CONFIDENTIAL MATERIALS OMITTED AND FILED SEPARATELY WITH
THE SECURITIES AND EXCHANGE COMMISSION. ASTERISKS DENOTE OMISSIONS
MANUFACTURING AGREEMENT
MANUFACTURING AGREEMENT, dated September 29, 2006, by and between CYTOGEN
CORPORATION, a Delaware corporation ("Cytogen") and LAUREATE PHARMA, INC., a
Delaware corporation ("Laureate").
W I T N E S S E T H :
_ _ _ _ _ _ _ _ _ _
WHEREAS, Cytogen wishes to engage the services of Laureate to produce
Filled ProstaScint Product and Filled Sodium Acetate Product (each as
hereinafter defined) in accordance with the provisions hereof.
NOW, THEREFORE, it is agreed as follows:
1. Definitions. The following terms shall have the meanings specified in
-----------
this paragraph 1. Other terms are defined in this Agreement and, throughout this
Agreement, those terms shall have the meanings respectively ascribed to them.
(a) "Affiliate" means, with respect to a party, any individual or
entity which controls, is controlled by or is under common control with such
party. For purposes of this definition, "control" means an equity or income
interest of fifty percent (50%) or more in, or the possession, directly or
indirectly, of the power to cause the direction of the management, activities or
policies of such individual or entity, whether through the ownership of voting
securities or other equity interest, by contract or otherwise.
(b) "Batch" means (i) with respect to CYT-351, the specific quantity
of CYT-351 which is produced as a result of the performance of [**]; (ii) with
respect to CYT-356, the specific quantity of CYT-356 which is produced from the
conjugation of a Batch of CYT-351, or the conjugation of a specified identified
portion of a Batch of CYT-351 or the conjugation of combined batches of CYT-351;
and (iii) with respect to sodium acetate buffer solution, the specific quantity
of sodium acetate buffer solution produced during the course of a single
manufacturing run.
(c) "Bulk Sodium Acetate" means sodium acetate prior to being filled
into vials.
(d) "Cytogen SOPs" means Cytogen's written standard operating
procedures to be utilized in connection with the manufacture, production and
in-process release testing of ▇▇▇-▇▇▇, ▇▇▇-▇▇▇, Filled ProstaScint Product and
Filled Acetate Product, true and complete copies of which have been delivered to
Laureate.
(e) "Cytogen Supplied Materials" means (i) the CYT-351 [**] Cell
Line, (ii) [**] linker chelator, and (iii) Product-Dedicated Equipment
chromatography columns, multi-use resins and filtration cassettes, components
and supplies, required in connection with the production by Laureate of CYT-351,
Filled ProstaScint Product or Filled Sodium Acetate Product, provided at
Cytogen's sole cost and expense.
(f) "CYT-351" means the monoclonal antibody intermediate product
which is used in manufacturing ProstaScint.
(g) "CYT-356" means the immunoconjugated form of CYT-351 (sometimes
referred to in the course of manufacture and production of Filled ProstaScint
Product as bulk ProstaScint).
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(h) "Facility" means Laureate's manufacturing and filling premises
located in Princeton, New Jersey.
(i) "FDA" means the United States Food and Drug Administration and
shall include any division or center thereof.
(j) "Filled Sodium Acetate Product" means vials filled with sodium
acetate solution from an identified Lot which are in a form ready for release
and shipment from the Facility.
(k) "Filled ProstaScint Product" means the vials filled with CYT-356
from an identified Lot which are in a form ready for release and shipment from
the Facility.
(l) "cGMP" means current Good Manufacturing Practices for the
manufacture and testing of pharmaceutical materials, as specified in the Code of
Federal Regulations and associated regulatory agency guidelines as currently
interpreted and practiced by Laureate at the Facility.
(m) "Hollow-Fiber Bioreactor Run" means cells grown for approximately
[**] in the [**] bioreactor using a [**].
(n) "Incoming Acceptance Tests" means, with respect to each Cytogen
Supplied Material, the analysis or testing thereof supplied to Laureate by
Cytogen pursuant to paragraph 6(b) hereof and to be performed by Laureate in
order to determine whether or not such Cytogen Supplied Product conforms to the
applicable approved Specifications.
(o) "Laureate SOPs" means Laureate's written standard operation
procedures utilized by Laureate in connection with its operational activities at
the Facility.
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(p) "Lot" means a Batch or a specific identified portion of a Batch
of ▇▇▇-▇▇▇, ▇▇▇-▇▇▇ or sodium acetate, as applicable, which is produced in the
course of Laureate's performance of a single manufacturing production run.
(q) "Manufacturing Procedures" means the activities, processes,
procedures, instructions and batch records provided to Laureate by Cytogen
pursuant to paragraph 6(a) hereof and to be utilized by Laureate in the
production of ▇▇▇-▇▇▇, ▇▇▇-▇▇▇, Filled ProstaScint Product and Filled Sodium
Acetate Product.
(r) "Product Dedicated Equipment" shall mean columns, certain filter
housings and filling components, as specified in the Specifications, Cytogen
SOPs, Laureate SOPs, or Manufacturing Procedures, as applicable, that are only
used in the Manufacturing Procedures.
(s) "Production Campaign" shall mean: (i) [**] Hollow-Fiber
Bioreactor Runs, for convenience labeled runs [**], with the runs being done in
[**], such that [**] would be staggered approximately [**] apart; (ii) [**], the
combination of the [**] Hollow-Fiber Bioreactor Runs, to generate CYT-351; (iii)
a total of up to [**] of the CYT-351 to generate [**] of CYT-356. Only [**]
would be carried out in this initial campaign. The remaining CYT-351 shall be
stored by Laureate up to [**] or until Cytogen requests that this remaining
CYT-351 be conjugated; (iv) a total of up to [**] of conjugated antibody in
vials, approximately [**]; and (v) up to [**] sodium acetate fills, each fill
utilizing a volume of sodium acetate buffer solution as specified in the Batch
Record including all Services required to supply Cytogen with Filled Sodium
Acetate Product.
