EXHIBIT 10.49
Confidential Materials omitted and filed separately with the
Securities and Exchange Commission. Asterisks denote omissions.
CONTRACT MANUFACTURING AGREEMENT
BY AND BETWEEN
LAUREATE PHARMA L.P.
AND
CYTOGEN CORPORATION
DATED
JANUARY 15, 2003
TABLE OF CONTENTS
Page
1. Definitions..........................................................1
2. Commencement; Expiration.............................................6
3. Consideration........................................................7
4. Payments.............................................................8
5. Performance of Services; Other Assistance; FDA Fees.................12
6. Manufacturing and Testing; Approvals; SOPs..........................13
7. Materials Delivery; Testing.........................................15
8. Payment Dates; Late Payments........................................19
9. Renovation Schedule; Regulatory Matters and Approvals;
Order Dates........................................................20
10. Stability Testing; Shipping.........................................22
11. Cytogen's Covenants, Representation and Warranties..................23
12. Laureate's Covenants, Representations and Warranties;
Limited Liability..................................................24
13. Indemnities.........................................................28
14. Contact Individuals.................................................30
15. No Biohazards.......................................................30
16. Termination.........................................................30
17. Insurance...........................................................32
18. Confidentiality.....................................................33
19. Notices.............................................................34
20. Non-Exclusivity.....................................................35
21. Entire Agreement....................................................36
22. Governing Law.......................................................36
23. Assignment..........................................................36
24. Independent Contractors.............................................37
25. No Waiver...........................................................37
26. Force Majeure.......................................................37
27. Third Parties.......................................................37
28. Interpretation......................................................38
29. Singular Terms......................................................38
30. Headings............................................................38
31. Counterparts........................................................38
32. Severability........................................................39
ii
MANUFACTURING AGREEMENT
-----------------------
MANUFACTURING AGREEMENT, dated January 15, 2003, 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
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 a single
[**] hollow-fiber run; (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 CYTll-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) ""Cytogen SOPs" means Cytogen's written standard operating
procedures to be utilized in connection with the manufacture, production
and in-process release testing of CYT-351, Filled ProstaScint Product and
Filled Acetate Product.
(d) "Cytogen Supplied Materials" means all ingredients, raw materials,
resins, components and supplies, except for water and facility derived
process gasses, required in connection with the production by Laureate of
CYT-351, Filled ProstaScint Product or Filled Sodium Acetate Product.
(e) "CYT-351" means the monoclonal antibody intermediate product which
is used in manufacturing ProstaScint.
(f) "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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(g) "Facility" means Laureate's manufacturing and filling premises
located in Princeton, New Jersey.
(h) "Facility Fee" means the fee for facility access and utilization
provided for in paragraph 3(a).
(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) "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.
3
(n) "Laureate SOPs" means Laureate's written standard operation
procedures utilized by Laureate in connection with its operational
activities at the Facility.
(o) "Lot" means a Batch or a specific identified portion of a Batch of
CYT-356 or sodium acetate, as applicable, which is produced in the course
of Laureate's performance of a single manufacturing production run.
(p) "Manufacturing Procedures" means the activities, processes,
procedures and instructions provided to Laureate by Cytogen pursuant to
paragraph 6(a) hereof and to be utilized by Laureate in the production of
CYT-351, Filled ProstaScint Product and Filled Sodium Acetate Product.
(q) "On Hand CYT" means the quantity of CYT-351 in the possession of
Cytogen on the date hereof and to be supplied by Cytogen to Laureate in
connection with Laureate's performance of the Primary Production Campaign.
(r) "Optional Production Campaign" means Laureate's performance of (i)
up to two (2) [**] hollow fiber runs to the end of producing CYT-351, (ii)
against Cytogen's order therefor, Laureate's performance of up to two (2)
conjugations of the quantity of CYT-351 produced pursuant to Laureate
performance of the [**] hollow fiber runs referenced in clause (i) of this
definition to the end of producing ProstaScint including all Services to
supply Cytogen with Filled ProstaScint Product and (iii) against Cytogen's
order therefor, Laureate's performance of up to two (2) sodium acetate
fills, each fill utilizing a volume of sodium acetate buffer solution as
specified in the Batch record to the end of supplying Cytogen with Filled
Sodium Acetate Product.
