------------------------------------------------

SPECIFICATION […***…]

 

Parameter    Test    Specification

[…***…]  

        […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

[…***…]  

   […***…]      […***…]

  […***…]

 

 

***Confidential Treatment Requested

 

D-30

--------------------------------------------------------------------------------

Exhibit E

Product Price

During the first three (3) years from the date of the receipt by Savient of the
first commercial batch of the Product, the Price of the Product shall be as
follows:

(i)      For each gram, […***…] United States Dollars (USD$[…***…]) for any
aggregated quantities of the Product up to and including […***…] ordered during
any calendar year that commercial batches of Product are shipped, i.e. after the
first commercial batch of Product has been shipped.

(ii)     For each gram, […***…] United States Dollars (USD$[…***…]) for any
aggregated quantities of the Product between […***…] and […***…] ordered during
any calendar year as above.; and

(iii)    For each gram, […***…] United States Dollars (USD$[…***…]) for any
aggregated quantities of the Product equal to or greater than […***…] ordered
during any calendar year as above.

The Parties agree that Savient will enter into a supply agreement with NOF, the
supplier of […***…], and will order and pay for PEG needed in Product
manufacture on an ongoing basis. In the event that BTG purchases PEG directly
from NOF or any other manufacturer, the cost of the PEG will be invoiced to
Savient.

Beginning on the Third (3rd) anniversary of the date of receipt of the first
commercial batch of Product by Savient, and on each successive first (1st)
January thereafter, the Price of the Product shall increase by an amount equal
to the average increase in the United States Consumer Pricing Index (CPI) over
the immediately preceding twelve (12) month period; such percentage increase
shall be applied to each amount specified in (i) through (iii) above.

 

 

***Confidential Treatment Requested

--------------------------------------------------------------------------------

Exhibit F

Residual Rights Agreement

--------------------------------------------------------------------------------

AMENDED AND RESTATED

RESIDUAL RIGHTS AGREEMENT

This Amended and Restated Residual Rights Agreement (“Agreement”) is entered
into on the 17th day of July, 2005, by and between Savient Pharmaceuticals,
Inc., a public company duly organized under the laws of the State of Delaware
(“Savient”) and Bio-Technology General (Israel) Ltd., a private company duly
organized under the laws of the State of Israel (“BTG”), to replace and
supersede the Residual Rights Agreement previously signed and dated 20 June,
2005.

(Savient and BTG shall be referred to jointly as the “Parties” and individually
as a “Party”).

WHEREAS, BTG is a wholly owned subsidiary of Savient; and

WHEREAS, the Parties are parties to a Manufacturing Services Agreement effective
January 1, 1996 (the “Manufacturing Agreement”) and a Research and Development
Services Agreement dated January 1, 1996 (the “R & D Agreement”) (the
Manufacturing Agreement and the R & D Agreement being collectively referred to
hereunder as the “Inter-Company Agreements”); and

WHEREAS, pursuant to the Share Purchase Agreement (the “SPA”) and the Asset
Purchase Agreement (“APA”), each dated March 23, 2005 (the SPA and APA,
collectively, the “Divestiture Agreements”), Savient intends to sell to Ferring
B.V. all of the issued and outstanding share capital of BTG, and to Ferring
International Centre S.A. (together with Ferring B.V., the “Buyer”) all of
Savient’s right, title and interest in and to certain assets and rights of
Savient in the drug products and drug candidates developed and/or manufactured
at BTG pursuant to the Inter-Company Agreements (the “Divestiture” and the
“Divested Products”, respectively), but not in any case in the drug candidate
known as “Peguricase” (a/k/a “Puricase”); and

WHEREAS, the development of Puricase is ongoing and Savient shall require, and
BTG is willing to render, continued development, manufacturing and other
services of BTG in relation to Puricase, following the Closing (as defined in
the Divestiture Agreements); and

WHEREAS, the Parties wish to record certain specific understandings in relation
to certain […***…] technology (the “[…***…] Technology”) as to which Savient has
retained title, in furtherance of the understandings set out in the SPA in
relation thereto, which […***…] Technology forms part of the Puricase
Technology, but which can also be used for the manufacture of other

 

 

***Confidential Treatment Requested

 

- 1 -

--------------------------------------------------------------------------------

products (all products that may be manufactured using the […***…] Technology,
other than Puricase, Divested Products and HA (as defined below), being referred
to herein as “[…***…] Products”); and

WHEREAS, the Parties wish to record certain specific understandings in relation
to the OCS-funded project, known as BTG-271 (“BTG-271”), in furtherance of the
understandings set out in the SPA in relation thereto; and

WHEREAS, certain of the Divested Products, Puricase, the […***…] Technology and
BTG-271 were developed at BTG within the framework of research and development
programs carried out with the support of the Office of the Chief Scientist at
the Ministry of Industry, Trade and Labor (“Approved Programs” and the “OCS”
respectively) and Savient has ownerships rights thereto but BTG possesses other
rights as set forth in Savient’s letter to the OCS of July 15, 2003 (the “OCS
Letter”), a copy of which is attached as Annex “A”; and

WHEREAS, the Parties have agreed to terminate the Inter-Company Agreements and
wish to record their understandings in relation to the continued development
and/or manufacture of Puricase and/or other services that may be rendered by BTG
in relation thereto; and

WHEREAS, the Parties wish to record their understandings in relation to the
royalties that may be payable to the OCS (“Royalties”) in relation to the
Divested Products, Puricase, other products embodying Puricase Technology,
[…***…] Products and BTG-271, all subject to and effective as from the Closing.

Now therefore, in consideration of the foregoing premises, which are
incorporated into and made a part of this Agreement, and of the mutual covenants
which are recited herein, the Parties agree as follows:

 

1.        Termination of the Inter-Company Agreements

 

  1.1.

Prior to the Closing, Savient and BTG shall comply with the terms and conditions
of the Inter-Company Agreements, including any payment obligations by Savient
thereunder. Notwithstanding anything to the contrary contained in the
Inter-Company Agreements, all of the provisions of the Inter-Company Agreements
shall automatically terminate effective as of the Closing, including provisions
that were intended to survive termination. Savient shall not have any further
obligation to pay BTG in respect of Reimbursable Costs (as such term is defined
in the R & D Agreement) or Processing Fees (as such term is defined in the
Manufacturing Agreement) that may be outstanding as of such time in relation to
Divested Products, and BTG shall be considered as having waived such payments.

 

 

***Confidential Treatment Requested

 

- 2 -

--------------------------------------------------------------------------------

  1.2.

In connection with such terminations, and for the avoidance of doubt, the
Parties agree that:

 

  1.2.1.

Notwithstanding the provisions of Section 1.1 and Section 3.2 of the
Manufacturing Agreement, title to all work in process relating to Divested
Products and inventory of Divested Products shall automatically vest in the
Buyer, as of the Closing;

 

  1.2.2.

Notwithstanding the provisions of Section 1.1 above and Section 11.3 of the
Manufacturing Agreement, as of the Closing, BTG shall process and deliver
Divested Products ordered prior to the Closing to the Buyer or the Buyer’s
designee, and Savient shall have no responsibilities in relation thereto;

 

  1.2.3.

As of the Closing, Savient and BTG agree that any liability of Savient to pay
BTG for development activities, regulatory or other services of any nature that
may have been carried out by BTG for Savient prior to the Closing under the R &
D Agreement or otherwise have been satisfied as of the Closing; and

 

  1.2.4.

The provisions of the Manufacturing Term Sheet attached hereto as Annex “D”
shall apply to work in process relating to Puricase existing as of the Closing
and the delivery of Puricase that may have been ordered prior to the Closing.

 

2.          Ownership in Technology; Patent Rights; Other Rights

 

  2.1.

Savient has and shall have the exclusive right, title and interest in and to
Puricase and the Puricase Technology, subject to (i) BTG’s irrevocable and
perpetual right to conduct research and development with the Puricase Technology
developed in the course of Approved Programs, excluding clinical trials that BTG
is not in a position to monitor from Israel and (ii) BTG’s right to manufacture
Puricase in Israel. BTG shall have commercialization rights with respect thereto
only as provided in Section 6 herein or as provided in the Divestiture
Agreements. In the case of clauses (i) and (ii), BTG’s rights shall always
remain subject to the terms and conditions of any existing supply, manufacturing
or development agreement between the Parties. For the avoidance of doubt,
Savient and an additional manufacturer on its behalf approved by the OCS, will
have the right to use the […***…] Technology in order to manufacture Puricase.

 

 

***Confidential Treatment Requested

 

- 3 -

--------------------------------------------------------------------------------

  2.2.

Savient has and shall have the exclusive right, title and interest in the
[…***…] Products and the […***…] Technology subject to BTG’s exclusive,
irrevocable, perpetual and unconditional license for purposes of research and
development and production. BTG shall have commercialization rights with respect
thereto only as provided in Section 6 herein or as provided in the Divestiture
Agreements.

 

  2.3.

For the purposes of this Agreement, the term “Puricase Technology” means the
technology described in the patent applications listed on Annex “B” as 1.1 (the
“Puricase Patents”), and any developments, discoveries, inventions,
improvements, designs, methods, processes, techniques, devices, formulae and
trade secrets which may be developed, acquired and conceived by BTG and are
derived from any Development Program in relation to Puricase which have been or
may be carried out at any time after the submission of the Puricase Patents and
all patents that may be issue from patent applications claiming or describing
such technology, information and know-how and filed in addition to the Puricase
Patents after their submission.

 

    

For the purposes of this Agreement, the term “[…***…] Technology” means the
technology described in the patent applications listed on Annex “B” as 1.2 (the
“[…***…] Patents”) and any developments, discoveries, inventions, improvements,
designs, methods, processes, techniques, devices, formulae and trade secrets
which have been or may be developed, acquired and conceived by BTG and are
derived from any Development Program which have been or may be carried out at
any time after the submission of the […***…] Patents and all patents that may
issue from patent applications claiming or describing such technology,
information and know-how and filed in addition to the […***…] Patents after
their submission.

 

    

For the purposes of this Agreement, “Development Programs” shall mean research
and development work carried out by BTG for Savient.

 

  2.4.

The Puricase Patents, and the […***…] Patents (collectively, the “Savient
Patents”) are owned by Savient. BTG shall have no rights with respect to the
Savient Patents, other than as provided herein or as provided in the Divestiture
Agreements. Savient has the sole control over filing and prosecuting
applications for United States and foreign patents covering the Puricase
Technology and the […***…] Technology and may file and prosecute the same in
Savient’s name. The cost for all such filings and

 

 

***Confidential Treatment Requested

 

- 4 -

--------------------------------------------------------------------------------

    

prosecutions are and shall be borne by Savient. BTG and its employees and
consultants shall provide Savient, without compensation other than recovery of
out of pocket expenses, with the necessary authorizations, powers of attorney
and other documents and assistance reasonably requested by Savient from time to
time to file, secure and maintain Savient’s patent rights in connection with the
Savient Patents and BTG hereby grants to Savient powers of attorney to execute
and file on BTG’s behalf any documents reasonably necessary to secure and
maintain such patent rights.

 

    

For the purposes of this Agreement, the term “Savient Patents” means the patents
listed on Annex B and any disclosures, continuations, continuations-in-part,
divisionals, provisionals, PCT applications, reissuances, revisions,
substitutions, conversions, renewals, extensions, prolongations, and
reexaminations thereof, any technology and inventions covered thereby, and any
corresponding international, regional, and national applications and patents.

 

  2.5.

BTG shall, from time to time and as soon as practicable following Savient’s
request, provide Savient with documentation describing the current Puricase
Technology and […***…] Technology held by or under the control of BTG and any
other report reasonably requested by Savient. For the avoidance of doubt,
Puricase Technology and […***…] Technology shall be described in sufficient
detail to allow Savient to manufacture Puricase, or use the […***…] Technology
(as the case may be) it being understood and agreed, however, that Savient shall
not commence manufacture of Puricase or of a […***…] Product (i) unless so
permitted by the OCS, if such permission is required; and (ii) unless in
compliance with any agreement between the Parties relating to such manufacture
and supply; and (iii) provided that such permission by the OCS does not trigger
any additional obligations of BTG vis-à-vis Savient or the OCS, above and beyond
those provided in such agreement of manufacture and supply or in this Agreement.
In any event, BTG may retain copies of such documentation for archival purposes.

 

  2.6.

For the sake of clarity:

 

  2.6.1.

Nothing herein is intended to derogate from BTG’s ownership of the real
property, tools, machinery and equipment which have been or may be acquired by
it in furtherance of, or incidental to, the Development Programs;

 

 

***Confidential Treatment Requested

 

- 5 -

--------------------------------------------------------------------------------

  2.6.2.

Neither “Puricase Technology” nor “[…***…] Technology” shall be deemed to
include general methods of production or analysis that are generally known in
the pharmaceutical industry but have been or will be applied to a Divested
Product, HA, Puricase or any […***…] Product.

 

  2.7.

Savient hereby grants BTG and its Affiliates a non-transferable,
royalty-bearing, perpetual, worldwide nonexclusive, unconditional (save for the
reasonable consideration to be paid for commercialization rights hereunder)
license, under the Puricase Patent to develop products which are not PEGylated
recombinant porcine uricase (urate oxidase), and to manufacture and
commercialize any such product, it being understood and agreed, however, that
the royalties that will be due and payable by BTG to Savient in respect of the
commercialization rights to any such product, and other terms and conditions of
such license, shall be subject to the negotiation, in good faith, of a mutually
acceptable license agreement containing normal and customary terms for
transactions of a similar nature (the “License Agreement”). Should the Parties
fail to execute the License Agreement within 90 (ninety) days of either Party
initiating such negotiations, then the matter may be referred for resolution by
either Party, in accordance with the provisions and the procedures attached
hereto as Annex F. Nothing in the Parties’ failing to execute the License
Agreement or the initiation or conduct of any such procedures shall bar BTG from
exercising the license granted to it pursuant to this Section 2.7 pending the
decision of the expert.

