[*] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS
AMENDED.
Exhibit 10.13
THIS AGREEMENT made in duplicate as of this 14 day of June, 2004.
BETWEEN:
MDS NORDION, a division of MDS (Canada) Inc.
having a place of business at
▇▇▇ ▇▇▇▇▇ ▇▇▇▇
▇▇▇▇▇▇, ▇▇▇▇▇▇▇, ▇▇▇▇▇▇ ▇▇▇▇▇▇
("Nordion")
AND:
MOLECULAR INSIGHT PHARMACEUTICALS, INC.
having a place of business at
▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇▇▇▇, ▇▇▇▇▇ ▇▇▇
("Molecular Insight Pharmaceuticals")
WHEREAS:
I. Molecular Insight Pharmaceuticals is the owner or licensee of a certain
compound known as BMIPP (as defined), a heart diagnostic imaging agent;
II. Nordion has expertise in the development of pharmaceutical processes and
radiolabelling of compounds;
III. Molecular Insight Pharmaceuticals has developed techniques and
demonstrated an ability to label Precursor with 1-123 to form BMIPP;
IV. Molecular Insight Pharmaceuticals desires that Nordion undertake at its
facility a development program based upon Molecular Insight
Pharmaceutical's technique which will allow Molecular Insight
Pharmaceuticals' Precursor to be labeled with 1-123 to form BMIPP;
V. Molecular Insight Pharmaceuticals desires that Nordion establish a
facility at its site in Vancouver, British Columbia, to produce and supply
BMIPP for use in support of Molecular Insight Pharmaceuticals' Phase III
Clinical Trials and in support of Molecular Insight Pharmaceuticals' drug
submission to the FDA.
NOW THEREFORE in consideration of the mutual covenants and agreements herein
contained, and subject to the terms and conditions hereinafter set out, the
parties hereto agree as follows:
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ARTICLE 1 - DEFINITIONS
For the purposes of this Agreement:
1.1 "Affiliate" shall mean an entity or person which controls, is controlled
by or is under common control with either party. For purposes of this
Section 1.1 control shall mean (a) in the case of corporate entities, the
direct or indirect ownership of more than one-half of the stock or
participating shares entitled to vote for the election of directors, and
(b) in the case of a partnership, the power to direct the management and
policies of such partnership.
1.2 "BMIPP" shall mean a pharmaceutical product containing 1-123 labeled
Precursor in diagnostic dosage form for cardiac imaging.
1.3 "Background Technology" shall mean all Nordion proprietary technology
existing prior to the Effective Date, including patents, copyright,
know-how, techniques, methods, processes and trade secrets which Nordion
owns or which is licensed to Nordion and, in each case, which is in
existence in the form of a writing, prototype or can otherwise be
demonstrated to be the property of Nordion prior to the Effective Date.
1.4 "Batch" shall mean a production batch of BMIPP manufactured under this
Agreement.
1.5 "Clinical Trial Batch Size" shall have the meaning attributed in Section
4.1.
1.6 "Clinical Trials" shall mean Phase III human trials for clinical
development of BMIPP in the United States.
1.7 "Commercial Phase" shall mean the period of supply of BMIPP commencing
after NDA regulatory approval has been received in the United States by
Molecular Insight Pharmaceuticals, from the FDA.
1.8 "Current Good Manufacturing Practices" or "cGMP(s)" shall mean the good
manufacturing practices required by the FDA and as set forth in the FD&C
or FDA rules and regulations for the manufacturing, testing and quality
control of pharmaceutical materials as applied to compounds, which
practices are current on the Effective Date of this Agreement and may be
supplemented, amended or modified from time to time.
1.9 "Development Phase" shall mean the period commencing from the Effective
Date until completion of the activities described in Schedule A.
1.10 "Effective Date" shall mean the date first above written.
3
1.11 "FDA" shall mean the United States Food and Drug Administration.
1.12 "FD&C" shall mean the United States Federal Food, Drug and Cosmetic Act,
as amended.
1.13 "Facility" shall mean the facility to be established by Nordion at its
manufacturing site in Vancouver, British Columbia as described in Schedule
B and pursuant to cGMPs, to be used for the production of BMIPP for
diagnostic applications and purposes.
1.14 "IND" shall mean an Investigational New Drug Application as defined by the
rules and regulations promulgated under the FD&C and U.S. Public Health
Service Act and any supplements, modifications or amendments thereunder.
1.15 "Isotope" or "I-123" shall mean Iodine 123.
1.16 "Master Validation Plan" shall mean the program mutually agreed to by the
parties by which documented evidence provides assurance that the Process
will consistently produce BMIPP that meets Specifications.
1.17 "NDA" shall mean a new drug application as defined in the rules and
regulations promulgated under the FD&C and U.S. Public Health Service Act,
as supplemented, modified or amended from time to time.
1.18 "Precursor" shall mean (beta)-methyl-p-iodophenyl-pentadecanoic acid
specified in Schedule C and produced pursuant to cGMPs.
1.19 "Process" shall mean the method of formulation, dispensing, and testing of
the BMIPP developed under this Agreement and in compliance with cGMPS.
1.20 "Reference Standards" shall mean the cGMP compliant compounds as specified
in Schedule D.
1.21 "Specification(s)" shall mean those final specifications for BMIPP as set
out in Schedule E, as amended by mutual agreement of the parties from time
to time.
ARTICLE 2 - PURPOSE
2.1 Scope and Object
The scope and object of this Agreement is to carry out the development of
the Process in accordance with the responsibilities and obligations
attributed to each of the parties as set out in this Agreement. In
addition,
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this Agreement shall provide for the establishment of a Facility to be
utilized, amongst other purposes, in the production and supply of BMIPP as
required in support of Molecular Insight Pharmaceuticals' BMIPP Phase III
Clinical Trial and NDA submission to the FDA.
ARTICLE 3 - DEVELOPMENT PHASE
3.1 Development Activities
During the Development Phase, Nordion and Molecular Insight
Pharmaceuticals shall carry out their respective obligations described and
attributed in Schedule A, it being understood that some activities may be
reasonably delayed to the extent that such activity is premised on the
work or provision of data, information or technology by the other party.
It is understood and acknowledged that due to the developmental nature of
the activities to be carried out during the Development Phase, the time
for completion and sequence for carrying out the activities as set out in
Schedule A shall serve as a guide. Each party shall use their commercially
reasonable best efforts in order to carry out, in a timely manner, their
respective obligations and responsibilities set out in Schedule A.
If either party, acting in good faith, materially fails to satisfy any
milestone or is unable to meet such milestone in accordance with the
timing set out in Schedule A, such party shall provide written notice
thereof to the other party and the parties shall determine a reasonable
corrective action plan and revised milestone schedule. If the parties are
unable to determine a reasonable corrective action plan and revised
milestone schedule, the parties may submit such matter to binding
arbitration in Vancouver, British Columbia, pursuant to and conducted
under the International Commercial Arbitration Act of British Columbia,
which arbitration shall be conducted before a single arbitrator possessing
appropriate industry experience as selected by the parties. If the parties
cannot agree on a single arbitrator, the arbitrator shall be appointed in
accordance with the International Commercial Arbitration Act of British
Columbia. The decision of the arbitrators shall be final and binding.
The parties acknowledge and agree that Schedule A may be amended during
the course of the Development Phase to accommodate unforeseen events and
results. All such changes to Schedule A shall be made by written agreement
of the parties. If any change to Schedule A materially impacts the scope
of work to be provided by Nordion, Nordion will provide a written estimate
of the increase in hours of work at the rates set forth in Section 6.3,
which must be approved in advance by Molecular Insight Pharmaceuticals. No
work on such scope change shall be carried out by
[*] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS
AMENDED.
