CLINICAL MANUFACTURE AND SUPPLY AGREEMENT
THIS AGREEMENT (the "Agreement") is entered into on February 21, 2000 by
and between International Isotopes Inc., a Texas corporation, with its principal
place of business at 3100 Jim Christal Road, Denton, Texas 76207 ("I3"), and
NeoRx Corporation, a Washington corporation, with its principal place of
business at 410 West Harrison Street, Seattle, Washington 98119-4007 ("NeoRx").
WITNESSETH
WHEREAS, NeoRx has obtained an exclusive license under certain patents and
the right to use certain technology and processes to make, use, sell and
distribute the Product (as hereafter defined), which is a radiopharmaceutical
product, for clinical and commercial purposes; and
WHEREAS, I3 is in the business of manufacturing a full range of
radiochemicals and radiopharmaceuticals, and is the sole owner of a
radiopharmaceutical manufacturing facility located in Denton, Texas (the
"Building"); and
WHEREAS, NeoRx and I3 have entered into that certain Design Phase
Agreement, through which I3 has agreed to design the Clinical Manufacturing
Facility and Process for the benefit of NeoRx, and NeoRx has agreed to pay I3
for such services; and
WHEREAS, the parties desire to set forth the terms under which I3 will
install and qualify the Clinical Manufacturing Facility and Process within the
Building to be used for Processing the Product for use in Clinical Trials;
WHEREAS, NeoRx desires that I3 manufacture and supply to and on behalf of
NeoRx certain quantities of the Product for use in Clinical Trials, and I3 is
willing to perform such services to and on behalf of NeoRx, all in accordance
with the terms and conditions set forth in this Agreement;
NOW THEREFORE, in consideration of the foregoing promises and agreements
set forth herein, the parties agree as follows:
ARTICLE I - DEFINITIONS
1.1 "Affiliate" of a Party means any corporation or other business entity
controlled by, controlling or under common control with such Party. For this
purpose, "control" means direct or indirect beneficial ownership of thirty-five
percent (35%) or more of the voting and income interest in such corporation or
other business entity.
1.2 "Building" means the entire 25,000 square foot radiopharmaceutical
manufacturing facility owned by I3 and located in Denton, Texas.
1.3 "Calibration Time" is 12:00 noon Central Time on the day following the
manufacturing date of a particular Batch of Product.
[ * ] DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A
REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSION.
1.4 "Certificate of Analysis" means a written certificate produced by I3
verifying that a particular dose of Product meets all Product Specifications,
and that the methodology used to Process the Product met all Requirements, cGMP
and all other applicable laws and regulations.
1.5 "Change Control" means a procedure, governed by I3's Standard
Operating Procedures, for assessing the potential impact on the regulatory
status, validation status, and safety of any proposed change to a Validated
Process or the validated equipment and utilities associated with that Process
prior to implementation of that change.
1.6 "Clinical Batch" means a production batch of the Product intended to
have uniform character and quality that is Processed by I3 in accordance with
the terms and conditions of this Agreement. [ * ]
1.7 "Clinical Facility Information" means all written information given to
the FDA to support the approval of the Clinical Manufacturing Facility as being
qualified and Validated to manufacture the Product for Clinical Trials.
1.8 "Clinical Facility Qualification Plan" has the meaning as set forth in
Section 2.1(b).
1.9 "Clinical Facility Qualification Report" has the meaning as set forth
in Section 2.4(a).
1.10 "Clinical Facility Validation Plan" has the meaning as set forth in
Section 2.1(c).
1.11 "Clinical Facility Validation Report" has the meaning as set forth in
Section 2.4(b).
1.12 "Clinical Manufacturing Facility" means that portion of the Building
that will be designed and constructed in accordance with the Construction
Specifications for use as a radiopharmaceutical manufacturing facility, and
which is to be dedicated to the clinical manufacture of the Product.
1.13 "Clinical Trials" means any trials for clinical development of
pharmaceutical products defined as "Phase I," "Phase II," "Phase III," or
"Treatment IND" in FDA regulations, as amended from time to time.
1.14 "Construction Specifications" means the specifications for the
construction, characteristics and operations of the Clinical Manufacturing
Facility and the Process as set forth in the Construction Design Plans attached
hereto as Exhibit A, which may be amended from time to time by written agreement
of the parties.
1.15 "Construction Fee" has the meaning as set forth in Section 2.2.
1.16 "cGMP" means the current good manufacturing practices required by the
FDA and set forth in the FD&C Act or FDA regulations, policies, or guidelines in
effect at a particular time for the manufacture, testing and quality control of
pharmaceutical materials as applied to
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drugs except to the extent that another jurisdiction within the North American
Market imposes standards for the manufacture, testing and quality control of
pharmaceutical materials as applied to drugs are higher or more stringent than
those required by the FDA, in which case such standards will apply.
1.17 "Dedicated Moveable Equipment" means all equipment except hot cells
and glove boxes purchased by NeoRx for exclusive use in Processing the Product.
1.18 "Dedicated Fixed Equipment" means hot cells and glove boxes purchased
by NeoRx for exclusive use in Processing the Product.
1.19 [ * ]
1.20 "Effective Date" means the date this Agreement is entered into, as
indicated in the first paragraph of this Agreement.
1.21 "Facility Master File" or "FMF" means the Facility Master File dossier
prepared by I3 and filed with the FDA, which provides the FDA with specific (and
proprietary) chemistry, manufacturing and controls information for the Building.
1.22 "FDA" means the United States Federal Food and Drug Administration.
1.23 "FD&C Act" means the United States Federal Food, Drug and Cosmetic
Act, as amended.
1.24 "IND" means an Investigational New Drug application and any
supplements thereto, as defined in FDA regulations, as amended from time to
time.
1.25 "Installation Qualification" means the program employed by I3 by which
it is established that the equipment and systems used in the Process are capable
of consistently operating within established limits and tolerance for purposes
of Processing the Product for use in Clinical Trials.
1.26 "Inventions" has the same meaning as set forth in Section 11.2(a).
1.27 "Master Batch Record" means the document which sets forth the
methodology and formulae for Processing each Batch. I3 may amend the Master
Batch Record from time to time; provided, however, that I3 shall make such
amendment only in accordance with its written Standard Operating Procedures
governing Change Control for a validated process, and shall notify the FDA
Master File dossier and NeoRx of such amendment prior to the implementation
thereof.
1.28 "Milestones" means the Milestones as set forth on Exhibit B, which
reflect the timeline during which I3 will complete the construction,
qualification and validation of the Clinical Manufacturing Facility, as such
construction, qualification and validation are further described in Article II.
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1.29 "New Drug Application" or "NDA" means the application for marketing a
new drug product filed by NeoRx with the FDA.
1.30 "Operation Qualification" means the program employed by I3 by which it
is established that the equipment and systems used in the Process are capable of
Processing Product that consistently meets the Requirements.
1.31 "Performance Qualification" means the program by which it is
established that the Process, and all equipment and systems associated
therewith, are effective and reproducible.
1.32 "PHS Act" means the United States Public Health Service Act, as
amended.
1.33 "Primary Completion Date" has the meaning as set forth in Section 2.1.
1.34 "Processing," "Process," and "Processed" shall have comparable
meanings and mean the act of manufacturing, handling, storing, analyzing,
packaging in dosage form, inspecting and labeling Product in accordance with the
Master Batch Record, Product Specifications, the Requirements, cGMP and all
other applicable federal, state and local laws and regulations for the
manufacture of the Product for use in Clinical Trials.
1.35 "Process Qualification" means a defined set of procedures, materials
and controls by which three (3) consecutive Clinical Batches are produced
according to the Master Batch Record procedures and the resulting Diagnostic and
Therapeutic Doses meet all Product Specifications.
1.36 "Process Validation" means the defined set of procedures, materials,
and controls as set forth in the Clinical Facility Information, by which
documented evidence provides a high degree of assurance that the Process will
consistently produce the Product that meets all Product Specifications and other
quality criteria and attributes as mutually agreed upon by the parties and as
set forth in the applicable I3 process validation protocol.
1.37 "Product" means a [ * ]
1.38 "Product Specifications" means the composition of the Product, along
with the set of analytical tests, methods, and acceptance criteria for Product
attributes which must be met in order to prove that the Product meets the
standards of quality, purity, identity and strength accepted by the FDA for this
substance. Product Specifications are a critical part of the Requirements and
are filed with the FDA as part of an FMF, NDA, IND or otherwise and set forth in
the Clinical Facility Information. All Product Specifications are set forth on
Exhibit C, which may be amended from time to time by written agreement of the
parties and as dictated by the FDA and applicable laws and regulations.
1.39 "Proprietary Information" means all information concerning a party
(the "Disclosing Party") which is furnished to or created by (such as notes,
analysis, compilations, studies, interpretations or other documents) the other
party or its directors, officers, employees,
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agents, advisors or Affiliates (collectively, the "Receiving Party") as a result
of entering into this Agreement and in furtherance hereof.
1.40 "Purchase Order" means the written or electronic document sent by
NeoRx from time to time to I3 that sets forth the number of Diagnostic and/or
Therapy Doses ordered and the expected delivery dates.
1.41 "Quality Control Tests" means the analytical testing of Product
attributes performed by I3 according to the test methods specified by the
Requirements, to determine whether a given dose meets its Product
Specifications.
1.42 "Requirements" means those Product Specifications, Process parameters,
cGMP and other governmental requirements relating to the Product, as set forth
in Exhibit D, which may be revised from time to time upon written agreement of
the parties and as dictated by the FDA and applicable laws and regulations. Upon
such revision, I3 shall immediately implement any modified documents and/or
procedures pertinent to the revised Requirements. Should the revision to the
Requirements have a material effect on the cost of Processing the Product, the
parties agree to meet and negotiate in good faith any price changes for the
purchase of the Product.