4
(t) "ProstaScint" means the compound capromab pendetide formulated by
conjugating the murine monoclonal antibody CYT-351 to the [**].
(u) "Quality Agreement" means a detailed agreement specifying the
quality and regulatory procedures and responsibilities of the parties hereunder
with respect to the production of bulk CYT-351, CYT-356, Bulk Sodium Acetate,
Filled ProstaScint Products and Filled Sodium Acetate Products to be entered
into contemporaneously with, or shortly after, this Agreement.
(v) "Services" means the activities undertaken by Laureate in the
course of Laureate's performance of the Production Campaign and associated
activities and testing, or any part thereof.
(w) "Specifications" means Cytogen's approved specifications with
respect to CYT-351, CYT-356, Bulk Sodium Acetate, the Cytogen Supplied
Materials, Filled ProstaScint Product and Filled Sodium Acetate Product, as
applicable, provided to Laureate. Specifications may be amended from time to
time by mutual written agreement of Laureate and Cytogen subject to the approval
by the FDA of each amendment, if necessary.
2. Commencement; Orders; Options; Expiration. (a) This Agreement shall
-------------------------------------------
commence on the date hereof.
(b) Cytogen hereby orders from Laureate the Services required to be
performed by Laureate in connection with Laureate's conduct of the Production
Campaign.
(c) Subject to the provisions hereof, this Agreement shall expire on
such date as when Laureate has completed the Production Campaign for [**] of
conjugated antibody and the Filled ProstaScint Product and the Sodium Acetate
Product resulting therefrom
5
have been shipped from the Facility in accordance with paragraph 10 hereof,
subject to release by Cytogen of the Filled ProstaScint Product and the Filled
Sodium Acetate Product in accordance with the terms of the Quality Agreement.
The parties anticipate that the initiation of Hollow-Fiber Bioreactor Runs in
the Production Campaign on or about [**] with completion of Hollow-Fiber
Bioreactor Runs on or before [**] and purification, conjugation and filling of
the resulting material in [**].
3. Consideration and Payment. In consideration of Laureate's performance
-------------------------
of Services hereunder, Cytogen agrees to pay to Laureate the development and
service fees listed in Appendix 1 (the "Service Fees") to perform the Production
Campaign and Services. Customer shall pay Laureate the Service Fees in
accordance with the payment schedule set forth in Appendix 1. Laureate will
invoice the Customer for Product-Dedicated Equipment, resins and supplies that
Laureate purchases for the Production Campaign. An administrative fee equal to
[**] of Laureate's actual cost of such materials and equipment purchased for the
Production Campaign will be added to the invoices. Payments and non-refundable
deposits are due [**] days from the date of invoice, except that the Service
Fees' payments are due at the times indicated in Appendix 1. Late payments are
subject to an interest charge of [**].
4. Liquidated Damages. For purchase orders received after November 1,
------------------
2006, in the event Cytogen cancels an order for [**] Hollow-Fiber Bioreactor
Runs, Cytogen agrees to pay Laureate liquidated damages of $500,000 payable
within [**] of cancellation.
5. Performance of Services; Other Assistance; FDA Fees. (a) All Services
----------------------------------------------------
shall be performed by Laureate at Laureate's facility in Princeton, NJ in
accordance with the Quality Agreement.
6
(b) Any FDA fee with respect to the licensing of facilities at which
commercial manufacture of Cytogen marketed pharmaceutical products occurs shall
be borne and paid for by Cytogen ("Establishment Fee"). Laureate will
immediately inform Cytogen of any and all FDA approved and marketed
pharmaceutical products manufactured by Laureate in the Facility for a third
party in addition to Laureate's manufacturing services hereunder. Laureate shall
have the right to perform manufacturing services for third parties at the
Facility.
6. Manufacturing and Testing; Approvals; SOPs. (a) Cytogen has provided
--------------------------------------------
Laureate in writing with the Manufacturing Procedures which shall include all
requisite technical specifications, manufacture and production process
information, batch records, instructions and procedures, testing and quality
control instructions and procedures, formulae, storage instructions with respect
to the manufacture of ▇▇▇▇▇▇ ▇▇▇▇▇▇▇, ▇▇▇-▇▇▇, ▇▇▇-▇▇▇, Filled ProstaScint
Product, Filled Sodium Acetate Product or intermediates of any nature and all
such other information, knowledge, data and know-how as would allow one
reasonably practiced in the art to produce and manufacture ▇▇▇▇▇▇ ▇▇▇▇▇▇▇,
▇▇▇-▇▇▇, ▇▇▇-▇▇▇, Filled ProstaScint Product and Filled Sodium Acetate Product.
(b) Cytogen has provided Laureate in writing with the Incoming
Acceptance Tests which shall include all requisite analyses and tests with
respect to each Cytogen Supplied Material, the methodology of each such analysis
and test, the sample size of the applicable Cytogen Supplied Material to be
utilized in connection with the performance of the applicable analyses and/or
tests and the period following Laureate's receipt of such Cytogen Supplied
Material at the Facility during which the applicable analyses or tests are to be
conducted.
7
(c) Cytogen has provided Laureate in writing with the Specifications
for each of ▇▇▇▇▇▇ ▇▇▇▇▇▇▇, ▇▇▇-▇▇▇, ▇▇▇-▇▇▇, Filled ProstaScint Product and
Filled Sodium Acetate Product.
(d) Laureate will provide to Cytogen the Laureate SOPs for approval.
Such Laurate SOPs shall be provided by Laureate and reviewed and approved by
Cytogen (such approval not to be unreasonably withheld or delayed) in accordance
with the Target Project Timeline (as hereinafter defined).