 

  2.8.

The provisions of this Section 2 shall survive the termination or expiration of
this Agreement.

 

3. Research & Development; Regulatory Services; Manufacturing Services

 

  3.1.

BTG hereby agrees to the extent and on the terms set out in Annexes “C” and “D”
hereto (as such Annexes may be modified or superseded by a final definitive
agreement between the Parties) to (i) complete the ongoing research and
development currently being conducted in respect to Puricase; (ii) transfer the
process to BTG’s facility in Be’er Tuvia, Israel; (iii) produce a sufficient
quantity of Puricase as required for Phase 3 clinical trials and the initial
commercial launch of Puricase and perform all related stability and other
testing and activities required for worldwide regulatory filing; (iv) render
assistance to Savient in

 

 

***Confidential Treatment Requested

 

- 6 -

--------------------------------------------------------------------------------

 

relation to the worldwide regulatory filings related thereto; and (v) remain a
back-up supplier to the new manufacturer (if any) throughout the time period set
forth in Section E of Annex “D” attached hereto or any successive Manufacturing
Services Agreement between the Parties.

 

  3.2.

In the event that BTG breaches any of its obligations to Savient under this
Section 3, in addition to any other remedies that may be available to Savient in
law or equity, BTG shall, promptly upon Savient’s request, cooperate and
collaborate with Savient in applying to the OCS for Savient to carry out the
work in question through a third party. Nothing in the foregoing should be
construed as relieving BTG from its contractual obligations pursuant to Section
3.1, and Annexes “C” and “D” attached hereto.

 

4. Technology Transfer

 

    

Subject to the approval of the OCS, Savient shall be entitled to request BTG to
render to Savient and/or its third party manufacturer technical assistance
relating to the transfer of the Puricase Technology or the […***…] Technology.
The terms and conditions upon which BTG shall be obligated to render such
assistance in relation to the Puricase Technology are set out in Annex “E”
attached hereto.

 

5. Compliance with Law for the Encouragement of Research and Development in
Industry and the Regulations, Rules and, Procedures Promulgated Thereunder
(collectively, the “Law”)

 

  5.1.

BTG hereby confirms and acknowledges that as from the Closing BTG and/or the
Buyer (as the case may be) shall be fully responsible for the payment of
Royalties pursuant to the Law in relation to income derived from the Divested
Products and income derived by BTG from the commercial exploitation of a […***…]
Product pursuant to the license granted to it by Savient pursuant to Section 6.2
below, and BTG hereby agrees to indemnify Savient for any liability that may be
imposed upon it by the OCS in relation thereto. BTG shall provide Savient with
copies of its semi-annual reports to the OCS in relation to the payment of such
Royalties, together with evidence of payment. Moreover, BTG shall notify Savient
of any audit conducted by the OCS in respect thereto and the result of such
audit, and provide Savient with copies of any written audit report. BTG has been
using the […***…] Technology in the production of caroboxpeptidase as of
February 2005, and Royalties pursuant to

 

 

***Confidential Treatment Requested

 

- 7 -

--------------------------------------------------------------------------------

 

the Law in relation to income derived from carboxypeptidase are thus payable to
the OCS. As there is uncertainty as to whether these Royalties should be
allocated to OCS file 27141 (Puricase) and/or OCS file 10281 (APA), it is hereby
agreed that BTG and Savient shall mutually refer the question of the allocation
of such Royalties and the relevant background information to Keren Tmurah at the
OCS (“Keren Tmurah”) within 30 days of this Agreement, and Keren Tmurah’s
directives shall be binding upon the Parties.

 

  5.2.

Savient hereby confirms and acknowledges that as from the Closing Savient shall
be fully responsible for the payment of Royalties pursuant to the Law in
relation to income derived by Savient from Puricase, Puricase Technology, a
[…***…] Product and the […***…] Technology and hereby agrees to indemnify BTG
for any liability that may be imposed upon it by the OCS in relation thereto.

 

  5.3.

Due to the fact that BTG shall remain a conduit for the payment of Royalties as
set forth in Section 5.2, and in order to ensure Savient’s compliance with the
requirements of the Law, Savient irrevocably and unconditionally undertakes to
periodically provide BTG with the funds required for making such payments of
Royalties in a timely manner. In furtherance thereof:

 

  5.3.1.

Savient shall provide BTG with semi-annual reports on its development and
commercialization activities in respect of Puricase, Puricase Technology, the
[…***…] Products and the […***…] Technology, and any other information related
thereto, that may be requested by the OCS from time to time, for conveyance to
the OCS, as required. Such reports shall be accompanied by a financial report
signed by Savient’s Chief Financial Officer showing the calculation of the
amounts due to the OCS pursuant to the Law in respect of the period covered by
the said report and the funds necessary to make the appropriate payments to the
OCS, it being understood and agreed, however, that the funds will be transferred
by Savient to BTG by no later than 15 (fifteen) days before timely payment has
to be made by BTG to the OCS. Such financial reports shall be certified by an
independent auditor, once a year, at Savient’s expense.

 

  5.3.2.

Savient shall keep complete, accurate and correct books of account and records
consistent with sound business and US generally accepted accounting

 

 

***Confidential Treatment Requested

 

- 8 -

--------------------------------------------------------------------------------

 

principles and practices, in such form and in such details as to enable the
verification and the determination of the amounts due to the OCS in respect of
Puricase, Puricase Technology, the […***…] Products and the […***…] Technology.
Savient shall retain such books of account for 7 (seven) years after the end of
each calendar year.

 

  5.4.

BTG hereby undertakes to irrevocably and unconditionally remit the funds
received from Savient pursuant to Section 5.3.1 above to the OCS in a timely
manner, without any set-offs, deductions or withholdings of any nature.

 

  5.5.

BTG and Savient shall comply with any request by the OCS to conduct, inter alia,
an audit at Savient. In such event, BTG and/or the OCS shall be entitled to
appoint a representative to inspect, during normal business hours, and to take
copies of Savient’s books of accounts, records and other documentation to the
extent relevant or necessary for the ascertainment or verification of the
amounts due to the OCS under the Law, at Savient’s expense.

 

6. […***…] Patents

 

  6.1.

In addition to BTG’s rights in relation to the […***…] Technology, as set out in
Section 2.2 above, Savient hereby grants BTG and its Affiliates an irrevocable,
fully paid-up, transferable, non-royalty-bearing, perpetual, worldwide,
exclusive, unconditional license, under the […***…] Patents, to offer for sale,
sell and import Divested Products and HA. Nothing in the foregoing shall be
construed as a representation on BTG’s part, that such license, or the rights
set out in Section 2.2, are required in order to develop, manufacture or
commercialize any or all of the Divested Products or HA.

 

  6.2.

Savient hereby grants BTG and its Affiliates a non-transferable,
royalty-bearing, perpetual, worldwide nonexclusive, unconditional (save for the
reasonable consideration to be paid for commercialization rights hereunder)
license, under the […***…] Patents to offer for sale, sell and import […***…]
Products, it being understood and agreed, however, that the royalties that will
be due and payable by BTG to Savient in respect of the commercialization rights
and other terms and conditions of such license, shall be subject to the
negotiation, in good faith, of a mutually acceptable license agreement
containing normal and customary terms for transactions of a similar nature (the
“[…***…] License Agreement”). Should the Parties fail to execute the […***…]
License Agreement within 90 (ninety) days of either Party

 

 

***Confidential Treatment Requested

 

- 9 -

--------------------------------------------------------------------------------

 

initiating such negotiations, then the matter may be referred for resolution by
either Party, in accordance with the provisions and the procedures attached
hereto as Annex F. Nothing in the Parties’ failing to execute the […***…]
License Agreement or the initiation or conduct of any such procedures shall bar
BTG from exercising the license granted to it pursuant to this Section 6.2
pending the decision of the expert. Nothing in the foregoing shall derogate from
the terms and conditions of any existing supply, manufacturing or development
agreement between the Parties.

 

  6.3.

Should Savient decide to abandon a […***…] Patent at any time during the first 5
(five) years following the Closing; Savient undertakes to notify BTG in writing
at least 60 (sixty) days prior to the date on which such […***…] Patent would
become finally abandoned in the absence of action on the part of the party
prosecuting or maintaining such patent. Savient shall afford BTG the right,
during such 60 (sixty) day period, to acquire such patent application or
patents. Should the Parties fail to reach a mutually acceptable agreement as to
the terms and conditions upon which BTG may acquire such patent applications or
patents, Savient shall be entitled to abandon the same.

 

7. BTG-271

 

  7.1.

Prior to the Closing, Savient shall either (a) transfer the patent applications
listed in Annex “G” attached hereto (the “BTG-271 Patents”) to a third party and
arrange with the OCS for a full release of BTG’s obligation to pay royalties to
the OCS with respect to subsequent sales in relation thereto or (b) transfer the
BTG-271 Patents to BTG.

 

  7.2.

Subject to OCS approval, BTG undertakes to relinquish its rights in the BTG-271
project under the OCS Letter in the event that the BTG-271 Patents are
transferred to a third party prior to the Closing or as envisaged under Section
7.3 below.

 

  7.3.

Notwithstanding the foregoing, should negotiations between Savient and Eager
BioGroup Ltd., a corporation registered in Israel, or any affiliated company
registered in Israel and controlled by Prof. Max Herzberg, be ongoing at the
time of the Closing, Savient shall have an additional period of 90 (ninety) days
from the Closing in order to finalize such transaction (the “Eager
Transaction”), and Savient shall bear the cost of the BTG-271 Patents throughout
such time period. Should the Eager Transaction not be consummated with OCS
approval within such time period, for any reason whatsoever, then the BTG-271
Patents shall be transferred to BTG.

 

 

***Confidential Treatment Requested

 

- 10 -

--------------------------------------------------------------------------------

  7.4.

Should the BTG-271 Patents be transferred to BTG, then BTG-271 shall be treated
as a “Divested Product” for purposes hereof.

 

8. Promoter Patents

 

  8.1.

BTG hereby grants Savient a fully paid-up, non-royalty-bearing, perpetual,
worldwide nonexclusive license, with the right to sub-license, under the patents
and patent applications listed in Annex “H” attached hereto (the “Promoter
Patents”), to use the Osm B promoter claimed therein to make, have made, use,
offer for sale, sell and import Puricase, it being understood and agreed,
however, that the manufacture “of Puricase outside of Israel is subject to the
approval of the OCS.

 

  8.2.

BTG shall favorably consider any request by Savient to expand the scope of the
license granted to it under Section 8.1. In such circumstances, the Parties
shall negotiate in good faith with a view towards entering into a mutually
acceptable license agreement containing normal and customary terms for
transactions of a similar nature.

 

  8.3.

Should BTG decide to abandon any of the Promoter Patents at any time during the
first 5 (five) years following the Closing, BTG undertakes to notify Savient in
writing, at least 60 (sixty) days prior to the date on which such Promoter
Patent would become finally abandoned in the absence of action on the part of
the party prosecuting or maintaining such patent. BTG shall afford Savient the
right, during such 60 (sixty) day period, to acquire such patent application or
patents. Should the Parties fail to reach a mutually acceptable agreement as to
the terms and conditions upon which Savient may acquire such patent applications
or patents, BTG shall be entitled to abandon the same.

 

9. Indemnification

 

    

Each Party shall indemnify, hold harmless and defend the other Party and its
officers, directors and employees against damages, costs and expenses (including
reasonable attorney’s fees) incurred as a result of such Party’s failure to
comply with its undertakings under this Agreement.

 

10. Term; Effect of Termination

 

  10.1.

This Agreement shall enter into force and effect upon the Closing and shall
continue to be in force for as long as the Puricase Technology and the […***…]
Technology is in use by either Party.

 

 

***Confidential Treatment Requested

 

- 11 -

--------------------------------------------------------------------------------

  10.2.

Should the Divestiture Agreements be terminated without the Closing taking
place, for any reason whatsoever, this Agreement shall be null and void.

 

  10.3.

The termination of this Agreement for whatever cause shall not prejudice or
affect the accrued rights and obligations of either Party.

 

11. Disclosure of Information

 

  11.1.

BTG and its Affiliates shall not furnish copies of documents, patents, patent
applications, copyrights, drawings, specifications, bills of materials, devices,
equipment, prototypes and other information relating to the Puricase Technology
other than as contemplated by this Agreement (and other than to any of their
respective Affiliates) and shall not, without the prior approval of Savient,
disclose such information to any third party, except to the extent that such
disclosure is necessary for BTG’s manufacture of Puricase for Savient, and then
only if (i) such disclosure is subject to the same limitations on the recipient
as on BTG, and (ii) such limitations are set forth in a written agreement in
form and substance satisfactory to Savient. “Affiliate”, as used herein, means,
any corporation which controls, is controlled by, or is under common control
with, BTG, following the Closing. A corporation shall be deemed to control
another corporation if it owns, directly or indirectly, more than 50% (fifty
percent) of the voting shares, or has the power to elect more than half the
directors, of such other corporation. For purposes of this Section 11.1,
“Puricase Technology” shall not include information which is in or becomes, part
of the public domains through no act or omission by BTG or any of its employees.

 

  11.2.

No publication with respect to any activity undertaken pursuant to a Development
Program shall be made, nor any manuscript submitted for publication, without the
prior review and written approval of Savient such approval not to be
unreasonably withheld.

 

  11.3.

The Parties agree that remedies at law may be inadequate to protect against
breach of this Section 11, and in case of such a breach BTG hereby consents to
the granting of injunctive relief, whether temporary, preliminary or final, in
favor of Savient without proof of actual damages.

 

  11.4.

The provisions of this Section 11 shall survive the termination or expiration of
this Agreement.