5
Nordion prior to Nordion's receipt of Molecular Insight Pharmaceuticals'
written approval of such change.
The parties, upon signing this Agreement, shall each designate a program
manager, who shall be responsible for coordinating communication and
monitoring performance under this Agreement. The program managers shall
meet monthly, in person or by telephone, for the purpose of reviewing the
status of the project, assessing progress against the milestones and
activities set forth in Schedule A, and determining the percentage of each
milestone completed and the payments earned, if any, in connection with
each milestone. Minutes of meetings shall be prepared, maintained and
provided to each of the parties.
3.2 Development Phase Work
In consideration of Nordion performing the Development Phase services,
Molecular Insight Pharmaceuticals shall pay Nordion in accordance with the
rates set out in Schedule F, which schedule includes amounts payable upon
achievement of milestones as well as amounts payable for each Batch
produced and supplied by Nordion hereunder. All amounts due Nordion shall
be paid by Molecular Insight Pharmaceuticals within thirty (30) days of
the date appearing on Nordion's invoice. Such invoice shall, unless
otherwise agreed, be payable in United States dollars.
3.3 Facility Program
In consideration of Nordion establishing the Facility, Molecular Insight
Pharmaceuticals will pay to Nordion a non-reimbursable facility fee of
[**********************] United States dollars (US $[********]) upon
execution of this Agreement.
After the Facility is completed, Nordion shall, in consultation with
Molecular Insight Pharmaceuticals, develop and implement a Master
Validation Plan for the Facility that will allow the production of BMIPP
under cGMPs in the volumes required by Molecular Insight Pharmaceuticals
for Phase III clinical supply as described in Section 4.1. The costs of
preparation, development and implementation of the Master Validation Plan
will be borne by Nordion. Prior to implementation, both parties shall in
writing approve the Master Validation Plan. Nordion shall ensure that the
Facility is available for the production of BMIPP for supply to Molecular
Insight Pharmaceuticals on a priority basis at least three days per week
to be mutually agreed between the parties.
3.4 Repairs and Maintenance
6
After the Facility is established, Nordion shall maintain such Facility in
satisfactory operating condition as required by the Specifications,
Process and cGMPs, and all other applicable laws, regulations, rules or
orders. The cost of repairs, preventive maintenance and service contracts
for the Facility shall be borne by Nordion.
3.5 Commercial Phase Negotiations
Within thirty (30) days after completion of Milestone 2 under the
Development Phase, the parties shall for a period of at least sixty (60)
days enter into good faith negotiations for the supply of BMIPP to
Molecular Insight Pharmaceuticals, during the Commercial Phase.
ARTICLE 4 - BATCH SIZE IN SUPPORT OF NDA SUBMISSION
4.1 Clinical Supply Batch Size
The Batch size for Clinical Trial supply shall be thirty (30) doses of
BMIPP. The maximum number of vials available for shipment from any Batch
will be twenty (20) doses with the remainder being retained by Nordion for
archival and quality assurance testing. BMIPP will be shipped in an
appropriate lead shield, which will be provided at Nordion's expense. All
necessary labels for shipment will be provided by Molecular Insight
Pharmaceuticals and shall meet all applicable regulatory requirements.
ARTICLE 5 - GENERAL MANUFACTURE AND
SUPPLY OBLIGATIONS OF NORDION
5.1 BMIPP Supply
Nordion agrees to (i) use the Process to produce Batches of BMIPP that
meet the Specifications and are manufactured in conformance with cGMPs and
(ii) ship BMIPP to customers as directed by Molecular Insight
Pharmaceuticals. Nordion reserves the right to withhold from shipment any
Batch which does not conform to Specifications. The price of any Batch
required by Molecular Insight Pharmaceuticals during the term of this
Agreement shall be as set out in Schedule F. The parties agree that
Molecular Insight Pharmaceuticals will provide BMIPP at its expense and
Nordion will supply isotopes and other supplies at its expense.
5.2 Compliance with Law; Handling of BMIPP
While Precursor, Isotope and BMIPP are in its possession or under its
control, Nordion shall be responsible for compliance with applicable
statutory and regulatory requirements in the United States and Canada
regarding the development, manufacture, handling, storage, labeling,
7
packaging, transportation and shipment of the Precursor, Isotope and
BMIPP.
5.3 Testing and Documentation
Nordion shall maintain accurate and complete production records with
respect to the Process, Batches and shipments and Molecular Insight
Pharmaceuticals shall have access to such records in order to determine
that each Batch was produced and tested in compliance with the
Specifications and cGMP requirements.
The tests and analyses provided in the Specifications as well as the
nature and form of records may be amended by Nordion from time to time,
subject to the consent of Molecular Insight Pharmaceuticals, which shall
not be unreasonably withheld after Nordion shall have delivered to
Molecular Insight Pharmaceuticals, in writing, an explanation of such
changes and why they are necessary or advisable.
ARTICLE 6 - GENERAL
MOLECULAR INSIGHT PHARMACEUTICALS OBLIGATIONS
6.1 Precursor and Reference Standards
Molecular Insight Pharmaceuticals or, at Molecular Insight
Pharmaceuticals' discretion its designee, shall provide Precursor and
Reference Standards to Nordion at no charge, which meets the
specifications in Schedules C and D in sufficient quantities to permit
Nordion to meet its obligations hereunder. Nordion shall only use
Precursor and Reference Standards for the manufacture of BMIPP pursuant to
this Agreement. Nordion shall store Precursor and Reference Standards in
accordance with its applicable specifications set out in Schedule C and D
respectively. Molecular Insight Pharmaceuticals shall at all times retain
title in and to such materials in Nordion's possession.
6.2 Unavailability or Scarcity of Precursor or Reference Standards
Molecular Insight Pharmaceuticals will notify Nordion upon Molecular
Insight Pharmaceuticals becoming aware of a shortage of supply of
Precursor or Reference Standards, if such shortage will impact the
manufacture of the BMIPP. Except as set out below, Molecular Insight
Pharmaceuticals shall not be liable for any delays or shortages in the
supply of Precursor or Reference Standards, provided however, that any
such shortages or delays in Precursor or Reference Standards supply will
excuse Nordion's performance of activities related to such Batch of BMIPP
only to the extent that Nordion's non-performance was caused by the
8
Precursor or Reference Standards supply delay or shortage and only for a
period of time equal to the delay.
6.3 Additional Compensation to Nordion
In addition to the amounts set forth in Schedule F, Molecular Insight
Pharmaceuticals will compensate Nordion based on the rate of one hundred
and twenty-five United States dollars (US$125.00) per person per hour for
the time spent by Nordion on the following activities only and upon
Molecular Insight Pharmaceuticals prior written request:
(i) preparing and hosting Facility audits requested by Molecular Insight
Pharmaceuticals including FDA preaudit inspections;
(ii) preparing responses to FDA inquiries and preparation by Nordion of
information requested by Molecular Insight Pharmaceuticals in
support of Molecular Insight Pharmaceuticals' BMIPP NDA submission;
and
(iii) attending meetings with the FDA.
Molecular Insight Pharmaceuticals shall reimburse Nordion for all costs
incurred for travel and accommodation in carrying out the foregoing
activities. Nordion shall provide an estimate of all such activities to
Molecular Insight Pharmaceuticals prior to incurring the expenditure.
ARTICLE 7 - BMIPP SHIPMENTS
7.1 Orders and Shipments
During the term of this Agreement, Molecular Insight Pharmaceuticals will
forward orders to Nordion at its Kanata, Ontario facility by facsimile.