1.43 "Standard Operating Procedures" ("SOPs") means I3's internal written
standard operating procedures, controlled by I3's quality assurance unit,
governing all aspects of manufacturing and testing Product under cGMP.
1.44 [ * ]
1.45 "Validated" means the condition of having passed standards for
Installation Qualification, Operation Qualification and Performance
Qualification, as well as meeting all Construction Specifications, all Process
Validation requirements, and validation of the analytical methods.
1.46 "Validation Completion Date" has the meaning as set forth in Section
2.1.
1.47 "Waste" means all (a) rejected or unusable Product, (b) Product not
purchased by NeoRx for whatever reason, and (c) waste relating to I3's
Processing of Product.
ARTICLE II - CONSTRUCTION OF MANUFACTURING
FACILITY AND PROCESS
2.1 CONSTRUCTION OF CLINICAL MANUFACTURING FACILITY
(a) CONSTRUCTION. I3 will construct the Clinical Manufacturing Facility
and Process in accordance with the Construction Specifications and the
Milestones. [ * ]
(b) QUALIFICATION. I3 will prepare and NeoRx will approve a qualification
plan for the Clinical Manufacturing Facility and Process (the "Clinical Facility
Qualification Plan"), which will set forth the steps to be followed by I3 in
causing the Clinical Manufacturing Facility and
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Process to be qualified for use in clinical trials. I3 shall prepare and
execute, and deliver to NeoRx no later than thirty (30) days after the Primary
Completion Date, a final Clinical Facility Qualification Report indicating that
the construction of the Clinical Manufacturing Facility and the Process are
complete and qualified and that I3 has satisfied all aspects of the Clinical
Facility Qualification Plan. I3 acknowledges that any or all data included in
the final Clinical Facility Qualification Report may be used by NeoRx for
purposes of completing the CMC section of the IND.
(c) VALIDATION. I3 will prepare and NeoRx will approve a validation plan
for the Clinical Manufacturing Facility and Process (the "Clinical Facility
Validation Plan"), which will set forth the steps to be followed by I3 in
causing the Clinical Manufacturing Facility, analytical methods and Process to
be Validated. [ * ] I3 acknowledges that any or all data included in the final
Clinical Facility Validation Report may be used by NeoRx for purposes of
completing the CMC section of the NDA.
(d) COSTS. I3 shall be solely responsible for the payment of all costs in
connection with the construction of the Clinical Manufacturing Facility and
Process and obtaining all equipment associated therewith other than Dedicated
Moveable Equipment and Dedicated Fixed Equipment; provided, however, that if,
upon the prior written consent of NeoRx, I3 writes specifications for and
purchases the Dedicated Moveable Equipment and Dedicated Fixed Equipment on
behalf of NeoRx, then NeoRx shall reimburse I3 for the cost of such Dedicated
Equipment plus a 10% markup.
(e) DEDICATED EQUIPMENT. NeoRx shall be solely responsible for the cost of
Dedicated Moveable Equipment and Dedicated Fixed Equipment (collectively, the
"Dedicated Equipment"), whether such equipment is purchased or leased by NeoRx
or I3. NeoRx shall remain the sole owner of all Dedicated Equipment that is
purchased, and will maintain UCC filings documenting NeoRx's ownership therein
during the Term of this Agreement. Upon the expiration of this Agreement, I3
shall promptly return at NeoRx's sole expense all Dedicated Equipment to NeoRx
in good working condition less reasonable wear and tear; provided, however, that
if NeoRx indicates in writing to I3 that NeoRx intends to sell the Dedicated
Fixed Equipment at any time within sixty (60) days of the expiration or
termination of this Agreement (the "Sales Notice"), I3 shall have the right to
purchase the Dedicated Fixed Equipment from NeoRx at a rate equal to the
original book value minus 10% for each year the Dedicated Fixed Equipment has
been in service; provided, further, that I3 must exercise its right, if any, to
purchase the Dedicated Fixed Equipment within thirty (30) days of NeoRx sending
the Sales Notice to I3.
2.2 CONSTRUCTION FEE
In consideration of I3's construction of the Clinical Manufacturing
Facility, NeoRx shall pay to I3 a flat fee of [ * ] (the "Construction Fee").
NeoRx shall pay the Construction Fee to I3 in the following four installments:
(a) [ * ] upon full execution of this Agreement; (b) [ * ] upon completion and
execution of the Clinical Facility Qualification Plan, as described in Section
2.1(b); (c) [ * ] upon completion and execution of the final Clinical Facility
Validation Report, as described in Section 2.1(b); and (d) [ * ] upon filing the
NDA package associated
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with the Product. NeoRx's obligation to pay each installment is conditioned upon
its receipt of an invoice from I3 for the payment of each installment; provided,
however, that NeoRx's obligation to pay the final installment of the
Construction Fee is conditioned on NeoRx's acceptance of a final NDA package
associated with the Product.
2.3 PERFORMANCE CHARACTERISTICS
I3 will construct the Clinical Manufacturing Facility so that it shall have
the capacity to Process Product (a) in accordance with the Product
Specifications, the Requirements, cGMP and all applicable federal, state and
local laws, regulations, rules and orders and (b) in the amounts set forth in
Section 3.3. The Clinical Manufacturing Facility shall be built according to the
development documents created in the Design Phase Services Agreement that was
executed between the parties on September 20, 1999.
2.4 CLINICAL FACILITY REPORTS
(a) QUALIFICATION. At such times as are set forth in the Clinical Facility
Qualification Plan, I3 shall prepare and submit to NeoRx a report (the "Clinical
Facility Qualification Report") summarizing the activities performed pursuant to
the Clinical Facility Qualification Plan, including but not limited to facility
qualifications that are needed to begin producing Product for Phase III Clinical
Trials. I3 shall also prepare and submit to NeoRx a final Clinical Facility
Qualification Report, as described in Section 2.1(b), at such time as the
Clinical Manufacturing Facility and Process are Qualified, but no later than
thirty (30) days after the Primary Completion Date.
(b) VALIDATION. At such times as are set forth in the Clinical Facility
Validation Plan, I3 shall prepare and submit to NeoRx a report (the "Clinical
Facility Validation Report") summarizing the activities performed pursuant to
the Clinical Facility Validation Plan. I3 shall also prepare and submit to NeoRx
a final Clinical Facility Validation Report, as described in Section 2.1(c), at
such time as the Clinical Manufacturing Facility and Process are Validated, but
no later than six (6) months after the Primary Completion Date.
2.5 FACILITY EXCLUSIVITY
During the Term, I3 may not use the Clinical Manufacturing Facility for any
purpose other than Producing Product pursuant to this Agreement or for
conducting such additional activities as instructed by NeoRx and agreed upon by
the parties.
2.6 REPAIRS AND MAINTENANCE
I3 shall perform all maintenance required to maintain the Clinical
Manufacturing Facility and Process in good operating condition as required by
the Construction Specifications, Requirements, cGMP and all other applicable
federal, state and local laws, regulations, rules or orders. In the event of any
conflict between the applicable laws, regulations, rules or orders of any
jurisdictions, I3 will notify NeoRx of such conflict and the parties shall act
in good faith to resolve such conflict or to determine which laws, regulations,
rules or orders take precedence;
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provided, however, that at all times the Parties shall comply with the
requirements of cGMP. The cost of all repairs and maintenance to the Clinical
Manufacturing Facility and/or Process, and the replacement of any equipment
other than Dedicated Equipment, shall be borne by I3. NeoRx will bear all
expenses for repairs to or replacement of the Dedicated Equipment provided that
I3 has been operating the Dedicated Equipment under normal operating procedures
and conditions.
2.7 MODIFICATIONS
If, at any time during the Term of this Agreement after the Clinical
Manufacturing Facility and Process are Validated, the parties determine that
modifications to the Clinical Manufacturing Facility or Process are required as
a result of errors committed by I3 in carrying out the Clinical Facility
Qualification Plan, then I3 shall make such modifications and bear all costs and
expenses associated therewith. The costs for all other modifications to the
Clinical Manufacturing Facility or Process as determined, or agreed to, by
NeoRx, including those needed to meet agreed upon changes in the Requirements or
complete agreed upon additional construction, shall be borne solely by NeoRx,
subject to NeoRx's prior written authorization.
2.8 DEDICATED PERSONNEL
During the Term of this Agreement, I3 shall dedicate the personnel listed
on Exhibit E to the (a) construction, qualification and Validation of the
Clinical Manufacturing Facility, the Commercial Manufacturing Facility (as
described in the Commercial Manufacturing and Supply Agreement) and the Process,
and (b) the Processing of the Product. If any person listed on Exhibit E
terminates his or her employment with I3 during the Term of this Agreement, I3
shall replace that individual within two (2) months with someone of the same
level of experience.
ARTICLE III- MANUFACTURE & SUPPLY; OTHER SERVICES
3.1 NEORX'S SOURCE OF PRODUCT
(a) NORTH AMERICA. During the Term of this Agreement, NeoRx will obtain
from I3 at least [ * ] of its requirements of the Product for use in Clinical
Trials performed in North America that are associated with the use of the
Product for treatment of multiple myeloma; provided, [ * ] Accordingly, NeoRx
may, from time to time during the Term, obtain from third party manufacturers up
to twenty percent (20%) of its requirements of the Product for use in multiple
myeloma related Clinical Trials performed in North America.
(b) OTHER. [ * ] I3 shall have no obligation or right to Process Product
that is to be used for such purposes.