(e) Within [**] after execution of this Agreement, Laureate shall
notify Cytogen in writing of any additional information, processes, or
procedures needed by Laureate in order to complete the Production Campaign or
Services.
(f) In the event that Laureate gives notice pursuant to paragraph
6(e) of its need for additional information, processes or procedures necessary
in order to complete the Production Campaign or Services, Laureate and Cytogen
shall mutually prepare an action plan (the "Plan") with respect to enabling
Laureate to perform the Production Campaign and to provide Services as required
herein. Each of Laureate and Cytogen agrees to undertake reasonable commercial
efforts to implement the Plan to the end of providing Laureate with the
capability of rendering Services and performing the Production Campaign in
conformance with this Agreement.
(g) [**].
(h) Cytogen has provided to Laureate the Cytogen SOPs, Specifications
and Batch documentation in writing.
8
7. Change Orders.
-------------
(a) The Service Fees are subject to a number of specific and general
assumptions. The specific assumptions relate to the Scope and Program design and
objectives, timing, capital expenditure requirements, if any, and other matters
relating to the completion of the Production Campaign (the "Program
Assumptions"). Laureate also assumes that Cytogen will cooperate and perform its
obligations under the Agreement, that no event outside the control of Laureate
will occur, including, without limitation, the events described in Section 26,
and that there are no changes to any applicable laws, rules or regulations that
affect the Production Campaign (the foregoing assumptions together with the
Program Assumptions, collectively, the "Assumptions"). In the event that any of
the Assumptions require modification or the Production Campaign objectives
cannot be achieved based on the Assumptions or Cytogen requests additional
services (each being, a "Modification") then the scope of services may be
amended as provided in paragraph (b) of this Section 6.
(b) In the event a Modification is identified by Cytogen or by
Laureate, the identifying Party shall notify the other Party as soon as is
reasonably possible. Laureate shall use reasonable efforts to provide the
Customer with a change order containing an estimate of the required adjustments
to the Service Fees within [**] of receiving or delivering such notice (the
"Change Order"). The Customer shall use its best efforts to respond in writing
to such Change Order promptly. If Customer does not approve such Change Order
and has not terminated this Agreement and the Program in accordance with Section
22 but wants the Program to be modified to take into account the Modification,
then Customer and Laureate shall use commercially reasonable efforts to agree on
a Change Order that is mutually acceptable. If practicable, Laureate may, in its
discretion, continue to work on the Production Campaign but
9
Laureate shall not be obligated to continue to work on the Production Campaign
during any such negotiations. Laureate shall not commence work with respect to a
Change Order unless authorized in writing by Cytogen.
8. Materials Delivery; Testing.
---------------------------
(a) All costs and expenses of any nature or kind whatsoever with
respect to Cytogen Supplied Materials or the shipment and delivery thereof to
the Facility shall be borne and paid by Cytogen in accordance with the terms and
conditions agreed to by Cytogen with the vendor and/or carrier, as applicable,
following receipt of the vendor's or carrier's invoice.
(b) Title to all Cytogen Supplied Materials shall remain in Cytogen
notwithstanding the storage and Laureate's possession thereof at the Facility.
Laureate shall use reasonable care to maintain any such Cytogen Supplied
Materials stored at Laureate's facility in accordance with all applicable laws,
rules, procedures and regulations including, but not limited to, cGMPs.
(c) Cytogen agrees to deliver or cause to be delivered to the
Facility such of the Cytogen Supplied Materials as are necessary to perform or
complete a process or activity part of the Manufacturing Procedures not less
than [**] nor more than [**] prior to the scheduled performance of such process
or activity, subject to the timely notification by Laureate of the need for such
materials.
(d) Following receipt of a Cytogen Supplied Material at the Facility,
Laureate shall perform the applicable analysis thereof or test thereon provided
for in the Incoming Acceptance Tests. Laureate shall promptly provide the
written results of such tests to Cytogen. Cytogen shall promptly review the test
results to determine conformity to the
10
Specifications of the Cytogen Supplied Material. Laureate shall not release the
Cytogen Supplied Materials for performance of the Services until Cytogen has
notified Laureate, in writing, that the Cytogen Supplied Materials meet the
Specifications based upon the results of such testing.
(e) In the event that either party determines that the Cytogen
Supplied Material does not meet Specifications or is otherwise unsuitable for
use in connection with the production of ▇▇▇▇▇▇ ▇▇▇▇▇▇▇, ▇▇▇-▇▇▇, ▇▇▇-▇▇▇,
Filled ProstaScint Product or Filled Sodium Acetate Product, such party shall
promptly notify the Cytogen Contact Individual or Laureate Contact Individual
(each as hereinafter defined), as the case may be, of such determination and the
results of the applicable analyses or tests performed.
(f) In the event that either party provides notice under paragraph
7(e), Cytogen shall promptly inform Laureate in writing of the action it wishes
Laureate to take with respect to the Cytogen Supplied Material in question,
including reanalysis, retesting, disposal, return or such other action as
otherwise specified by Cytogen. Costs incurred by Laureate under this paragraph
7(e) shall be invoiced to Cytogen in accordance with paragraph 3 hereof.
(g) Cytogen shall use its reasonable commercial efforts to deliver or
cause to be delivered to the Facility, Cytogen Supplied Material in replacement
of any material which does not meet Specifications or is otherwise unsuitable in
the production of ▇▇▇-▇▇▇, ▇▇▇-▇▇▇, Filled ProstaScint Product or Filled Sodium
Acetate Product to the end that the date scheduled by Laureate for the use of
such Cytogen Supplied Product in connection with the performance of a
Manufacturing Procedure is maintained.
