EXHIBIT 10.23
BMIPP Supply Agreement
THIS AGREEMENT made in duplicate as of this 12th day of January, 2006.
BETWEEN:
MDS NORDION, a division of MDS (Canada) Inc.
having a place of business at
000 Xxxxx Xxxx
Xxxxxx, Xxxxxxx, Xxxxxx
("Nordion")
AND:
MOLECULAR INSIGHT
PHARMACEUTICALS, INC.
having a place of business at
000 Xxxxxx Xxxxxx
Xxxxxxxxx Xxxxxxxxxxxxx, 00000 XXX
("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 production of radiochemicals, in the
development of radiopharmaceuticals, processes, and in the radiolabelling
of compounds;
III. Nordion has expertise in designing and overseeing the construction of
facilities for the radiolabelling of compounds;
IV. Nordion and Molecular Insight Pharmaceuticals entered into an Agreement as
of the 16th day of June, 2004, as amended, for the purpose of undertaking a
development program to establish a process permitting Molecular Insight
Pharmaceutical's precursor (cold BMIPP) to be labeled with I-123 to form a
radiopharmaceutical (the "Development Agreement");
V. Molecular Insight Pharmaceuticals desires that Nordion establish a Facility
at its site in Vancouver, British Columbia, to accommodate growth and
expansion of the process developed under the Development Agreement
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for the production and supply of BMIPP to Molecular Insight Pharmaceuticals
for Clinical Trials and Commercial Phase supply.
VI. Molecular Insight Pharmaceuticals desires that upon completion of the
Facility established under this Agreement that Nordion transition the
manufacture of BMIPP from the existing facility to the new Facility
established under this Agreement.
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:
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 "Batch" shall mean a production batch of BMIPP manufactured under this
Agreement and shall be of the size set forth on Schedule D attached hereto.
1.3 "BMIPP" shall mean I-123 labeled beta-methyl-iodo-phenyl-pentadecanoic acid
in diagnostic dosage form for use in cardiac imaging (and also known as
iodofiltic acid I-123).
1.4 "Clinical Trials" shall mean Phase III human trials for clinical
development of BMIPP for the purpose of seeking pharmaceutical approval in
the United States.
1.5 "Commercial Phase" shall mean the period of supply of BMIPP commencing
after NDA regulatory approval has been received in the United States from
the FDA by Molecular Insight Pharmaceuticals.
1.6 "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.
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1.7 "Effective Date" shall mean the date first above written.
1.8 "Excipients" shall mean the compounds specified on Schedule G.
1.9 "FDA" shall mean the United States Food and Drug Administration.
1.10 "FD&C" shall mean the United States Federal Food, Drug and Cosmetic Act, as
amended.
1.11 "Facility" shall mean a new facility to be established by Nordion at its
manufacturing site in Vancouver, British Columbia as described in Schedule
A and pursuant to cGMPs, to be used for the production of BMIPP for
Clinical Trial and Commercial Phase supply.
1.12 "Facility Milestone(s)" shall mean the milestones relating to the
establishment of the Facility as described in Schedule A.
1.13 "Facility Program" shall mean the program by which Nordion shall establish
the Facility in accordance with the Facility Milestones as described in
Schedule A.
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 "Molecular Insight Pharmaceuticals Background Technology" shall mean
technology conceived, created, developed or reduced to practice by
Molecular Insight Pharmaceuticals prior to or during the Term of this
Agreement or independently of this Agreement, including, without
limitation, patents, know-how, techniques, methods, processes, drawings,
schematics, procedures, protocols, parameters, engineering details,
functional descriptions, data and database content, technical or scientific
information, manuals and trade secrets, which Molecular Insight
Pharmaceuticals owns, uses, conceives, creates, develops, reduces to
practice or provides in performing under this Agreement, or which is
licensed to Molecular Insight Pharmaceuticals and which is in existence in
the form of a writing, prototype or can otherwise be demonstrated to be
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the property of Molecular Insight Pharmaceuticals, or to which Molecular
Insight Pharmaceuticals has the rights.