3.2 PROCESS AND SUPPLY OF PRODUCT
(a) GENERAL. I3 shall (a) Process the Product in strict conformity with
the Requirements, cGMP requirements and all other applicable laws, rules and
regulations, (b) maintain all documentation and quality control records
regarding the Products as described
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herein, and (c) supply the Product to the appropriate party in accordance with
the terms of this Agreement. I3 shall have no right to use, test or distribute
the Product for any reason other than as expressly provided in this Agreement.
(b) PROCESS AND SUPPLY. During the Term, I3 will Process and supply to
NeoRx such doses of the Product as NeoRx may order from I3 pursuant to Purchase
Orders. To fulfill the Purchase Orders, each week during the Term of this
Agreement I3 shall Process such Batches, or partial Batches, as is necessary to
produce only the number of doses of the Product ordered and scheduled for
delivery during such week.
(c) SITE OF PROCESSING; SUBCONTRACTING. I3 will Process all of the Product
at the Clinical Manufacturing Facility. Under no circumstances will I3 Process
any Product at any other location or subcontract out to a third party all or any
part of the Processing or testing of the Product without NeoRx's prior written
consent.
(d) APPROVAL FOR MANUFACTURING CHANGES. I3 agrees that no changes will be
made to any materials, Requirements, equipment, Processing or Quality Control
Tests without NeoRx's prior written approval. Subsequent to such approval from
NeoRx, I3 may then make such approved changes, so long as, in any event, (i)
such changes are permitted by applicable governmental regulations and the terms
of any licenses, registrations, authorizations or approvals previously granted
by the applicable governmental entity with respect to the Product and (ii) NeoRx
receives copies of all documentation relating to such approved changes. If the
changes require the additional license, registration, authorization, or approval
of any applicable governmental entity, I3 may not implement the changes until it
receives written notice from NeoRx that the governmental entity has authorized
or approved the change. I3 shall cooperate fully with NeoRx in preparing, and
will provide all necessary data and information for, a submission requesting
authorization or approval of a change in materials, Requirements, equipment,
Processing or Quality Control Tests.
3.3 I3'S PROCESS CAPABILITIES
During the Term of this Agreement I3 will be capable of Processing and
shipping up to [ * ] The parties acknowledge and agree that during the Term of
the Agreement, the actual number of Clinical Batches I3 will Process and ship
per week will be dependant on the Purchase Orders I3 receives from NeoRx.
3.4 SCHEDULED FACILITY SHUTDOWN
The parties agree that during the final two weeks of December of each year,
I3 will cease production of the Product to conduct maintenance to the Clinical
Manufacturing Facility and Process.
3.5 ORDERS AND FULFILLMENT
(a) PURCHASE ORDERS. NeoRx shall deliver to I3 (i) by the close of
business on Monday of each week during the Term of this Agreement, a written or
electronic Purchase Order
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for the number of batches, and delivery dates, that NeoRx desires to purchase
for delivery during the following calendar week and (ii) by the close of
business on Thursday of each week during the Term of this Agreement, an
amendment to the Purchase Order described in clause (i) that specifies the
number of each fill size of Diagnostic Doses and/or Therapy Doses that NeoRx
desires to purchase for delivery during the following calendar week. Each dose
shall be shipped in such manner, and to such location, as directed by NeoRx.
(b) ADDITIONAL PROVISIONS IN PURCHASE ORDERS. To the extent any Purchase
Order, invoice or acknowledgement form contains any provisions additional or
contrary to the provisions of this Agreement, such additional or contrary
provision shall have no force or effect and the terms of this Agreement shall
control.
(c) NOTICE OF INABILITY TO FULFILL. I3 shall notify NeoRx by telephone and
in writing immediately if I3 acquires any information that it will not be able
to fulfill the then most recent Purchase Orders. I3 shall promptly notify NeoRx
by telephone and in writing of any other production issues (including any
proposed or potential shutdown of the Clinical Manufacturing Facility for any
reason) or other information of which I3 becomes aware which may affect the
regulatory status of the Product or the ability of I3 to supply Product in
accordance with this Agreement and the Purchase Orders.
3.6 PROJECTED PURCHASES
Within thirty (30) days after the Effective Date, NeoRx shall provide a
twelve (12) month forecast (each, a "Forecast") to I3 that shows the projected
monthly number of Clinical Batches to be purchased. This Forecast shall be
maintained as a twelve (12) month rolling schedule and shall be updated at least
quarterly or more often if significant changes in demand are forecast. In
addition, NeoRx shall prepare a schedule of projected weekly purchases (each a
"Weekly Purchase Schedule") of Clinical Batches for the first three (3) months
following the Effective Date. This Weekly Purchase Schedule shall be maintained
as a three (3) month rolling schedule and will be updated at least monthly. The
parties acknowledge that any projections or estimates set forth in any Forecast
or Weekly Purchase Schedule are subject to change by reason of unknown or
unforeseen factors. Accordingly, the parties agree that such estimates shall not
be binding on NeoRx and may be modified weekly by NeoRx in light of its actual
purchasing needs provided that NeoRx will not order from I3 any Product in
excess of I3's maximum production capabilities as described in Section 3.3.
3.7 COMPLIANCE WITH LAW; HANDLING OF PRODUCT
While the Product is in its possession or under its control, I3 shall be
responsible for complying with all applicable federal, state and local
governmental statutory and regulatory requirements, including requirements
relating to the manufacture, handling, storage, labeling, packaging,
transportation and shipment of the Product. In performing its obligations under
this Agreement, I3 shall comply with all applicable environmental and health and
safety laws and shall be solely responsible for determining how to carry out
these obligations; provided, however, that I3 shall consult with NeoRx where
cGMP or labeling issues arise. In addition to the foregoing, at all times I3
will take all reasonable actions necessary to avoid spills and other
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safety concerns to persons, and damage to property or the environment resulting
from the Product or any intermediates or raw materials thereof.
3.8 TESTING AND DOCUMENTATION
I3 shall certify monthly in writing, to NeoRx's reasonable satisfaction,
that each Batch was produced and tested in compliance with (i) the Requirements,
(ii) cGMP requirements, (iii) the IND or NDA (whichever is applicable) relevant
to the Product, and (iv) all other applicable regulatory documents, in
accordance with procedures agreed between I3 and NeoRx. The tests and analyses
provided in the Requirements and the written certification referenced therein
may be amended from time to time by mutual written consent of the parties. I3
shall also provide to NeoRx a Certificate of Analysis for each Clinical Batch
that I3 processes.
3.9 OTHER SERVICES
I3 shall perform the following services during the Term of the Agreement:
(a) Obtaining, installing and qualifying all equipment to be used in
Processing the Product; provided, however, that NeoRx may obtain by purchase or
lease certain of the Dedicated Equipment as agreed to by the parties.
(b) Validating in accordance with cGMP all analytical methods and
manufacturing processes, which are to be developed by NeoRx in consultation with
I3. All changes to an established Validation Process shall be agreed upon by the
parties prior to the implementation thereof.
(c) Performing ongoing Quality Control Tests and stability studies on the
Product according to agreed upon test methods and specifications, and retaining
samples of Product associated with each such test and stability study. I3 shall
perform such other tests as are consistent with cGMP, as are required by the FDA
and/or any other governmental entity with respect to I3's manufacture of the
Product hereunder. I3 shall maintain all retained samples in a suitable storage
facility (under conditions as agreed to by the parties) for such time as NeoRx
may reasonably require. All such samples shall be available for inspection and
testing by NeoRx at reasonable times and upon reasonable notice.
(d) Training all appropriate I3 and NeoRx personnel with respect to the
operation of the Processes, the specifications of which are to be agreed upon by
the parties.
(e) Maintaining the Clinical Manufacturing Facility and Process so that it
complies with the Construction Specifications and Requirements throughout the
Term of this Agreement, and ensuring that each dose of Product delivered to
NeoRx meets all Product Specifications.
3.10 WASTE DISPOSAL
I3 shall be responsible for the treatment and/or disposal of all Waste
generated at I3 during the manufacturing process in accordance with established
federal, state and local
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environmental and OSHA laws and regulations, and the maintenance of detailed and
complete records related thereto.
ARTICLE IV - RAW MATERIALS
4.1 (166)HOLMIUM CHLORIDE
NeoRx will contract with a third party for the supply of (166)Holmium
chloride, which will be delivered to I3 directly. The delivery of
(166)Holmium chloride to I3 shall be pursuant to the delivery terms to be
stated in the supply agreement between NeoRx and the third party supplier of
(166)Holmium chloride, or as otherwise agreed to by NeoRx and such third
party supplier. NeoRx, in consultation with I3, will establish a procedure
for just-in-time delivery of (166)Holmium chloride from third party suppliers
to I3, with the amount of each delivery dependant on the actual Purchase
Orders received by I3 during the Term of this Agreement. The (166)Holmium
chloride shall be delivered to I3 in sufficient time to allow all Processing,
testing, packaging and release of the Product to be completed the same day
for delivery to the freight carrier for shipment that day. Any late
deliveries of (166)Holmium chloride may cause I3 to miss the evening shipment
deadline, in which case I3 shall not be held accountable or liable for the
costs thereof. NeoRx shall be responsible for the cost of all (166)Holmium
chloride, including all charges associated with the shipment of the
(166)Holmium chloride to the Manufacturing Facility. I3 agrees that it will
use the (166)Holmium chloride provided by NeoRx only for Processing the
Product, unless otherwise instructed by NeoRx. NeoRx shall remain the sole
owner of all (166)Holmium chloride that is purchased, and will maintain UCC
filings documenting NeoRx's ownership therein during the Term of this
Agreement.
I3 is responsible for either (a) verifying the quality of the
(166)Holmium chloride to ensure that it will meet the Requirements when
Processing the Product, or (b) relying on certificates from the manufacturers
of the (166)Holmium chloride with spot-checks performed by I3. I3 shall
notify NeoRx immediately of any (166)Holmium chloride that is not suitable
for Processing the Product, and I3 shall not be accountable for the cost
thereof or for late shipments as a result of its receipt of unsuitable
(166)Holmium chloride.
