EXHIBIT 10.1
Confidential Materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
MANUFACTURING AGREEMENT
MANUFACTURING AGREEMENT, dated September 10, 2004, by and between CYTOGEN
CORPORATION, a Delaware corporation ("Cytogen") and LAUREATE PHARMA L.P., a
Delaware limited partnership ("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
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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 [**] hollow-fiber
runs; (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 XXX-000, XXX-000, 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).
(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 [**].
(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.
(p) "Lot" means a Batch or a specific identified portion of a Batch of
XXX-000, XXX-000 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 XXX-000, XXX-000, 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 [**], such
that [**] would be staggered approximately [**] or less apart, and [**] would be
similarly time-staggered; (ii) [**] purifications, each of the combination of
[**] of the [**] Hollow-Fiber Bioreactor Runs, to generate CYT-351; (iii) a
total of [**] conjugations of the CYT-351 to generate [**] Lots of CYT-356. Only
[**] conjugations 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 [**] lots of conjugated
antibody in vials, approximately [**] vials per lot; and (v) [**] 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.
(t) "ProstaScint" means the compound capromab pendetide formulated by
conjugating the murine monoclonal antibody CYT-351 to the linker-chelator
[**] (CYT-063).
(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
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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 all [**]
Lots of conjugated antibody and the Filled ProstaScint Product and the Sodium
Acetate Product resulting therefrom 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 completion of the [**] Lot shall be on or before [**].
3. Consideration and Payment. In consideration of Laureate's performance
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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 thirty (30) 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 [**]. Cytogen shall receive a
credit against the Service Fees in the amount of [**] that has been prepaid by
Cytogen against the Service Fees for materials and preparation of cGMP
documentation purchased by Cytogen prior to the date hereof. Such credit shall
be applied against amounts owed by Cytogen on the first invoices that are
received from Laureate under the terms of this Agreement.
4. Liquidated Damages. Subject to the provisions hereof, in the event
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Cytogen does not order, or cancels the order for, [**] hollow fiber runs,
Cytogen agrees to pay Laureate liquidated damages of [**]. In such event,
Cytogen shall pay Laureate [**] of this liquidated damages [**] to Laureate no
later than [**]. The [**] of the liquidated damages [**] will be paid no later
than [**].
5. Performance of Services; Other Assistance; FDA Fees. (a) All Services
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shall be performed by Laureate at Laureate's facility in Princeton, NJ in
accordance with the Quality Agreement.
(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
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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 Xxxxxx Xxxxxxx, XXX-000, XXX-000, 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 Xxxxxx Xxxxxxx,
XXX-000, XXX-000, 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.
(c) Cytogen has provided Laureate in writing with the Specifications
for each of Xxxxxx Xxxxxxx, XXX-000, XXX-000, 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 ten (10) days 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) Laureate shall commence and complete the Production Campaign in
accordance with the Target Project Timeline attached hereto as Appendix 2 (the
"Target Project Timeline") and acknowledges that time is of the essence with
respect to the production
and delivery of XXX-000, XXX-000, Filled ProstaScint Product and Filled Sodium
Acetate Product.
(h) Cytogen has provided to Laureate the Cytogen SOPs, Specifications
and Batch documentation in writing.
7. Materials Delivery; Testing.
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(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 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 Xxxxxx Xxxxxxx, XXX-000, XXX-000,
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 XXX-000, XXX-000, 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 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 Xxxxxx Xxxxxxx,
XXX-000, XXX-000, 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.
8. Payment Dates; Late Payments. (a) Invoices by Laureate with respect to
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amounts due in respect of paragraph 3 or 4 shall be payable upon such term as
are set forth in paragraphs 3 and 4, respectively, hereof.
(b) 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
Xxxxxx Xxxxxxx, XXX-000, XXX-000, 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.
9. Regulatory Matters and Approvals; Order Dates. (a) Laureate agrees to
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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 first Batch 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 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"), is
not currently approved by FDA as part of the ProstaScint manufacturing process.