4
(s) "Primary Production Campaign" means Laureate's performance of (i)
two (2) conjugation runs utilizing the On Hand CYT to the end of producing
ProstaScint including all Services to supply Cytogen with Filled
ProstaScint Product and (ii) two (2) sodium acetate fills, each fill
utilizing a volume of sodium acetate buffer solution as specified in the
Batch record including all Services to the end of supplying 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
glycl-tyrosyl-(N-diethyltriaminepentaacetic acid)-lysine hydrochloride.
(u) "Services" means the activities undertaken by Laureate in the
course of Laureate's performance of the Primary Production Campaign and, if
applicable, the Optional Production Campaign or any part thereof.
(v) "Specifications" means Cytogen's approved specifications with
respect to CYT-351, CYT-356, 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.
5
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 Primary
Production Campaign.
(c) Cytogen shall have the option, such option to be exercised not
later than March 1, 2003, to order from Laureate the Services required to
be performed by Laureate in connection with Laureate's conduct of one (1)
or two (2) hollow fiber runs identified in clause (i) of the definition of
Optional Production Campaign, the number of such hollow fiber runs to be
notified to Laureate in the event of the exercise of the option granted
hereby.
(d) Subject to the provisions hereof, this Agreement, in the event
Cytogen does not exercise the option granted Cytogen pursuant to paragraph
2(c) hereof, shall expire on such date as Laureate has (i) completed the
Primary Production Campaign and (ii) the Filled ProstaScint Product and the
Sodium Acetate Product resulting therefrom have been shipped from the
Facility in accordance with paragraph 10(b) hereof.
(e) Subject to the provisions hereof, in the event Cytogen exercises
the option granted Cytogen pursuant to paragraph 2(c) hereof, Cytogen, in
its discretion, may order from Laureate the Services required to be
performed by Laureate in connection with Laureate's conduct of either or
both of the conjugation(s) and fill(s) described in clauses (ii) and (iii)
6
of the definition of Optional Production Campaign. In the event Cytogen
does not order either of the Services as aforesaid, on or before September
1, 2003 then this Agreement shall expire ten (10) business days thereafter
unless Cytogen has notified Laureate within such ten (10) business day
period, that the CYT-351 produced by Laureate by reason of Cytogen's
exercise of option granted Cytogen pursuant to paragraph 2(c) does not meet
Specifications. Cytogen agrees to take all commercially reasonable actions
necessary that the CYT-351 so produced is shipped from the Facility not
later than fifteen (15) days following the conclusion of the ten (10)
business day period provided for in this paragraph 2(e).
(f) Subject to the provisions hereof, in the event that Cytogen places
an order with Laureate pursuant to paragraph 2(e), this Agreement shall
expire on December 31, 2003.
3. Consideration. In consideration of Laureate's performance of services
hereunder, Cytogen agrees to pay Laureate as follows:
(a) A facility access and utilization fee in the aggregate amount of
$1,000,000;
(b) $[**] for each performance by Laureate of a [**] hollow fiber run
to the end of producing CYT-351 and the purification of the quantity of
CYT-351 so produced;
(c) $[**] for each performance by Laureate of the Services required
with respect to the conjugation of CYT-351 necessary to produce
ProstaScint, including the Services to be performed by Laureate to the end
of supplying Cytogen with Filled ProstaScint Product hereunder;
7
(d) $[**] for each performance by Laureate of the Services necessary
to supply Cytogen with vials of Filled Sodium Acetate Product such vials to
be filled from a volume of bulk sodium acetate buffer solution as specified
in the Batch record.
(e) $[**] for each instance in which Laureate performs a media fill
validation run in support of the Services required to be performed by
Laureate to produce Filled ProstaScint Product or Filled Sodium Acetate
Product.
(f) $[**] such amount being the agreed monetary value of Laureate's
performance of the set-up activities which the parties have agreed are to
be undertaken by Laureate in connection with Laureate's performance of the
Primary Production Campaign and which are identified as part of Exhibit A.