 

- 12 -

--------------------------------------------------------------------------------

12. Non - Compete

 

    

From the Closing Date until the expiration of the later to expire (following
issuance) of the Puricase Patents; BTG agrees not to, and shall cause its
Affiliates not to, use the Puricase Technology to manufacture, promote, market
or sell any Competing Product in the Territory, or to license or sublicense the
Puricase Technology to any third party. As used in this Agreement, “Competing
Product” shall mean any prescription pharmaceutical product that (i) contains
uricase as an active ingredient or (ii) has a primary use in a particular
country, based on a majority of prescription use in such country, for the
treatment of gout (in any form). As used in this Agreement, “Territory” shall
mean, collectively, every country in the world.

 

13. Governing Law and Dispute Resolution

 

  13.1.

This Agreement and any disputes hereunder shall be governed by and construed in
accordance with the laws of the State of New York, United States of America,
without giving effect to any choice or conflict of law provision or rule that
would cause the application of any other laws.

 

  13.2.

Save as provided in Section 6.2 hereof, any disputes, claims or controversies
between the Savient and BTG in connection with this Agreement, including any
question regarding its formation, existence, validity, enforceability,
performance, interpretation, breach or termination (any such dispute, claim or
controversy, a “Dispute”), shall be finally resolved by binding arbitration.

 

  13.3.

Any arbitration hereunder shall be conducted under the Rules of Arbitration of
the London Court of International Arbitration. The arbitration shall be
conducted in the English language before three arbitrators chosen according to
the following procedure: within 20 (twenty) days after commencement of the
arbitration, each of Savient and BTG shall appoint one arbitrator, and within 20
(twenty) days after the appointment of both such arbitrators, the two
arbitrators so chosen shall choose the third arbitrator. If the two arbitrators
chosen by Savient and BTG cannot agree on the choice of the third arbitrator
within a period of 20 (twenty) days after their appointment, then the third
arbitrator shall be appointed by the London Court of International Arbitration.

 

  13.4.

Each of the arbitrators shall be a lawyer or former judge. The chairman of the
three arbitrators shall have experience arbitrating disputes in the
pharmaceutical industry.

 

  13.5.

Any arbitration that would otherwise be conducted pursuant to this Section 13
that relates to the subject matter of any arbitration

 

- 13 -

--------------------------------------------------------------------------------

 

conducted pursuant to Section 10.15 of the SPA shall be combined into a single
arbitration before the same panel of three arbitrators, conducted in accordance
with Section 10.15 of the SPA.

 

  13.6.

Each of the Asset Buyer and the Seller hereby irrevocably waives all rights to
trial by jury in any Dispute.

 

  13.7.

The place of the arbitration shall be London, England.

 

14. Miscellaneous

 

  14.1.

Unless the context explicitly dictates otherwise, all references herein to
“patents” and/or “patent applications” herein shall be deemed to include any
disclosures, continuations, continuations-in-part, divisionals, provisionals,
PCT applications, reissuances, revisions, substitutions, conversions, renewals,
extensions, prolongations, and re-examinations thereof, any technology and
inventions covered thereby, and any corresponding international, regional and
national applications.

 

  14.2.

From time to time after the date hereof and prior to the Closing, the Parties
may modify and/or replace any of Annexes C, D or E hereto, which modified or
replaced Annexes shall automatically constitute part of this Agreement.

 

  14.3.

Nothing in this Agreement or in the Divestiture Agreements shall derogate from
BTG’s rights under the Technology Transfer Agreement effective February 1, 1998,
pursuant to which BTG acquired Savient’s process for the manufacture of sodium
hyaluronate (“HA”), as described and claimed in U.S. Patent No. 4,780,414, and
the related patent applications, patents, trademarks and domain names listed in
Annex “I”. Savient and its employees shall provide BTG, without compensation,
with the necessary authorizations, powers of attorney and other documents and
assistance reasonably requested by BTG from time to time to record the
assignment of said intellectual property rights from Savient to BTG.

 

  14.4.

This Agreement constitutes the entire agreement between Savient and BTG with
respect to the subject matter hereof, and supersedes any prior agreements or
understandings between Savient and BTG with respect to such matters.

 

  14.5.

Each Party agrees to execute, acknowledge and deliver such further documents and
instruments and do any other acts, from time to time, as may be reasonably
necessary, to effectuate the purposes of this Agreement.

 

- 14 -

--------------------------------------------------------------------------------

  14.6.

Neither this Agreement nor any of the rights, interests, or obligations
hereunder may be assigned by either Party without the prior written consent of
the other Party hereto, except that either Party may assign its rights hereunder
to any entity that acquires all or substantially all of such Party’s business or
assets (provided that no such assignment shall relieve the assigning Party of
its obligations hereunder, and the assigning Party shall remain primarily liable
for such obligations). Subject to the foregoing, this Agreement shall be binding
upon and inure to the benefit of the Parties and their respective successors and
permitted assigns.

 

  14.7.

All notices, requests, demands, claims and other communications hereunder shall
be in writing. Any notice, request, demand, claim or other communication
hereunder shall be deemed duly delivered four Business Days after it is sent by
registered or certified mail, return receipt requested, postage prepaid, or one
Business Day after it is sent by overnight delivery via a reputable national
courier service, in each case to the intended recipient as set forth below:

If to Savient:

Savient Pharmaceuticals Inc.

One Tower Center, l4th Floor

East Brunswick, New Jersey 08816, USA

Telecopy: +1-732-418-9065

Attention: Philip K. Yachmetz, Esq.

If to BTG:

Bio-Technology General (Israel) Ltd.

Kiryat Weizmann

Building 17

Rehovot 76326, Israel

Telecopy: +972-8-9409041

Attention: Dr. Dov Kanner

A “Business Day” shall be any day other than (i) a Saturday or Sunday or (ii) a
day on which banking institutions located in New York, New York, United States
of America or in Israel are permitted or required by law, executive order or
governmental decree to remain closed.

Any Party may give any notice, request, demand, claim, or other communication
hereunder using any other means (including personal delivery, expedited courier,
messenger service, telecopy,

 

- 15 -

--------------------------------------------------------------------------------

telex, ordinary mail, or electronic mail), but no such notice, request, demand,
claim or other communication shall be deemed to have been duly given unless and
until it actually is received by the Party for whom it is intended. Any Party
may change the address to which notices, requests, demands, claims and other
communications hereunder are to be delivered by giving the other Party notice in
the manner herein set forth.

 

  14.8.

Savient and BTG may mutually amend or waive any provision of this Agreement at
any time. No amendment or waiver of any provision of this Agreement shall be
valid unless the same shall be in writing and signed by both of the Parties.

 

  14.9.

Any term or provision of this Agreement that is invalid or unenforceable in any
situation in any jurisdiction shall not affect the validity or enforceability of
the remaining terms and provisions hereof or the validity or enforceability of
the offending term or provision in any other situation or in any other
jurisdiction. If the final judgment of a court of competent jurisdiction
declares that any term or provision hereof is invalid or unenforceable, the
Parties agree that the body making the determination of invalidity or
unenforceability shall have the power to reduce the scope, duration or area of
the term or provision, to delete specific words or phrases, or to replace any
invalid or unenforceable term or provision with a term or provision that is
valid and enforceable and that comes closest to expressing the intention of the
invalid or unenforceable term or provision, and this Agreement shall be
enforceable as so modified.

 

  14.10.

Except as otherwise specifically provided to the contrary in this Agreement,
each of the Parties shall bear its own costs and expenses (including legal fees
and expenses) incurred in connection with this Agreement and the transactions
contemplated hereby.

 

  14.11.

This Agreement may be executed in one or more counterparts, each of which shall
be deemed an original; but such counterparts shall together constitute but one
and the same instrument.

[Intentionally Left Blank]

 

- 16 -

--------------------------------------------------------------------------------

IN WITNESS WHEREOF the Parties hereto have set their signatures as of the date
first mentioned above.

 

/s/ Christopher Clement

SAVIENT PHARMACEUTICALS, INC.

By: Christopher Clement

Title: President and Chief Executive Officer

/s/ Philip K. Yachmetz

BIO-TECHNOLOGY GENERAL (ISRAEL) LTD.

By: Philip K. Yachmetz

Title: Director

List of Annexes:

 

Annex “A”

  

OCS letter

Annex “B”

  

Puricase Patents

Annex “C”

  

Development and Regulatory Work - Puricase

Annex “D”

  

Term Sheet for Manufacture of Puricase

Annex “E”

  

Term Sheet for Technology Transfer

Annex “F”

  

Expert Procedures

Annex “G”

  

BTG-271 Patents

Annex “H”

  

List of osmB promoter patents/patent applications

Annex “I”

  

List of HA Patents, Trademarks and Domain Names

--------------------------------------------------------------------------------

Annex A

OCS letter

--------------------------------------------------------------------------------

LOGO [g101482g0228150627095.jpg]   

One Tower Center

  

Fourteenth Floor

  

East Brunswick, NJ 08816

  

Telephone: 732-418-9300

  

Facsimile: 732-418-9065

  

www.savientpharma.com

July 15, 2003

Mr. Avi Feldman, Esq.

General Counsel to the

Office of the Chief Scientist

Ministry of Industry, Trade and Labor

4 Mevo Hamatmid Street

Jerusalem 91021

Dear Mr. Feldman,

Re:    Bio-Technology General (Israel) Ltd. (“BTG Israel”)

We have been informed of the meeting that took place in Jerusalem on June 15,
2003 with the participation of representatives of the Chief Scientist (the “CS”)
and BTG Israel.

We understand that during the course of the meeting, the parties resolved
certain issues that arose in relation to CS-approved R & D programs at BTG
Israel (the “Approved Programs”) as follows:

 

1. BTG Israel will have title to all future Approved Programs, relating to new
projects.

 

2. BTG Israel will have an exclusive irrevocable and perpetual right from us to
conduct R&D with technology developed in the course of Approved Programs which
are completed or ongoing, excluding clinical trials that BTG Israel is not in a
position to monitor from Israel; and

 

3. Except as otherwise approved by the CS, BTG Israel will have an exclusive
right from us to manufacture in Israel products developed through Approved
Programs..

We understand that the CS will not unreasonably withhold its consent to the
conduct of such R&D activities outside of Israel if BTG Israel is finable to
carry out such activities, or the manufacture of such products outside of
Israel, if commercially unfeasible or if BTG Israel is unable to carry out such
activities.

We also understand it was agreed that upon receipt of our agreement to the
foregoing, funds withheld by the CSO upon the 2002 audit as well as funds that
would otherwise have been payable in 2002 (if properly spent and reported) will
be immediately released to BTG Israel.

--------------------------------------------------------------------------------

On the basis of such understandings, and without waiving any rights that we may
have from time to time under the Law for the Encouragement of Research and
Development in Industry, we hereby confirm our agreement to the understandings
set out above.

Respectfully yours,

 

/s/ Sim Fass

Savient Pharmaceuticals, Inc.

By:   Sim Fass Title:   Chairman & CEO cc:   Mr. Amos Efrati   Mr. Shaul
Freilich   Deputies to the Chief Scientist   Y. Baratz   D. Kanner  

R. Shaw

--------------------------------------------------------------------------------

Annex B

Puricase Patents

 

1. New Applications

 

  1.1. Puricase

 

File

Reference      

    Country           Status             Appln No             Appln Date      
   Title […***…]   […***…]   […***…]   […***…]   […***…]   

[…***…]

[…***…]   […***…]   […***…]   […***…]   […***…]   

[…***…]

 

  1.2. Protein Purification

 

File

Reference      

    Country           Status             Appln No             Appln Date      
   Title […***…]   […***…]   […***…]   […***…]   […***…]   

[…***…]

 

 

***Confidential Treatment Requested

--------------------------------------------------------------------------------

Annex C

Development and Regulatory Work

Puricase

The following outline summarizes the key elements of ongoing development work
and regulatory services relating to Puricase which will be required from BTG as
from the Closing, certain elements of which are required under agreement with
the OCS. This outline will form the basis of a detailed work plan covering these
activities, which will be concluded prior to the Closing. It is anticipated that
the detailed work plan when completed, will include a specific list of
deliverables and a timetable for performance and delivery.

While every effort has been utilized to make this outline as comprehensive as
possible, certain activities shown here may need to be expanded to include
normal and customary related activities.

[…***…]

A total of two pages were omitted pursuant to a request for confidential
treatment.

 

 

***Confidential Treatment Requested

--------------------------------------------------------------------------------

Annex D

Term Sheet

Manufacturing Services

The following outline summarizes the key elements of manufacturing services that
will be required from BTG as contract manufacturer with respect to the
manufacturing Puricase (the “Product”), as required from BTG as from the
Closing. This outline will form the basis of a detailed work plan covering these
activities, which will be concluded prior to the Closing. It is anticipated that
the detailed work plan when completed, will include a specific list of
deliverables and a timetable for performance and delivery.

While every effort has been utilized to make this outline as comprehensive as
possible, certain activities shown here may need to be expanded to include
normal and customary related activities.

[…***…]

A total of five pages were omitted pursuant to a request for confidential
treatment.

 

 

***Confidential Treatment Requested

--------------------------------------------------------------------------------

Annex E

Term Sheet

Technology Transfer

The following outline summarizes the key elements of the technology transfer
relating to Puricase which may be required from BTG, after the Closing. This
outline will form the basis of a detailed work plan covering these activities,
which will be concluded prior to the Closing. It is anticipated that the
detailed work plan when completed, will include a specific list of deliverables
and a timetable for performance and delivery.

While every effort has been utilized to make this outline as comprehensive as
possible, certain activities shown here may need to be expanded to include
normal and customary related activities.

These terms and conditions shall be binding upon the Parties, unless and until
superseded by a definitive Technology Transfer Agreement and/or a detailed work
plan:

[…***…]

 

 

***Confidential Treatment Requested

--------------------------------------------------------------------------------

ANNEX F

Expert Procedures

Pursuant to Sections 2.5 and 6.2 of the Residual Rights Agreement:

[…***…].