4.2 DOTMP
NeoRx will contract with a third party for the supply of DOTMP, which will
be delivered to I3 directly. The delivery of DOTMP to I3 shall be pursuant to
the delivery terms to be stated in the supply agreement between NeoRx and the
third party supplier of DOTMP, or as otherwise agreed to by NeoRx and such third
party supplier. NeoRx, in consultation with I3, shall determine the amount of
DOTMP that I3 will maintain in inventory for use in Processing the Product.
NeoRx shall be responsible for the cost of all DOTMP and will perform stability
studies on the bulk DOTMP; provided, however, that I3 shall perform stability
studies for radiolabeled DOTMP in addition to any other stability studies
performed pursuant to Section 3.8(c). I3 agrees that it will use the DOTMP
provided by NeoRx only for Processing the Product, unless otherwise instructed
by NeoRx. NeoRx shall remain the sole owner of all DOTMP that is purchased, and
will maintain UCC filings documenting NeoRx's ownership therein during the Term
of this Agreement.
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I3 is responsible for either (a) verifying the quality of the DOTMP to
ensure that it will meet the Requirements when Processing the Product, or (b)
relying on certificates from the manufacturers of the DOTMP with spot-checks
performed by I3. I3 shall notify NeoRx immediately of any DOTMP that is not
suitable for Processing the Product, and I3 shall not be accountable for the
cost thereof or for late shipments as a result of its receipt of unsuitable
DOTMP.
4.3 OTHER
I3 will contract with third parties and pay for the supply of all raw
materials, other than shipment boxes (as described in Section 6.2(c)),
(166)Holmium chloride (as described in Section 4.1) and DOTMP (as described in
Section 4.2), that are necessary to manufacture and package the Product in
dosage form. I3 shall be responsible for obtaining the type and amount of all
such other raw materials necessary to fulfill all Purchase Orders, the cost of
which shall be covered by I3; accordingly, NeoRx shall not be responsible for
paying suppliers directly, or reimbursing I3, for the cost of obtaining such raw
materials other than through the payment to I3 of the purchase price for the
Product as described in Article V.
4.4 UNAVAILABILITY OR SCARCITY OF (166)HOLMIUM CHLORIDE OR DOTMP
The parties acknowledge that NeoRx's obligation to supply (166)Holmium
chloride and DOTMP to I3 is conditional upon its ability to obtain a sufficient
supply of such raw materials. NeoRx will use reasonable efforts to notify I3
upon NeoRx's knowledge of a shortage of either (166)Holmium chloride or DOTMP
if such shortage will impact the manufacture of the Product.
ARTICLE V - PURCHASE PRICE AND PAYMENT
5.1 BATCH FEE
For each [ * ] Clinical Batch of Product Processed by I3 during the Term of
this Agreement, NeoRx shall pay to I3 a fee based on the following schedule:
BATCH PER WEEK PRICE PER BATCH
-------------- ---------------
[ * ] [ * ]
The price per Batch includes the cost of labor, materials and overhead to
manufacture and test the finished vials and is exclusive of the cost of
(166)Holmium chloride, DOTMP, Shipment Boxes, Customer Service and distribution.
5.2 MINIMUM PURCHASE AGREEMENT
Upon the Clinical Manufacturing Facility becoming fully operational and the
Process meeting all Process Qualifications as required pursuant to Section
2.1(a), and through the Term of this Agreement, NeoRx agrees to purchase from I3
a minimum of one Clinical Batch per week other than during (a) the final two
weeks of December of each year, during which I3 will cease production of the
Product to conduct maintenance to the Clinical Manufacturing Facility and
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Process as stated in Section 3.4, or (b) any week during which the Manufacturing
Facility is not in operation.
5.3 SHIPPING CHARGES
NeoRx, in consultation with I3, shall arrange for the shipment of the
Product from the Clinical Manufacturing Facility to NeoRx, or such other
location as determined by NeoRx. NeoRx shall be responsible for the payment of
all shipping charges (including, without limitation, freight, handling,
insurance, customs, duties and all other transportation related items)
associated with such shipments. NeoRx shall make all payment directly.
5.4 INVOICES
I3 shall invoice NeoRx bi-weekly for any Product Processed by I3 in
response to Purchase Orders during the two weeks prior to the date of each
invoice. NeoRx shall pay for such Product within thirty (30) days of its receipt
of such invoice, with a two (2%) discount allowed for payment in full within ten
(10) days from the date of NeoRx's receipt of such invoice. I3 shall reference
the applicable Purchase Orders on all invoices. If NeoRx disagrees in good faith
for any reason with the amount of an invoice, NeoRx shall notify I3 in writing
of such disagreement within ten (10) business days of receipt of such invoice,
and the Parties shall promptly endeavor to resolve the dispute in good faith
according to Section 13.3; provided, however, that NeoRx shall timely pay all
amounts not in dispute. If NeoRx is found to have incorrectly disputed any
amount of any invoice, NeoRx shall promptly pay such amount to I3 together with
interest at an annual rate of eighteen percent (18%) from the date of the
invoice through the date of payment.
5.5 MARKET CHANGES
In the event of any unanticipated and severe changes in market conditions
or other circumstances affecting the costs of the Product, the parties agree to
discuss such changed circumstances and to negotiate in good faith appropriate
adjustments to the price of the Product to reflect such changes.
ARTICLE VI - DELIVERY
6.1 DELIVERY
All Product purchased by NeoRx hereunder shall be delivered F.O.B. place of
manufacture. All Product to be shipped from the Clinical Manufacturing Facility
pursuant to a NeoRx Purchase Order shall be identified and designated by I3 as
to specified doses (and complete shipping advice) for delivery to NeoRx as soon
as possible in I3's Process of the Product. I3 shall be responsible for properly
packaging each Clinical Dose for shipment and preparing the shipping labels
according to the corresponding Purchase Order.
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6.2 PACKAGING AND SHIPPING MATERIALS
(a) PACKAGING AND SHIPPING MATERIALS. NeoRx will provide all packaging and
shipping materials, other than labels, associated with shipments of the Product.
NeoRx will be responsible for testing to United States Department of
Transportation standards. All costs associated with developing and obtaining the
packaging and shipping materials, other than labels, shall be borne by NeoRx.
(b) LABEL ARTWORK. NeoRx, in consultation with I3, will provide final
artwork for all labels used on the packaging and shipping materials, which shall
comply with all FDA regulations. All costs associated with the purchase and
supply of such labels shall be borne byI3.
(c) SHIPMENT BOXES. NeoRx will contract with third parties for the supply
of lead shipment boxes to be used by I3 in shipping the Product to or on behalf
of NeoRx. NeoRx shall remain the sole owner of all shipment boxes that are
purchased, and will maintain UCC filings documenting NeoRx's ownership therein
during the Term of this Agreement. Upon the termination of this Agreement, I3
shall promptly return all shipment boxes in I3's inventory to NeoRx.
6.3 INSPECTION AND ACCEPTANCE
(a) REJECTION OF DOSES. All Product shipped from the Clinical
Manufacturing Facility shall comply with the Product Specifications and
Requirements. Each dose of Product delivered by I3 according to a Purchase Order
shall be accompanied by a Certificate of Analysis relating to such dose. Any
party receiving a dose of Product from I3 pursuant to a Purchase Order may
reject such dose if (i) I3 fails to deliver a Certificate of Analysis prior to
use of such dose or as required by the FDA, (ii) such party finds that the dose
does not meet the Product Specifications, (iii) NeoRx finds that such dose was
not Processed in strict accordance with the Requirements and other terms of this
Agreement, or (iv) such party finds that the dose was shipped improperly or
untimely. If any party rejects a dose pursuant to the preceding sentence, then
the party will return such dose to I3 along with a written notice stating the
reasons justifying such rejection, and I3 shall promptly replace such rejected
doses. I3 will be responsible for all costs associated with any rejected doses,
up to the value of the rejected dose, and will reimburse NeoRx for any damages,
costs and expenses incurred by NeoRx as a result of such rejected dose(s) up to
an amount equal to the value of the rejected dose(s).
(b) DISAGREEMENT WITH REJECTION. If I3 disagrees with NeoRx's
determination that a shipment of Product does not meet the Product
Specifications and Requirements, the parties will (i) replace the rejected
dose(s) as soon as practicable, and then (ii) meet to review all relevant data
to determine the cause of such rejection. The parties will make every reasonable
effort to resolve the disagreement amicably. If the parties cannot resolve the
disagreement, the parties will select a mutually agreeable outside consulting
firm to review all applicable and pertinent information and data to determine
the cause of the rejection. The party against whom the consulting firm rules
shall bear all costs associated with the rejected dose(s) and the consulting
firm. If both parties are deemed to share responsibility for the rejection, then
such costs shall be allocated on a pro-rata share of the assigned blame. If the
cause cannot be determined then each
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party shall pay 50% of the costs. I3 cannot be in breach of this Agreement
because of an improper rejection or the inability to promptly supply replacement
Product after an improper rejection.
ARTICLE VII - REPRESENTATIONS AND WARRANTIES
7.1 LABOR AND EQUIPMENT
I3 represents that it shall furnish all qualified labor, validated
equipment and facilities necessary to Process Product in the amounts, and in the
timely manner, as set forth in each Purchase Order.
7.2 RAW MATERIALS
I3 represents that it will purchase all raw materials, other than
(166)Holmium chloride, DOTMP and Shipment Boxes necessary to Process, label and
store the Product in strict accordance with the Requirements, cGMP and all
applicable laws or regulations and shall be responsible for vendor qualification
and all raw material testing in accordance with written standard operating
procedures and applicable I3 raw material specifications for chemical and
microbiological characteristics, and shall comply with all applicable federal,
state and local laws and regulations.