(h) In the event a Cytogen Supplied Material fails to meet
Specifications and Cytogen is unable to timely deliver or cause to be delivered
to the Facility the
11
applicable Cytogen Supplied Material in replacement thereof so as to maintain
the date scheduled by Laureate (as notified to Cytogen under paragraph 7(c)) for
use of such Cytogen Supplied Product in connection with the performance of a
Manufacturing Procedure, then Laureate may, in its discretion and without
liability for any delay in the manufacture of ▇▇▇▇▇▇ ▇▇▇▇▇▇▇, ▇▇▇-▇▇▇, ▇▇▇-▇▇▇,
Filled ProstaScint Product and Filled Sodium Acetate Product, revise the Target
Project Timeline and give notice of such revised schedule to Cytogen to the end
that Laureate may perform any commitment Laureate may have to any third party or
Affiliate with respect to utilization of the Facility as permitted under this
Agreement; provided, however, that Laureate will use commercially reasonable
efforts to attempt to negotiate to defer the performance of any such commitment
to a third party or Affiliate to the end that Laureate may perform the Services
required with respect to Laureate's order under paragraph 2(b) on a priority
basis. Notwithstanding the foregoing, when the Cytogen Supplied Materials or
Product Dedicated Equipment that are compliant with the Specifications have been
provided to Laureate, Laureate shall use commercially reasonable efforts to
complete the Production Campaign in accordance with the Target Project Timeline
(appropriately adjusted to account for any delays).
(i) The applicable provisions of the Quality Agreement shall be
complied with in the event Laureate utilizes the services of any third party
sub-contractors in connection with Laureate's performance of this Agreement.
Cytogen shall pre-approve, in writing, any such third party sub-contractors, who
have not previously been approved by Cytogen, to be utilized by Laureate.
(j) Cytogen shall own all data relating to the Services and
Production Campaign performed by Laureate pursuant to the terms hereof. All
original documents for the Production Campaign will remain with Laureate, with
Cytogen receiving photocopies thereof.
12
9. Payment Dates; Late Payments. (a) Invoices by Laureate with respect to
----------------------------
amounts due in respect of paragraph 3 shall be payable upon such term as are set
forth in paragraph 3 hereof.
(b) Undisputed invoices due for Services performed in accordance with
Quality Agreement due pursuant hereto and not timely paid shall bear interest at
the rate of [**] on the unpaid balance thereof.
(c) Time is of the essence with request to payments due hereunder.
Unless otherwise specified herein, in the event that an invoice remains unpaid
for [**] following written notice by Laureate to Cytogen of such failure to pay,
Laureate may, in addition to its rights under paragraph 16 hereof, (i) suspend
the performance of its obligations hereunder with respect to the manufacture of
▇▇▇▇▇▇ ▇▇▇▇▇▇▇, ▇▇▇-▇▇▇, ▇▇▇-▇▇▇, Filled ProstaScint Product and/or Filled
Acetate Product until such time as payment is made and (ii) in the event of such
suspension, Laureate may exercise its right, as provided for in paragraph 7(i),
to revise the Target Project Timeline.
10. Regulatory Matters and Approvals; Order Dates. (a) Laureate agrees to
----------------------------------------------
use its commercially reasonable efforts to the end that Laureate has the
capability to perform the Services and the Manufacturing Procedures to be
utilized in connection with the performance of Production Campaign with respect
to the end of producing the [**] of ProstaScint not later than the date
specified in the Target Project Timeline.
(b) Cytogen agrees that it shall not, with respect to an order of
Filled ProstaScint Product or Filled Sodium Acetate Product, specify a date for
the fulfillment of all or part of such order inconsistent with Laureate's
capability to perform at the Facility a
13
Manufacturing Procedure necessary in connection with the fulfillment thereof
prior to the date provided for in the Target Project Timeline.
(c) In connection with this Agreement the parties have
contemporaneously entered into and delivered a Quality Agreement, with respect
to the quality and regulatory procedures and responsibilities of the parties
hereunder with respect to the production of Filled ProstaScint Products and
Filled Sodium Acetate Products. The Quality Agreement does, inter alia, provide
for, among other things, Cytogen's responsibility for approving the release from
storage and use of each Cytogen Supplied Material in connection with the
production of Filled ProstaScint Product and Filled Sodium Acetate Product, any
intermediate compounds produced in the course of the performance of a
Manufacturing Procedure, the release for shipping of Filled ProstaScint Product
and Filled Sodium Acetate Product from the Facility, and Cytogen's
responsibility for all regulatory approval or activities necessary in connection
with the Manufacturing Procedures, and shall further specify Cytogen's right to
inspect the Facility, the obligations of the parties upon any FDA inspection of
the Facility, all records to be maintained by each party with respect to the
manufacture and production of Filled ProstaScint Product and Filled Acetate
Product, including without limitation, Batch production records, in-process test
data, environmental monitoring data, testing data by Lot for Filled ProstaScint
Product, Filled Sodium Acetate Product or intermediates and such of the
foregoing as shall appear on invoices with respect to Filled ProstaScint Product
or Filled Sodium Acetate Product released for shipment by Cytogen.
(d) Cytogen acknowledges that the [**] Process ("[**] Process"), and
[**] Process ("FP Filling Process") are not currently approved by FDA as part of
the ProstaScint manufacturing process. Cytogen will take appropriate actions to
provide for the proper
14
notification to FDA regarding these process changes, and will provide copies of
any such notifications sent by Cytogen to FDA, to Laureate. Cytogen acknowledges
that the [**] Process and [**] Process are the processes Cytogen has specified
Laureate to perform as part of the Manufacturing Procedures to be supplied by
Cytogen to Laureate pursuant to this Agreement. Laureate shall have no liability
of any nature or kind whatsoever by reason of its performance of its obligations
hereunder which arises from, or is the result of, Laureate's utilization of the
[**] Process and [**] Processes as Manufacturing Procedures in connection with
the manufacture of ▇▇▇-▇▇▇, ▇▇▇-▇▇▇, Filled ProstaScint Product or Filled Sodium
Acetate Product. Laureate shall maintain the [**] bioreactor and [**] machine in
working order and in compliance in all material respects with all applicable
laws, rules and regulations.