(g) $[**] in the event that Cytogen exercises the option granted
Cytogen under paragraph 2(c) hereof, such amount being the agreed monetary
value of Laureate's performance of the set-up activities which the parties
have agreed are to be undertaken by Laureate in connection with Laureate's
performance of the Option Production Campaign and which are included in
Exhibit A.
4. Payments. (a) The amount due under paragraph 3(a) shall be payable
$250,000 on the date hereof, $250,000 on April 1, 2003, $250,000 on July 1, 2003
and $250,000 on October 1, 2003. The amounts payable to Laureate under this
paragraph 4(a) shall
8
be due and payable by Cytogen to Laureate notwithstanding prior fulfillment by
Laureate of its obligations hereunder to the end that this Agreement has expired
in accordance with the provisions of paragraph 2(d) hereof.
(b) In connection with Cytogen's order with respect to the Primary
Production Campaign made hereby pursuant to paragraph 2(b), the following
amounts shall be due and payable:
(i) $157,500 upon the execution and delivery hereof;
(ii) an amount equal to [**] percent of the amount provided for
in paragraph 3(c), 3(d) or 3(e) shall be payable on the date Laureate
commences the applicable Services part of the Manufacturing Procedures
required to be performed in respect of paragraph 3(c), 3(d), or 3(e);
(iii) an amount equal to [**] percent of the amount due under
paragraphs 3(c), 3(d) and 3(e) shall be payable ten (10) business days
following the date the Laureate Contact Individual, as hereinafter
defined, notifies Cytogen that the document review to be undertaken by
Laureate with respect to Filled ProstaScint Product, Filled Sodium
Acetate Products or the media fill validation run, as applicable, has
been undertaken and such documents have been determined by Laureate to
be complete and correct; provided, that, within such ten (10) business
9
day period, Cytogen has not notified Laureate that the Filled
ProstaScint Product, the Filled Sodium Acetate Product or the media
fill validation run does not meet Specifications.
(c) In the event of Cytogen's exercise of the option granted pursuant
to paragraph 2(c) with respect to the Optional Production Campaign, the
amounts set forth below shall be due and payable as follows:
(i) On the date of Cytogen's exercise of the option granted
Cytogen pursuant to paragraph 2(c), the sum of $136,800 in respect of
the payment required under paragraph 3(g) hereof plus an amount equal
to [**] percent of the aggregate amount due under paragraph 3(b)
hereof;
(ii) an amount equal to [**] percent of the aggregate amount
payable and provided for under paragraph 3(b) shall be payable on the
date that Laureate commences the Manufacturing Procedures which are
part of the Services to be performed in respect of paragraph 3(b).
(iii) an amount equal to [**] percent of the amount payable and
provided for in paragraph 3(b) shall be due and payable on the date
that Laureate, in accordance with the Quality Agreement, has completed
performance of the applicable Manufacturing Procedures part of the
Services to the end that there has been produced CYT-351 ready to be
conjugated to form ProstaScint.
(iv) upon a Cytogen order under paragraph 2(e) hereof, an amount
equal to [**] percent of each aggregate amount due under paragraphs
3(c), 3(d) and 3(e), as applicable, such applicability to be
10
determined in with the terms of such order, if being understood that
in connection with the fulfillment of any such order it will be
necessary for Laureate to perform a media fill identified in paragraph
3(e);
(v) with respect to Laureate's performance of a Cytogen order
under paragraph 2(e), an amount equal to [**] percent of each
aggregate amount due under paragraphs 3(c), 3(d) or 3(e), as
applicable, such applicability to be determined in accordance with the
terms of such order, shall be payable on the date Laureate commences
the applicable Manufacturing Procedures part of the Services to be
performed in respect of paragraph 3(c), 3(d) or 3(e);
(vi) with respect to Laureate's performance of a Cytogen order
under paragraph 2(e), an amount equal to [**] percent of the aggregate
amount due under paragraphs 3(c), 3(d) or 3(e), as applicable, such
applicability to be determined in accordance with the terms of such
order, shall be payable ten (10) business days following the date the
Laureate Contact Individual (as hereinafter defined) notifies Cytogen
that the document review to be undertaken with respect to Filled
ProstaScint Product, Filled Sodium Acetate Product or media fill
validation run, as applicable, has been undertaken and such documents
by Laureate have been determined to be complete and accurate; provided
11
that within such ten (10) business day period Cytogen has not notified
Laureate that the Filled ProstaScint Product, the Filled Sodium
Acetate Product or the media fill validation run does not meet
Specifications.