7.3 CLINICAL MANUFACTURING FACILITY AND PROCESS
I3 represents that it will maintain the Clinical Manufacturing Facility and
Process according to the Requirements, Construction Specifications, cGMP and all
applicable laws and regulations.
7.4 PROCESSING REQUIREMENTS
I3 extends to NeoRx and to any purchaser of Products from or through NeoRx
the following warranties: Each and every dose of the Product that I3 sells to
NeoRx shall on and before delivery to or on behalf of NeoRx:
(a) Be Processed, manufactured, produced, packaged and labeled in strict
accordance with (i) the Requirements, (ii) all federal (including FDA), state
and local laws, statutes, regulations or other requirements relating thereto and
applicable to the intended use of such Product, (iii) cGMP, (iv) FMF pertaining
to the Process and the Facility (which I3 will file with the FDA), and (v) any
information provided by I3 to NeoRx for inclusion in a NDA or IND. I3 grants to
NeoRx permission to reference I3's FMF in NeoRx's regulatory filings with the
FDA pertaining to the Product.
(b) Not be adulterated or misbranded within the meaning of the Federal
Food, Drug and Cosmetic Act, 21 USC 301 ET SEQ., the Fair Packaging and Labeling
Act, 15 USC 1451 ET SEQ., or other applicable federal, state or local statutes,
regulations or other requirements. For purposes of this warranty, the Product
shall be adulterated or misbranded on or before the date of delivery to the end
user if as a result of any defect in the manufacture, preparation, packaging or
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storage of the Product by I3 prior to the delivery to the end user, the Product
subsequently became adulterated or misbranded under the Federal Food, Drug and
Cosmetic Act or equivalent state laws.
7.5 RECORDS RELATING TO WASTE DISPOSAL
I3 represents that it shall obtain and maintain all waste generator
licenses, disposal manifests and other records in accordance with applicable
federal, state and local laws and regulations.
7.6 CHANGES TO PRODUCT AND PROCESS
I3 represents that it shall not implement any changes, material or
otherwise, relating to the Product, its Requirements (including Product
Specifications), or Validated Process without NeoRx's prior written approval of
such change. A change is defined as any variation in the written procedures
currently in place that (i) impacts the regulatory commitments for the Product,
(ii) may require revalidation, (iii) may affect the quality, purity, identity or
strength of the Product or dose of the Product or (iv) would necessarily result
in changing, altering or modifying the Requirements, test methods, sampling
procedures, qualification procedures, Facility Master File or Master Batch
Record relating to the Product.
7.7 CHANGES AND WRITTEN AUTHORIZATION
Changes, extensions, or other modifications to this Agreement may be made
by mutual agreement at any time during the period of performance hereof. Changes
to this Agreement will be executed only by individual(s) authorized by the
respective parties to make such changes. Changes will take the form of a fully
executed modification to this Agreement.
7.8 SAFETY PROCEDURES
I3 represents that it shall have primary responsibility for adopting and
enforcing safety procedures for the handling and production of the Products at
the Clinical Manufacturing Facility that comply in all material respects with
all federal, state and local environmental and occupational safety and health
requirements.
7.9 LIMITATIONS ON WARRANTIES
(a) Except as otherwise expressly set forth in this agreement, I3 makes no
representations and extends no warranties of any kind, either express or
implied, including any express or implied warranties of merchantability or
fitness for a particular purpose.
(b) Except as otherwise expressly set forth in this agreement, NeoRx makes
no representations and extends no warranties of any kind.
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7.10 LIMITATION ON LIABILITY
Other than as expressly set forth in this agreement, neither party shall be
liable to the other for direct, indirect, special, incidental, or consequential
damages (including loss of profits) whether based on contract, tort, or any
other legal theory.
ARTICLE VIII - PERMITS; RECORDS AND AUDITS
8.1 LICENSES AND PERMITS
(a) NEORX. NeoRx shall be responsible for obtaining and maintaining such
drug licenses, registrations, listings, authorizations and approvals as the FDA
or any other applicable governmental entity may require to enable the use of
Product in Clinical Trials and marketing of the Product wherever such activities
will occur. I3 shall take all reasonable actions necessary to assist NeoRx in
obtaining and maintaining all such licenses, registrations, listings,
authorizations and approvals. NeoRx and/or its designee shall serve as the point
of contact with the FDA and any other applicable governmental entity concerning
such licenses, registration, authorizations or approvals, but may, as
appropriate, request I3's assistance with FDA and/or other applicable
governmental entity communications.
(b) I3. I3 shall be responsible, in coordination with NeoRx, for obtaining
and maintaining all necessary licenses, registrations, authorizations, and
approvals, other than those required to market the Product or use it in Clinical
Trials, which are necessary to perform its obligations under this Agreement,
including its activities relating to the manufacturing, handling, storing,
labeling, packaging, transporting and shipping the Product under cGMP conditions
and other regulatory requirements including, but not limited to, the use and
handling of radioactive materials. I3 shall provide NeoRx with copies of any
correspondence sent from I3 to governmental entities relating to the Product at
the time such correspondence is sent by I3; provided, if it becomes necessary
for I3 to provide any NeoRx proprietary and/or confidential information to any
third party or governmental authorities, it shall not do so without the express
written authorization of NeoRx, and then only after adequate steps have been
taken to ensure the confidentiality of such information. I3 shall provide NeoRx
with copies of any comments, responses, notices or other correspondence received
by I3 from any governmental entity relating to the Product within two (2) days
of receipt of such correspondence by I3 purged of any I3 proprietary information
and/or trade secrets.
8.2 OPERATIONAL RECORDS
During the Term of this Agreement, and for five (5) years after I3's
Processing any Product (unless a longer time is required by applicable law), I3
shall maintain records and samples necessary to evidence compliance with (a) all
applicable governmental laws, regulations and other requirements relating to the
manufacture of the Product; (b) relevant sections of the IND or NDA (whichever
is applicable) relevant to the Product, and corresponding licenses,
registrations, authorizations or approvals for foreign jurisdiction(s) as
advised by NeoRx; and (c) the Product Specifications. I3 may also retain records
with respect to its obligations and performance under this Agreement. I3 shall
also maintain ongoing detailed and complete records
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relating to (a) Purchase Orders received, (b) raw materials purchased and
stored, (c) Product manufactured, (d) manufacturing steps and processes, (e)
quality assurance and quality control procedures for the Product, (f)
qualification reports, (g) shipment of the product and any returns (h) disposal
of Waste, and the like. I3 will provide reasonable access thereto to NeoRx from
time to time upon NeoRx's reasonable request.
8.3 GOVERNMENTAL RECORDS AND AUDITS
(a) RECORDS AND AUDITS. I3 will cooperate with NeoRx as requested thereby
in obtaining and maintaining all FDA and other regulatory approvals necessary to
enable NeoRx to use the Products as intended under this Agreement. I3 shall
prepare and supply to NeoRx all documents and updates to records with regard to
Processing the Products that are required by the FDA. I3 shall submit to all
inquiries and inspections by the FDA. I3 shall promptly notify NeoRx of any FDA
interactions and/or correspondence relating to I3's operations that could
relate, directly or indirectly, to the Product. I3 shall provide NeoRx with
copies of all documents, reports or communications received from any federal,
state or local governmental authorities that relate in any way to I3's
Processing and/or storing the Product and all I3 documents responding thereto.
I3 shall immediately inform NeoRx of all FDA audits pertinent to NeoRx's Product
or Requirements and shall permit NeoRx's personnel and representatives who are
trained in I3's audit procedures to be present and participate in such audits.
Similarly, NeoRx shall inform I3 in advance of FDA planned audits of NeoRx if
such audits relate directly to the Products. I3 shall immediately provide NeoRx
with copies of any regulatory letters or other documents issued by the FDA and
received by I3 in connection with the audit or any inspection relating to the
Product, and allow NeoRx to participate in the drafting of responses to any FDA
inspectional observations or regulatory letters.
(b) INSPECTIONS. If NeoRx is required by any governmental authority to
have inspected or approved the site of manufacturing or storing the Product or
any raw materials related thereto, I3 shall permit officials of the governmental
authority to inspect the facility where the Product is manufactured or stored.
NeoRx has the right to have a NeoRx representative present in the Clinical
Manufacturing Facility during all scheduled FDA inspections of the Clinical
Manufacturing Facility and/or Process.
8.4 STABILITY TESTING AND SAFETY RECORDS
I3 shall maintain full, accurate and complete records and reports with
respect to all stability testing and sample retention and shall supply NeoRx
with copies thereof as requested by NeoRx along with reasonable samples and
specimens of Product on which such testing was performed to the extent that
providing samples and specimens does not negatively impact I3's ability to
maintain the stability or sample retention program. In addition, at least once
per quarter and at any time upon ten days' written notice from NeoRx, I3 shall
provide NeoRx with copies of all Certificates of Analysis and may audit I3's
records relating solely to I3's manufacture of the Product.
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8.5 INSPECTIONS
I3 shall permit employees and/or representatives of NeoRx to be present in
the Clinical Manufacturing Facility during normal business hours in order to
determine whether the Products are being Processed (including manufacturing,
receiving, sampling, analyzing, handling, packaging and labeling) and shipped,
and Waste is being disposed of, in conformity with the terms of this Agreement.