1.18 "Nordion Background Technology" shall mean technology, conceived, created,
developed or reduced to practice by Nordion prior to or during the Term of
this Agreement or independently of this Agreement, including, without
limitation, patents, know-how, techniques, methods, processes, drawings,
schematics, procedures, protocols, parameters, engineering details,
functional descriptions, data and database content, technical or scientific
information, manuals and trade secrets, which Nordion owns, uses,
conceives, creates, develops, reduces to practice or provides in performing
under this Agreement, or which is licensed to Nordion and which is in
existence in the form of a writing, prototype or can otherwise be
demonstrated to be the property of Nordion or to which Nordion has the
rights.
1.19 "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.
1.20 "Precursor" shall mean b-methyl-p-iodophenyl-pentadecanoic acid specified
in Schedule G and produced pursuant to cGMPs.
1.21 "Process" shall mean the method of formulation, dispensing and testing of
the BMIPP developed pursuant to the Development Agreement and in compliance
with cGMPs, which shall be adjusted to accommodate an increase in
production capability for Clinical Trial and Commercial Phase supply.
1.22 "Quality Agreement" shall mean the agreement set out in Schedule "F".
1.23 "Reference Standards" shall mean the cGMP compliant compounds as specified
in Schedule G.
1.24 "Specification(s)" shall mean those final specifications for BMIPP as set
out in Schedule B, as amended by mutual agreement of the parties from time
to time.
1.25 "Term" shall mean the Initial Term and each Renewal Term as defined in
section 14.1
The following Schedules attached to this Agreement are hereby incorporated by
reference:
SCHEDULE A: Description of Facility Program, Facility Milestones, Facility
Schedule
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SCHEDULE B: BMIPP Specifications
SCHEDULE C: Facility Construction Fees
SCHEDULE D: Price of Batches for Clinical Trial Supply
SCHEDULE E: Indicative Pricing of BMIPP for Commercial Phase Supply
SCHEDULE F: Quality Agreement
SCHEDULE G: Specifications for Precursor, Reference Standards, and Excipients
ARTICLE 2 - PURPOSE
2.1 SCOPE AND OBJECT
The scope and object of this Agreement is to establish a new facility at
Nordion's manufacturing site in Vancouver, British Columbia to implement
the Process for the production and supply of BMIPP for Clinical Trials and
Commercial Phase supply in accordance with the responsibilities and
obligations attributed to each of the parties as set out in this Agreement,
which represents an increase in production and supply from that set forth
in the Development Agreement.
ARTICLE 3 - FACILITY PROGRAM
3.1 FACILITY CONSTRUCTION
In consideration of Nordion establishing the Facility, Molecular Insight
Pharmaceuticals will pay to Nordion the fees as set out in Schedule C,
provided that the respective milestone(s) for establishing the Facility as
set forth on Schedule A attached hereto are successfully met by Nordion.
Nordion shall establish the Facility in accordance with its 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
Molecular Insight Pharmaceuticals. It is understood and acknowledged that
due to the nature of the activities to be carried out during the
establishment of the Facility, 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.
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If either party, acting in good faith, materially fails to satisfy any
Facility 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. The payment schedule
set forth on Schedule C shall be revised appropriately to reflect the
revised milestone schedule. If the parties are unable to agree to a
reasonable corrective action plan or revised milestone schedules after good
faith negotiations for a period of 15 days, either party may submit such
matter to binding arbitration pursuant to the JAMS Streamlined Rules and
Procedures (except that each side shall be entitled to take up to two
depositions prior to the arbitration hearing), with such arbitration to be
held in Boston, MA. The arbitration shall be held before one arbitrator
with appropriate experience with respect to such dispute who shall be
mutually agreed upon by the parties and if there is no agreement by the
parties (within 10 days of submission to arbitration) then such arbitrator
shall be selected pursuant to Rule 12 of the JAMS Streamlined Rules and
Procedures. The arbitrator shall have the authority to modify the contract
in a manner consistent with the arbitrator's resolution of such dispute and
shall be entitled to use equitable remedies to enforce the arbitration
decision. The arbitration decision may also be enforced by any court of
competent jurisdiction. The costs (including attorneys fees) of the
arbitration and the fees of the arbitrator shall be allocated as the
arbitrator deems appropriate.