Cytogen will take appropriate actions to provide for the proper notification to
FDA regarding this process change, and will provide copies of any such
notifications sent by Cytogen to FDA, to Laureate. Cytogen acknowledges that the
[**] Process is the process 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 as
a Manufacturing Procedure in connection with the manufacture of XXX-000,
XXX-000, Filled ProstaScint Product or Filled Sodium Acetate Product. Laureate
shall maintain the [**] in working order and in compliance in all material
respects with all applicable laws, rules and regulations.
10. Stability Testing; Shipping. Laureate shall deliver the Filled
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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 thirty (30) days 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.
11. Cytogen's Covenants, Representation and Warranties. Cytogen covenants,
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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 XXX-000,
XXX-000, Filled ProstaScint Product and Filled Sodium Acetate Product in
accordance with cGMP, (ii) meet Specifications and are suitable for use in the
manufacture of Xxxxxx Xxxxxxx, XXX-000, XXX-000, 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 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 Xxxxxx Xxxxxxx, XXX-000, XXX-000, 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.
12. Laureate's Covenants, Representations and Warranties; Limited
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Liability. (a) Laureate covenants, represents and warrants to and with Cytogen
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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.
(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
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.
(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 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, at
its sole cost and expense, 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 may be deducted by Cytogen from amounts due under this Agreement.
In the event that no amount is then due under this Agreement by Cytogen to
Laureate, then Cytogen may invoice Laureate for the cost of such Cytogen
Supplied Material, including without limitation, any costs incurred by Cytogen
with respect to the shipping and delivery thereof. Time is of the essence with
respect to Laureate's payment of invoices rendered by Cytogen 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 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 (collectively, "Fiber-Run
Procedures") 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 (defined as approximately [**] purified in a
single purification from [**] hollow-fiber reactor runs) or a reasonable
quantity of Filled ProstaScint Product (defined as approximately [**] vials from
a single conjugation Batch of CYT-351) only in the event Laureate's performance
of the Fiber-Run Procedures was not in conformance with the Manufacturing
Procedures. In such event, the provisions of paragraph 12(c) shall apply.
13. 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 Xxxxxx
Xxxxxxx, XXX-000, XXX-000, Filled ProstaScint Product or Filled Sodium Acetate
after the receipt 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 [**].
(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 13 ("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 settlement or compromise by the
indemnified party made without the indemnifying party's prior written consent.
14. 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.
15. 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.
16. 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 ninety (90) days following receipt by Cytogen of notice by
Laureate), or by either party with at least sixty (60) days, 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
(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 ninety (90) days 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.
17. 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 thirty (30) days, prior written notice to the
other party.
18. Confidentiality. All written information 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 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 the 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
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.
19. 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:
Xxxxxxx X. Xxxxxxxxx
Senior Vice President, Operations
Cytogen Corporation
000 Xxxxxxx Xxxx Xxxx
Xxxxxxxxx, XX 00000
Fax No.: 0-000-000-0000
WITH A COPY TO:
Xxxxxxx X. Xxxxxx, Esq.
Senior Vice President and General Counsel
Cytogen Corporation
000 Xxxxxxx Xxxx Xxxx
Xxxxxxxxx, XX 00000
Fax No.: 0-000-000-0000
IF TO LAUREATE:
Xxxxxx X. Xxxxxx, Ph.D.
President
Laureate Pharma L.P.
000 Xxxxxxx Xxxx Xxxx
Xxxxxxxxx, XX 00000
Fax No.: 0-000-000-0000
WITH A COPY TO:
Xxxxxxxxxx Xxxxxxx PC
00 Xxxxxxxxxx Xxxxxx
Xxxxxxxx, Xxx Xxxxxx 00000
Attention: Xxxx X. Xxxxxxxx
Telephone: (000) 000-0000
Facsimile: (000) 000-0000
20. 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.
21. 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 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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 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.
27. 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.
28. 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.
29. 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.
30. 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.
31. 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 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.
32. 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 32
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.
* * * * * * * *
IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be
executed by their duly authorized representatives.
LAUREATE PHARMA L.P. CYTOGEN CORPORATION
By: Laureate Pharma Inc., its
General Partner
By /s/ Xxxxxx Xxxxxx By /s/ Xxxxxxx X. Xxxxxx
------------------------------ -------------------------------------
Xxxxxx Xxxxxx, PhD. Xxxxxxx X. Xxxxxx
President President and Chief Executive Officer
Appendix 1
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Appendix II
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