11. Stability Testing; Shipping. Laureate shall deliver the Filled
-----------------------------
ProstaScint Product and the Filled Sodium Acetate Product EXW (Incoterms 2000)
at the Facility to a carrier designated by Cytogen. Cytogen shall pay all
shipping charges associated with the delivery of the Filled ProstaScint Product
and the Filled Sodium Acetate Product. Title to the CYT-351, Filled ProstaScint
Product and Filled Sodium Acetate Product shall pass to Cytogen upon Laureate's
release, and Cytogen's acceptance, of the forgoing materials. Unless otherwise
agreed, Cytogen agrees to take all commercially reasonable actions necessary to
the end that Filled ProstaScint Product and Filled Sodium Acetate Product are
shipped from the Facility not later than [**] following the release by Cytogen
of the Filled ProstaScint Product and the Filled Sodium Acetate Product for
shipment under the terms of the Quality Agreement. Any extensions are to be
agreed upon in writing with Cytogen's recognition that it will be assessed
Laureate's listed storage fees which are set forth in Appendix 1. Laureate will
perform stability testing on behalf of Cytogen according to Cytogen's written
instructions.
15
12. Cytogen's Covenants, Representation and Warranties. Cytogen covenants,
--------------------------------------------------
represents and warrants to and with Laureate as follows:
(a) Cytogen shall use its commercially reasonable efforts to
dutifully and timely perform its obligations and responsibilities hereunder,
including, without limitation, any obligation or responsibility provided for in
the Manufacturing Procedures, Incoming Acceptance Tests and the Quality
Agreement.
(b) Cytogen shall use its commercially reasonable efforts to assure
that all Cytogen Supplied Materials, when received at the Facility, (i) are
approved by Cytogen for use in connection with the manufacture of ▇▇▇-▇▇▇,
▇▇▇-▇▇▇, Filled ProstaScint Product and Filled Sodium Acetate Product in
accordance with cGMP, (ii) meet Specifications and are suitable for use in the
manufacture of ▇▇▇▇▇▇ ▇▇▇▇▇▇▇, ▇▇▇-▇▇▇, ▇▇▇-▇▇▇, Filled ProstaScint Product or
Filled Sodium Acetate Product, (iii) comply with Cytogen's quality standards and
(iv) each such Cytogen Supplied Material which is subject to the provisions of
the Food, Drug and Cosmetics Act, 21 USCS Section 301, et seq. ("FDC Act"), as
-- ---
and when received at the Facility, is not adulterated or misbranded within the
meaning of the FDC Act or any applicable state law in which the definitions of
adulteration of misbranding are substantially the same as those contained in the
FDC Act, or an article which may not, under the provisions of the FDC Act, be
introduced into interstate commerce.
(c) Cytogen shall not authorize for shipment from the Facility Filled
ProstaScint Product or Filled Sodium Acetate Product subject to the provisions
of the FDC Act, which is adulterated or misbranded within the meaning of the FDC
Act or any applicable state law in which the definitions of adulteration and
misbranding are substantially the same as those
16
contained in the FDC Act, or an article which may not, under the provisions of
the FDC Act, be introduced into interstate commerce.
(d) To the best of Cytogen's knowledge, Laureate's manufacture and
production of ▇▇▇▇▇▇ ▇▇▇▇▇▇▇, ▇▇▇-▇▇▇, ▇▇▇-▇▇▇, Filled ProstaScint Product or
Filled Acetate Product, including, without limitation, Laureate's performance of
its Services hereunder in conformity with the Manufacturing Procedures, the
Incoming Acceptance Tests and the Quality Agreement and Cytogen's marketing,
sale, distribution and promotion of Filled ProstaScint Product and Filled Sodium
Acetate Product do not infringe or violate the intellectual property rights of
any third party.
(e) Cytogen has all requisite corporate power and authority to enter
into this Agreement and perform its obligations and responsibilities hereunder,
including, without limitation, all such obligations and responsibilities
provided for in the Manufacturing Procedures, Incoming Acceptance Tests and the
Quality Agreement.
13. Laureate's Covenants, Representations and Warranties; Limited
----------------------------------------------------------------------
Liability. (a) Laureate covenants, represents and warrants to and with Cytogen
---------
as follows:
(i) Laureate's maintenance of the Facility and performance of
manufacturing and other services hereunder shall conform in all material
respects with all applicable cGMPs and Cytogen's written instructions
including without limitation, the Specifications.
(ii) Laureate shall not ship any Filled ProstaScint Product, Filled
Sodium Acetate Product or any intermediate manufactured or formed in the
course of production of Filled ProstaScint Product and Filled Sodium
Acetate
17
Product unless the release for shipment and subsequent shipment have been
authorized in writing by Cytogen.
(iv) Laureate has all requisite power and authority to enter into this
Agreement and perform its obligations hereunder, including, without
limitation, all such obligations and responsibilities provided for in the
Manufacturing Procedures, Incoming Acceptance Tests and the Quality
Agreement.
(v) Laureate shall use commercially reasonable efforts to perform (in
accordance with the Target Project Timeline) its obligations and
responsibilities hereunder, including without limitation, any obligation or
responsibility provided for in the Manufacturing Procedures, Incoming
Acceptance Tests and the Quality Agreement.
(vi) Laureate will not knowingly infringe the intellectual property
rights on any third party during the performance of the Services hereunder.