Each order will set forth the quantity to be produced and shipped, the
identity of the recipient, delivery destination protocol number, IND
number, applicable USNRC materials license number and IRS number. Delivery
of BMIPP to Molecular Insight Pharmaceuticals or as otherwise directed by
Molecular Insight Pharmaceuticals shall be FOB transport vehicle at
Nordion's facility in Vancouver, British Columbia. Risk of loss of BMIPP
shall pass to Molecular Insight Pharmaceuticals at point of delivery.
During the term of this Agreement Nordion shall use commercially
reasonable best efforts to meet Molecular Insight Pharmaceuticals' orders
and delivery requirements. Prior to the first shipment of BMIPP to any
third party site, Molecular Insight Pharmaceuticals shall obtain from such
third party and provide to Nordion such third party's license evidencing
proper legal authority for the receipt and possession of the BMIPP by such
third party. Molecular Insight Pharmaceuticals shall obtain all approvals,
licenses and permits required to import BMIPP into the United States.
9
Nordion shall make shipping arrangements with AirNet Express or such other
carrier designated by Nordion and reasonably approved by Molecular Insight
Pharmaceuticals. All shipping costs incurred to deliver BMIPP shall be
borne by Molecular Insight Pharmaceuticals.
Molecular Insight Pharmaceuticals shall be entitled to cancel any Batch
ordered from Nordion by providing to Nordion at least two (2) business
days written notice of cancellation prior to the later of commencement of
production or the scheduled production date. The failure to give notice
hereunder shall result in Molecular Insight Pharmaceuticals being required
to pay the full purchase price of such Batch to Nordion. All orders for
BMIPP shall be forwarded by Molecular Insight Pharmaceuticals and received
by Nordion by the Friday Noon (Eastern time) prior to the week in which
BMIPP is to be manufactured.
7.2 Warranty/Recall
Nordion warrants the BMIPP will meet the Specifications and be
manufactured in accordance with cGMP's and be free from defects in
material and workmanship for the period from the date of manufacture to
the expiry date set out on each vial of BMIPP.
If either party discovers that a Batch of BMIPP does not meet the
Specifications, then the discovering party shall promptly communicate with
the other party. If Molecular Insight Pharmaceuticals determines that the
failure to meet Specifications results from an act, failure to act or
other fault of Nordion, or agent of Nordion, Nordion will promptly:
(i) repair or replace such batch of BMIPP; and
(ii) pay for shipping costs of replacement of BMIPP.
In the event that Nordion disputes Molecular Insight Pharmaceuticals'
determination that the fault id due to Nordion and/or its agent, the
parties will select a mutually acceptable outside consulting firm which
will be instructed to review the applicable information and data and
confirm or dissent from Molecular Insight Pharmaceuticals' determination.
If the consulting firm confirms Molecular Insight Pharmaceuticals'
determination, Nordion will have the obligations set out in this Section
and Nordion will pay the fees of such consulting firm. If the consulting
firm dissents from Molecular Insight Pharmaceuticals' determination or
determines that the failure to meet Specifications was due to products,
information or services supplied by Molecular Insight Pharmaceuticals,
Nordion will not have the obligations set out in this Section with respect
to the disputed Batch and Molecular Insight Pharmaceuticals will pay the
fees for such consulting firm.
10
ARTICLE 8 - LICENSE
8.1 Royalty-Free License
Molecular Insight Pharmaceuticals hereby provides to Nordion a
nonexclusive, nontransferable, royalty-free license during the term of
this Agreement to use the patents, data, information and technology
provided by Molecular Insight Pharmaceuticals relating to BMIPP and the
radiolabelling of 1-123 with Precursor for the sole purpose of assisting
Nordion in carrying out its obligations set out in this Agreement.
Molecular Insight Pharmaceuticals represents and warrants that the
technology provided by Molecular Insight Pharmaceuticals relating to BMIPP
allows for BMIPP to be terminally sterilized while still meeting the
specifications set out in Schedule E.
ARTICLE 9 - MOLECULAR INSIGHT PHARMACEUTICALS
REPRESENTATIONS AND WARRANTIES
9.1 Molecular Insight Pharmaceuticals' Representations and Warranties
Molecular Insight Pharmaceuticals represents, warrants and covenants that:
(i) it has full right, power and authority to enter into this Agreement;
(ii) it is the owner or has the right of use of the patents, data,
information and technology supplied to Nordion by Molecular Insight
Pharmaceuticals to assist Nordion in manufacturing BMIPP and in
carrying out its obligations hereunder;
(iii) to Molecular Insight Pharmaceuticals' knowledge, there is no action
or proceeding pending or threatened against Molecular Insight
Pharmaceuticals before any court, administrative agency or other
tribunal which might have an adverse material effect on its ability
to perform its obligations hereunder;
(iv) it has the right to grant the license in section 8.1 and right to
permit Nordion to use the patents, technology and know how provided
to the extent required to assist Nordion in carrying out its
obligations under this Agreement;
(v) it has not received any notice of adverse claim or infringement of
any patent, copyright, or misappropriation of trade secrets in
connection with the use and exploitation of the Precursor, Reference
Standard or BMIPP;
(vi) to Molecular Insight Pharmaceuticals' best information and belief,
use or sale of Precursor, Reference Standards and BMIPP and the
data, information, technology and know how used in the Process and
manufacture of BMIPP contributed by Molecular Insight
Pharmaceuticals do not infringe any valid third party patent,
11
pending published patent application or other intellectual property
right.
ARTICLE 10 - NORDION'S REPRESENTATIONS AND WARRANTIES
10.1 Representations and Warranties
Nordion represents, warrants and covenants that:
(i) it has full right and authority to enter into this Agreement;
(ii) it is the owner or has the right to use the data, information and
technology contributed by it with respect to the Background
Technology and other proprietary technology contributed by Nordion
during the Agreement;
(iii) the Background Technology contributed by Nordion does not, to
Nordion's best information and belief, infringe any patents,
copyright or other industrial or intellectual property rights of
third parties;
(iv) it has not received any notice of adverse claim of infringement of
any patent or misappropriation of trade secrets in connection with
the use and exploitation of the data, information and technology
used with respect to Background Technology contributed by Nordion;
and
(v) to Nordiont's knowledge, there is no action or proceeding pending or
threatened against Nordion before any court, administrative agency
or other tribunal which might have a adverse material effect on
Nordion's ability to perform its obligations hereunder.
ARTICLE 11 - INDEMNITY
11.1 Indemnification by Molecular Insight Pharmaceuticals
Molecular Insight Pharmaceuticals agrees to indemnify, defend and hold
Nordion and its Affiliates and their respective directors, officers,
employees and agents, harmless from and against any damages, claims,
liabilities and expenses (including, but not limited to, reasonable
attorney's fees) resulting from any third party claims or suits ("General
Claims Against Nordion") arising out of (a) Molecular Insight
Pharmaceuticals' or a third party's use, handling or shipment of Reference
Standards, Precursor or BMIPP, (b) Molecular Insight Pharmaceuticals'
breach of any of its obligations, warranties or representations hereunder,
or (c) Molecular Insight Pharmaceuticals' negligent acts or omissions or
willful misconduct. Notwithstanding the foregoing, Molecular Insight
Pharmaceuticals will not be required to indemnify, defend and hold Nordion
and its Affiliates and their respective directors, officers, employees and
agents harmless from and against any General Claims Against Nordion to the
extent that such claims arise out of (i) Nordion's
12
breach of any of its obligations, warranties or representations hereunder;
(ii) Nordion's negligent acts or omissions or willful misconduct; (iii)
any failure of Nordion to manufacture, handle, store, label, package,
transport or ship BMIPP in accordance with this Agreement, cGMPs or any
other applicable laws, rules, regulations or other requirements of any
applicable governmental entity; or (iv) any failure of Nordion to
manufacture BMIPP consistent with the Specifications and requirements set
forth herein or with the applicable sections of Molecular Insight
Pharmaceuticals' IND in the United States. Notwithstanding anything in
this Section 11.1, "General Claims Against Nordion" shall not include "IP
Claims Against Nordion" as described in Section 11.3.