5. Performance of Services; Other Assistance; FDA Fees. (a) All Services
shall be performed by Laureate in accordance with the Quality Agreement.
(b) Upon agreement of the parties, Laureate will assist Cytogen in
connection with validation studies, transfers of data, methodologies and
procedures to a third party retained by Cytogen for the manufacture,
production and in-process and release testing of XXX-000, XXX-000 of Filled
ProstaScint Product and/or Filled Sodium Acetate Product, internal
inspections of plant and warehouse premises, inspections by the FDA of
Cytogen facilities and such other activities as may be agreed by the
parties.
(c) Assistance rendered by Laureate under paragraph 5(b) shall be
invoiced to Cytogen in an amount equal to (a) the product determined by
multiplying the aggregate hours expended by Laureate personnel in rendering
such assistance by $[**] per hour plus (B) out-of-pocket costs incurred by
Laureate that have been approved by Cytogen. Alternatively, the parties may
agree on a fixed price for the subject matter or activity in question.
(d) 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
12
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 will provide
Laureate in writing upon the execution hereof with the Manufacturing Procedures
which shall include all requisite technical specifications, manufacture and
production process information, instructions and procedures, testing and quality
control instructions and procedures, formulae, storage instructions with respect
to the manufacture of 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 CYT-351, CYT-356, Filled
ProstaScint Product and Filled Sodium Acetate Product.
(b) Cytogen will provide Laureate in writing upon the execution hereof
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.
13
(c) Cytogen will provide Laureate in writing upon the execution hereof
with the Specifications for each of CYT-351, CYT-356, Filled ProstaScint
Product and Filled Sodium Acetate Product.
(d) Within ten (10) days after Laureate's receipt in writing of the
Manufacturing Procedures, the Incoming Acceptance Tests, and the
Specifications, Laureate shall notify Cytogen of its ability or inability
to render Services hereunder in conformance with the Manufacturing
Procedures, to perform the Incoming Acceptance Tests and to manufacture
CYT-351, CYT-356, Filled ProstaScint Product or Filled Acetate Product
conforming to the applicable specifications.
(e) In the event that Laureate gives notice pursuant to paragraph 6(d)
of its inability to provide Services in conformance with the Manufacturing
Procedures, to perform the Incoming Acceptance Tests or to manufacture
CYT-351, CYT-356, Filled ProstaScint Product or Filled Sodium Acetate
Product conforming to the applicable Specifications, the rights and
obligations of the parties under this Agreement shall be suspended without
liability. Following any such notice, Laureate shall prepare an action plan
("Plan") with respect to enabling Laureate to provide Services as required
herein for Cytogen's approval, such approval not to be unreasonably
withheld or delayed. Laureate agrees to undertake reasonable commercial
efforts to implement the Plan to the end of having the capability of
rendering Services in conformance with the Manufacturing Procedures and to
14
perform the Incoming Acceptance Tests and to manufacture CYT-351, CYT-356,
Filled ProstaScint Product and Filled Sodium Acetate Product conforming to
the applicable Specifications.
(f) Notwithstanding anything in this Agreement to the contrary, in the
event the Laureate inability with respect to which Laureate has given
notice pursuant to paragraph 6(d) is not resolved by Xxxxx 0, 0000, Xxxxxxx
shall have the option to terminate this Agreement without penalty. In the
event Cytogen exercises such option, the rights and obligations of the
parties hereunder shall wholly cease without further or other liability and
Laureate shall immediately refund to Cytogen any amount then paid by
Cytogen to Laureate with respect to the Facility Fee and those fees for
Services or otherwise due under paragraph 5(c) which have not yet been
performed by Laureate. Time is of the essence with respect to payment of
the refund provided for in this paragraph 6(f).
(g) Laureate shall provide to Cytogen and Cytogen shall provide to
Laureate the Laureate SOPs and the Cytogen SOPs, as applicable, on the date
of execution hereof.