(b) EXCEPT AS PROVIDED IN PARAGRAPH 12(a), LAUREATE MAKES NO OTHER
REPRESENTATION AND WARRANTY OF ANY KIND, EXPRESSED OR IMPLIED, AS TO
MERCHANTABILITY, FITNESS FOR PARTICULAR PURPOSE OR ANY OTHER MATTER WITH RESPECT
TO FILLED PROSTASCINT PRODUCT AND/OR FILLED SODIUM ACETATE PRODUCT OR ANY
INTERMEDIATE FORMED IN THE COURSE OF MANUFACTURE OF FILLED PROSTASCINT PRODUCT
AND/OR FILLED SODIUM ACETATE PRODUCT, OR ANY OTHER MATTER WITH RESPECT TO FILLED
PROSTASCINT PRODUCT OR FILLED SODIUM ACETATE
18
PRODUCT WHETHER USED ALONE OR IN COMBINATION WITH OTHER SUBSTANCES.
(c) In the event of any failure of Laureate to perform in conformity
with its covenants, representations and warranties hereunder, Laureate shall,
[**], replace such quantity of Filled ProstaScint Product and/or Filled Sodium
Acetate Product which Cytogen does not release for shipment consistent with
Cytogen's covenant, representation and warranty made in paragraph 11(c) hereof
because of such failure as promptly as practicable after receiving the Cytogen
Supplied Materials necessary to manufacture such replacement quantity. The cost
of such Cytogen Supplied Materials, including the cost and expense of Cytogen's
delivering or causing the same to be delivered to the Facility [**] from amounts
due under this Agreement. In the event that no amount is then due under this
Agreement by Cytogen to Laureate, then [**] for the cost of such Cytogen
Supplied Material, including without limitation, any costs [**] with respect to
the shipping and delivery thereof. [**] with respect to [**] of invoices
rendered by [**] in accordance with this paragraph 12(c). THE FOREGOING SHALL BE
CYTOGEN'S EXCLUSIVE REMEDY HEREUNDER IN THE EVENT OF ANY FAILURE BY LAUREATE TO
PERFORM IN CONFORMITY WITH ITS COVENANTS, REPRESENTATIONS, AND WARRANTIES
HEREUNDER.
(d) Laureate shall not be liable for, and Cytogen assumes
responsibility for, all personal injury and property damage resulting from the
handling, possession or use of Filled ProstaScint Product and Filled Sodium
Acetate Product following Cytogen's release of same for shipment and Laureate's
placement of same with a carrier for shipment. In no event shall either party be
liable to the other party for special, incidental or
19
consequential damages or loss of profits whether the claim giving rise to the
same is for breach of a covenant, warranty or representation, is in contract,
negligence, strict liability or otherwise.
(e) It is understood and agreed that Laureate's obligations with
respect to performance of any [**] hollow fiber runs, purification of the
material so produced, conjugated and filled [**] are to perform the same in
conformance with the Manufacturing Procedures and test for conformance to
Specifications as provided in the Quality Agreement. Laureate shall be liable
for any failure of its performance of the Fiber-Run Procedures to yield CYT-351
of any specific quality specification, or a reasonable quantity of CYT-351 or a
reasonable quantity of Filled ProstaScint Product (defined as approximately [**]
from a single conjugation Batch of CYT-351) only in the event Laureate's
performance of the [**]was not in conformance with the Manufacturing Procedures.
In such event, the provisions of paragraph 12(c) shall apply.
14. Indemnities. (a) Cytogen agrees to indemnify and hold Laureate
-----------
harmless from any damages, liabilities, losses and expenses (including, without
limitation, reasonable attorneys' fees in seeking indemnification hereunder or
any claim by a third person) and amounts paid in settlement of any claim or suit
of any nature or kind whatsoever which may be sustained or suffered by Laureate
arising with respect to paragraph 9(d) hereof or arising out of, based upon or
by reason of, any Cytogen Supplied Material not Conforming to the covenant,
representation and warranty made by Cytogen in paragraph 11(b) at the time of
receipt at the Facility.
(b) In the event a Cytogen Supplied Material does not meet
Specifications or is otherwise unsuitable for use in the manufacture of ▇▇▇▇▇▇
▇▇▇▇▇▇▇, ▇▇▇-▇▇▇, ▇▇▇-▇▇▇, Filled ProstaScint Product or Filled Sodium Acetate
after the receipt
20
thereof at the Facility by reason of any action, act or activity by Laureate
which does not conform to the Cytogen's approved Specifications, Laureate SOPs,
Cytogen SOPs, cGMP, the Manufacturing Procedures, the Incoming Acceptance Tests
or the Quality Agreement (or Laureate's failure to act in conformity with any of
the foregoing), Laureate's obligation hereunder shall be to indemnify Cytogen
for the actual cost of the Cytogen Supplied Material in question and all costs,
fees and expenses incurred by Cytogen in delivering or causing the delivery of
the same to the Facility.
(c) Cytogen agrees to defend, indemnify and hold Laureate harmless
from any and all claims by third persons or governmental entities, damages,
liabilities, losses and expenses (including, without limitation, reasonable
attorney's fees in seeking indemnification hereunder or defending any claim by a
third person or a governmental entity) and amounts paid in settlement of any
claim or suit of any nature or kind whatsoever relating to the sale of the
Filled ProstaScint Product or Filled Sodium Acetate Product.
(d) The obligations of the indemnifying party under this paragraph 13
are conditioned upon the delivery of written notice to the indemnifying party of
any potential claim arising under this paragraph 14 ("Claim") promptly after the
indemnified party becomes aware of such claim. The indemnifying party shall
manage and control, at its sole expense, the defense of the Claim and its
settlement. The indemnified party shall cooperate with the indemnifying party
and may, at its option and expense, be represented in any such action or
proceeding. The indemnifying party shall not be liable for any litigation costs
or expenses incurred by the indemnified party without indemnifying party's prior
written authorization. In addition, the indemnifying party shall not be
responsible for any liability resulting from any
21
settlement or compromise by the indemnified party made without the indemnifying
party's prior written consent.