11.2 Indemnification by Nordion
Nordion agrees to indemnify, defend and hold Molecular Insight
Pharmaceuticals and its Affiliates and their respective directors,
officers, employees and agents, harmless from and against any damages,
claims, liabilities and expenses (including, but not limited to,
reasonable attorney's fees) resulting from any third party claims or suits
("General Claims Against Molecular Insight Pharmaceuticals") arising out
of (a) Nordion's manufacture, handling, storage, labeling, packaging or
delivery of the BMIPP; (b) Nordion's breach of any of its obligations,
warranties or representations hereunder; (c) Nordion's negligent acts or
omissions or willful misconduct; (d) any failure of the BMIPP to meet the
Specifications; or (e) any failure of Nordion to manufacture, handle,
store, label, package, transport or ship BMIPP in accordance with this
Agreement or cGMPs or any other applicable laws, regulations or other
requirements of any applicable governmental entity. Notwithstanding the
foregoing, Nordion will not be required to indemnify, defend and hold
Molecular Insight Pharmaceuticals and its Affiliates and their respective
directors, officers, employees and agents harmless from and against any
General Claims Against Molecular Insight Pharmaceuticals to the extent
that such claims arise out of (i) Molecular Insight Pharmaceuticals'
breach of any of its obligations, warranties or representations hereunder;
(ii) Molecular Insight Pharmaceuticals' negligent acts or omissions or
willful misconduct; (iii) any defect or failure of Reference Standards or
Precursor to meet applicable specifications or (iv) Molecular Insight
Pharmaceuticals' or third party's use of BMIPP. Notwithstanding anything
in this Section 11.2, "General Claims Against Molecular Insight
Pharmaceuticals" shall not include "IP Claims Against Molecular Insight
Pharmaceuticals" as described in Section 11.4.
11.3 Intellectual Property Claims Against Nordion
Molecular Insight Pharmaceuticals agrees to indemnify, defend and hold
Nordion and its Affiliates and their respective directors, officers,
13
employees and agents, harmless from and against any damages, claims,
liabilities and expenses (including, but not limited to, reasonable
attorneys' fees) resulting from any third party claims or suits arising
out of any proceeding instituted by or on behalf of a third party based
upon a claim that the Process, method of manufacture, use or sale of the
Reference Standards, Precursors or BMIPP infringes a United States or
Canadian patent or any other intellectual property or proprietary right of
a third party ("IP Claims Against Nordion"). Notwithstanding the
foregoing, to the extent the Process or method of manufacture is developed
or contributed by Nordion, Molecular Insight Pharmaceuticals will not be
required to indemnify, defend or hold harmless Nordion or its Affiliates,
and their respective directors, officers, employees and agents from and
against IP Claims Against Nordion.
11.4 Intellectual Property Claims Against Molecular Insight Pharmaceuticals
Nordion agrees to indemnify, defend and hold harmless Molecular Insight
Pharmaceuticals and its Affiliates, and their respective directors,
officers, employees and agents from and against any damages, claims,
liabilities and expenses (including, but not limited to, reasonable
attorney's fees) resulting from any third party claims or suits arising
out of any proceeding instituted by or on behalf of a third party based
upon a claim that the Background Technology, the method of manufacture of
BMIPP or the Process, to the extent developed or contributed by Nordion,
infringes a United States or Canadian patent or any other intellectual
property or proprietary right of a third party ("IP Claims Against
Molecular Insight Pharmaceuticals").
11.5 Infringement
In the event that any portion of the Background Technology or technology
developed or contributed by Nordion under this Agreement becomes the
subject of a claim for a patent, copyright or other industrial or
intellectual property rights infringement action by a third party, Nordion
may,
(i) if such technology was contributed by Nordion, procure the right to
continue using the radiolabelling technology within a reasonable
time not to exceed sixty (60) days; or
(ii) modify the Process (to the extent developed or contributed by
Nordion) to become non-infringing; or
(iii) if neither (i) nor (ii) are possible, upon written notice to
Molecular Insight Pharmaceuticals immediately cease its activities
and/or terminate this Agreement.
The cost and expense of any opinion of counsel sought by Nordion under
this section shall be borne by Nordion. Nordion reserves the right to
control and direct the defense and/or settlement of such claim with legal
counsel of its choosing; provided, however, that it may not settle such
14
claims without the prior written consent of Molecular Insight
Pharmaceuticals, which shall not be unreasonably withheld or delayed;
provided, further that no such consent from Molecular Insight
Pharmaceuticals shall be required if such settlement includes a full
release of Molecular Insight Pharmaceuticals.
In the event that any portion of the Process that was developed or
contributed by Molecular Insight Pharmaceuticals becomes the subject of a
claim for a patent, copyright or other industrial or intellectual property
rights infringement action by a third party, Molecular Insight
Pharmaceuticals may, (i) within a reasonable time not to exceed sixty (60)
days procure the right to continue using the Process or technology, (ii)
modify the Process, to the extent contributed by Molecular Insight
Pharmaceuticals, to become non-infringing or (iii) if neither (i) nor (ii)
are reasonably possible, Molecular Insight Pharmaceuticals may terminate
this Agreement upon written notification to Nordion. Molecular Insight
Pharmaceuticals reserves the right to control an direct the defense and/or
settlement of such claims with legal counsel of its choosing; provided,
however, that it may not settle such claims without the prior written
consent of Nordion, which shall not be unreasonably withheld or delayed;
provided, further that no such consent from Nordion shall be required if
such settlement includes a full release of Nordion.
11.6 Indemnification Procedures
A party (the "indemnitee") which intends to claim indemnification under
this Article 11 shall promptly notify the other party (the "Indemnitor")
in writing of any action, claim or other matter in respect of which the
Indemnitee or any of its directors, officers, employees or agents intend
to claim such indemnification; provided, however, the failure to provide
such notice within a reasonable period of time shall not relieve the
Indemnitor of any of its obligations hereunder except to the extent the
Indemnitor is materially prejudiced by such failure. The Indemnitor shall
be entitled to control the defense of and/or settle any such action, claim
or other matter. The Indemnitee agrees to the complete control of such
defense or settlement by the Indemnitor, provided, however, any settlement
of such claims shall require the Indemnitee's prior written consent unless
such settlement includes a full release of the Indemnitee, in which case
no consent shall be required. The Indemnitee and its directors, officers,
employees and agents shall co-operate fully with the Indemnitor and its
legal representatives in the investigation and defence of any action,
claim or other matter covered by this indemnification. The Indemnitee
shall have the right, but not the obligation, to be represented by counsel
of its own selection and at its own expense.
15
ARTICLE 12 - PATENTS AND TECHNOLOGY
12.1 Ownership of Work Performed
The portion of the Process as developed or contributed by Molecular
Insight Pharmaceuticals shall be the sole and exclusive property of
Molecular Insight Pharmaceuticals. Except to the extent the Process is
developed or contributed by Molecular Insight Pharmaceuticals, Molecular
Insight Pharmaceuticals agrees and acknowledges that any and all ideas,
technology, method, data, information, inventions, improvements,
derivative works and works of authorship conceived, written, created or
first reduced to practice in the performance of the development of the
Process, Background Technology and improvements to the Background
Technology during the term of this Agreement, shall be the sole and
exclusive property of Nordion.