7. Materials Delivery; Testing. (a) Laureate shall prepare for Cytogen on
Cytogen's forms therefor, requisition and purchase orders for Cytogen Supplied
material to be used in connection with the manufacture of Filled ProstaScint
Product and Filled Sodium Acetate Product. Following preparation of the same,
Laureate shall forward to Cytogen each such requisition and purchase order,
together with the applicable requisition and purchase order number, for
Cytogen's review, approval and execution thereof. It shall be Cytogen's
15
obligation hereunder to timely place the approved and executed requisition and
purchase order with the applicable vendor for Cytogen's account to the end that
the Cytogen Supplied Materials identified therein are delivered or caused to be
delivered to the Facility at the time provided for in paragraph 7(d).
(b) 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.
(c) Title to all Cytogen Supplied materials shall remain in Cytogen
notwithstanding the storage and Laureate's possession thereof at the
Facility.
(d) Within 30 days of Cytogen's order for Filled ProstaScint Product
and/or Filled Sodium Acetate Product, Laureate will provide Cytogen in
writing of Laureate's intended dates for the conduct of each process or
activity part of the Manufacturing Procedures necessary to be performed by
Laureate to fill such order. Unless otherwise agreed, 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 twenty (20)
days nor more than ninety (90) days prior to the date Laureate has
scheduled the performance of such process or activity.
16
(e) 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. In the event the performance
of an analysis or test determines that the Cytogen Supplied Material does
not meet Specifications or is otherwise unsuitable for use in connection
with the production of XXX-000, XXX-000, Filled ProstaScint Product or
Filled Sodium Acetate Product, Laureate shall promptly notify the Cytogen
Contact Individual (as hereinafter defined) of such determination and the
results of the applicable analyses or tests performed.
(f) In the event that Laureate 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(f) shall be invoiced to Cytogen in accordance with paragraph
5(c) 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.
17
(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(d)) 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 XXX-000, XXX-000, Filled ProstaScint Product and Filled
Sodium Acetate Product, revise the schedule provided to Cytogen pursuant to
paragraph 7(d) 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; provided,
however, that Laureate will attempt to negotiate to defer the performance
of any 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.
(i) Notwithstanding anything to the contrary in this Agreement,
Laureate shall not be obligated to utilize the On-Hand CYT in connection
with any Manufacturing Procedure until such time as Cytogen has documented
to Laureate's reasonable satisfaction that the On Hand CYT has been
stability tested as required by any applicable law or regulation and
otherwise meets Specifications.
18
(j) The applicable provisions of the Quality Agreement shall be
complied with in the event Laureate utilizes the services of third party
sub-contractors in connection with Laureate's performance of this
Agreement.
8. Payment Dates; Late Payments. (a) Invoices by Laureate with respect to
amounts due in respect of paragraph 3(a), (b), (c), (d),or (e) shall be payable
upon Cytogen's receipt thereof.
(b) Undisputed invoices by Laureate with respect to amounts due under
paragraph 5 five hereof shall be payable within thirty (30) days of the
invoice date.
(c) Invoices due for Services performed in accordance with Quality
Agreement due pursuant hereto and not timely paid shall bear interest at
the rate of one and one half percent (1.5%) per month on the unpaid balance
thereof.
(d) Time is of the essence with request to payments due hereunder. In
the event that an invoice remains unpaid for five (5) business days
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 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(h), to revise the schedule provided to Cytogen pursuant to
paragraph 7(d).
19
9. Regulatory Matters and Approvals; Order Dates. (a) Laureate agrees to
use its reasonable commercial efforts to the end that Laureate has the
capability to perform the Manufacturing Procedures to be utilized in connection
with the performance of two conjugation runs with respect to the On Hand CYT to
the end of producing ProstaScint not later than May 31, 2003 and to perform the
Manufacturing Procedures to be utilized in connection with the [**] day hollow
fiber runs and the purification of the quantity of CYT-351 resulting therefrom
beginning on or about July 1, 2003.
(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 paragraph 9(a).