After the Facility is completed, Nordion shall, in consultation with
Molecular Insight Pharmaceuticals, develop and implement a Master
Validation Plan that will allow the production of BMIPP under cGMPs for
Clinical Trial supply and for Commercial Phase supply. Prior to
implementation, both parties shall in writing approve the Master Validation
Plan which approval will not be unreasonably withheld.
The parties acknowledge and agree that Schedule A may be amended during the
course of establishing the Facility 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 cost, which must be approved in advance by Molecular Insight
Pharmaceuticals. No work on such scope change shall be carried out by
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
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shall meet monthly, in person or by telephone, for the purpose of reviewing
the status of the project and assessing progress against the milestones and
activities set forth in Schedule A. Minutes of meetings shall be prepared,
maintained and provided to each of the parties. Prior to the monthly
meetings, Nordion shall prepare and submit to Molecular Insight
Pharmaceuticals a written report that sets forth in reasonable detail the
progress of the Facility construction and indicates any problems that are
known to Nordion or reasonably anticipated by Nordion to occur that either
may result in the schedule for the Facility not being met in a timely
manner or may result in a cost increase to be borne by Molecular Insight
Pharmaceuticals.
3.2 USE OF THE FACILITY
During the Term of this Agreement after transition to the Facility, Nordion
shall ensure that the Facility is available for the production of BMIPP for
supply to Molecular Insight Pharmaceuticals on an exclusive basis and
Nordion shall only use the Facility for the production of BMIPP for
Molecular Insight Pharmaceuticals. Nordion further agrees that it shall not
(i) use other facilities for the production of BMIPP unless Molecular
Insight Pharmaceuticals consents to the use of such other facilities in
writing, such consent not to be unreasonably withheld, and (ii) manufacture
BMIPP for any third party unless directed to do so in writing by Molecular
Insight Pharmaceuticals.
3.3 MOLECULAR INSIGHT PHARMACEUTICALS RIGHT TO OBSERVE, INSPECT AND AUDIT
During the Facility Program, upon ten (10) days prior written notice to
Nordion, Molecular Insight Pharmaceuticals and any third-party consultant
or auditor appointed by Molecular Insight Pharmaceuticals, such consultant
and/or auditor being subject to a confidentiality agreement with and
reasonably acceptable to Nordion, shall have reasonable access to observe
and inspect the Facility for the purpose of determining the progress
against Facility Milestones.
3.4 OWNERSHIP OF PHYSICAL ASSETS
At all times Nordion will retain all right and title in and to the physical
assets and real property that comprise the Facility and, for the purposes
of this section 3.4, BMIPP and Molecular Insight Pharmaceuticals supplied
components shall not be considered a physical asset. Upon the expiration or
termination of this Agreement, Nordion, as owner of the Facility, shall be
responsible for any and all costs, expenses and actions necessary in
connection with the reconditioning, dismantling or disposing of the
Facility or any parts thereof including, without limitation, any disposal,
decommissioning or reclamation costs.
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3.5 REPAIRS AND MAINTENANCE
After the Facility is established, Nordion shall maintain such Facility in
satisfactory operating condition as required by the FDA, 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.