 

 

***Confidential Treatment Requested

--------------------------------------------------------------------------------

Annex G

BTG-271 Patents

--------------------------------------------------------------------------------

CONFIDENTIAL    

BTG 271 Patent Applications

 

Docket ID    File Ref.    Country    Status    Substatus    Appl. No    Appl.
Date    Expiry   Applicant/
Patentees

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]    […***…]    […***…]  
[…***…]

A total of three pages were omitted pursuant to a request for confidential
treatment.

 

 

***Confidential Treatment Requested

 

647/IP/BTG 271 Patent Applications   1   8 March, 2005

--------------------------------------------------------------------------------

Annex H

osmB promoter patents/patent application

 

Docket

ID

  File Ref   Country  

Annuity

Due

  Status   Applic. No   Appl. Date  

Grant

No.

 

Grant

Date

  Expiry   Application/
Patentees

[…***…]

  […***…]   […***…]   […***…]   […***…]   […***…]   […***…]           […***…]  
[…***…]

[…***…]

  […***…]   […***…]       […***…]   […***…]   […***…]               […***…]

[…***…]

  […***…]   […***…]       […***…]   […***…]   […***…]               […***…]

[…***…]

  […***…]   […***…]       […***…]   […***…]   […***…]               […***…]

[…***…]

  […***…]   […***…]   […***…]   […***…]   […***…]   […***…]   […***…]   […***…]
  […***…]   […***…]

[…***…]

  […***…]   […***…]   […***…]   […***…]   […***…]   […***…]   […***…]   […***…]
  […***…]   […***…]

 

 

***Confidential Treatment Requested

--------------------------------------------------------------------------------

Annex I

List of HA Patents, Trademarks and Domain Names

 

1.         Patents

Refer to attached list

 

2.         Design

Right Registrations

 

  2.1. US: Des. 403064 - Filed June 28, 1995, Granted December 22, 1998,
Expiration date December 22, 2012.

 

  2.2. Israel: Design 23832 - Filed January 22, 1995, Granted June 20, 1995;
Expiration date January 22, 2010.

 

3.         Trademarks

Refer to attached list

 

4.         Domain

Names

 

Name    Domain biolon    .info biolon    .co.il biolon    .us biolon    .com
euflexxa    .com nuflexa    .com nuflexxa    .com

--------------------------------------------------------------------------------

CONFIDENTIAL    

HA PATENTS

 

File Ref.    Country    Status    Appl. No    Appl. Date    Grant No   
Grant Date    Expiry    Applicant/
Patentees

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]    […***…]    […***…]   
[…***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]    […***…]    […***…]   
[…***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]    […***…]    […***…]   
[…***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]    […***…]    […***…]   
[…***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]    […***…]    […***…]   
[…***…]

[…***…]

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[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]    […***…]    […***…]   
[…***…]

 

 

***Confidential Treatment Requested

--------------------------------------------------------------------------------

CONFIDENTIAL    

HA TRADEMARKS

 

File Ref.    Country    Trademark    Class    Reg. Owner    Appl. No.    Appl.
Date    Reg. No.    Reg. Date    Status

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]    […***…]    […***…]   
[…***…]    […***…]

A total of four pages were omitted pursuant to a request for confidential
treatment.

 

 

***Confidential Treatment Requested

 

1

--------------------------------------------------------------------------------

Exhibit G

Product Specifications

--------------------------------------------------------------------------------

  Summary of Release Testing of Bulk Uricase Intermediate

 

       

Parameter

 

  

Test

 

  

Provisional Acceptance Criteria

 

  

Revision

 

[…***…]

   […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]    […***…]    […***…]   
[…***…]    […***…]    […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]    […***…]    […***…]   
[…***…]    […***…]    […***…]    […***…]    […***…]    […***…]    […***…]   
[…***…]    […***…]    […***…]    […***…]    […***…]    […***…]    […***…]   
[…***…]    […***…]    […***…]    […***…]    […***…]    […***…]    […***…]   
[…***…]    […***…]

 

 

***Confidential Treatment Requested

--------------------------------------------------------------------------------

  Summary of Release Testing of PEG-uricase API

 

       

Parameter

 

  

Test

 

  

Provisional Acceptance Criteria

 

  

Revision

 

[…***…]    […***…]    […***…]    […***…] […***…]    […***…]    […***…]   
[…***…]    […***…]    […***…]    […***…] […***…]    […***…]    […***…]   
[…***…] […***…]    […***…]    […***…]    […***…] […***…]    […***…]    […***…]
   […***…] […***…]    […***…]    […***…]    […***…]      […***…]    […***…]   
[…***…]      […***…]    […***…]    […***…]      […***…]    […***…]    […***…]  
   […***…]    […***…]    […***…]      […***…]    […***…]    […***…]

 

 

***Confidential Treatment Requested

--------------------------------------------------------------------------------

FIRST AMENDMENT TO COMMERCIAL SUPPLY AGREEMENT

THIS AMENDMENT is made and entered into this 24th day of September, 2007,
(hereinafter the “Effective Date”).

 

BETWEEN:

  

SAVIENT PHARMACEUTICALS, INC.

  

a Delaware corporation, (hereinafter “Savient”)

  

AND

  

BIO-TECHNOLOGY GENERAL (ISRAEL) Ltd.

  

an Israeli corporation, (hereinafter “BTG”)

WHEREAS:

Savient and BTG are parties to a Commercial Supply Agreement with an effective
date of March 20, 2007, (hereinafter, the “Agreement”) pursuant to which BTG
agreed to manufacture and supply a certain Bulk Product, as defined in the
Agreement, to Savient, and Savient agreed to purchase such Bulk Product from
BTG; and

Savient and BTG have held discussions relating to the modification and amendment
of the Agreement to clarify a certain provision relating to the adjustment of
Bulk Product Forecasts.

NOW THEREFORE in consideration of the mutual promises and agreements and
covenants contained herein, the adequacy of such consideration has been agreed
and acknowledged by each party, and in accordance with the provisions of Section
14.08 of the Agreement, the parties hereto agree as follows:

 

1.

Definitions.   All of the Definitions contained in Article 1 of the Agreement
shall have the same meanings herein unless specifically stated otherwise. Any
capitalized terms not specifically defined herein, shall have the same meaning
ascribed to them as set forth in the Agreement.

 

2.

Modification of Bulk Product Forecasts.   Section 5.06 of the Agreement is
hereby repealed in its entirety and is replaced with the following,

“Any Bulk Product Forecast that is not a Firm Order is to be considered a
forecast or estimate to be used for planning purposes, and shall not be
construed as a firm commitment by Savient to BTG and thus can be increased or
reduced by Savient from time to time. Savient shall be entitled at any time up
until and including the time that a Firm Forecast or Estimated Forecast becomes
a Firm Order, to increase or decrease such monthly Firm Forecast or Estimated
Forecast for Bulk Product, provided, however, such increases or decreases on a
monthly basis shall not be greater than […***…] percent ([…***…]%) of the
originally forecasted quantity for such month, provided, however, (a) each month
may not be increased and

 

 

***Confidential Treatment Requested

--------------------------------------------------------------------------------

- 2 -

 

decreased more than one time, and, (b) any such monthly increase or decrease as
contemplated herein shall be expressed in whole batch quantities of not less
than one (1) batch. As a request by Savient to increase the quantity of Bulk
Product in a Firm Forecast prior to its becoming a Firm Order may require longer
lead times for delivery than requested by Savient, both Parties shall agree
jointly on a new delivery date as close as possible to the requested date having
due regard for BTG’s commercial commitments to Third Parties and its own
production needs, such agreement to not be unreasonably withheld, conditioned or
delayed. Once a Firm Forecast becomes a Firm Order, Savient may not reduce it,
but may request that BTG increase the quantity of Bulk Product subject to a Firm
Order and BTG shall use commercially reasonable efforts to fill the increased
order.”

 

3.

No Modification.   Except as expressly provided for herein, the Agreement shall
remain in full force and effect without amendment. If there is any conflict or
inconsistency between this Amendment and the Agreement, this Amendment shall
prevail. This Amendment contains the entire agreement between the parties hereto
with respect to the subject matter contemplated herein and shall not be modified
or amended except by a written instrument signed by both parties hereto.

IN WITNESS WHEREOF, the parties have caused this Amendment to be executed by
their respective duly authorized officers as of the date first written above.

 

SAVIENT PHARMACEUTICALS, INC.    

BIO-TECHNOLOGY GENERAL

(ISRAEL) Ltd.

  By:  

    /s/Philip K. Yachmetz

    By:  

    /s/Dov Kanner

        Philip K. Yachmetz           Dov Kanner    

    Executive Vice President &

    Chief Business Officer

          Managing Director  

--------------------------------------------------------------------------------

SECOND AMENDMENT TO COMMERCIAL SUPPLY AGREEMENT

THIS SECOND AMENDMENT is made and entered into this 24th day of January, 2009,
(hereinafter the “Effective Date”).

 

BETWEEN:

  

SAVIENT PHARMACEUTICALS, INC.

  

a Delaware corporation, (hereinafter “Savient”)

  

AND

  

BIO-TECHNOLOGY GENERAL (ISRAEL) Ltd.

  

an Israeli corporation, (hereinafter “BTG”)

WHEREAS:

Savient and BTG are parties to a Commercial Supply Agreement with an effective
date of March 20, 2007, (hereinafter, the “Agreement”) pursuant to which BTG
agreed to manufacture and supply a certain Bulk Product, as defined in the
Agreement, to Savient, and Savient agreed to purchase such Bulk Product from
BTG; and

Savient and BTG have subsequently amended the Agreement on September 24, 2007,
(the “First Amendment”) and have issued a Letter Agreement dated July 30, 2008,
(the “Letter Agreement”) pertaining to the Agreement; and

Savient and BTG desire to further amend the Agreement in accordance with the
terms and conditions of this Second Amendment.

NOW THEREFORE in consideration of the mutual promises and agreements and
covenants contained herein, the adequacy of such consideration has been agreed
and acknowledged by each party, and in accordance with the provisions of Section
14.08 of the Agreement, the parties hereto agree as follows:

 

1. Definitions.   All of the Definitions contained in Article 1 of the Agreement
shall have the same meanings herein unless specifically stated otherwise. Any
capitalized terms not specifically defined herein, shall have the same meaning
ascribed to them as set forth in the Agreement.

 

2. Replacement of Exhibits to Agreement.   The parties agree that the exhibits
which are appended to this Second Amendment shall supersede and replace their
counterparts as previously executed by and between the parties. For purposes of
clarity the following exhibits to the Agreement are hereby repealed and replaced
with the attached exhibits:

 

  i)          Exhibit

C, “Current Provisional Bulk Product Specifications”

  ii)         Exhibit

D, “Quality Agreement”

  iii)        Exhibit

G, “Product Specifications”

--------------------------------------------------------------------------------

- 2 -

 

3. No Modification. Except as expressly provided for herein, the Agreement shall
remain in full force and effect without amendment. If there is any conflict or
inconsistency between this Amendment and the Agreement, this Amendment shall
prevail. This Amendment contains the entire agreement between the parties hereto
with respect to the subject matter contemplated herein and shall not be modified
or amended except by a written instrument signed by both parties hereto.

IN WITNESS WHEREOF, the parties have caused this Amendment to be executed by
their respective duly authorized officers as of the date first written above.

 

SAVIENT PHARMACEUTICALS, INC.    

BIO-TECHNOLOGY GENERAL

(ISRAEL) Ltd.

By:  

    /s/Philip K. Yachmetz

    By:  

    /s/Dov Kanner

      Philip K. Yachmetz           Dov Kanner  

    Senior Vice President &

    General Counsel

          Managing Director

--------------------------------------------------------------------------------

Exhibit C

Current Provisional Bulk Product Specifications

--------------------------------------------------------------------------------

SPECIFICATION- […***…]

      Table 1. Tests Performed on […***…]

 

Parameter    Test    Specifications

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]

[…***…]

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[…***…]

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[…***…]

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[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]    […***…]    […***…]   
[…***…]    […***…]    […***…]    […***…]    […***…]    […***…]    […***…]

[…***…]

 

 

***Confidential Treatment Requested

 

C-1

--------------------------------------------------------------------------------

      Table 2. Tests Performed on […***…]

 

Parameter    Test    Specifications

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

 

 

***Confidential Treatment Requested

 

C-2

--------------------------------------------------------------------------------

Exhibit D

Quality Agreement

--------------------------------------------------------------------------------

QUALITY ASSURANCE RESPONSIBILITY AGREEMENT

BETWEEN

SAVIENT PHARMACEUTICALS, INC.

AND

BIO-TECHNOLOGY GENERAL (ISRAEL) LTD.

(COMMERCIAL PHASE)

 

D-2

--------------------------------------------------------------------------------

Table of Contents

 

1.

 

Purpose and Scope:

     1   

2.

 

Definitions:

     1   

3.

 

Notification of Process Deviations and Documentation of Changes:

     3   

4.

 

Materials:

     4   

5.

 

Manufacturing, Packaging, Inspection and Test:

     6   

6.

 

Release and Shipment of Product(s):

     8   

7.

 

Deviations in Process or Product:

     8   

8.

 

Storage of Product(s):

     9   

9.

 

Traceability of Product(s):

     9   

10.

 

Conflict of Terms:

     9   

11.

 

Compliance with Laws:

     9   

12.

 

Inspections:

     9   

13.

 

Observations by SAVIENT:

     10   

14.

 

Adverse Events:

     10   

15.

 

Stability:

     11   

16.

 

Regulatory Action:

     11   

17.

 

Annual Report to FDA:

     11   

18.

 

APPENDIX I:

     13   

19.

 

APPENDIX II:

     14   

20.

 

APPENDIX III:

     17   

 

D-3

--------------------------------------------------------------------------------

ARTICLE 1

PURPOSE AND SCOPE:

1.01    Savient Pharmaceuticals, Inc. (“SAVIENT”) and Bio-Technology General
(Israel) Ltd. (“BTG”) have entered into a Supply Agreement of (event date)
herewith (the “Supply Agreement”).