15. Contact Individuals. Each of Laureate and Cytogen shall designate an
--------------------
individual ("Laureate Contact Individual" or "Cytogen Contact Individual," as
applicable) who shall be responsible for the day-to-day contacts between the
parties and who shall receive copies of all written correspondence, notices and
the like with respect to a party's performance of its obligations and
responsibilities hereunder.
16. No Biohazards. The Laureate Contact Individual and the Cytogen Contact
-------------
Individual will establish a standard operating procedure to identify materials
that are or may be biohazardous. Materials so identified may not be brought into
the Facility and may not be a Cytogen Supplied Material.
17. Termination. (a) In addition to termination resulting from the
-----------
expiration of this Agreement in accordance with paragraph 2, this Agreement can
be terminated by Laureate for nonpayment of any sums due hereunder (remaining
unpaid for more than [**] following receipt by Cytogen of notice by Laureate),
or by either party with at least [**], advance written notice:
(i) on account of a material breach of this Agreement by the other
party, unless the offending party cures the violation before expiration of
the notice period; or
(ii) when the other party makes a general assignment for the benefit
of its creditors, has a custodian, receiver or any trustee appointed for it
or a substantial part of its assets or commences any voluntary proceeding
under any bankruptcy law; or
22
(iii) when a court having jurisdiction over the other party shall
enter a decree or order for relief in any involuntary case under applicable
bankruptcy law and such decree or order shall continue unstayed and in
effect for a period of [**] or more.
(b) Termination for any reason by either party under this paragraph
16 will not prejudice that party's remaining contractual rights, including,
without limitation, rights to damages, nor terminate the obligations set forth
in paragraphs 3, 4, 14 and 18 hereof, to the extent such obligations have
accrued according to those terms.
18. Insurance. Throughout the term of this Agreement Cytogen shall obtain
---------
and maintain in full force and effect product liability insurance (issued by an
insurance company licensed to do business in the State of New Jersey) in the
amount of [**] and cause Laureate to be named as an additional insured thereon.
Laureate now maintains general liability insurance and property damage liability
insurance in the amount of [**] for the Facility, and shall cause Cytogen to be
named as an additional insured thereon. Each party shall, at all times during
the term of this Agreement, maintain in full force and effect and on deposit at
the office of the other party, a Certificate of Insurance or a duplicate
original of the insurance policy required above, together with evidence of
payment of all premiums therefor. Each such policy shall provide that it shall
not be cancelable without at least [**], prior written notice to the other
party.
19. Confidentiality. All written information (regardless of media)
---------------
provided by either party to the other hereunder including, but not limited to,
volume requirements, pricing, delivery schedules and process data formulae,
regulatory submissions, know-how and other information, including without
limitation, proprietary information and materials (whether or not patentable)
regarding a party's technology, is the disclosing party's confidential
proprietary
23
information. The receiving party agrees not to disclose any such information or
use such information except for purposes of performance hereunder, for a period
of [**] after the termination of this Agreement with regard to business related
information, and for a period of [**] with regard to technical information,
provided that the receiving party may use or disclose any such information that
it can demonstrate through written records: (1) is already known to it at the
time of disclosure to the receiving party; (2) becomes publicly known through no
fault of the receiving party; or (3) is disclosed to the receiving party by a
third party who is free to make such disclosure. The parties each agree that
they shall provide confidential information received from the other party only
to their respective employees, consultants, investors, prospective investors and
advisors who have a need to know and have an obligation to treat such
information and materials as confidential under terms no less restrictive than
those set forth herein. All confidential and proprietary information disclosed
hereunder shall be, at the option of the disclosing party, immediately returned
to the disclosing party, or destroyed (and such destruction certified by an
officer of the receiving party) upon the earlier of termination of this
Agreement, or the request of the disclosing party. Notwithstanding anything set
forth herein to the contrary, this paragraph 18 shall not prohibit the receiving
party from disclosing confidential or proprietary information of the disclosing
party that is required to be disclosed by the receiving party to comply with
applicable laws, including without limitation the rules and regulations
promulgated by FDA or the United States Securities and Exchange Commission, or
to comply with governmental regulations, provided that the receiving party
provides prior written notice of such disclosure to the disclosing party and
takes reasonable and lawful actions to avoid and/or minimize the degree of such
disclosure. Any announcements or similar publicity with respect to the execution
of this Agreement shall be agreed upon between the parties in advance of such
24
announcement. The parties agree that any such announcement will not contain
confidential business or technical information of the other party. Except as
otherwise expressly agreed between the parties in writing, no right is granted
to a party to use in any manner the name of the other party or any other trade
name or trademark of the other party.
20. Notices. All notices required to be given under this Agreement shall
-------
be deemed given when delivered personally or when mailed by registered or
certified mail, return receipt requested, or when sent by Federal Express or an
equivalent overnight delivery service, addressed to the parties at their
respective addresses set forth below or to such other addresses at which notice
shall have been duly given. It is understood and agreed that this paragraph 19
is not intended to govern the day-to-day business communications necessary
between the parties in performing the duties, in due course, under the terms of
this Agreement.
IF TO CYTOGEN:
▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇▇▇▇
Senior Vice President, Operations
Cytogen Corporation
▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇ ▇▇▇▇
▇▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇
Fax No.: ▇-▇▇▇-▇▇▇-▇▇▇▇
WITH A COPY TO:
▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇, Esq.
Senior Vice President and General Counsel
Cytogen Corporation
▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇ ▇▇▇▇
▇▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇
Fax No.: ▇-▇▇▇-▇▇▇-▇▇▇▇
25
IF TO LAUREATE:
▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇, Ph.D.
President and Chief Executive Officer
Laureate Pharma, Inc.