ARTICLE 13 - REGULATORY MATTERS
13.1 Regulatory Status
Upon Nordion's reasonable request, Molecular Insight Pharmaceuticals shall
provide updates to Nordion on (i) the progress of Clinical Trials related
to BMIPP, and (ii) submissions to the FDA and other jurisdictions and
regulatory agencies for marketing authorization with respect to BMIPP.
13.2 Molecular Insight Pharmaceuticals Responsibilities
It shall be the responsibility of Molecular Insight Pharmaceuticals or its
designee to file, obtain and maintain an IND, registrations, listings,
authorizations and approvals as the FDA or any other applicable
governmental entity may require to enable use of BMIPP in Clinical Trials
in the United States. Nordion shall provide directly to Molecular Insight
Pharmaceuticals, or at Nordion's discretion for the purpose of protection
of its proprietary technology with respect to the manufacture of the
Isotope, directly to the regulatory authority all required information in
its possession necessary to assist Molecular Insight Pharmaceuticals in
filing, obtaining and maintaining all licenses, registrations, listings,
authorizations and approvals of any governmental entities necessary for
the use of BMIPP in support of Molecular Insight Pharmaceuticals' BMIPP
NDA submission.
13.3 Nordion Responsibilities
Nordion shall be responsible for obtaining and maintaining all necessary
Facility licenses, registrations, authorizations and approvals which are
necessary to develop, manufacture, handle, store, label, package,
16
transport and ship BMIPP under cGMP conditions and other regulatory
requirements including, but not limited to, the use and handling of
radioactive materials.
At Nordion's expense, Nordion shall update its existing 1-123 bulk
chemical or facility description Drug Master File ("DMF") with the FDA as
may be required for Molecular Insight Pharmaceuticals' NDA for BMIPP in
accordance with Schedule A. Nordion hereby grants Molecular Insight
Pharmaceuticals a right of reference to such DMF, and upon request shall
provide a letter of access to the DMF allowing regulatory review of the
DMF by the FDA in conjunction with Molecular Insight Pharmaceuticals'
BMIPP submissions. At Nordion's expense, Nordion shall apply for and seek
a DMF for BMIPP in accordance with Schedule A.
13.4 Government Inspections, Compliance Review and Inquiries
Upon request of any governmental entity or any third party entity
authorized by a governmental entity, such entity shall, for the purpose of
regulatory review, have access to observe and inspect the (i) Facility,
(ii) procedures used for the storage of Reference Standards and Precursor,
and (iii) manufacturing, testing, storage and shipping of BMIPP, including
Process development operations, and auditing the Facility for compliance
with cGMP and/or other applicable regulatory standards. Nordion shall give
Molecular Insight Pharmaceuticals prompt written notice of any upcoming
inspections or audits by a governmental entity of the Facility or any of
the foregoing and shall allow Molecular Insight Pharmaceuticals to
participate in such audits by being present at any FDA close out meeting
and shall provide Molecular Insight Pharmaceuticals with a written summary
of such inspection or audit following completion thereof. Nordion agrees
to use commercially reasonable efforts to promptly rectify or resolve any
deficiencies noted by a government entity in a report or correspondence
issued to Nordion.
13.5 Access to the Facility
Molecular Insight Pharmaceuticals shall have reasonable access to the
Facility at least once per calendar quarter during the Development Phase
for the purpose of observing Process development relating to BMIPP.
Molecular Insight Pharmaceuticals shall provide to Nordion at least five
(5) business days prior written notice of requested access to the Facility
for the purpose of this Section. All such information disclosed to
Molecular Insight Pharmaceuticals or its employees or agents, shall be
deemed to be Nordion's Confidential Information as such term is defined in
Section 14.1 of this Agreement.
13.6 Recalls
17
Molecular Insight Pharmaceuticals shall notify Nordion promptly if BMIPP
is the subject of a recall or correction (a "Recall"), and Molecular
Insight Pharmaceuticals and/or its designee shall have sole responsibility
for the handling and disposition of such Recall. Molecular Insight
Pharmaceuticals and/or its designee shall bear the costs of any Recall of
BMIPP unless and to the extent such Recall shall have been the result of
Nordion's or its employees acts of omissions or any product defects for
which Nordion is responsible in which case Nordion shall to such extent be
responsible for all of Molecular Insight Pharmaceuticals' out-of-pocket
costs incurred for:
(i) notification of recall to Nordion and third parties;
(ii) return shipment of any defective BMIPP to Nordion; and
(iii) replacement of BMIPP.
In the event that Nordion disputes Molecular Insight Pharmaceuticals'
determination that the fault is due to Nordion and/or to its agent, the
parties will select a mutually agreeable outside consulting firm which
will be instructed to review the applicable information and data and to
confirm or dissent from Molecular Insight Pharmaceuticals' determination.
If the consulting firm confirms Molecular Insight Pharmaceuticals'
determination, Nordion will pay the fees of such consulting firm. If the
consulting firm dissents from Molecular Insight Pharmaceuticals'
determination Nordion will not have the obligations set forth herein with
respect to the Recall and Molecular Insight Pharmaceuticals will pay the
fees of such consulting firm. Molecular Insight Pharmaceuticals and/or its
designee shall maintain records of all sales, shipping records of BMIPP
and customers in sufficient detail to adequately administer a Recall for
the period of time as required by applicable regulation.
13.7 New Regulatory Requirements
Each party shall promptly notify the other of new regulatory requirements
of which it becomes aware which are relevant to the manufacture of BMIPP
under this Agreement and which are required by the FDA and other
applicable governmental entities and the parties shall confer with each
other with respect to the best means to implement and comply with such
requirements.
13.8 Records
Nordion shall maintain all records necessary to evidence compliance with
(i) all applicable laws, regulations and other requirements of applicable
governmental entities in the United States and Canada relating to the
supply and manufacture of BMIPP; (ii) the Specifications; and (iii)
obligations under this Agreement. All such records shall be maintained by
18
Nordion for at least two (2) years after termination or expiration of this
Agreement. Nordion shall provide to Molecular Insight Pharmaceuticals
reasonable access to such records upon request. Prior to destruction of
any record after such time, Nordion shall give written notice to Molecular
Insight Pharmaceuticals. Molecular Insight Pharmaceuticals shall have the
right to request that Nordion maintain such records in an off site storage
facility for such longer periods as Molecular Insight Pharmaceuticals
requests, provided that Molecular Insight Pharmaceuticals pays all costs
associated with such off site storage.
ARTICLE 14 - CONFIDENTIALITY
14.1 Confidentiality and Exceptions
During the term of this Agreement and for a period of ten (10) years
thereafter, each party hereto shall maintain in confidence the content of
the transactions contemplated herein, all technology including Background
Technology and improvements thereto, Nordion proprietary technology,
Molecular Insight Pharmaceuticals proprietary technology, trade secrets,
know-how, data, processes, methods, techniques, formulas and test data
(collectively "Confidential Information") and other information disclosed
to such party by the other party which is identified as "Confidential
information" by the disclosing party. This obligation of confidentiality
shall not apply to the extent that it can be established by the party in
receipt of such information, that the information:
(i) was already known to the receiving party at the time of disclosure;
(ii) was generally available to the public or otherwise part of the
public domain at the time of its disclosure;
(iii) became generally available to the public or otherwise part of the
public domain after its disclosure to the receiving party through no
act or omission of the receiving party;
(iv) was disclosed to the receiving party by a third party who was not
known or ought to be known to the receiving party to have
obligations restricting disclosure of such information; or
(v) was independently developed by the receiving party without any use
of Confidential Information of the disclosing party.
Each party agrees that it will take the same steps to protect the
confidentiality of the other party's Confidential Information as it takes
to protect its own proprietary and confidential information, which shall
in no event be less than commercially reasonable steps. Each party, and
its employees and agents shall protect and keep confidential and shall not
use, publish or otherwise disclose to any third party, except as permitted
by this Agreement, as necessary to perform its obligations hereunder, or
19
with the other party's written consent, the other party's Confidential
Information.