This document (the “Quality Agreement”) defines the quality assurance
responsibilities between SAVIENT and BTG. This Quality Agreement applies only to
the manufacture and supply by BTG to SAVIENT of the Product (as defined in the
Supply Agreement).

ARTICLE 2

DEFINITIONS:

2.01    Capitalized terms used but not otherwise defined in this Quality
Agreement will have the meanings ascribed thereto in the Supply Agreement. For
ease of reference, the following definitions from the Supply Agreement which are
used in this Quality Agreement are copied in full below, amended where
appropriate for the purposes of this Quality Agreement:

 

  (i)

“BLA” means a Biologics License Application filed with the FDA and/or any other
application required for the purpose of marketing or selling or using a
therapeutic or prophylactic product to be filed with a governmental agency in a
non-U.S. country or group of countries, including, without limitation, a Product
License Application or Marketing Authorization in the European Union.

 

  (ii)

“Bulk Product” shall mean the bulk solution of polyethylene glycol (PEG)
conjugate of uricase ordered by Savient from BTG pursuant to the Supply
Agreement.

 

  (iii)

“Bulk Product Specifications” shall mean the manufacturing and quality
specifications for the Bulk Product, including, without limitation, unit
descriptions established from time to time in accordance with section 3.01 of
the Supply Agreement.

 

  (iv)

“Business Day” shall mean any day other than (i) Friday, Saturday or Sunday or
(ii) a day on which banking institutions located in New York, New York, United
States of America or in Israel are permitted or required by law, executive order
or governmental decree to remain closed.

 

  (v)

“cGMP” shall mean current good manufacturing practices as set forth in Title 21,
Parts 210 and 211 of the C.F.R. and 21 C.F.R. Part 312 (IND) and Part 314 (NDA),
and 21 C.F.R. Part 600 (Biological Products), as established and amended by the
FDA.

 

D-4

--------------------------------------------------------------------------------

  (vi)

“FDA” shall mean the United States Food and Drug Administration or, where
applicable, its regulatory equivalent in a foreign jurisdiction.

 

  (vii)

“Facility” shall mean, as applicable, the Be’er Tuvia manufacturing facility
located at Beer Tuvia Industrial Zone, POB 571, Kiryat Malachi 83104, Israel

 

  (viii)

“IND” shall mean an Investigational New Drug application, as defined in 21
C.F.R. 312.3, and filed with the FDA or any equivalent foreign Regulatory
Agency.

 

  (ix)

“Legal Requirements” shall mean (i) any present and future national, state,
local or similar laws (whether under statute, rule, regulation or otherwise),
(ii) requirements under permits, orders, decrees, judgments or directives, and
requirements of applicable Regulatory Agencies (including, without limitation,
cGMP) and (iii) regulations pertaining to BLAs (with respect to each of the
foregoing, as amended or revised from time to time).

 

  (x)

“Process” or “Processing” shall mean the act of purification, preparation,
filling, testing and any other pharmaceutical manufacturing procedures, or any
part thereof (including, but not limited to, product or process specifications,
testing or test methods, raw material specifications or suppliers, equipment,
etc.), relating to, as applicable, Bulk Product and Product.

 

  (xi)

“Product” shall mean pharmaceutical products containing Bulk Product ordered by
Savient pursuant to the Supply Agreement.

 

  (xii)

“Regulatory Agency” shall mean with respect to the United States, the FDA, or,
in the case of a country in the Territory other than the United States, such
other appropriate regulatory agency with similar responsibilities.

 

2.03      

In addition, the following definitions apply to this Quality Agreement:

(i)          “Bulk Product” shall mean bulk solution of polyethylene glycol
(PEG) conjugate of uricase in its final formulation which is in Process, and has
been produced for sterilization, filling or other finishing activities.

(ii)         “Filled Product” shall mean sterile Product that is in Process and
has been filled into its final primary packaging for further labeling or
packaging activities.

(iii)        “Final Product” shall mean finished Product in its final packaged
and labeled form which is ready for distribution to the marketplace or third
party distributors for sale or clinical use.

(iv)        “Release” shall mean control, approval and authorization of
shipment.

 

D-5

--------------------------------------------------------------------------------

ARTICLE 3

NOTIFICATION OF PROCESS DEVIATIONS AND DOCUMENTATION OF

CHANGES:

3.01      BTG shall provide to SAVIENT, within […***…] Business Days of BTG’s
discovery of its occurrence, written notification of (i) any deviation from the
Process as set forth in the Bulk Product Specifications and the BLA and any
deviation from cGMP requirements, regulations and standards, and any event that
represents an unexpected or unforseeable event that may affect safety, purity or
potency of Bulk Product; and (ii) any deviation in the quality (purity, physical
and chemical properties) of the Bulk Product from the Bulk Product
Specifications. Appendix I sets forth a list of examples of deviations from the
Process, for purposes of illustration only, and is not intended to be
comprehensive or definitive.

(i)          BTG shall not conduct any retesting or reprocessing as the result
of deviations described above without prior written authorization from SAVIENT
Quality Assurance unless a delay of retesting or reprocessing would result in
increased risk to the safety, purity or potency of the Bulk Product or Product.

3.02     Any changes to be made to this Quality Agreement in accordance with the
provisions set out in this section 3 must be documented as an addendum to this
Quality Agreement, and must be signed by authorized representatives from each of
the BTG QA department and the SAVIENT QA department, in addition to authorized
representatives from any other departments as may be specified in relation to
the matters set forth in section 3.3 below. This Quality Agreement will be
reviewed by BTG and SAVIENT on a periodic basis (approximately once per year)
and revised as appropriate.

 

3.03     Change

Control

(i)          Specifications that control the Process for the manufacture,
including packaging, holding, and test of Bulk Product and Product, must be
signed by authorized representatives from BTG and SAVIENT Quality Assurance,
SAVIENT Regulatory Affairs, and SAVIENT Manufacturing. Such documents include,
but are not limited to Bulk Product Specifications (including specifications for
intermediate), Product Specifications (including specifications for product,
component and packaging). Changes to such documents must be signed by authorized
representatives from SAVIENT Quality Assurance, SAVIENT Manufacturing and
SAVIENT Regulatory Affairs.

(ii)         Changes to additional documents that control the Process for the
manufacture of Bulk Product and Product (including test methods, manufacturing
procedures and batch records) must be assessed according to the BTG change
control process described in section 3.4. Any change that would have an impact
on the Process, Bulk Product or Product, or require submissions to or approvals
from any Regulatory Agency must receive prior written approval by authorized
representatives from SAVIENT Quality Assurance, SAVIENT Manufacturing and
SAVIENT Regulatory Affairs. If there is no such impact, BTG may proceed with the
change, but must notify SAVIENT Quality

 

 

***Confidential Treatment Requested

 

D-6

--------------------------------------------------------------------------------

Assurance no later than […***…] days from the initiation of the BTG change
control process. If SAVIENT does not agree with BTG’s assessment of impact,
SAVIENT must respond to BTG no later than within […***…] days of receipt of
notification.

(iii)        The stability protocol as well as any changes to the stability
protocol must be approved by SAVIENT QA and SAVIENT Regulatory Affairs.

(iv)        Critical Raw Materials. The current specifications for Critical Raw
Materials are attached as Appendix III. The Parties acknowledge and agree that
these specifications may be amended from time to time by the supplier of the
material. With respect to such amendments:

BTG shall notify SAVIENT as soon as reasonable practicable, but no later than
within […***…] days of receipt of notification by BTG.

The Parties will meet and agree as to suitability of the material produced
according to the amended specification for manufacture of the Bulk Product.

3.04       BTG will utilize a documented system of written procedures for the
control of changes to documents relating to raw materials, packaging materials,
labeling, suppliers, equipment, manufacturing methods, batch size, product,
intermediates and raw materials specifications, sampling, analytical test
methods and Release requirements and any other Processing by BTG, relating to
the Bulk Product.

3.05       Any changes to any matter relating to the manufacture and supply of
Bulk Product by BTG shall be governed by the procedures set out in the Supply
Agreement at Article 3 in relation to changes to the Bulk Product
Specifications, and Article 6 in relation to changes to the Process.

3.06       SAVIENT Regulatory Affairs will have responsibility for determining
the regulatory impact of any proposed change. SAVIENT Regulatory Affairs will
determine the classification and requirements for notification to, or approval
by FDA. SAVIENT is responsible for communication of any changes to FDA. SAVIENT
Regulatory Affairs will have responsibility to advise BTG of any changes to the
BLA prior to submission.

BTG will ensure that changes are evaluated and qualified in accordance with all
applicable ICH (International Conference on Harmonization) requirements in
addition to all Legal Requirements, including but not limited to:

ICH Guideline Q5E Comparability of Biotechnological/Biological Products Subject
to Changes in Their Manufacturing Process.

 

 

***Confidential Treatment Requested

 

D-7

--------------------------------------------------------------------------------

ARTICLE 4

MATERIALS

 

4.01

Procurement of Components

BTG will procure all the components described in the Bulk Product Specifications
in such quantities as may be necessary to meet Purchase Orders placed by SAVIENT
pursuant to the Supply Agreement, and store the components in appropriate
storage conditions under quarantine until tested.

 

4.02

Inspection and Testing of Materials

Upon receipt, BTG shall sample in accordance with acceptable statistical
methods, inspect and test containers of all materials to be used in the Process
or in connection with the supply and manufacture of Bulk Product on a
batch-by-batch basis, in accordance with the Bulk Product Specifications.

 

4.03

Bulk Product

BTG will be responsible for ensuring that Bulk Product is manufactured, tested
and stored in compliance with all applicable ICH guidance documents (including,
without limitation, the guidance contained therein for master and working cell
banks) in addition to all Legal Requirements. ICH Guidance includes, but is not
limited to:

Q5D Quality of Biotechnological Products: Derivation and Characterization of
Cell Substrates Used for Production of Biotechnological/Biological Products.

Q7A, Good Manufacturing Practices Guidance for Active Pharmaceutical Ingredients

 

4.04

Retention, Storage and Handling of Materials and Product Samples

BTG shall sample and retain such amounts of Bulk Product and of all materials to
be used in the Process or in connection with the supply and manufacture of Bulk
Product (“Retains”) except water, compressed gasses and any highly volatile
compounds as set forth in Appendix II or as otherwise required in accordance
with applicable Legal Requirements. BTG will store for five years, or such
longer period as may be required in accordance with Appendix II or by Legal
Requirement, sample Product and Retains for each batch or lot of intermediates
and raw materials. Reasonably prior to the expiry of such retention period, or
upon termination of this Quality Agreement, BTG shall offer all such materials
to SAVIENT. Any labor costs of BTG employees and/or Third Party expenses
incurred by BTG related to the transfer of such materials shall be reimbursed by
SAVIENT in the manner and at the rates set forth on Exhibit B to the Supply
Agreement.

A schedule of specific Retains, storage conditions and retention periods for
Puricase® is listed in Appendix II.

 

4.05

Transmissible Spongiform Encephalopathy (TSE)

BTG will provide a written TSE declaration that all materials (including
non-dedicated equipment) used in the manufacturing process are free from animal
derived material. In addition, BTG must have available, on site, written TSE
declarations from the supplier, where appropriate, of raw material used in the
manufacturing process verifying exclusion

 

D-8

--------------------------------------------------------------------------------

of animal derived material. If BTG is unable to provide the above declarations,
BTG will comply with applicable TSE laws and regulations and will obtain all
associated TSE documentation as requested by SAVIENT. This documentation may
include a TSE Certificate of Suitability in accordance with European directive
75/318/EEC as amended by directive 1999/82/EEC, the note for guidance
EMEA/410/01 rev2 as amended and AP-CSP(99)4, Appendix 2, as amended.

 

4.06

Supplier Audits

BTG and SAVIENT will provide each other with copies of supplier audit reports
for materials used in the Process or manufacture of the Product.

ARTICLE 5

MANUFACTURING, PACKAGING, INSPECTION AND TEST:

5.01     The Processing, packaging, and labeling of Bulk Product will be
performed and documented by BTG. BTG will not subcontract any of the Processing,
packaging, and labeling functions except as may be permitted in accordance with
the Bulk Product Specifications, and if so permitted, in accordance with the
provision set forth in Section 2.05 of the Supply Agreement.

5.02     BTG shall not Process or store Bulk Product in the same building in
which BTG manufactures, stores or processes potentially hazardous substances
(including, without limitation, certain antibiotics such as beta-lactam and
cephalosporins, cytotoxic compounds, toxins or poisons such as pesticides or
herbicides, (collectively, “Potential Contaminants”) unless the Potential
Contaminants are stored or manufactured in contained environments and in
compliance with all Legal Requirements and the Bulk Product is Processed and
stored in compliance with building, cleaning, validation and changeover
requirements of all cGMPs and all Legal Requirements. BTG shall promptly notify
SAVIENT if any of the Potential Contaminants are manufactured, processed OI
stored in any portion of the Facility which may result in the introduction of
Potential Contaminants into the areas of such facilities where the Bulk Product
is Processed. Savient is aware that other products are processed in the
Facility, the nature of those other products existing today and that certain
equipment (multi-use equipment) is used in the processing of both the Bulk
Product and these other existing products. Savient has also had the opportunity
to assess the risk to the Processing of Bulk Product of the use of such certain
multi-use equipment with respect to the other existing products. However, in the
instance where BTG intends to introduce a new product or substance to its
Facility which is out of the matrix of existing products and use such multi-use
equipment in the processing or handling of such new product or substance,
Savient will need to reassess the risks to the Processing of Bulk Product with
this new product or substance utilizing the multi-use equipment. Therefore,
whenever BTG plans to introduce a new product or molecular entity which is out
of the matrix of existing products to equipment shared with Puricase production,
BTG will provide no less than […***…] days prior notice of its intent, and will
contemporaneously make supporting cleaning validation data/rationale available
to Savient. Savient will make its assessment of the risk potential for
adulteration of its own product through examination of cleaning validation

 

 

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documentation prior to any further Puricase production and will respond to BTG
within […***…] days of its receipt of cleaning validation data/rationale as to
its conclusion(s) about the introduction.