ARTICLE 4 - GENERAL MANUFACTURE AND SUPPLY OBLIGATIONS OF NORDION
4.1 BMIPP SUPPLY AND TRANSITION
After the Facility is established, Nordion agrees to (i) use the Process to
produce Batches of BMIPP (in quantities specified on Schedule D or Schedule
E, as applicable) that meet the Specifications, FDA requirements and are
manufactured in conformance with cGMPs and (ii) make arrangements for
shipment of BMIPP to third parties on behalf of Molecular Insight
Pharmaceuticals as directed by Molecular Insight Pharmaceuticals. All
Batches shall be shipped in regulatory approved lead xxxxxxx. Nordion
reserves the right to withhold from shipment any Batch, or portion thereof,
which does not conform to Specifications. Nordion, at the time of execution
of this Agreement, may be supplying BMIPP from an alternative facility
under the Development Agreement. After completion of the Facility Program
pursuant to this Agreement and provided that Nordion is capable of
manufacturing BMIPP in the Facility, Nordion shall transition manufacture
BMIPP to the Facility established pursuant to this Agreement within thirty
(30) days. Nordion shall provide written notice to Molecular Insight
Pharmaceuticals of completion of the Facility.
4.2 FACILITY RESERVATION FEE
After completion of the Master Validation Plan and commencing with the
first full month after the date on which Nordion is ready to commence
manufacture of BMIPP in the Facility (of which Nordion shall notify
Molecular Insight Pharmaceuticals in writing), Molecular Insight
Pharmaceuticals shall, during the remainder of the Term, pay to Nordion a
Facility reservation fee of ** ("Facility Reservation Fee"), which fee
shall not be refundable or reimbursable but shall be credited in a given
month towards amounts owed by Molecular Insight Pharmaceuticals for the
purchase of Batches in such month. Payment of the purchase price for
Batches delivered in excess of the Facility
* confidential treatment requested *
9
Reservation Fee in a given month shall be invoiced to Molecular Insight
Pharmaceuticals.
4.3 CLINICAL TRIAL SUPPLY PRICING
The price for a Batch supplied to Molecular Insight Pharmaceuticals for
Clinical Trials shall be as set out in Schedule D and shall be payable as
set forth in Section 4.8 herein.
4.4 COMMERCIAL PHASE PRICING
Within thirty (30) days after completion of the Facility Program and
Process scale up for Commercial Phase supply (of which Nordion shall notify
Molecular Insight Pharmaceuticals in writing), the parties shall negotiate
in good faith, for a period not to exceed thirty (30) days, the pricing
terms for the supply of BMIPP to Molecular Insight Pharmaceuticals during
the Commercial Phase. Indicative pricing for the supply of BMIPP during the
Commercial Phase is outlined in Schedule E. Such indicative pricing shall
only serve as the basis for negotiation and discussion and shall not be
binding; provided, however, that if the parties are unable to agree to
pricing terms at the end of such 30-day negotiation period, then the
initial price for BMIPP during the Commercial Phase shall be the lesser of
(i) ** as set forth on Schedule E or (ii)
the highest price per dose offered by Nordion during such negotiation
period. Once the parties have agreed upon the pricing terms, such terms and
conditions shall be added to Schedule E and form a part of this Agreement.
4.5 COMPLIANCE WITH LAW; HANDLING OF BMIPP
While Precursor, Reference Standards, Isotope, Excipients and BMIPP are in
its possession or under its control, Nordion shall be responsible for
compliance in all material respects with applicable statutory and
regulatory requirements in the United States and Canada.
4.6 TESTING, DOCUMENTATION, AND QUALITY ASSURANCE
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, tested and prepared for shipment in
compliance with all applicable laws, rules, regulations, as well as 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,
* confidential treatment requested *
10
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. The parties agree to
execute the Quality Agreement in substantially the form attached as
Schedule "F". Nordion shall manufacture, test, pack and prepare for
shipment, BMIPP in conformance with cGMPs and regulations applicable to the
shipment of radioactive materials and subject to the Quality Agreement.
Molecular Insight Pharmaceuticals shall be entitled to audit Nordion's
quality assurance processes in accordance with the Quality Agreement.
4.7 LABELS
Molecular Insight Pharmaceuticals shall be solely responsible for, and
shall provide and approve the form and content of, the labels (except lot
number and expiry date which shall be the responsibility of Nordion) to be
applied to BMIPP. Label form and content (other than lot number and expiry
date) shall remain the liability and exclusive property of Molecular
Insight Pharmaceuticals. Such labels shall not be used by Nordion after
termination or expiration of this Agreement and the label provided by
Molecular Insight Pharmaceuticals may only be used by Nordion for the
purpose of performing its obligations under this Agreement.