(c) Laureate will timely advise Cytogen of Laureate's renovation plans
and renovation work to be undertaken with respect to the Facility. Cytogen
and/or Laureate will prepare and timely submit to the FDA all necessary
documentation to the end that the FDA approves the Facility for the
manufacture and production of XXX-000, XXX-000, Filled ProstaScint Product
and Filled Sodium Acetate Product.
(d) Within ten (10) business days following the execution and delivery
hereof, the parties endeavor to prepare a detailed attachment specifying
the quality and regulatory procedures and responsibilities of the parties
20
hereunder with respect to the production of Filled ProstaScint Products and
Filled Sodium Acetate Products ("Quality Agreement"). The Quality Agreement
will, inter alia, provide for Cytogen's responsibility for approving the
release from storage and use of each Cytogen Supplied Raw 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.
(e) In the event a Quality Agreement is not concluded on or before
March 1, 2003, either party may elect to terminate this Agreement. Upon
such termination, the rights and obligations of the parties shall wholly
cease without further or other liability and Laureate shall immediately
refund to Cytogen any amount then paid by Cytogen to Laureate with respect
21
to the Facility Fee and all payments received by Laureate for Services
which have not been reasonably accepted by Laureate. Time is of the essence
with respect to the payment of the refund provided for in this paragraph
9(e).
(f) Cytogen acknowledges that the [**] Purification Process ("[**]
Process"), as a result of the "predicate clause" part of 21 C.F.R. Part 11,
has been "grandfathered" for purposes of compliance with 21 C.F.R. Part 11.
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 as 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.
10. Stability Testing; Shipping. (a) Cytogen shall be responsible and shall
perform at its sole cost and expense all stability testing necessary or
advisable to be undertaken with respect to CYT-351, CYT-356, the On-Hand CYT,
Filled ProstaScint Product, Filled Sodium Acetate Product, Cytogen Supplied
Materials or any intermediate formed in the course of performance of the
Manufacturing Procedures.
(b) (i)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
22
Facility not later than fifteen (15) days following the conclusion of the
ten (10) business day period provided for in paragraph 4(b)(iii) hereof.
11. 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 reasonable commercial 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 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.
23
(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 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
Liability. (a) Laureate covenants, represents and warrants to and with Cytogen
as follows:
24
(i) Laureate's maintenance of the Facility or renovations, if
any, thereto, and performance of manufacturing and other services
hereunder shall conform in all material respects with applicable
cGMPs.
(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.
(iii) To the best of Laureate's knowledge, no process performed
by Laureate in the course of manufacturing Filled ProstaScint Product
and/or Filled Sodium Acetate Product violates or infringes the
intellectual property rights of any third party.
(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 its reasonable commercial efforts to
dutifully and timely perform its obligations and responsibilities
25
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 ACETATE PRODUCT OR ANY
INTERMEDIATE FORMED IN THE COURSE OF MANUFACTURE OF FILLED PROSTASCINT
PRODUCT AND/OR FILLED ACETATE PRODUCT, OR ANY OTHER MATTER WITH RESPECT TO
FILLED PROSTASCINT PRODUCT OR FILLED 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
26
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 [**] day 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
27
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 [**] grams 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(f) 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
Specification or is otherwise unsuitable for use in the manufacture of
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
28
activity by Laureate which does not conform to the Cytogen SOPs, the
Laureate 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 and for any additional
Establishment Fee in the event such failure requires Laureate to perform an
obligation hereunder after December 31, 2003. Laureate waives any
additional Facility Fee in the event such failure requires Laureate to
perform an obligation hereunder after December 31, 2003.
(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 which are founded
upon or in any manner involve Filled ProstaScint Product or Filled Sodium
Acetate Product and which arise or occur following Cytogen's release for
shipment from the Facility of Filled ProstaScint Product and/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")
29
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
30
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 serious violation 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.
31
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 $10,000,000 and cause Laureate an additional insured thereon. Laureate
now maintains general liability insurance and property damage liability
insurance in the amount of $2,000,000 for the Facility. 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. Neither party shall disclose to any third party,
except as may be required by law, the substance of this Agreement. 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 five (5) years after the termination of this
Agreement with regard to business related information, and for a period of ten
(10) years with regard to technical information, provided that the receiving
32
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 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 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
33
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
Vice President Research and Development
Cytogen Corporation
000 Xxxxxxx Xxxx Xxxx
Xxxxxxxxx, XX 00000
Fax No.: 0-000-000-0000
34
With a copy to:
Xxxx and Xxxx LLP
000 Xxxxxxx Xxxx Xxxx
Xxxxxxxxx, XX 00000
Fax No.: 0-000-000-0000
If to Laureate:
Xxxxxx X. Xxxxxx, Phd.