5.03       BTG will provide to SAVIENT: a copy of all master batch record
documents and production and control records, a Certificate of Analysis
(PEG-uricase API and uricase), executed batch records and associated batch
documentation, which shall include, without limitation: formulation records,
label records, manufacturing records, environmental monitoring data,
microbiological data, in-process and final analytical data, including lab
control results, sterility data, deviations/out-of-specification reports and
cleaning records for any critical product contact equipment (for example,
fermentors or any other non-dedicated product contact equipment).

 

    (i)

Translation: BTG will provide an English translation of all such documents,
including, without limitation, all reports, notes or comments on records that
are not part of the master batch record but if any of the foregoing documents
are only available in a language other than English, the Parties shall agree
upon an English language template for such document(s), and BTG shall provide to
Savient an English language translation of any deviations from the
template(s). When required by SAVIENT, translations shall be performed by an
independent, translation firm. Translations by a third party firm must be
verified by BTG to ensure translation of company or process specific
language. Any labor costs of BTG employees and/or Third Party expenses incurred
by BTG in relation thereto shall be reimbursed by SAVIENT in the manner and at
the rates set forth on Exhibit B to the Supply Agreement.

5.04       Upon request by SAVIENT, BTG will provide access to additional
records that are not normally part of the batch record but which bear a
reasonable relation to the Bulk Product for SAVIENT to review, which may
include, without limitation, maintenance and use records, water testing data,
training records, raw material release records, log books, receiving and
shipping records, inventory records and vendor qualification records Any labor
costs of BTG employees and/or Third Party expenses Incurred by BTG in relation
thereto shall be reimbursed by SAVIENT in the manner and at the rates set forth
on Exhibit B to the Supply Agreement.

5.05       BTG will retain copies of all completed batch records for a minimum
of […***…] years, or such longer period as may be required by Legal
Requirement. Reasonably prior to the expiry of such retention period, or upon
termination of this Quality Agreement, BTG shall offer such completed batch
records to SAVIENT. Any labor costs of BTG employees and/or Third Party expenses
incurred by BTG related to the transfer of such materials shall be reimbursed by
SAVIENT in the manner and at the rates set forth on Exhibit B to the Supply
Agreement.

5.06       Use of BTG Manufacturing Space for Bulk Product

BTG has alloted an amount of manufacturing floor space at the Facility for the
Processing of Bulk Product (Purification Area in the Agreement). This space may
be used for the production of other products subject to the following
limitations:

 

 

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(i)      BTG may use the Purification Area for alternate product manufacturing
only during periods when the Purification Area is not used for the Processing of
Bulk Product.

(ii)     BTG adheres to all relevant cGMPs including, without limitation,
procedures for prevention of mix-ups, prevention of contamination, labeling
requirements, cleaning requirements and changeover requirements

(iii)    BTG, shall not, under any circumstances utilize any equipment dedicated
to the Processing of Bulk Product for such alternate product manufacturing

(iv)    BTG adheres to limits and procedures described in section 5.2 for
Potential Contaminants.

ARTICLE 6

RELEASE AND SHIPMENT OF PRODUCT(S):

6.01     Bulk Product shall be Released in accordance with the procedures set
forth in the Supply Agreement, together with the additional obligations
described in this section of the Quality Agreement. BTG QA will review the
records described in section 5.3 above. Following review and acceptance by BTG
QA, BTG will send copies of these documents to SAVIENT QA. SAVIENT QA and
Manufacturing will then review the documentation and notify BTG whether or not
documentation is acceptable. If such documentation is not reasonably acceptable
to SAVIENT, BTG will cooperate in taking such steps as SAVIENT may reasonably
require to ensure that the documentation, and any Processing described therein
complies with the Bulk Product Specifications and all Legal Requirements.

6.02     BTG QA will be responsible for the QC testing of Filled Product until
such time as a third party laboratory has been qualified to perform such
testing. BTG will provide a Certificate of Analysis and/or stability results for
each batch that BTG tests. Savient QA will be responsible for the review of the
manufacturing batch record for Filled Product, review of the Certificate of
Analysis and Release of the Filled Product.

6.03     SAVIENT QA will be responsible for the Release of the Final Product.

6.04     Product shall be delivered in accordance with the provisions of Article
7 of the Supply Agreement.

6.05     BTG will not ship any SAVIENT products to any destination, as
identified by SAVIENT, unless prior approval has been received from SAVIENT.

ARTICLE 7

DEVIATIONS IN PROCESS OR BULK PRODUCT:

In the event of a notification of a deviation by BTG in accordance with section
0 above, BTG shall investigate and fully document in English such deviation
within […***…] days of its discovery. If BTG cannot resolve the deviation within
the […***…]-day period, BTG will provide

 

 

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weekly updates of the investigation progress. At SAVIENT’s request, BTG shall
conduct such additional or more detailed investigation of the deviation as
SAVIENT may reasonably instruct. Investigation documentation will be retained by
BTG as part of the batch documentation for the batch affected. When a deviation
has occurred, SAVIENT will have the final review and decision making
responsibility as to the impact of the deviation on the Bulk Product or Product,
which will include the disposition of affected lots.

ARTICLE 8

STORAGE OF PRODUCT(S):

Bulk Product will be stored under appropriate storage conditions and in a secure
area to ensure that they comply with the Bulk Product Specifications, including
all the label requirements, quality specifications and attributes as well as
Legal Requirements.

ARTICLE 9

TRACEABILITY OF PRODUCT(S):

SAVIENT will be responsible for traceability of products to first consignee
within the US. BTG will be responsible for traceability from the finished
product lot number to raw material and component lots used in manufacture.

ARTICLE 10

CONFLICT OF TERMS:

To the extent that there exists any conflict between the terms of this Quality
Agreement and the Supply Agreement, the latter shall prevail. To the extent that
there exists any conflict between the terms of this Quality Agreement and any
Legal Requirements, the latter shall prevail.

ARTICLE 11

COMPLIANCE WITH LAWS:

BTG will ensure that all of its activities pursuant to this Agreement are
performed in accordance with all Legal Requirements (including cGMPs), the
respective Bulk Product Specifications, conditions of the BLA, and BTG’s
Standard Operating Procedures (SOPs). BTG will ensure that the Bulk Product
supplied by it to SAVIENT shall not itself cause the Final Product to be
adulterated or misbranded within the meaning of the Federal Food, Drug, and
Cosmetic Act and regulations.

 

D-12

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ARTICLE 12

INSPECTIONS:

Each party shall advise the other of any governmental communication, inspection
or report, including, without limitation, that of any appropriate regulatory
agency in any jurisdiction with responsibilities similar to those of the FDA in
respect of the United States, any environmental agency, health agency or other
governmental or administrative agency having jurisdiction over the Product or
the Processing. The notifying party shall promptly notify the other party by fax
and telephone, to the person and on the contact numbers set out below:

TO SAVIENT:

 

  ●    Contact Name:   Eric Nickerson, Senior Director Quality Assurance   ●   
Telephone:   732-418-9300   ●    Fax:   732-418-0766

TO BTG:

 

  ●    Contact Name:   Yosefa Bilman, Senior Director Quality Assurance   ●   
Telephone:   972-8-861-2007   ●    Fax:   972-8-861-2166

 

D-13

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ARTICLE 13

OBSERVATION BY SAVIENT:

Observation by SAVIENT or its authorized representative shall be governed the
following. Observation will be limited to […***…] quality audit every
[…***…]. One additional quality audit may be conducted within the […***…] period
if BTG receives a communication from any regulatory authority threatening
license approval or supply of the Product due to compliance deficiencies at BTG
facilities or if BTG was found to be in material non-compliance of this
Agreement during or since the last quality audit. Person-in-Plant visits may be
conducted at the discretion of SAVIENT during the manufacture of Bulk Product at
BTG facilities. The frequency and duration of any additional visits must be
agreed to by SAVIENT and BTG.

ARTICLE 14

ADVERSE EVENTS:

14.1     BTG will provide to SAVIENT within […***…] of becoming aware, any
information from any source that suggests an adverse event or serious adverse
event has occurred. This information will include any adverse drug experience or
reaction reports or any other information indicating that the product has any
toxicity, sensitivity reactions or is otherwise alleged to cause illness or
injury due to a possible product quality problem, adulteration or misbranding.

14.2     Quality Assurance Investigations. Upon notification to BTG that SAVIENT
has received an SAE, AE, product complaint or inquiry regarding a Product
supplied or incorporating a Bulk Product supplied, BTG shall conduct a quality
assurance investigation to determine if any process or testing deviations or
events may have contributed to the SAE, AE, product complaint or inquiry. BTG
shall provide a written report on the results of the investigation to SAVIENT in
not more than […***…] days from Savient’s notification. In cases where a more
comprehensive investigation might be required, the Parties will jointly develop
an investigation plan. BTG shall reasonably cooperate with SAVIENT and
regulatory agencies regarding an investigation or inquiry that may be initiated
by a regulatory agency or otherwise required in response to a consumer or
healthcare professional. BTG shall further provide SAVIENT with all data or
other information that SAVIENT may reasonably require in connection with any
reports or correspondence that SAVIENT provides to the regulatory agency,
consumer or healthcare professional relative to any such AE, SAE or product
complaint. BTG shall make records accessible to SAVIENT for purposes of FDA or
other regulatory agency inspection.

14.3     Exchange of Drug Safety Requests. The Parties shall immediately provide
each other with copies of all drug safety requests from all governmental and
other regulatory health authorities. Proposed answers affecting the Product will
be exchanged between the Parties before submission and the Parties shall
cooperate with respect to such answers. SAVIENT shall

 

 

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have the ultimate decision-making authority with respect to the answers relating
to the Product. The Parties shall exchange decisions from applicable health
authorities immediately.

ARTICLE 15

STABILITY:

BTG will perform the stability testing, data interpretation, reporting and
updating of stability information to regulatory documents for the Product and
Bulk Product and for Product until such time as a third party laboratory has
been qualified to perform such testing. Stability related activities for which
BTG is responsible shall be completed in accordance with the timing specified in
stability protocols and BTG procedures.

ARTICLE 16

REGULATORY AFFAIRS:

Each Party shall advise the other Party of any regulatory action of which it is
aware which would affect the Product in any country of the Territory.

ARTICLE 17

ANNUAL REPORT TO FDA:

BTG will prepare a summary of all changes to the product, production process,
quality controls, equipment or facilities that have a potential to affect the
identity, strength, quality, purity or potency of the Product. Such data will be
prepared and sent to SAVIENT within thirty days of the end of the review
period. BTG will also ensure that the results of all stability testing performed
within the review period are sent to Savient within thirty days of the end of
the review period.

 

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   Approvals

 

    

Print Name

 

   Signature    Date SAVIENT QA   

Eric Nickerson

 

   /s/Eric Nickerson    19-FEB-2009 BTG QA   

Yosefa Bilman

 

   /s/Yosefa Bilman    19/02/09

 

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APPENDIX I

Listing of Example Deviations

The following is a non-exclusive list of deviations requiring notification in
accordance with Article 3:

[…***…]

 

 

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APPENDIX II

Schedule of Retains, Storage Conditions and Retention Periods for Puricase®

The following is a list of the reserve/retention samples that are taken during
the manufacturing processes of bulk uricase and PEG-uricase as well as from the
final bulk uricase and the final bulk PEG-uricase (Bulk Product).

The document was prepared based on the following BTG QC SOPs:

[…***…]

[…***…]

[…***…]

[…***…]

Table I details the reserve/retention samples that are taken during the
manufacturing process of bulk uricase and from the final bulk uricase.

Table 2 details the reserve/retention samples that are taken during the
manufacturing process of PEG-uricase and from the final hulk PEG-uricase (Bulk
Product).

All IPC samples (including reserve/retention samples) are to be discarded after
the Bulk Product is released by BTG QA.

Uricase retention and reserve samples will be kept for […***…] after
manufacturing. PEG-Uricase retention and reserve samples will be kept for
[…***…] years after manufacturing.

 

 

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Table 1. Reserve/Retention Samples for Bulk Uricase (IPC and Final)

Process Step   Sample name   Number of
Samples   Storage
Temperature […***…]   […***…]   […***…]   […***…] […***…]   […***…]   […***…]  
[…***…]   […***…]   […***…]       […***…]   […***…]   […***…]   […***…]  
[…***…]   […***…]   […***…]   […***…]   […***…]   […***…]   […***…]   […***…]  
[…***…]   […***…]   […***…]   […***…]   […***…]   […***…]   […***…]   […***…]  
[…***…]   […***…]   […***…]   […***…]   […***…]   […***…]   […***…]   […***…]  
[…***…]   […***…]   […***…]   […***…]   […***…]   […***…]   […***…]  

[…***…]

 

[…***…]

  […***…]   […***…]   […***…]   […***…]   […***…]   […***…]   […***…]   […***…]
  […***…]      

[…***…]

  […***…]   […***…]   […***…]   […***…]  

   […***…]

 

 

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Table 2. Reserve/Retention Samples for PEG-Uricase API (IPC and Final)

Process Step   Sample name   Number of
Samples   Storage
Temperature […***…]   […***…]   […***…]   […***…] […***…]   […***…]   […***…]  
[…***…]   […***…]   […***…]   […***…]   […***…]   […***…]     […***…]   […***…]
  […***…]   […***…]   […***…]     […***…]   […***…]     […***…]   […***…]    
[…***…]   […***…]   […***…]   […***…]   […***…]   […***…]  

 

 

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APPENDIX III

Critical Raw Materials Used in the Production of Recombinant Uricase and
PEG-Uricase

 

 

Material

 

   Manufacturer    Cat. No.    Testing    Source    Origin

[…***…]

 

   […***…]    […***…]    […***…]    […***…]    […***…]

 

 

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SPECIFICATION […***…]

 

Parameter   Test   Specification […***…]      […***…]      […***…] […***…]     
[…***…]      […***…] […***…]      […***…]      […***…] […***…]      […***…]     
[…***…] […***…]      […***…]      […***…] […***…]      […***…]      […***…]
[…***…]      […***…]      […***…] […***…]      […***…]      […***…] […***…]     
[…***…]      […***…] […***…]      […***…]      […***…] […***…]      […***…]     
[…***…]

 

 

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Exhibit G

Product Specifications

--------------------------------------------------------------------------------

SPECIFICATION- […***…]

 

Parameter    Test    Specification […***…]    […***…]    […***…] […***…]   
[…***…]    […***…]    […***…]    […***…]    […***…]    […***…] […***…]   
[…***…]    […***…]    […***…]    […***…] […***…]    […***…]    […***…]   
[…***…]    […***…]    […***…]    […***…] […***…]    […***…]    […***…]   
[…***…]    […***…] […***…]    […***…]    […***…]    […***…]    […***…]   
[…***…]    […***…]    […***…]    […***…] […***…]    […***…]    […***…]   
[…***…]    […***…]

[…***…]

 

 

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THIRD AMENDMENT TO COMMERCIAL SUPPLY AGREEMENT

THIS THIRD AMENDMENT is made and entered into this 1st day of July, 2010,
(hereinafter the “Effective Date”).