4.8 PAYMENT
Nordion shall invoice Molecular Insight Pharmaceuticals for the purchase
price of Batches of BMIPP and all undisputed amounts shall be paid by
Molecular Insight Pharmaceuticals within thirty (30) days of the date of
the invoice. Any undisputed amounts which remain unpaid after the
aforementioned thirty (30) day period shall bear interest calculated
monthly based on the prime lending rate as published by the Canadian
Imperial Bank of Commerce in Ottawa, Ontario, plus 3%.
In the event Molecular Insight Pharmaceuticals disputes any particular
invoiced item or amount, Molecular Insight Pharmaceuticals shall pay the
non-disputed portion of the invoice and the parties shall attempt in good
faith to resolve the dispute pertaining to the balance within fifteen (15)
days of receipt of the notice of dispute issued by either party. If the
parties are unable to resolve such dispute after good faith negotiations
for a period of 15 days, either party may submit such matter to binding
arbitration pursuant to the JAMS Streamlined Rules and Procedures (except
that each side shall be entitled to take up to two depositions prior to the
arbitration hearing), with such arbitration to be held in Boston, MA. The
arbitration shall be held before one arbitrator with appropriate
11
experience with respect to such dispute who shall be mutually agreed upon
by the parties and if there is no agreement by the parties (within 10 days
of submission to arbitration) then such arbitrator shall be selected
pursuant to Rule 12 of the JAMS Streamlined Rules and Procedures. The
arbitrator shall have the authority to modify the contract in a manner
consistent with the arbitrator's resolution of such dispute and shall be
entitled to use equitable remedies to enforce the arbitration decision. The
arbitration decision may also be enforced by any court of competent
jurisdiction. The costs (including attorneys fees) of the arbitration and
the fees of the arbitrator shall be allocated as the arbitrator deems
appropriate. Nordion shall not be entitled to terminate this Agreement in
connection with an invoice being disputed in good faith by Molecular
Insight Pharmaceuticals.
With respect to non-payment of undisputed amounts, Nordion shall not be
entitled to suspend manufacturing activities or terminate this Agreement
pursuant to section 14 unless and until the aggregate undisputed amount
that is due and unpaid equals or exceeds US$100,000.00.
ARTICLE 5 - GENERAL MOLECULAR INSIGHT PHARMACEUTICALS
OBLIGATIONS
5.1 PRECURSOR, REFERENCE STANDARDS AND EXCIPIENTS
Molecular Insight Pharmaceuticals or, at Molecular Insight Pharmaceuticals'
discretion, its designee, shall provide to Nordion, at no charge,
Precursor, Reference Standards and Excipients which meet the specifications
in Schedule G in sufficient quantities to permit Nordion to meet its
obligations hereunder. Nordion shall only use Precursor, Reference
Standards and Excipients provided hereunder for the manufacture of BMIPP
pursuant to this Agreement. Molecular Insight Pharmaceuticals shall at all
times retain title in and to such materials in Nordion's possession.
5.2 UNAVAILABILITY OR SCARCITY OF PRECURSOR, REFERENCE STANDARDS OR EXCIPIENTS
Molecular Insight Pharmaceuticals will notify Nordion upon Molecular
Insight Pharmaceuticals becoming aware of a shortage of supply of
Precursor, Reference Standards or Excipients, if such shortage will impact
the manufacture of the BMIPP. Molecular Insight Pharmaceuticals shall not
be liable for any delays or shortages in the supply of Precursor, Reference
Standards or Excipients; provided, however, that any such shortages or
delays in Precursor, Reference Standards or Excipients supply will not
affect any amounts payable by Molecular Insight Pharmaceuticals pursuant to
section 4.2 and shall excuse Nordion's performance of activities related to
such Batch of BMIPP to the extent that
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Nordion's non-performance was caused by the Precursor, Reference Standards
or Excipients supply delay or shortage and only for a period of time equal
to the delay.