President
Laureate Pharma L.P.
000 Xxxxxxx Xxxx Xxxx
Xxxxxxxxx, XX 00000
Fax No.: 0-000-000-0000
With a copy to
Xxxxxxxxxx & Xxxxx LLP
00 Xxxxxxxxxxx Xxxxx
Xxx Xxxx, XX 00000
Attn: Xxxxxx X. Xxxxx
Fax No.: 0-000-000-0000
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.
35
(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 twelve
(12) months 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 in the
case of an assignment to an Affiliate shall not be unreasonably withheld;
otherwise this Agreement shall be binding upon and inure to the benefit of the
parties hereto and their respective permitted successors and assigns.
36
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.
37
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.
38
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. Xxxxxxxxx
--------------------------------- --------------------------------
Xxxxxx Xxxxxx, PhD. Xxxxxxx X. Xxxxxxxxx
President Vice President Research and
Development
39
Cytogen Setup Schedule - Exhibit A
Department Activity Work Training Total Cum. Hours Labor Contractor Total
---------- -------- hours hours Hours ---------- Costs Cost Cost
----- -------- ----- ----- ---------- -----
Supply Chain SOPs 4 9 13 13 [**] [**] [**]
Purchasing 120 0 120 133 [**] [**] [**]
Quality Control Test Methods 102 0 102 102 [**] [**] [**]
Set-up 112 0 112 214 [**] [**] [**]
Quality Assurance SOPs 64 16 80 80 [**] [**] [**]
Batch Records 16 0 16 96 [**] [**] [**]
Records 40 0 40 136 [**] [**] [**]
Management
Manufacturing - Documentation 4 16 20 20 [**] [**] [**]
Conjugation
Preparation 52 0 52 72 [**] [**] [**]
Manufacturing - Documentation 4 16 20 20 [**] [**] [**]
Filling Sodium
Acetate
Preparation 0 0 0 20 [**] [**] [**]
-- Filling Documentation 4 4 8 8 [**] [**] [**]
ProstaScint
Preparation 0 0 0 8 [**] [**] [**]
--ProstaScint Documentation 4 4 8 8 [**] [**] [**]
Media Fill
Preparation 8 0 8 16 [**] [**] [**]
--Acetate Media Documentation 4 0 4 4 [**] [**] [**]
Fill
Preparation 0 0 0 4 [**] [**] [**]
Manufacturing SOPs 28 8 36 36 [**] [**] [**]
-Antibody
Protection
Batch Records 36 0 36 72 [**] [**] [**]
Equipment 0 0 0 72 [**] [**] [**]
setup
Area 56 0 56 128 [**] [**] [**]
preparation
Manufacturing SOPs & MBR's 28 30 58 58 [**] [**] [**]
-Protein
Purification
Validation
Equipment 108 0 108 166 [**] [**] [**]
setup
Equipment 240 0 240 240 [**] [**] [**]
Facilities Revise 56 0 56 56 [**] [**] [**]
renovation
plans
Relocate 24 0 24 80 [**] [**] [**]
equipment
Recommission 24 0 24 104 [**] [**] [**]
Rad Suite
Equipment 40 0 40 144 [**] [**] [**]
maint./calibration
SOPs/PMs 24 16 40 184 [**] [**] [**]
As-built 40 0 40 224 [**] [**] [**]
updates/documentation
Total 1361 [**] [**] [**]
Notes: 1) Shaded area totals $[**] and represents set up activities outlined
in 3(g) of the supply agreement.
2) Set up for primary production campaign [3(f)] of $[**] are total of
non-shaded areas.
3) Primary Production Campaign set up fees payment schedule: [**]% due
upon contract signing; [**] due on date Laureate commences Manufacturing
procedures under 4(b)(ii) of the Supply Agreement.