NeoRx acknowledges that its employees and/or representatives may be required to
first execute I3's confidentiality agreements and to complete all necessary I3
training and shall at all times comply with established health and safety
procedures as set forth in that document and I3's overall health and safety
requirements specified to them at the time they are in the Clinical
Manufacturing Facility. In addition to the foregoing, and in conformity with FDA
rules and regulations as well as all laws, rules and regulations as may be
applicable to NeoRx, I3 shall further permit employees or representatives of
NeoRx to inspect and sample Products designated for delivery to NeoRx and
otherwise provide NeoRx with such information as it may reasonably be required
to determine whether the Products are being Processed in accordance with FDA
rules and regulations as well as all laws, rules and regulations as may be
applicable to NeoRx and the provisions of this Agreement. NeoRx shall reject all
or any portion of any Products designated by I3 for delivery to NeoRx that do
not meet the Product Specifications and Requirements; and upon such rejection,
NeoRx shall have no payment obligation to I3 with respect to such rejected
Products. I3 shall promptly replace any Products that are rejected by NeoRx. If
I3 disagrees with NeoRx's determination that a shipment of Product does not meet
the Product Specifications and Requirements the two parties will seek resolution
of the disagreement per Section 6.3 (b) of this document.
ARTICLE IX - REGULATORY MATTERS
9.1 GENERAL
I3 and NeoRx shall be jointly responsible for the maintenance of any and
all regulatory documents covering the Product, the Process, and/or the Clinical
Manufacturing Facility and shall make all such documents available to NeoRx for
its review upon NeoRx's request.
9.2 NEW DRUG APPLICATIONS
I3 shall cooperate with NeoRx with respect to any NDA or IND obligations
relating to the Product that are imposed by the FDA or foreign regulations
(including without limitation the completion of the Chemistry and Manufacturing
Controls section of such NDA), and NeoRx shall be the exclusive owner of the NDA
and IND. I3 agrees to comply with all commitments made in the NDA and IND
regarding I3's manufacturing responsibilities as described herein and therein.
9.3 NOTICE OF SAFETY RELATED INFORMATION
I3 shall provide NeoRx with prompt notice of any information it receives
relating to the safety of the Product, including any confirmed or unconfirmed
information on adverse, serious, or unexpected events associated with the use or
toxicity of the Product regardless of the source.
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For serious (based on a good faith evaluation), unexpected events, notice must
be given by telephone within one (1) business day after receipt of the
information and followed by written notice not less than one (1) week
thereafter. NeoRx, with I3's cooperation, shall be responsible for responding to
the FDA and filing any reports with the FDA concerning such reactions (including
Drug Experience Reports) caused by the Product.
9.4 NEW REGULATORY REQUIREMENTS
Each party shall promptly notify the other of new or amended regulatory
requirements of which it becomes aware that are relevant to the Processing of
the Product under this Agreement and that are required by the FDA, other
applicable governmental entity or other applicable laws or governmental
regulations, and shall confer with each other with respect to the best means to
comply with such requirements.
ARTICLE X - RECALLS
The parties agree to immediately inform each other in writing of all
incidents and/or any Product that is alleged or proved to be the subject of
recall, market withdrawal or correction and shall cooperate with each other in
such recall, market withdrawal or correction. Any such recall, market withdrawal
or correction shall be at the sole expense of I3 if the Product does not meet
the Processing Requirements specified in Section 7.4. NeoRx shall have sole
responsibility for the conduct of the recall and interface with customer and
regulatory authorities in connection with the recall. NeoRx will Keep I3
apprised of all aspects of the recall and shall consult with I3 on all critical
aspects of the recall. The parties shall disclose to each other all information
necessary to prevent recurrence of the event or circumstance.
ARTICLE XI - CONFIDENTIALITY; OWNERSHIP AND DISCLOSURES
11.1 CONFIDENTIAL INFORMATION
Except to the extent expressly authorized by this Agreement, during the
Term of this Agreement and for seven (7) years thereafter, neither Party shall:
(a) disclose, publish, or make available any Proprietary Information
disclosed to it by the other to any third party, including employees who do not
need to know or have access to such Proprietary Information; or
(b) sell, transfer, or otherwise use or exploit any such Proprietary
Information disclosed to it by the other Party; or
(c) knowingly permit the sale, transfer, use or exploitation by a third
party of any such Proprietary Information which may have been disclosed to such
third party, including employees who do not need to know or have access to such
Proprietary Information.
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11.2 OWNERSHIP
(a) INVENTIONS. NeoRx and I3 agree that NeoRx owns all intellectual
property rights related to the Product and each owns preexisting intellectual
property rights related to the development of the Clinical Manufacturing
Facility and Process and that all right, title and interest in all such prior
intellectual property rights shall remain in the respective party (collectively
these rights shall be called "Background Rights"). NeoRx shall solely own the
intellectual rights in any inventions, improvements and discoveries, if any,
which are developed jointly by the parties or by I3 individually associated
directly with the Product. I3 and NeoRx shall own jointly the intellectual
rights in the inventions, improvements and discoveries (collectively the "Joint
Inventions"), if any, which are developed jointly by the parties or by I3
individually associated with the Clinical Manufacturing Facility or Process,
including all rights to seek or obtain patent coverage for all or any part of
the Clinical Manufacturing Facility or Process. The parties agree to work
together in good faith to protect any such Joint Inventions, including the
filing of any patent applications. As co-owners of the Joint Inventions and any
patents related thereto (a) I3 shall not exploit such Joint Inventions or
related patents, through license or otherwise, with respect to any radiolabeled
product based on the DOTMP or EDTMP family, and (b) NeoRx shall have full power
and authority to exploit such Joint Inventions in any manner NeoRx deems
appropriate, including the granting of licenses related thereto, and I3 hereby
consents to NeoRx making any such license and agrees to execute any documents
necessary to acknowledge such consent; provided, however, that NeoRx will not
allow any manufacturer that competes directly with I3 to use the Joint
Inventions, through license or otherwise, unless such use is associated with the
production of NeoRx products or a derivative thereof. In the event that either
party elects not to participate equally in the cost of filing, prosecuting and
maintaining in force patent applications or patents or other action to protect
Joint Inventions, then the other party shall have the right, at its sole
expense, to pursue such protection and shall be entitled to retain all right,
title and interest in any resulting patents subject to the other party retaining
an irrevocable, royalty free, nonexclusive license to use such Joint Inventions
(a "Joint Invention License"). In the event I3 obtains a Joint Invention
License, I3 shall not exploit such Joint Invention License, through sublicense,
use or otherwise, with respect to any radiolabeled product based on the DOTMP or
EDTMP family. In the event NeoRx obtains a Joint Invention License, it shall
have full power and authority to exploit such Joint Invention License in any
manner NeoRx deems appropriate, including the granting of sublicenses related
thereto, and I3 hereby consents to NeoRx making any such sublicense and agrees
to execute any documents necessary to acknowledge such consent; provided,
however, that NeoRx will not allow any manufacturer that competes directly with
I3 to use the Joint Inventions, through sublicense or otherwise, unless such use
is associated with the production of NeoRx products or a derivative thereof.
(b) PROPRIETARY INFORMATION. Each party's respective Proprietary
Information that is supplied to the other party to assist it in carrying out its
obligations hereunder shall remain the property of the supplying party and shall
be returned to such party upon termination of this Agreement.
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11.3 LIMITATIONS; DISCLOSURES
(a) LIMITATIONS. For purposes of this Agreement, the term Proprietary
Information shall not include information which:
(i) is in the public domain or becomes generally available to the
public through no fault of either party; or
(ii) the Receiving Party can show by documentary evidence was within
its possession or control prior to its being furnished to the Receiving
Party by or on behalf of the Disclosing Party pursuant hereto, free of any
obligation of confidentiality; or
(iii) the Receiving Party can show by documentary evidence that came
into its possession or control subsequent to the date of this agreement
from a third party free of any obligation of confidentiality; or
(iv) was independently developed by the Receiving Party without the
aid, application or use of the Proprietary Information disclosed; or
(v) is required to be disclosed by applicable law order of any
governmental authority of competent jurisdiction (provided, that in such
event, the Receiving Party shall provide the other party with notice of
such law or order and provide reasonable cooperation in connection with any
attempt to challenge or limit the scope of such disclosure).
(b) DISCLOSURES. During the Term of this Agreement, neither Party shall
make any press release or other disclosure of the terms of this Agreement
without the prior written consent of the other Party, except as required by a
court of competent jurisdiction and pursuant to the disclosure requirements of
federal or state regulatory agencies, including the Securities and Exchange
Commission. NeoRx and I3 shall jointly redact all Proprietary Information from
this Agreement for filing with the Securities and Exchange Commission, and will
jointly make a request for confidential treatment of such redactions.
ARTICLE XII - INDEMNIFICATION AND INSURANCE
12.1 INDEMNIFICATION BY NEORX
NeoRx shall defend, indemnify, and hold harmless I3, its officers, agents,
employees and Affiliates from any loss, claim, action, damage, expense or
liability (including defense costs and reasonable attorneys' fees) arising out
of NeoRx's (a) breach, violation or nonfulfillment of any of its covenant,
agreements, representations or warranties under this Agreement, (b) handling,
possession, or use of the Products, (c) negligent acts or omissions or willful
misconduct, or (d) breach of any third party's trade secret rights, except for
and to the extent that such loss, claim, action, damage, expense or liability is
based on, arises out of, or is due to I3's (i) breach of any of its
representations or warranties hereunder, (ii) negligent act or omission, (iii)
willful misconduct, (iv) failure to Process the Product according to the
Requirements or consistent with
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the applicable sections of the IND or NDA (whichever is applicable) and any
corresponding licenses, registrations, authorizations or approvals of any
governmental entity, or (v) failure to manufacture, handle, store, label,
package, transport or ship the product in accordance with cGMP or any other
applicable law, regulation, or other requirements of any applicable governmental
entity.