5.3 ADDITIONAL COMPENSATION TO NORDION
In addition to the amounts set forth In Schedule C, Molecular Insight
Pharmaceuticals will compensate Nordion based on the rate of ** 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; and
(iii) attending meetings with the FDA.
Molecular Insight Pharmaceuticals shall reimburse Nordion for all
reasonable 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 6 - BMIPP SHIPMENTS
6.1 ORDERS AND SHIPMENTS
During the Term of this Agreement, Molecular Insight Pharmaceuticals will
forward orders to Nordion at its Ottawa, Ontario facility by facsimile or
such other method as agreed by the parties. Each order will set forth the
quantity of BMIPP to be produced and prepared for shipment, the identity of
the recipient, delivery destination protocol number, IND/NDA 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 Ex Works (Incoterms 2000) at Nordion's
facility in Vancouver, British Columbia. Risk of loss of BMIPP shall pass
to Molecular Insight Pharmaceuticals at point of delivery at Nordion's
facility in Vancouver, British Columbia.
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 BMIPP by such
* confidential treatment requested *
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third party. Molecular Insight Pharmaceuticals shall obtain all approvals,
licenses and permits required to import BMIPP into the United States.
Nordion shall make shipping arrangements with AirNet Express or such other
carrier designated by Nordion and reasonably approved by Molecular Insight
Pharmaceuticals. All BMIPP shipping costs incurred from the point of
delivery transport vehicle Nordion's facility in British Columbia 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 of
cancellation 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.
6.2 LIMITED PRODUCT WARRANTY
Nordion provides a product warranty, and does warrant for each Batch, that
BMIPP will (i) conform with the Specifications, (ii) be manufactured,
tested, processed, packed and prepared for shipment in accordance with
cGMP's and (iii) 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. All warranty obligations of Nordion with respect to a
particular Batch shall cease and have no effect to the extent that any
defect in such Batch arises from accident, abuse, misuse, alteration or
gross negligence by Molecular Insight Pharmaceuticals or its suppliers. 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) replace such batch of BMIPP; and
(ii) pay for shipping costs of replacement of BMIPP.
In the event that Nordion reasonably disputes Molecular Insight
Pharmaceuticals' determination that the fault is 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'
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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.
ARTICLE 7 - LICENSE/OWNERSHIP
7.1 ROYALTY-FREE LICENSE
Molecular Insight Pharmaceuticals hereby provides to Nordion a
non-exclusive, nontransferable, royalty-free license during the Term of
this Agreement to use Molecular Insight Pharmaceuticals Background
Technology relating to BMIPP and the radiolabelling of Precursor with I-123
for the sole purpose of assisting Nordion in carrying out its obligations
set out in this Agreement.
7.2 OWNERSHIP
Molecular Insight Pharmaceuticals Background Technology shall remain the
sole and exclusive property of Molecular Insight Pharmaceuticals. Except to
the extent that the Process is developed or contributed by Molecular
Insight Pharmaceuticals, Molecular Insight Pharmaceuticals agrees and
acknowledges that any and all ideas, know how, techniques, technology,
methods, data, information, inventions or improvements that are conceived,
written, created or first reduced to practice in the performance of the
Process, the Nordion Background Technology and, subject to the limitations
set forth in the second paragraph of this section 7.2, improvements to the
Nordion Background Technology by Nordion or its employees shall be and
remain the sole and exclusive property of Nordion.
The parties acknowledge and agree that the process, to the extent jointly
developed by Nordion and Molecular Insight Pharmaceuticals during the Term
of this Agreement, whereby the Isotope is attached to the Precursor shall
be proprietary technology jointly owned by both Nordion and Molecular
Insight Pharmaceuticals and each party may continue to use and exploit such
process as their own technology both during and after the Term of this
Agreement.
Nothing in this Agreement transfers or licenses any right, title or
interest to Molecular Insight Pharmaceuticals Background Technology or
Nordion Background Technology, except as expressly set out herein.