It is agreed that disclosure of data, information or technology by
Molecular Insight Pharmaceuticals or Nordion to the other under this
Agreement shall not constitute any grant, option or license under any
patent, technology or other rights, held by Molecular Insight
Pharmaceuticals or Nordion. Any use of the data, information and
technology provided by Molecular Insight Pharmaceuticals to Nordion which
relates to Precursor, Reference Standards or radiolabelling of Precursor
shall be for the limited purpose of assisting Nordion in carrying out its
obligations under this Agreement. All data, information, or technology
supplied by one party to the other to assist in carrying out the
obligations hereunder shall remain the property of such party and shall be
returned to the other party upon termination of this Agreement.
ARTICLE 15 - DISCLOSURE OF INFORMATION
15.1 Authorized Disclosure
Notwithstanding section 14.1 each party may disclose Confidential
Information to the extent such disclosure is reasonably necessary for
prosecuting or defending litigation and/or complying with applicable
government laws or regulations, provided that if a party is required by
law or regulation to make any such disclosure of the other party's
Confidential Information it will give reasonable notice to the other party
of such disclosure requirement.
ARTICLE 16 - TERM AND TERMINATION
16.1 Initial Term
The term of this agreement shall commence upon the Effective Date and,
unless terminated earlier pursuant to this agreement, or extended upon
mutual agreement of the parties, shall expire on December 31, 2005.
16.2 Termination Without Cause
Molecular Insight Pharmaceuticals may terminate this Agreement without
cause or penalty upon thirty- (30) day's prior written notice to Nordion.
Upon such termination, Nordion shall be entitled to retain all amounts
paid by Molecular Insight Pharmaceuticals and Molecular Insight
Pharmaceuticals shall pay to Nordion any amounts due and/or earned but not
yet paid.
20
16.3 Termination for Breach
This Agreement may be terminated by either party in the event of the
material breach by the other party of the terms and conditions hereof;
provided, however, the other party shall first give to the breaching party
written notice of the proposed termination of this Agreement (a "Breach
Notice"), specifying the grounds therefor. Upon receipt of such Breach
Notice, the breaching party shall have such time as necessary, but in any
event not more than thirty (30) days to cure such breach. Notwithstanding
the foregoing, if the breaching party does not cure such breach within
such cure period, the other party may terminate the Agreement without
prejudice to any other rights or remedies which may be available to the
non-breaching party.
16.4 Bankruptcy
This Agreement may be terminated by a party in the event the other party
files a petition in bankruptcy, is adjudicated a bankrupt, makes an
assignment for the benefit of its creditors, or otherwise seeks relief
under or pursuant to any bankruptcy, insolvency or reorganization statute
or proceeding, or if a petition in bankruptcy is filed against it which is
not dismissed within ninety (90) days or proceedings are taken to
liquidate the assets of such party.
ARTICLE 17 - SURVIVAL
17.1 Consequences or Termination or Expiration
Upon expiration or termination of this Agreement, the obligations of the
parties under Articles 9, 10, 11, 12, 14, 15, 19 and 24 shall survive such
expiration or termination in accordance with its terms.
ARTICLE 18-NOTICES
18.1 Any notice to be sent to a party hereunder shall be forwarded to:
Nordion at: MDS Nordion
▇▇▇ ▇▇▇▇▇ ▇▇▇▇
▇▇▇▇▇▇, ▇▇
▇▇▇ ▇▇▇
Attention: Senior Vice President, Nuclear Medicine
Fax:
Molecular Insight Pharmaceuticals at:
21
Molecular Insight Pharmaceuticals, Inc.
▇▇▇ ▇▇▇▇▇▇ ▇▇▇▇▇▇
▇▇▇▇▇▇▇▇▇, ▇▇
Attention: Chief Operating Officer
Fax: ▇▇▇-▇▇▇-▇▇▇▇
Any notice required or authorized to be given by a party to the other in
accordance with the provisions of this Agreement shall, unless otherwise
specifically stipulated, be in writing and delivered personally, by a
nationally recognized overnight courier, or if by electronic facsimile
confirmed by certified or registered mail. Notice shall be deemed
delivered upon receipt.
ARTICLE 19 - LIMITED LIABILITY
19.1 Disclaimer
In no event shall either party be liable to the other party for indirect,
punitive, contingent, incidental, special or consequential damages.
19.2 Limitation of Product Warranty
MOLECULAR INSIGHT PHARMACEUTICALS ACKNOWLEDGES THAT NORDION IS
MANUFACTURING AND SUPPLYING BMIPP TO MEET SPECIFICATIONS. EXCEPT AS
EXPRESSLY SET OUT IN THIS AGREEMENT, NORDION HEREBY DISCLAIMS ALL OTHER
WARRANTIES OR CONDITIONS, WHETHER EXPRESS OR IMPLIED, STATUTORY OR
OTHERWISE, INCLUDING BUT NOT LIMITED TO ANY IMPLIED WARRANTIES OR
CONDITIONS OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE.
ARTICLE 20 - ASSIGNMENT AND SUBCONTRACTING
20.1 No Assignment
This Agreement shall enure to the benefit of and shall be binding upon the
heirs, executors, administrators, successors and permitted assigns of the
parties. Neither Nordion nor Molecular Insight Pharmaceuticals shall
assign this Agreement or any portion of this Agreement without the written
approval of the other party, which approval shall not be unreasonably
withheld; provided, however, that Molecular Insight Pharmaceuticals may
assign this Agreement without Nordion's consent in connection with the
sale of all or substantially all of its stock or assets to a third party
or in connection with a merger, consolidation or similar transaction.
ARTICLE 21 - COMPLIANCE
21.1 Compliance with Laws
[*] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS
AMENDED.
22
This Agreement and Nordion's and Molecular Insight Pharmaceuticals'
obligations hereunder shall be carried out in compliance with all
applicable laws, by-laws, rules, regulations and orders of all applicable
Federal, State, Provincial and Municipal governments.
ARTICLE 22 - NON-WAIVER
22.1 Non-Waiver of Rights
Failure by either party to enforce at any time any of the provisions of
this Agreement shall not be constructed as a waiver of its rights
hereunder. Any waiver of a breach of any provision hereof shall not be
effective unless in writing and shall not affect either party's rights in
the event of any additional breach.
22.2 Force Majeure
Neither party shall be liable to the other for failure to perform or delay
in performing its obligations under this Agreement by virtue of the
occurrence of an event of Force Majeure. In the event of Force Majeure,
the party affected shall promptly notify the other and shall exert
commercially reasonable efforts to eliminate, cure or overcome such event
and to resume performance of its obligations. In the event such Force
Majeure affecting either party continues for more than thirty (30) days
the party not subject of the Force Majeure may terminate this Agreement.
"Force Majeure" shall mean an occurrence which prevents, delays or
interferes with the performance by a party of any of its obligations
hereunder if such event occurs by reason of any act of God, flood, power
failure, fire, explosion, casualty or accident, or war, revolution, civil
commotion, acts of public enemies, blockage or embargo, or any law, order
or proclamation of any government, failure of suppliers or usually
supplier to provide materials, equipment or machinery, interruption of or
delay in transportation, strike or labor disruption.