 

BETWEEN:    SAVIENT PHARMACEUTICALS, INC.    a Delaware corporation,
(hereinafter “Savient”)   

 

AND

  

 

BIO-TECHNOLOGY GENERAL (ISRAEL) LTD.

   an Israel corporation, (hereinafter “BTG”)

WHEREAS:

Savient and BTG are parties to a Commercial Supply Agreement with an effective
date of March 20, 2007, (hereinafter, the “Agreement”) pursuant to which BTG
agreed to manufacture and supply a certain Bulk Product, as defined in the
Agreement, to Savient, and Savient agreed to purchase such Bulk Product from
BTG; and

Savient and BTG have subsequently amended the Agreement on September 24, 2007,
(the “First Amendment”) and on January 24, 2009, (the “Second Amendment”), and
have issued a Letter Agreement dated July 30, 2008, (the “Letter Agreement”)
pertaining to the Agreement; and

Savient and BTG desire to further amend the Agreement in accordance with the
terms and conditions of this Third Amendment.

NOW THEREFORE in consideration of the mutual promises and agreements and
covenants contained herein, the adequacy of such consideration has been agreed
and acknowledged by each party, and in accordance with the provisions of Section
14.08 of the Agreement, the parties hereto agree as follows:

 

1. Definitions. All of the Definitions contained in Article 1 of the Agreement
shall have the same meanings herein unless specifically stated otherwise. Any
capitalized terms not specifically defined herein, shall have the same meaning
ascribed to them as set forth in the Agreement.

 

2. Application of Capacity Reservation Fees. The parties agree that Section
5.01(ii)(D)(2) of the Agreement is hereby replaced in its entirety as follows:

“(2) be credited, inclusive of interest, by BTG on a per batch basis by
providing a […***…]% discount on the value of each batch at the time of
invoicing for Bulk Product purchased by Savient until it is fully utilized,
provided however, except as otherwise provided in Sections 5.0l(ii)(F),
5.01(ii)(G) and 5.01(ii)(H), any uncredited Processing Capacity Reservation Fee,
inclusive of interest, which is

 

 

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remaining at the close of business on […***…] due to a failure by Savient to
take delivery of Bulk Product which conforms to the Commercial Bulk Product
Specifications and which is ordered pursuant to a Bulk Product Forecast provided
pursuant to Section 5.03 or an Amended Bulk Product Forecast provided pursuant
to Section 5.06 and which is otherwise properly amended pursuant to Section 5.05
shall be forfeited by Savient to BTG. For purposes of clarity, the credit of the
Processing Capacity Reservation Fee shall accrue upon the delivery of the Bulk
Product by BTG to Savient and shall be reflected on the invoice which relates to
the Bulk Product shipment in question; and”.

 

3. No Modification. Except as expressly provided for herein, the Agreement shall
remain in full force and effect without amendment. If there is any conflict or
inconsistency between this Amendment and the Agreement, this Amendment shall
prevail. This Amendment contains the entire agreement between the parties hereto
with respect to the subject matter contemplated herein and shall not be modified
or amended except by a written instrument signed by both parties hereto.

IN WITNESS WHEREOF, the parties have caused this Amendment to be executed by
their respective duly authorized officers as of the date first written above.

 

SAVIENT PHARMACEUTICALS, INC.

   

BIO-TECHNOLOGY GENERAL

(ISRAEL) LTD.

By:  

      /s/Philip K. Yachmetz

    By:  

      /s/Dov Kanner

 

      Philip K. Yachmetz

     

      Dov Kanner

 

      Senior Vice President &

      General Counsel

     

      Managing Director

 

 

***Confidential Treatment Requested

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FOURTH AMENDMENT TO COMMERCIAL SUPPLY AGREEMENT

THIS FOURTH AMENDMENT TO COMMERCIAL SUPPLY AGREEMENT (this “Fourth Amendment”)
is made and effective as of this 21st day of March 2012, (hereinafter the
“Amendment Effective Date”).

 

BETWEEN:    SAVIENT PHARMACEUTICALS, INC.
a Delaware corporation, (hereinafter “Savient”)   

 

AND

  

 

BIO-TECHNOLOGY GENERAL (ISRAEL) LTD.
an Israel corporation, (hereinafter “BTG”)

WHEREAS:

Savient and BTG are parties to a Commercial Supply Agreement with an effective
date of March 20, 2007, (hereinafter, the “Agreement”, modified as provided in
the next paragraph) pursuant to which BTG agreed to manufacture and supply a
certain Bulk Product, as defined in the Agreement, to Savient, and Savient
agreed to purchase such Bulk Product from BTG; and

Savient and BTG have subsequently amended the Agreement on September 24, 2007,
(the “First Amendment”), on January 24, 2009, (the “Second Amendment) and on
July 1, 2010, (the “Third Amendment”), and have issued a Letter Agreement dated
July 30, 2008, (the “Letter Agreement”) pertaining to the Agreement; and

Savient and BTG desire to further amend the Agreement in accordance with the
terms and conditions of this Fourth Amendment.

NOW THEREFORE in consideration of the mutual promises, agreements and covenants
contained herein, the adequacy of such consideration has been agreed and
acknowledged by each Party, and in accordance with the provisions of Section
14.08 of the Agreement, the Parties agree as follows:

 

1. Definitions. All of the Definitions contained in Article 1 of the Agreement
shall have the same meanings herein unless specifically stated otherwise. Any
capitalized terms not specifically defined herein, shall have the same meaning
ascribed to them as set forth in the Agreement.

 

2.

Addition and Replacement of Exhibits to Agreement. The Parties agree that the
exhibits which are appended to this Fourth Amendment shall, as applicable, be
added or supersede and replace their counterparts as previously executed by and
between

--------------------------------------------------------------------------------

 

the Parties. For purposes of clarity, the following exhibits to the Agreement
are hereby repealed and replaced with the attached exhibits:

 

  (a)

Exhibit C-1, “Current Commercial Bulk Product Specifications” which are the
current regulatory acceptance criteria and are added pursuant to Section
3.01(ii) of the Agreement;

 

  (b)

Exhibit C-2, “Modified Acceptance Criteria to be Used to Govern the Commercial
Supply Agreement” […***…] (the “Modified Acceptance Criteria”); and

 

  (c)

Exhibit E, “Product Price” […***…].

 

3.

Modified Payment Terms for Bulk Product. Savient and BTG acknowledge and agree
that, due to additions or modifications to the Current Commercial Bulk Product
Specifications, additional experience manufacturing Bulk Product may be required
in order to provide a higher level of assurance that Bulk Product can be
consistently manufactured in a manner that conforms to the Current Commercial
Bulk Product Specifications as set forth in Exhibit C-1 hereto. […***…] As more
fully set forth in clauses (a) through (c) herein below, Savient and BTG agree
to share financial responsibility with respect to (x) certain Bulk Product
manufactured by BTG under the Agreement […***…] and (y) Bulk Product
manufactured by BTG under the Agreement beginning with the production of […***…]
and ending after the completion of […***…] batches under this Agreement (the
“[…***…] Specification Batches”). After completion of the […***…] specification
batches the Current Commercial Bulk Product Specifications will be reassessed
and the Parties will mutually agree on any revisions thereto deemed necessary or
appropriate (which agreement shall not be unreasonably withheld, conditioned or
delayed) for submission to Regulatory Authorities in whose territories KRYSTEXXA
is licensed. After the acceptance by such Regulatory Authorities of any
revisions to the Current Commercial Bulk Product Specifications as set forth in
Exhibit C-1 hereto, unless the Parties mutually agree otherwise in writing, the
risk of failed batches and payment terms set forth in the Agreement (as amended
by Section 2(b) above) shall apply, in full force and effect, with respect to
all future Bulk Product manufactured by BTG pursuant to the Agreement. During
the pendency between the completion of the […***…] Specification Batches and the
acceptance of any revisions to the Current Commercial Bulk Product
Specifications by the pertinent Regulatory Authorities in whose territories
KRYSTEXXA is licensed, the parties agree that BTG shall continue to manufacture
batches of Bulk Product in accordance with the Modified Acceptance Criteria set
forth in Exhibit C-2 and

 

 

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any nonconformities in any such batches shall be resolved in accordance with
Section 3(b) of this Fourth Amendment.

(a)      Within […***…] business days after the full execution of this Fourth
Amendment, Savient shall pay to BTG a one-time payment of […***…] Dollars
($[…***…]),[…***…].

(b)      With respect to any of the […***…] Specification Batches of Bulk
Product manufactured by BTG under the Agreement (unless extended by mutual
written agreement of the Parties):

(i)     If any of the […***…] Specification Batches is deemed not to conform to
the Current Commercial Bulk Product Specifications and (A) such non-conformance
does comply with all of the Modified Acceptance Criteria and (B) such
non-conformance is not attributable in any way to human error (each such batch a
“Modified Acceptance Criteria Conforming Batch”), Savient shall pay BTG for such
batch at a rate of […***…] Dollars and […***…] cents ($[…***…]) per gram (e.g.,
[…***…] Dollars and […***…] cents ($[…***…]) on the basis of a […***…] batch),
rather than the Price. For purposes of clarity, human error may include, but is
not limited to, the introduction of foreign material, improper connection of
equipment, improper cleaning of equipment, and the failure to follow established
SOPs and master batch records.

(ii)     If any of the […***…] Specification Batches is deemed not to conform to
the Current Commercial Bulk Product Specifications and (A) such batch does not
conform to the Modified Acceptance Criteria, or (B) such non-conformance is
attributable in any way to human error caused by BTG, Savient shall have no
liability to BTG with respect to such Bulk Product.

(iii)    For any of the […***…] Specification Batches deemed to conform to the
Current Commercial Bulk Product Specifications, Savient shall pay BTG for such
batch in accordance with the terms and conditions of the Agreement, including
the then-current Price.

(c)      Savient may, in its sole discretion, apply, on a batch-by-batch basis,
[…***…] Dollar ($[…***…]) of the Processing Capacity Reservation Fee credit (or
such greater amount agreed upon as the then current per batch Processing
Capacity Reservation Fee credit due to the accrual of interest on the Processing
Capacity Reservation Fee amount) toward any payment owed to BTG in accordance
with clause (b) above.

In the event either Party determines that a batch of Bulk Product is a Current
Commercial Bulk Product Non-Conforming Batch it shall promptly notify the other
Party. If the other

 

 

***Confidential Treatment Requested

 

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Party does not agree with such determination, the Parties shall investigate and
fully document such non-conformance using typical out-of-specification
investigation techniques performed to the mutual satisfaction of the Parties (in
the case of specifications for which the analyses are not conducted at BTG,
Savient shall enable BTG to review all data related to those analyses). If
following such investigation the Parties do not agree whether a batch of Bulk
Product is a Current Commercial Bulk Product Non-Conforming Batch, the Parties
shall promptly appoint an independent specialist (appointed by mutual agreement
between the Parties, which agreement shall not be unreasonably withheld,
conditioned or delayed) who shall determine whether such batch of Bulk Product
is a Current Commercial Bulk Product Non-Conforming Batch. In the absence of
manifest error, the independent specialist’s decision shall be conclusive and
binding on the Parties.

 

4. Suspension of Manufacturing.  Without limiting the provisions of Section 5.08
of the Agreement, in the event that […***…]or more of the […***…] Specification
Batches (unless extended by mutual written agreement of the Parties) are deemed
to be Modified Specification Non-Conforming Batches, then Savient may, in its
sole discretion and without any penalty under the Agreement, suspend all
manufacture of Bulk Product under the Agreement. In the event that manufacture
of Bulk Product is suspended in accordance with the preceding sentence, Savient
shall be released from its purchase obligations under Section 6.01 of the
Agreement and no forecast or estimate shall be considered a Firm Order until
such time as BTG demonstrates to Savient’s reasonable satisfaction that the
manufacture of Bulk Product may be resumed with a reduced and manageable risk of
the manufacture of Modified Specification Non-Conforming Batches.

 

5. Remediation Plan.  Prior to the Amendment Effective Date, BTG and Savient (a)
[…***…] and (b) mutually agreed to implement investigations of […***…]. Appendix
1 sets forth the proposals for these investigations that have been agreed to by
the Parties and BTG shall, after the Amendment Effective Date, promptly pursue
such investigations and implement such changes which may be determined to be
necessary to the Facility to Savient’s reasonable satisfaction. Savient and BTG
shall agree on the terms and conditions for the implementation of the Facility
Changes, and the allocation of costs, in accordance with Section 6.03. If
Savient and BTG determine that Process Changes or Process development work is
needed to prevent Modified Specification Non-Conforming Batches (as
distinguished from equipment changes or work of general applicability to BTG’s
manufacturing activities), the Parties shall agree on the terms and conditions
for such additional Process development work in accordance with Section
6.02(iii).