▇▇▇ ▇▇▇▇▇▇▇ ▇▇▇▇ ▇▇▇▇
▇▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇
Fax No.: ▇-▇▇▇-▇▇▇-▇▇▇▇
WITH A COPY TO:
Safeguard Scientifics, Inc.
800 The Safeguard Building
▇▇▇ ▇▇▇▇▇ ▇▇▇▇ ▇▇▇▇▇
▇▇▇▇▇, ▇▇ ▇▇▇▇▇
Attn: Legal Department
Fax: (610) 975 - 0261
21. Non-Exclusivity. (a) Laureate may render manufacturing and other
---------------
services to any other party and use the Facility and Laureate personnel in
furtherance of rendering such services whether or not such third party is in
competition with Cytogen. Nothing herein limits or restricts Cytogen from using
any other party in the manufacture and supply of any materials, including the
materials to be supplied by Cytogen hereunder.
(b) Neither party shall, directly or through its representatives,
solicit for employment any officer, director, employee or consultant of the
other party during the term of this Agreement and for a period of [**]
thereafter.
22. Entire Agreement. (a) The Manufacturing Procedures, the Incoming
-----------------
Acceptance Tests and the Quality Agreement are deemed to be part this Agreement.
(b) This Agreement constitutes the entire agreement between the
parties in respect of the subject matter of this Agreement and supercedes all
previous oral or written negotiations, commitments, agreements, transactions or
understandings with respect to the subject matter hereof. No modifications to or
supplementation of this Agreement, whether
26
contained in any purchase order, confirmation or otherwise, shall be effective
unless made in writing and signed by the party to be charged with modification.
23. Governing Law. This Agreement shall be interpreted in accordance with
-------------
the laws of New Jersey where it is deemed to have been executed and where each
party has a place of business.
24. Assignment. No right or obligation of either party hereunder shall be
----------
assignable without the prior written agreement of the other party, which shall
not be unreasonably withheld or delayed; otherwise this Agreement shall be
binding upon and inure to the benefit of the parties hereto and their respective
permitted successors and assigns. For purposes of this Section 23, an assignment
shall include the merger or consolidation of any party with another entity or
the sale of all or substantially all of such party's equity interests.
25. Independent Contractors. The parties are independent contractors, and
-----------------------
this Agreement shall not be construed to create between Laureate and Cytogen any
other relationship such as, by way of example only, that of employer-employee,
principal-agent, joint-venturer, co-partners or any similar relationship, the
existence of which is expressly denied by the parties hereto.
26. No Waiver. A party's failure to require another party to comply with
---------
any provision of this Agreement shall not be deemed a waiver of such provision
or any other provision of this Agreement.
27. Force Majeure. No party shall be liable for the failure to perform its
-------------
obligations under this Agreement if such failure is occasioned by a contingency
beyond such party's reasonable control, including, but not limited to, acts of
terrorism, strikes or other labor disturbances, lockouts, riots, wars, fires,
floods or storms. A party claiming a right to excuse
27
performance under this paragraph 26 shall immediately notify the other party in
writing of the extent of its inability to perform, which notice shall specify
the occurrence beyond its reasonable control that prevents such performance and
an estimate of the time that the inability to perform is anticipated to last.
28. Third Parties. No person not a party to this Agreement not an
-------------
Affiliate of a party to this Agreement shall have or acquire any rights by
reason of this Agreement, nor shall any party to this Agreement have any
obligation or liabilities to such other person by reason of this Agreement.
29. Interpretation. The parties hereto acknowledge and agree that: (i)
--------------
each party and its counsel have reviewed and negotiated the terms and provisions
of this Agreement and have contributed to its revision; (i) the rule of
construction to the effect that any ambiguities are resolved against the
drafting party shall not be employed in the interpretation of this Agreement;
and (iii) the terms and provisions of this Agreement shall be construed fairly
as to all parties hereto and not in favor of or against any party, regardless of
which party was generally responsible for the preparation of this Agreement.
30. Singular Terms. Except as otherwise expressly provided herein or
--------------
unless the context otherwise requires, all references to the singular shall
include the plural as well.
31. Headings. The headings herein are inserted as a matter of convenience
--------
only, and do not define, limit or describe the scope of this Agreement or the
intent of the provisions hereof and shall not be used to interpret or construe
the terms and provisions of this Agreement.
32. Counterparts. This Agreement may be executed simultaneously in two or
------------
more counterparts, each of which shall be deemed an original, and all of which,
when taken
28
together, shall constitute one and the same instrument. The signature of any
party to any counterpart shall be deemed a signature to, and may be appended to,
any other counterpart.
33. Severability. This Agreement is intended to be valid and effective
------------
under any applicable law and, to the extent permissible under applicable law,
shall be construed in a manner to avoid violation of or invalidity under any
applicable law. Should any provisions of this Agreement be or become invalid,
illegal or unenforceable under any applicable law, the other provisions of this
Agreement shall not be affected and shall remain in full force and effect and,
to the extent permissible under applicable law, any such invalid, illegal or
unenforceable provision shall be deemed amended lawfully to conform with the
intent of the parties. Nothing in this paragraph 33 shall preclude a party
hereto from bringing an action for failure of consideration in the event a
material provision of this Agreement shall be held invalid, illegal or
unenforceable.
* * * * * * * *
29
IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be
executed by their duly authorized representatives.
LAUREATE PHARMA, INC. CYTOGEN CORPORATION
By /s/ ▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇, Ph.D. By /s/ ▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇
--------------------------- -------------------------------------
▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇, Ph.D. ▇▇▇▇▇▇▇ ▇. ▇▇▇▇▇▇
President & Chief Executive Officer President and Chief Executive Officer
30
APPENDIX 1
Service Fees
The Service Fees shall be payable as follows:
[**].
31