ARTICLE 23 - INSURANCE
23.1 Product Liability Insurance
During the term of this Agreement and for a period of one (1) year
thereafter Molecular Insight Pharmaceuticals at its own expense shall
provide and maintain a products liability insurance policy issued by a
reputable insurance company with respect to BMIPP. Such policy shall add
Nordion as an additional insured and shall have a limit of liability of
not less than [*************] United States dollars ($[*********]US) per
occurrence and in the aggregate. Molecular Insight Pharmaceuticals shall
23
be solely responsible for any deductible or retention associated with this
policy and such deductible or retention amounts shall not affect Nordion's
interests. The policy shall contain a cross liability clause and shall
provide for severability of interest such that breach of a policy
condition committed by any one insured shall not adversely affect the
rights of the other insured. Nordion shall be provided thirty (30) days'
prior written notice of any material change to the policy and such change
shall be subject to Nordion's prior written consent, which consent shall
not be unreasonably withheld. Nothing contained in this Section shall be
deemed to limit in any way the indemnification provisions contained in
this Agreement.
ARTICLE 24 - PUBLICATION
24.1 Publicity
The parties agree that, except as may otherwise be required by applicable
laws, regulations, rules or orders or in connection with obtaining
regulatory approvals for BMIPP, no information concerning this Agreement
and the transactions contemplated herein shall be made public by either
party without the prior written consent of the other, which consent shall
not be unreasonably withheld or delayed. In the event either party decides
to issue a press release announcing the execution of this Agreement, it
shall not do so without the prior written approval of the other party.
A copy of any proposed press release shall be provided to the other party
for approval at least three (3) business days prior to any proposed
release.
In the event that this Agreement or any portion of its contents is
required to be disclosed by Molecular Insight Pharmaceuticals or Nordion
pursuant to Security Exchange Commission rules or regulations or other
federal or state authorities, Molecular Insight Pharmaceuticals or
Nordion, as the case may be, shall provide reasonable notice to the other
prior to any such disclosure in order that, to the extent possible while
enabling the party to comply with the applicable laws, rules and
regulations, the content so disclosed does not include information which
may reasonably be considered by the other as confidential, proprietary
and/or commercially sensitive information.
ARTICLE 25 - DISPUTE RESOLUTION
25.1 Dispute Resolution
Except as otherwise set out, in the event that at any time during the term
of this Agreement, a disagreement, dispute, controversy or claim should
arise relating to the (i) interpretation of or performance under this
24
Agreement or the attribution of liability or breach thereof; or (ii)
scientific or technical issues in connection with Nordion or Molecular
Insight Pharmaceuticals' performance under this Agreement, the parties
will attempt, in good faith, to resolve their differences for a period of
thirty (30) days following written notice from one party to the other
specifying such dispute(s). In the event the parties are unable to work
out a resolution of the issue during such 30-day period, either party
shall be free to take any action and seek any remedy it may have at law or
in equity including specific performance and injunctive relief.
ARTICLE 26 - INDEPENDENT CONTRACTOR
26.1 No Joint Venture
The parties agree that with respect to the transactions contemplated
herein that they shall both be acting as independent contractors and
nothing herein shall constitute the parties as entering into a joint
venture or partnership, nor shall anything herein constitute either party
as an agent of the other for any purpose whatsoever.
ARTICLE 27 - SEVERABILITY
27.1 Invalid Provisions
If any provision or term of this Agreement is found unenforceable under
any of the laws or regulations applicable thereto, all other conditions
and provisions of this Agreement shall nevertheless remain in full force
and effect. Upon such determination that any term or other provision is
invalid, illegal or incapable of being enforced, the parties hereto shall
negotiate in good faith to modify this Agreement to effect the original
intent of the parties as closely as possible in a mutually acceptable
manner, in order that the transaction contemplated hereby be consummated
as originally contemplated to the greatest extent possible.
ARTICLE 28 - AGREEMENT
28.1 Entire Agreement
This Agreement, including the Schedules hereto which are incorporated
herein, constitute the entire agreement of the parties with respect to the
subject matter hereof and supersedes all proposals, oral or written, and
all negotiations, conversations, or discussions. This Agreement may not be
modified, amended, rescinded, canceled or waived, in whole or in part,
except by written amendment signed by both parties hereto.
25
ARTICLE 29 - LAW
30.1 Applicable Law
This Agreement shall be governed and construed in accordance with the laws
of the Province of Ontario, Canada, without reference to its principles on
conflict of laws. The application of the United Nations Convention for the
International Sale of Goods is expressly excluded.
26
IN WITNESS WHEREOF the parties hereto have executed this agreement as of
the date first above written.
MDS Nordion, Molecular Insight Pharmaceuticals, Inc.
a division of MDS (Canada) Inc.
By: /s/ ▇▇▇▇▇ ▇▇▇▇▇▇▇▇▇▇▇▇ By: /s/ ▇▇▇▇ ▇. ▇▇▇▇▇▇
--------------------------- ------------------------
#63441 v1 - Agreement/Molecular Insight/Final
SCHEDULE A
Scope of Work
Commence
ACTIVITY Duration -------------
-------- -------- Y weeks from
X weeks Effective Date
-------- --------------
1. Activity 1 - Technology Transfer
a) Review Customer Supplied Documentation 2 1
b) Write, review and approve Preliminary Safety Analysis Report(PSAR) 3 2
c) Experimental Design for Scale-Up 2 2
d) Scale-Up to 1 Ci (up to 10 runs maximum)
i) Show reproducibility of procedure 5 5
ii) Increase yield to 80% after quenching and isolation
(commercially reasonable best efforts)
iii) Verify autoclavability of formulation. Establish excipient
ranges
e) Scale up to 4 Ci (up to 5 runs) 3 10
f) Document experiments and archive data (HPLC traces, 3 13
logbooks, etc.)
Milestone 1 : Complete Technology Transfer 0 16
2. Activity 2- Reformulation and Purification
a) Develop HPLC Separation Method 6 4
b) Develop Automation: sample transfer and collection 4 4
c) Develop compatibility of HPLC collected fraction with 2 4
Formulation. Establish excipients
d) IQ/OQ and validate autoclave. 5 4
e) IQ/OQ/PQ for HPLC and equipment. 6 16
f) Draft Master Batch Record for Molecular Insight approval. 2 19
Milestone 2: Complete Reformulation and Purification 0 21
3. Activity 3- Develop Dispensing Equipment
a) Develop dispensing setup for 30 vial capability 10 9
- IQ/OQ/PQ Dispensing
- Seal and crimp
b) Develop container/ closure system 8 11
- Complete closure test and integrity
- Complete recoverability of dose from Container Test
c) Establish Class 100 conditions for dispensing box at vial 1 19
opening.
d) IQ/OQ/PQ Shielded boxes (SB) 2 20
- calibrate gauges
- establish airborne I-123 detection system
e) IQ/OQ/PQ Laminar Air Flow (LAF) Assembling Area. . 2 20
f) Initiate Environmental Monitoring in LAF, SB and 3 20
Controlled Access Room,
Milestone 3: Complete Dispensing Equipment Development 0 22
4. Activity 4- Develop Q.C. Test Methods
a) HPLC Method for Final Product. 4 22
- verify 1) BMIPP
2) UDCA
3) Any other identified
impurities as per specifications in
Schedule F.