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ARTICLE 8 - MOLECULAR INSIGHT PHARMACEUTICALS
REPRESENTATIONS AND WARRANTIES
8.1 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 Molecular Insight
Pharmaceuticals Background 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, to its knowledge, threatened against
Molecular Insight Pharmaceuticals before any court, administrative
agency or other tribunal which would have an adverse material effect
on its business or its ability to perform its obligations hereunder;
(iv) it has the right to grant the license in section 7.1 and right to
permit Nordion to use Molecular Insight Pharmaceuticals Background
Technology to the extent required to assist Nordion in carrying out
its obligations under this Agreement;
(v) it has not received any written notice of adverse claim or
infringement of any patent or other intellectual property right, or
misappropriation of trade secrets in connection with, the Molecular
Insight Pharmaceuticals Background Technology or the use and
exploitation of the Precursor, Reference Standard, Excipients or
BMIPP;
(vi) to Molecular Insight Pharmaceuticals' knowledge, making, using,
offering for sale or selling of Precursor, Reference Standards,
Excipients 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, pending published patent application or other
intellectual property right;
(vii) it is not under any obligations, contractual or otherwise, to any
other entity that might conflict, interfere or be inconsistent with
any of the provisions of this Agreement;
16
(viii) it shall obtain and maintain at its expense, all licenses, permits
and approvals necessary for it to perform its obligations under this
Agreement;
(ix) as of the Effective Date, it is not currently subject to any
proceeding pending or, to its knowledge, threatened for
reorganization, liquidation or dissolution for the benefit of its
creditors or otherwise;
(x) BMIPP shall not be misbranded within the meaning of the FD&C as a
result of the application of the label content supplied by Molecular
Insight Pharmaceuticals to Nordion pursuant to this Agreement, and
BMIPP is not an article which may not be introduced into interstate
commerce under the provisions of section 505 of the FD&C.
ARTICLE 9 - NORDION'S REPRESENTATIONS AND WARRANTIES
9.1 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 Nordion Background
Technology and other Nordion proprietary technology used during the
Term of this Agreement;
(iii) the Nordion Background Technology 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 other intellectual property right, or of misappropriation of
trade secrets, in connection with the use and exploitation of the
Nordion Background Technology;
(v) there is no action or proceeding pending or, to its knowledge,
threatened against Nordion before any court, administrative agency or
other tribunal which would have an adverse material effect on
Nordion's business or its ability to perform its obligations
hereunder;
(vi) as of the Effective date, Nordion is not currently subject to any
proceeding pending or, to its knowledge, threatened for
reorganization, liquidation or dissolution for the benefit of its
creditors or otherwise;
17
(vii) it shall obtain and maintain, at its expense, all Facility licenses,
permits and approvals necessary for it to manufacture BMIPP under this
Agreement and shall provide Molecular Insight Pharmaceuticals with
copies of such licenses, permits and approvals upon request;
(viii) the BMIPP delivered pursuant to this Agreement shall, at the time of
delivery by Nordion to Molecular Insight Pharmaceuticals, not be
misbranded (to the extent branded by Nordion) or adulterated within
the meaning of FD&C and effective at the time of delivery of the
BMIPP.
ARTICLE 10 - INDEMNITY
10.1 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 shipping of Reference
Standards, Precursor, Excipients or BMIPP (including in the event that
Nordion makes shipping arrangements on behalf of Molecular Insight
Pharmaceuticals), (b) Molecular Insight Pharmaceuticals' breach of any of
its material 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 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, or prepare for
shipment 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.
Notwithstanding anything in this section 10.1, "General Claims Against
Nordion" shall not include "IP Claims Against Nordion" as described in
section 10.3.