 

6.

Submission of Data to the FDA.  BTG acknowledges that in accordance with the
post-regulatory approval commitments made by Savient to the FDA with respect to
the FDA’s approval of the Product, Savient is required to submit to the FDA
revised specifications for Bulk Product and the supporting data therefore after
the completion of the manufacture of the […***…] Specification Batches. BTG
shall provide all information and assistance which is reasonably necessary or
useful in the preparation of such submissions in accordance with Section
3.02. All documents to be supplied by BTG pursuant to this

 

 

***Confidential Treatment Requested

 

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Section 6 shall be translated by BTG into the English language as may be
necessary. Any labor costs of BTG employees shall be reimbursed by Savient in
the manner and at the rates set forth on Exhibit B to the Agreement.

 

7. Savient Observation Rights.  During the Term, BTG shall make best efforts to
accommodate Savient’s requests to visit the facility where the Bulk Product is
manufactured and observe the manufacturing of the Bulk Product in order to
ensure that the Process complies with Applicable Law and the Product
Specifications. These visits will be at Savient’s sole cost and expense and will
take place during normal business hours and upon […***…] Business Days notice

 

8. Additional Agreement.  As an additional inducement to Savient for the
execution of this Fourth Amendment, BTG and its parent company, Ferring B.V.
will cause Ferring International Centre S.A. to execute, contemporaneously with
the execution of this Fourth Amendment, the OsmB Promoter License Agreement in
the form attached hereto as Appendix 2.

 

9. No Modification.  Except as expressly provided for herein, the Agreement
shall remain in full force and effect without amendment. If there is any
conflict or inconsistency between this Amendment and the Agreement, this
Amendment shall prevail. The Agreement, as modified by this Amendment, contains
the entire agreement between the parties hereto with respect to the subject
matter contemplated herein and shall not be modified or amended except by a
written instrument signed by both parties hereto.

IN WITNESS WHEREOF, the parties have caused this Amendment to be executed by
their respective duly authorized officers as of the date first written above.

 

SAVIENT PHARMACEUTICALS, INC.     

BIO-TECHNOLOGY GENERAL

(ISRAEL) Ltd.

   By:  

    /s/Philip K. Yachmetz

     By:  

    /s/Dov Kanner

         Philip K. Yachmetz            Dov Kanner     

    Senior Vice President &

    General Counsel

           Managing Director   

 

 

***Confidential Treatment Requested

 

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EXHIBIT C-1 to Fourth Amendment

Release Tests Performed on […***…]

 

Parameter    Test    Acceptance Criteria

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]   

[…***…]

 

[…***…]

[…***…]

  

[…***…]

 

   […***…]   

[…***…]

 

   […***…]

[…***…]

  

[…***…]

 

   […***…]   

[…***…]

 

   […***…]

[…***…]

 

   […***…]    […***…]

[…***…]

   […***…]    […***…]   

[…***…]

 

   […***…]

[…***…]

[…***…]

 

 

***Confidential Treatment Requested

 

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Tests Performed on […***…]

 

Parameter    Test    Acceptance Criteria

[…***…]

   […***…]    […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]

[…***…]

[…***…]

[…***…]

[…***…]

[…***…]

 

 

***Confidential Treatment Requested

 

- 7 -

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EXHIBIT C-2 to Fourth Amendment

  […***…] Specification

Parameter    U.S. Regulatory Agency Acceptance Criteria    Modified
Acceptance Criteria

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]    […***…]    […***…]    […***…]    […***…]    […***…]   
[…***…]    […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

 

 

***Confidential Treatment Requested

--------------------------------------------------------------------------------

  […***…] Specification

Parameter    U.S. Regulatory Agency Acceptance Criteria    Modified
Acceptance Criteria

[…***…]

  

[…***…]

   […***…]

[…***…]

  

[…***…]

   […***…]

[…***…]

  

[…***…]

   […***…]

[…***…]

  

[…***…]

   […***…]

[…***…]

  

[…***…]

   […***…]

[…***…]

 

  

[…***…]

 

  

[…***…]

 

[…***…]

  

[…***…]

 

  

[…***…]

 

  

[…***…]

 

  

[…***…]

 

[…***…]

  

[…***…]

 

   […***…]

[…***…]

  

[…***…]

 

   […***…]

[…***…]

  

[…***…]

 

   […***…]

[…***…]

  

[…***…]

 

   […***…]

[…***…]

  

[…***…]

 

   […***…]

[…***…]

  

[…***…]

 

   […***…]

[…***…]

  

[…***…]

 

   […***…]

[…***…]

  

[…***…]

 

   […***…]

[…***…]

  

[…***…]

 

   […***…]

 

 

***Confidential Treatment Requested

 

- 2 -

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EXHIBIT E to Fourth Amendment

Product Price

As and from […***…], the Price of the Product shall be as follows:

(i)        For each gram, […***…] Dollars (USD$[…***…]) for any aggregated
quantities of the Product up to and including […***…]] ordered during any
calendar year that commercial batches of Product are shipped, i.e. after the
first commercial batch of Product has been shipped.

(ii)       For each gram, […***…] Dollars (USD$[…***…]) for any aggregated
quantities of the Product between […***…] and […***…] ordered during any
calendar year as above; and

(iii)      For each gram, […***…] United States Dollars (USD$[…***…]) for any
aggregated quantities of the Product equal to or greater than […***…] ordered
during any calendar year as above.

The Parties agree that Savient will enter into a supply agreement with […***…],
the supplier of […***…], and will order and pay for […***…] needed in Product
manufacture on an ongoing basis. In the event that BTG purchases […***…]
directly from […***…] or any other manufacturer, the cost of the […***…] will be
invoiced to Savient.

Beginning on the […***…] anniversary of the date of receipt of the first
commercial batch of Product by Savient, and on each successive […***…]
thereafter, the Price of the Product shall increase by an amount equal to the
average increase in the United States Consumer Pricing Index (CPI) over the
immediately preceding […***…] period; such percentage increase shall be applied
to each amount specified in (i) through (iii) above.

 

 

***Confidential Treatment Requested

--------------------------------------------------------------------------------

APPENDIX 1

[…***…]

 

 

***Confidential Treatment Requested

 

- 2 -

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APPENDIX 2

OsmB Promoter License Agreement

This OsmB Promoter License Agreement (the “Agreement”) is entered into as of
this 21st day of March, 2012, with a retroactive effective date of July 18, 2005
(“Effective Date”), between Savient Pharmaceuticals, Inc., a Delaware
corporation (“Savient”) and Ferring International Centre S.A., a Swiss
corporation (“FIC”).

Introduction

WHEREAS on March 23, 2005, Ferring B.V., FIC and Savient executed a Share
Purchase Agreement and an Asset Purchase Agreement, and associated documents,
which accomplished the sale of Savient’s global biologics manufacturing business
comprising the transfer of all outstanding shares in Bio-Technology General
(Israel), Ltd. (“BTG”) and certain defined assets from Savient to Ferring B.V.
and FIC (the “BTG Divestiture”). Part of the BTG Divestiture included the
transfer of certain intellectual property rights from Savient and BTG to FIC;

WHEREAS Savient and BTG entered into an Amended and Restated Residual Rights
Agreement dated July 17, 2005, pursuant to which BTG performed certain
manufacturing development and bulk product manufacturing activities pending the
finalization of more definitive agreement relating to those activities and
wherein the parties stated their intention to license certain intellectual
property rights in certain patents from BTG to Savient in order to assure
Savient’s rights and liabilities to manufacture the Puricase product, now known
as pegloticase (the “RRA”);

WHEREAS, pursuant to the terms and conditions of the RRA, Savient and BTG
entered into a Development Agreement (the “DA”) and Commercial Supply Agreement
(the “CSA”), each dated March 20, 2007, both of which agreements upon their
execution superseded and replaced, in relevant part, the RRA;

WHEREAS pursuant to the terms and conditions of the DA and CSA, in Sections 2.02
(iii) and 2.01(iii) respectively, BTG has granted, and has undertaken to cause
its Affiliates to grant, to Savient a fully paid-up, royalty-free, non-exclusive
license in the Territory (defined in each of the DA and CSA as meaning,
collectively, each country of the world) to manufacture, have manufactured,
produce, have produced, develop, have developed, use, have used, offer for sale,
have offered for sale, sell, have sold, export, and have exported Bulk Product
under the BTG Licensed Improvements and BTG Know-How, as each term is defined in
the DA and CSA (collectively the “Pegloticase Licenses”);

WHEREAS the Closing of the transactions effectuating the BTG Divestiture
occurred on July 18, 2005, upon which all right, title and interest in and to
all intellectual property related to the global biologics manufacturing business
of BTG, including the intellectual property defined in the DA and CSA as BTG
Licensed Improvements and BTG Know-How transferred to and was vested in FIC (the
“BTG IP”); and

 

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WHEREAS, in view of FIC’s ownership of the BTG IP, Savient and FIC desire to
execute this Agreement in order to effectuate and perfect the Pegloticase
Licenses granted by BTG on and in accordance with the terms and conditions as
follows.

NOW THEREFORE in consideration of the recitals in the Introduction above, the
covenants and agreements herein, and other good and valuable consideration, the
receipt and sufficiency of which the parties acknowledge, the parties agree as
follows:

ARTICLE 1

As used herein, the following terms shall have the meanings ascribed to them as
follows:

 

1.1 “Affiliate” shall mean any person or entity controlling, controlled by or
under common control with a party to this Agreement.

 

1.2 “Patents” shall mean those patents listed in Exhibit 1, all foreign
counterparts thereto, and any disclosures, continuations, continuations-in-part,
divisionals, provisionals, PCT applications, reissuances, revisions,
substitutions, conversions, renewals, extensions, prolongations, and
reexaminations thereof, any technology and inventions covered thereby, and any
corresponding international, regional and national applications, whether
existing at present or in the future.

 

1.3 “Pegloticase” shall mean […***…].

 

1.4 “Territory” shall mean, collectively, each country in the world.

 

1.5 Capitalized terms used but not specifically defined herein shall have the
meaning ascribed to them in the DA and CSA.

ARTICLE 2

 

2.1 Grant of License.  FIC hereby grants to Savient a fully paid-up,
royalty-free, non-exclusive license in the Territory to manufacture, have
manufactured, produce, have produced, develop, have developed, use, have used,
offer for sale, have offered for sale, sell, have sold, export, and have
exported Pegloticase bulk product under the intellectual property owned by FIC
which embodies the BTG Licensed Improvements and BTG Know-How, as each term is
defined in the DA and CSA, including, without limitation the Patents. Such
license includes the right to sublicense solely for the purposes of effectuating
the rights granted to Savient hereunder. To the extent necessary or required,
upon request by Savient, FIC shall execute, and shall cause its Affiliates to
execute, any such additional documentation as may be necessary in order to give
effect to this license grant.

 

 

***Confidential Treatment Requested

 

- 4 -

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ARTICLE 3

This Agreement shall commence as of the Effective Date, and continue in full
force and effect until the expiration date of the last to expire of the Patents
or other patents which embody BTG Licensed Improvements or BTG Know-How.

ARTICLE 4

 

4.1 Entire Agreement. This Agreement constitutes the entire agreement between
the parties with respect to the subject matter hereof, and supersedes any prior
agreements or understandings, whether oral or written, between the parties and
their respective Affiliates with respect to such matters.

 

4.2 Modification. No modification of the terms hereof shall be effective except
by a written instrument signed by both parties.

 

4.3 Severability. The invalidity or unenforceability of any term or provision of
this Agreement shall not effect the other terms and provisions, and such invalid
or unenforceable term or provision will, in all events be construed and enforced
to the fullest extent permissible under applicable law.

 

4.4 Assignment. Either party may assign this Agreement and its rights and
obligations hereunder, provided that any such assignee agrees to be bound by the
terms, conditions and covenants of such assigning party hereunder. The Agreement
shall be binding upon and inure to the benefit of the parties, and their
respective successors and permitted assigns.

 

4.5 Dispute Resolution.  Any dispute arising between the parties with respect to
any provision of this Agreement or any matter relating to the performance of
either party hereunder shall first attempt to be resolved if reasonably possible
by good faith negotiation between designated executives of each party. In the
event of such dispute, the parties shall promptly designate respective
executives who shall then confer in good faith in an attempt to resolve the
dispute before any further action is commenced. In the event no mutual
resolution is possible using the foregoing method, either party may require the
other party to submit to non-binding mediation using a recognized dispute
resolution entity before court litigation is commenced.

 

4.6 Order of Precedence. In the event of a conflict or inconsistency that
relates to the subject matter hereof between any terms of this Agreement and the
DA, CSA or RRA, and in each such instance the Exhibits thereto, the terms of
this Agreement shall take precedence over any conflicting terms in the earlier
agreements.

 

4.7 Governing Law. This Agreement shall be deemed to have been made in the State
of New York, and will be construed and enforced and under and governed by the
internal laws of such state, without giving effect to conflicts of laws
principles.

 

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4.8 Counterparts. This Agreement may be signed in any number of counterparts,
any of which shall constitute an original and all of which when taken together
shall constitute one and the same instrument.

IN WITNESS WHEREOF, each party has caused it duly authorized representative to
execute this Agreement on the date first written above, effective as of the
Effective Date.

 

Savient Pharmaceuticals, Inc.     Ferring International Centre S.A.  

/s/ Philip K. Yachmetz

   

/s/ Lars Peter Brunse

  By:   Philip K. Yachmetz     By:   Lars Peter Brunse   Title:       SVP
& General Counsel     Title:     EVP Technical Operations  

 

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EXHIBIT 1 to OsmB Promoter License Agreement

 

Patent Number    Country    Expiry Date

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

[…***…]

   […***…]    […***…]

 

 

***Confidential Treatment Requested

 

- 7 -