- establish 1) Radiochemical Purity
2) Chemical purity - Quantitative method
Note: this is a method transferred from Molecular Insight
- Write and approve Standard Test Method (STM)
b) IQ/OQ/PQ Dose Calibrator 2 26
Write and Approve STM
c) Gamma Spectroscopy 1 26
- Calibration Protocol
- NIST traceability
- 159 keV Identification (ID) for I-123
- Write.and approve STM
d) Endotoxin Test (USP) 1 28
- Dilution to overcome Inhibition/Enhancement
- Maximum valid dilution
- Qualification of test method
- Write and approve STM
e) Sterility Test (USP) 1 28
- Establish sampling size
- Write and approve STM
f) Product Release Form (PRF) 1 29
- Identify all documents necessary for batch release
Milestone 4: Complete QC Test Methods Development 0 30
5. Activity 5- Validation of New Process
a) Write and approve Master Validation Plan 8 4
- Equipment: Analytical and Process
- Analytical Methods
- Process
- Final Product Stability
b) Method Transfer Validation 6 30
- Analytical Methods
- References Standards (shelf-life; ID)
- Precursor (ID; shelf-life)
c) Validation Protocols 2 36
d) Six Process Runs to fine tune process 6 28
e) Train Operators 6 28
- 3 Production technicians
- 3 QC/QA
- 2 Packaging
Milestone 5: Complete Validation of New Process 34
6. Activity 6- Perform GMP Equivalency Run (Validation Runs) 3 34
a) Perform three runs (1 Ci of I-123) 3 37
b) Compile all data for validation files 0 40
Milestone 6: Complete Validation Runs
7. Activity 7- Prepare Development Report
a) Document all experimentation 6 31
b) Archive all data/logbooks 6 31
c) Write and approve Development Report 6 39
- Process Description and Development
- Master Formula
- Impurities profiles (standards to be provided by
Molecular Insight)
- Excipient Ranges
- Final Product Specifications
- Scale-Up rationale
- Equivalence to previous formulation ( to be done in
conjunction with Molecular Insight at their cost)
- Qualification of Reference Standards to be done by
Molecular Insight
- Precursor made under cGMPs to be provided by
Molecular Insight
- Analytical Method and Validation to be done by
Molecular Insight
- Bioburden Profiles for Raw Material
- Environmental data - house isolates
- Molecular insight to provide stability indicating
methods for final product
- Define Utilities
- Cleaning Protocol
Milestone 7: Submit Development Report 45
8. Activity 8- DMF / CMC Package
a) Provide SOPs/STMs for CMC section of NDA 3 37
b) Provide flowcharts 3 37
c) Establish Review and Approval responsibility for 3 37
documents
d) Establish Recall procedure 3 37
e) Establish responsibilities of 3 37
1) Deviations
2) Change Control
3) Product Release
4) Failure Investigation
5) Out-of-Spec Investigation
6) Draft required procedures
Milestone 8: DMF/CMC Package Complete 40
9. Activity 9- Prepare for PAI
a) audit for cGMP compliance (with customer) 3 40
b) Review findings and establish action plan 3 40
c) Review costs of ongoing and enhanced compliance (to be 3 40
billed to Molecular Insight as required)
NOTE: PAI readiness will
require additional staffing and/or consultants that will be charged
to Molecular Insight.
Milestone 9: Ready for PAI 43
Pcdocs 62635
SCHEDULE B
FACILITY RESOURCES FOR CONTRACT MANUFACTURE OF BMIPP
THE FOLLOWING EQUIPMENT IS USED TO MANUFACTURE BMIPP:
- Laminar Flow Hood for reagent and equipment preparation
- Three Lead shielded glove boxed with HEPA filtration and Nuclear
Ventilation
- Box 1 reaction, separation, formulation box containing
semi-preparative automated HPLC for drug substance isolation
- Box 2 has the function to act as a dispensing area. The
dispensing environment is class 100
- Box 3 is the terminal sterilization box containing an
autoclave and a remote handling ball and tong manipulator
- Specialized shielding assemblies are used for the safe transport of
formulated unit dose radiopharmaceuticals
- Fume hood with nuclear ventilation for QC analysis
- HPLC equipment for QC analysis
- Dose calibrator
- Particle check station
- Gamma Spectroscopy system
- Refrigerator
SOME GENERAL FEATURES OF THE MANUFACTURING AREA AND SUPPORT SERVICES ARE:
- The room is environmentally and radiation monitored
- There are waste handling systems in place to deal with chemical waste
streams as well as solid and liquid radioactive wastes
- The entire manufacturing environment is cGMP regulated
- Qualified and trained staff with experience in diagnostic
radiopharmaceutical manufacture are employed
- The entire manufacturing facility is supported by a calibration department
- A fully outfitted microbiology lab is available for microbiological and
environmental tests (Most importantly LAL tests for pyrogenicity)
- There is an attached microbiology clean room used for sterility tests and
filtration.
- This clean room contains a class 100 glove box.
NOTE: EQUIPMENT OTHER THAN THAT LISTED ABOVE (SUCH AS HOT CELLS ETC.) MAY BE
USED DURING DEVELOPMENT
SCHEDULE C
BMIPP PRECURSOR SPECIFICATIONS
Note: 1. Supplied by Molecular Insight Pharmaceuticals and MDS Nordion to do
identification only
SCHEDULE D
REFERENCE STANDARDS SPECIFICATIONS
Note: 1. Supplied by Molecular Insight Pharmaceuticals and MDS Nordion to do
identification only
SPECIFICATION SHEET
TCI America, ▇▇▇▇ ▇ ▇▇▇▇▇▇▇▇▇▇ ▇▇,
▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇ Version Date 3/7/02 Form No. :SS. 057.02
Material BMIPP (INACTIVE COMPONENT/PRECURSOR) Code No.: Z3398
Formula: C(22)H(35)IO(2) Molecular Wt.: 458.42 CAS No.: 116754-87-1
Synonym(s): 15-(p-Iodophenyl)-
3-methylpentadecanoic Acid Storage Conditions: or = 95% SLT QC 358
After manufacture Purity, Melting point 51-56(degree)C SLT QC 322
After manufacture Purity, Water analysis (KF) Report results SLT QC 329
0 - 60 months Impurities, HPLC Related < or = 2.0 % any single species SLT QC 358
0 - 60 months Methyl 15-(p-Iodophenyl)-3 < or = 0.1% SLT QC 358
Methylpentadecanoate
After manufacture Heavy metals < or = 20 ppm SLT QC 332 (Method II)
After manufacture Residual Solvents
Hexane < or = 290 ppm SLT QC 340
Methanol < or = 3000 ppm SLT QC ▇▇▇
▇▇▇▇▇ ▇▇▇▇▇▇▇ < or = 5000 ppm SLT QC ▇▇▇
▇▇▇▇▇▇▇ < or = 5000 ppm SLT QC 340
Isopropanol < or = 5000 ppm SLT QC 340
After manufacture Organic Volatile Impurities
Methylene Chloride < or = 500 ppm SLT QC 340
SCHEDULE E
BMIPP SPECIFICATIONS
SPECIFICATION SHEET Page 1 of 1
DRUG PRODUCT SPECIFICATION SHEET
Molecular Insight, ▇▇▇ ▇▇▇▇▇▇ ▇▇, ▇▇▇▇▇▇▇▇▇, ▇▇ Version Date (ACTIVE COMPONENT)
02142 4/13/04
Material [(123)I]-BMIPP CODE NO.: MIP 1000
Formula: C(22)H(35)IO(2) Molecular Wt.: 454.42 CAS No.: 116754-87-1
Synonym(s): [(123)I]-15-(p-Iodophenyl)-3-methylpentadecanoic Acid
TEST ACCEPTANCE CRITERIA TEST METHOD TESTING SCHEDULE
Appearance Clear, Colorless Solution Visual observation Test Completed prior
STM 12 to release of drug
Radionuclide Identity Gamma-Photon emission at 159 +/- Gamma ray Spectroscopy, Test Completed prior
5 keV STM 23
to release of drug
Radionuclide Impurity 95% as I-123-BMIPP Reverse phase HPLC Test Completed prior
Radiometric detector to release of drug
STM 17
Chemical Concentration 0.36 to 0.44 mg/ml Reverse phase HPLC Test Completed prior
UV-VIS detector to release of drug
STM 17
Radiochemical Impurity