12.2 INDEMNIFICATION BY I3
I3 shall defend, indemnify, and hold harmless NeoRx, its officers, agents,
employees and Affiliates from any loss, claim, action, damage, expense or
liability (including defense costs and reasonable attorneys' fees) arising out
of or related to I3's (a) breach, violation or nonfulfillment of any of its
covenants, agreements, representations or warranties under this Agreement, (b)
negligent acts or omissions or willful misconduct, (c) disposal of any Waste,
(d) failure to Process the Products in accordance with the Requirements, cGMP,
any applicable laws or regulations, or the applicable sections of the IND or NDA
(whichever is applicable) or any corresponding licenses, registrations,
authorizations or approvals of any governmental entity (e) manufacture,
handling, storage, labelling, packaging or delivery of the Product, or (f)
breach of any third party's trade secret rights, except for and to the extent
that loss, claim, action, damage, expense or liability is based on, arises out
of, or is due to NeoRx's (i) negligent act or omission or willful misconduct or
(ii) breach of any its warranties or representations hereunder.
12.3 INJURIES TO EMPLOYEES
NeoRx agrees that, in the event of a personal injury to a NeoRx employee in
the course of his/her employment, NeoRx or its insurance carrier will be
responsible for worker's compensation payments to such employee. I3 agrees that,
in the event of a personal injury to a I3 employee in the course of his/her
employment, I3 or its insurance carrier will be responsible for worker's
compensation payments to such employee.
12.4 INDEMNIFICATION NOT A WAIVER
A party's right to demand and receive indemnification pursuant to this
Article XII shall not be such party's exclusive remedy, and the exercise by such
party of its right to demand and receive indemnification pursuant to this
Article XII shall not be deemed to prejudice, or to constitute or operate as a
waiver of, any other right or remedy that such party may be entitled to exercise
at law or equity.
12.5 PROCEDURE
Each party agrees to give the indemnifying party (a) prompt notice of any
claim or suit coming within the purview of the indemnities contained in this
Article XII, (b) all relevant facts in its possession or control, subject to the
treatment of such information pursuant to Article XI, (c) the right to exclusive
control of the defense of any action (at the indemnifying party's sole expense),
and (d) its cooperation in the defense of any such action.
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12.6 INSURANCE
(a) PRODUCT LIABILITY INSURANCE. NeoRx shall obtain and maintain in
effect, with financially sound and reputable insurers, product liability
insurance or indemnity policies which name I3 as an additional insured, with
respect to the manufacture, sale and use of commercial products produced by
NeoRx that contain Products. Such insurance policies shall be in an amount not
less than $5 million/$5 million for bodily injury and $5 million for property
damage.
(b) PRODUCT LIABILITY CLAIMS. Each party shall give the other prompt
written notice of any injury alleged to have occurred as a result of the use of
any Product, specifying the time, place and circumstances thereof and the names
and addresses of the persons involved. Each party shall also forward promptly to
the other copies of all papers received in respect of any matter arising out of
the alleged injury.
(c) MANUFACTURER'S INSURANCE. I3 shall obtain and maintain in effect, with
financially sound and reputable insurers, appropriate insurance policies, with a
minimum aggregate coverage of not less than $5,000,000 per annum, naming NeoRx
as an additional insured, with respect to the Processing of the Products
according to the Requirements.
(d) EVIDENCE OF INSURANCE. Each party shall supply to the other copies of
certificates of insurance giving evidence of procurement of the insurance in the
amounts specified in this Article XII (including the naming of the other party
as an additional insured, if required).
ARTICLE XIII - TERM AND TERMINATION
13.1 TERM
(a) Subject to the parties' ability to terminate this Agreement as set
forth in this Article XIII, the "Initial Term" of this Agreement shall commence
on the Effective Date and shall continue through [ * ] (the "Initial Term").
(b) Upon the expiration of the Initial Term, NeoRx shall have the option
of extending this Agreement for up to an additional three (3) year term (the
"Extension Term"); provided, that NeoRx shall exercise its option, if at all, in
writing no later than six (6) months prior to the end of the Initial Term. The
Initial Term and the Extension Term, if applicable, unless the Agreement is
terminated by either party pursuant to the terms of this Agreement, are
collectively referred to herein as the "Term."
13.2 TERMINATION BY EITHER PARTY
Either party may terminate this Agreement at any time after the happening
of any of the following events; provided, however, that the party terminating
this Agreement shall provide the other with written notice of such termination
prior to the date thereof:
(a) either party breaching any of its agreements, covenants,
representations or warranties as set forth in this Agreement and the breaching
party fails to cure such breach within fifteen (15) days of written notice
thereof from the non-breaching party; or
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(b) I3 fails to timely fulfill (i) [ * ] or (ii) [ * ], in accordance with
this Agreement and the applicable Purchase Orders; provided, however, that prior
to terminating this Agreement, a senior executive officer of NeoRx and a senior
executive officer of I3 will meet in good faith within fifteen (15) days of I3's
failure to timely fulfill the Purchase Orders as described above in an attempt
to resolve any disputes or delays; or
(c) a party is declared insolvent or bankrupt by a court of competent
jurisdiction, or a party is served with an involuntary petition against it as
part of an insolvency proceeding and such petition is not dismissed within sixty
(60) days after the filing thereof, or a voluntary petition of bankruptcy is
filed in any court of competent jurisdiction by a party, or a party makes or
executes any assignment for the benefit of creditors, or a receiver is appointed
to control the business of a party; or
(d) if clinical or market data do not support the clinical development or
commercialization of the Product, or if the FDA refuses to grant approval for
the clinical development or commercialization of the Product within a
commercially reasonable time, based on response data derived from clinical
trials; or
(e) the FDA, Texas Department of Health or other regulatory agency orders
I3 to cease Processing the Product or orders NeoRx to cease commercially
supplying Product; or
(f) the parties fail to meet two (2) consecutive Milestones; provided,
however, that prior to terminating this Agreement, a senior executive officer of
NeoRx and a senior executive officer of I3 will meet in good faith within
fifteen (15) days of the parties' failure to meet the second consecutive
Milestone in an attempt to resolve any disputes or delays; or
(g) I3 fails to meet either the Primary Completion Date or the Validation
Completion Date, in accordance with Article II; provided, however, that prior to
terminating this Agreement, a senior executive officer of NeoRx and a senior
executive officer of I3 will meet in good faith within fifteen (15) days of the
parties' failure to meet either Completion Date in an attempt to resolve any
disputes or delays.
Notwithstanding any provision in this Agreement to the contrary, I3 shall
continue to Process the Product, and deliver Product in response to any Purchase
Order, through the date of termination, unless such Process and delivery
requirements are waived in writing by NeoRx.
13.3 DISPUTES
Except as set forth in Sections 6.3 and 8.5, in the event of a good faith
dispute regarding the interpretation of this Agreement, the parties agree they
will endeavor to resolve such dispute amicably. In the event a dispute cannot be
resolved by the parties, then upon the written request of any party that
includes a summary of the dispute, the Chief Executive Officers, or other senior
executive officer, of each party shall promptly meet and endeavor to resolve the
dispute through good-faith negotiations within thirty (30) days of their receipt
of the dispute. If any dispute goes unresolved after following the foregoing
procedures, either party may terminate this Agreement.
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13.4 RETURN OF INFORMATION
Upon expiration or termination of this Agreement, I3 shall return to NeoRx
all originals and copies of manuals, correspondence documents, records, and all
written Proprietary Information it may have received or created concerning the
preparation of Product.
13.5 ASSIGNMENT
(a) NEORX. NeoRx may not assign its rights and/or delegate its obligations
under this Agreement to any third party without I3's prior written consent;
provided, however, that NeoRx may assign its rights and/or delegate its
obligations under this Agreement, without I3's prior written consent, to a third
party solely in connection with the sale, merger or transfer of substantially
all of the assets to which this Agreement relates, provided such assignee or
delegate agrees to be bound by the terms of this Agreement, and provided that
such action would not in any way impair or jeopardize any pending or actual
regulatory approval for the manufacture of Product or adversely affect the
regulatory status of the Product.
(b) I3. I3 may not assign its rights and/or delegate its obligations under
this Agreement to any third party without NeoRx's prior written consent;
provided, however, that I3 may assign its rights and/or delegate its obligations
under this Agreement, without NeoRx's prior written consent, to a third party
solely in connection with a merger, provided that such third party agrees to be
bound by the terms of this Agreement, and provided that such action would not in
any way impair or jeopardize any pending or actual regulatory approval for the
manufacture of Product or adversely affect the regulatory status of the Product.
13.6 RIGHTS ON TERMINATION
(a) CONTINUING OBLIGATIONS. Upon termination of this Agreement, each of
the parties shall continue to be bound by its obligations under Articles VII and
XI and Sections 12.1 through 12.5 of this Agreement.
(b) NEORX'S ADDITIONAL REMEDIES. If NeoRx terminates this Agreement
pursuant to Section 13.2(a) (for I3's breach of this Agreement) or Section
13.2(b) (for I3's failure to timely fulfill Purchase Orders) or 13.2(c) (for I3
being declared insolvent or bankrupt), then:
(i) Within sixty (60) days of such termination, I3 shall pay a
cancellation fee to NeoRx equal to [ * ]; provided, however, that if I3 has
assigned any of its rights and/or delegated any of its obligations under
this Agreement to any third party, then the cancellation fee owing to NeoRx
shall be [ * ]. The parties acknowledge and agree that NeoRx's actual
damages in the event of the termination of this Agreement as described
above would be extremely difficult or impracticable to determine;
therefore, the parties acknowledge that the termination fee reflects as
accurately as possible actual costs that would be incurred by NeoRx, is a
reasonable estimate of just compensation for such costs, and is not a
penalty; and
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(ii) I3 shall pay to NeoRx the amount of any excess costs or expense
incurred by NeoRx to obtain Product from a third party manufacturer; and
(iii) within thirty (30) days of such termination, I3 shall deliver to
NeoRx (A) all Dedicated Moveable Equipment in its then current condition,
subject to any regulatory requirements to the contrary, at I3's expense,
and (B) a commercially reasonable plan to transition the Processing of the
Product to a third party manufacturer. NeoRx shall be responsible for the
implementation of such transition plan. In the event that I3 fails to
deliver to NeoRx any Dedicated Moveable Equipment within such thirty (30)
days, then at NeoRx's discretion (C) I3 shall immediately deliver the
Dedicated Moveable Equipment to NeoRx, (D) NeoRx may purchase replacement
equipment and I3 shall reimburse NeoRx for all costs and expenses in making
such purchase, or (E) I3 shall immediately pay to NeoRx an amount equal to
such equipment's replacement value regardless of whether NeoRx purchases
replacement equipment. In the event I3 fails to deliver to NeoRx a
commercially reasonable transition plan, then within sixty (60) days of
termination I3 shall pay to NeoRx [ * ]; and
(iv) within seventy-five (75) days of such termination, I3 shall
deliver to NeoRx all Dedicated Fixed Equipment in its then current
condition, subject to any regulatory requirements to the contrary, at I3's
expense. In the event that I3 fails to deliver to NeoRx any Dedicated Fixed
Equipment within such seventy-five (75) days, then at NeoRx's discretion
(A) I3 shall immediately deliver the Dedicated Moveable Equipment to NeoRx,
(B) NeoRx may purchase replacement equipment and I3 shall reimburse NeoRx
for all costs and expenses in making such purchase, or (C) I3 shall
immediately pay to NeoRx an amount equal to such equipment's replacement
value regardless of whether NeoRx purchases replacement equipment; and
(iv) during the six (6) months following termination, if requested by
NeoRx I3 shall provide at least one hundred and sixty (160) person-hours of
the time of I3 employees, at no cost to NeoRx, to assist NeoRx in
establishing a third party facility for Processing the Product; and
(v) within thirty (30) days of such termination, I3 shall transfer
to NeoRx all remaining raw materials and shipping materials already paid
for by NeoRx (including, without limitation DOTMP), Batch records, standard
test methods and Specifications in I3's possession, along with all data,
documentation and other information directly relating to the Process
subject to any regulatory requirements to the contrary; and
(vi) immediately upon such termination, I3 shall cease using and
shall return to NeoRx any and all of NeoRx's Proprietary Information; and
(vii) I3 will, to the extent it is able to do so, continue to supply
Product as may be requested by NeoRx, at the prices set forth herein until
the earlier of (A) nine (9) months from the date of such termination, (B)
the natural expiration date of this Agreement, or (C) the date upon which
NeoRx has established an alternative source of manufacturing and supply
services with respect to the Product, which source is capable of
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performing at levels satisfactory to NeoRx and has received all requisite
regulatory and legal approvals to perform such manufacturing and supply
services.
(c) I3'S ADDITIONAL REMEDIES. If I3 terminates this Agreement pursuant to
Section 13.2(a) (for NeoRx's material breach of this Agreement) or 13.2(c) (for
NeoRx being declared insolvent or bankrupt), then:
(i) within thirty (30) days of such termination, NeoRx shall pay to
I3 any amounts not yet paid for the Construction Fee under this Agreement;
and
(ii) within sixty (60) days of such termination, NeoRx shall pay a
cancellation fee to I3 equal to [ * ]. The parties acknowledge and agree
that I3's actual damages in the event of the termination of this Agreement
as described above would be extremely difficult or impracticable to
determine; therefore, the parties acknowledge that the termination fee
reflects as accurately as possible actual costs that would be incurred by
I3, is a reasonable estimate of just compensation for such costs, and is
not a penalty.
ARTICLE XIV - FORCE MAJEURE
Neither Party hereto shall be liable to the other in damages for any delay
or default in such Party's performance hereunder if such delay or default is
caused by conditions beyond such Party's control including, but not limited to,
delays by the FDA or other governmental agency at no fault of a party, acts of
God, war, insurrection, civil commotion, destruction of production facilities or
materials by earthquake, fire, flood or storm, labor disturbances including
strikes or lockouts or epidemic ("Force Majeure"). Each Party hereto agrees to
promptly notify the other Party of any event of Force Majeure and to employ all
reasonable efforts toward prompt resumption of its performance hereunder when
possible if such performance is delayed or interrupted by reason of such event;
provided, however, that either party may terminate this Agreement if the parties
cannot fully resume performance hereunder within thirty (30) days of the
happening of an event of Force Majeure.
ARTICLE XV - MISCELLANEOUS
15.1 ASSIGNMENT
This Agreement shall be binding upon and inure to the benefit of the
Parties, their successors and permitted assigns.
15.2 GOVERNING LAW; VENUE; ATTORNEYS' FEES
This Agreement, and all matters relating hereto, shall be governed,
construed and interpreted in accordance with the laws of the State of
Washington, without giving effect to principles of conflicts of law. If either
party is reasonably required to initiate legal action to enforce this Agreement,
the prevailing party in such legal action shall be entitled to recover its
reasonably attorneys' fees and costs.
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15.3 ENTIRE AGREEMENT
This Agreement, along with each Purchase Order, contains the entire
understanding of the parties hereto relating to the subject matter contained
herein, supersedes all prior agreements, promises and understandings of the
parties. This Agreement may not be modified, amended or any provision waived
except by unanimous written consent of the parties.
15.4 NOTICES
All notices, demands, requests and other communications shall be in writing
or by written telecommunication, and shall be given when delivered personally to
the addressee or, if mailed, by certified mail, return receipt requested,
postage prepaid, or sent by written telecommunication, when delivered to the
addresses specified in the opening paragraph of this Agreement. Either party may
from time to time change its address, facsimile number or designated individual
by notice to the other party. Such notice, demand, request, and other
communications shall be deemed to have been given as of the date so delivered or
transmitted by facsimile (as long as the transmitting machine confirms
successful transmission) or, if mailed, three (3) business days after the date
so mailed, or, if sent by overnight courier service, one (1) business day after
the date so sent.
15.5 RELATIONSHIP OF PARTIES
The parties are acting herein as independent contractors and independent
employers. Nothing herein contained shall create or be construed as creating a
partnership, joint venture, joint employer or agency relationship between the
parties and no party shall have the authority to bind the other in any respect.
15.6 NO WAIVER
Any terms, covenants, or obligations of any party may be waived at any time
in writing executed by the party or parties for whose benefit such terms exist.
The failure to enforce any provision of this Agreement shall not constitute a
waiver of any term hereof. No waiver in any one or more instances shall be
deemed to be a further or continuing waiver of any other condition or any breach
of any other terms, covenants or representations.
15.7 SEVERABILITY
In the event that any provision of this Agreement shall be held invalid,
illegal or unenforceable under applicable law such provision shall be made to
conform to the law, and the remainder of this Agreement shall remain valid and
enforceable, unless such invalidity, illegality or unenforceability
substantially diminishes the rights and obligations, taken as a whole, of any
party.
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15.8 AGREEMENT APPROVAL
Each party hereby represents and warrants that all necessary corporate
approvals for this Agreement have been obtained, and the person whose signature
appears below has the authority necessary to execute this Agreement on behalf of
the party indicated.
15.9 CAPTIONS
The captions in this Agreement are solely for convenience of reference and
shall not be used for purposes of interpreting or construing the provisions
hereof.
15.10 NON-SOLICITATION
During the term of this Agreement and for one (1) year thereafter, the
Parties agree not to solicit for employment each other's employees except those
employees who have been terminated or laid off by either Party.
15.11 COUNTERPARTS
This Agreement may be executed in counterparts, each of which shall be
deemed to be an original and all of which together shall constitute one and the
same agreement.
15.12 FURTHER ASSURANCES
Each party agrees that it shall execute such further documents and perform
such further acts as may be necessary to comply with the terms of this
Agreement.
15.13 INTELLECTUAL PROPERTY
No trademark, trade name, logo, trade dress, copyright or license therein,
or other intellectual property rights (collectively, "Intellectual Property")
are conveyed by this Agreement, and neither party shall have the right to use
the other party's Intellectual Property for any purpose whatsoever without prior
written consent.
15.14 PRICING
All references to pricing in this Agreement shall be in terms of U.S.
dollars.
[signatures on following page]
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IN WITNESS WHEREOF, the Parties have caused this Agreement to be executed
by duly their authorized representatives, effective on this date first set forth
above.
INTERNATIONAL ISOTOPES INC. NEORX CORPORATION
By: By:
------------------------------ ------------------------------
Name: Name:
---------------------------- ----------------------------
Its: Its:
----------------------------- -----------------------------
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EXHIBIT A
CONSTRUCTION DESIGN PLAN
[See attached materials]
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EXHIBIT B
MILESTONES
[ * ]
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EXHIBIT C
FINAL COMPOUNDED PRODUCT SPECIFICATIONS
[ * ]
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EXHIBIT D
REQUIREMENTS
PROCESSING PROCEDURES
I3 shall Process each Batch in conformance with cGMP, Master Batch Records
and all applicable federal, state and local laws and regulations. In addition,
each Batch being Processed by I3 shall be subject to the following Batch
Processing Procedures:
(1) I3 will Process each Batch according to the conditions of the process
which was validated according to I3's Process Validation Protocol and Validation
Report.
(2) All Quality Control Tests will be performed using the Validation test
methods listed in the Product Specifications, and employing validated laboratory
instrumentation.
(3) At NeoRx's request, I3 will ship (at I3's cost) to NeoRx or its
assigned contractor test samples of Batches in such amounts as determined by the
parties.
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EXHIBIT E
DEDICATED PERSONNEL
[ * ]
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