10.2 INDEMNIFICATION BY NORDION
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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
preparation for shipment of BMIPP; (b) Nordion's breach of any of its
material obligations, warranties or representations hereunder; (c)
Nordion's negligent acts or omissions or willful misconduct; or (d) any
failure of the BMIPP to meet the Specifications. 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, Precursor
or Excipients to meet applicable specifications or (iv) Molecular Insight
Pharmaceuticals' or third party's use, handling or shipment of Reference
Standards, Precursor, Excipients or BMIPP. Notwithstanding anything in this
section 10.2, "General Claims Against Molecular Insight Pharmaceuticals"
shall not include "IP Claims Against Molecular Insight Pharmaceuticals" as
described in section 10.4.
10.3 INTELLECTUAL PROPERTY CLAIMS AGAINST NORDION
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
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 Molecular Insight Pharmaceuticals Background Technology, the
Process (only to the extent contributed by Molecular Insight
Pharmaceuticals), use or sale of the Reference Standards, Precursors,
Excipients or BMIPP infringes a patent or any other intellectual property
right of a third party in the United States or Canada ("IP Claims Against
Nordion"). 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.
10.4 INTELLECTUAL PROPERTY CLAIMS AGAINST MOLECULAR INSIGHT PHARMACEUTICALS
19
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 Nordion Background Technology, the method of manufacture of
BMIPP or the Process to the extent developed or contributed by Nordion,
infringes a patent or other intellectual property right of a third party in
the United States or Canada ("IP Claims Against Molecular Insight
Pharmaceuticals").
10.5 NORDION INFRINGEMENT
In the event that any portion of the Nordion Background Technology,
required in the manufacture of BMIPP, in the opinion of independent counsel
mutually selected by the parties, becomes the subject of a valid claim for
a patent, copyright or other intellectual property right infringement then
Nordion shall, for a period of at least sixty (60) days after issuance of
the opinion, use its commercially reasonable efforts to:
i) procure the right to continue using the technology, or
ii) modify the Nordion Background Technology to become non-infringing
(with all Nordion costs, including any increase to the cost of the
manufacturing of BMIPP by Nordion, to be borne by Nordion).
After expiry of the sixty (60) day period from the issuance of the
aforementioned opinion, if Nordion has been unable to remedy the
infringement in accordance with subparagraph i) or ii) above, Molecular
Insight Pharmaceuticals or Nordion, may upon written notice, suspend
manufacturing activities and/or terminate this Agreement. The provisions of
this section 10.5 are in addition to, and do not in any way limit, the
indemnification obligations of Nordion set forth in this section 10.
10.6 MOLECULAR INSIGHT PHARMACEUTICALS INFRINGEMENT
In the event that any portion of the Molecular Insight Pharmaceuticals
Background Technology required in the manufacture of BMIPP, in the opinion
of independent counsel mutually selected by the parties, becomes the
subject of a valid claim for a patent, copyright or other intellectual
property right infringement, then Molecular Insight Pharmaceuticals shall,
for a period of at least sixty (60) days after issuance of the opinion, use
its commercially reasonable efforts to:
20
i) procure the right to continue using the technology, or
ii) modify the Molecular Insight Pharmaceuticals Background Technology to
become non-infringing provided such modification does not increase the
cost of manufacture of BMIPP by Nordion (with all Molecular Insight
Pharmaceuticals' costs including any increase to the cost of the
manufacturing of BMIPP by Nordion to be borne by Molecular Insight
Pharmaceuticals).
After expiry of the sixty (60) day period from the issuance of the
aforementioned opinion, if Molecular Insight Pharmaceuticals has been
unable to remedy the infringement in accordance with subparagraph i) or ii)
above, Nordion or Molecular Insight Pharmaceuticals may upon written
notice, suspend manufacturing activities and/or terminate this Agreement.
The provisions of this section 10.6 are in addition to, and do not in any
way limit, the indemnification obligations of Molecular Insight
Pharmaceuticals set forth in this section 10.
10.7 INDEMNIFICATION PROCEDURES
A party (the "Indemnitee") intending to claim indemnification under this
Agreement 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.
ARTICLE 11 - REGULATORY MATTERS
11.1 REGULATORY STATUS
Upon Nordion's reasonable request, Molecular Insight Pharmaceuticals shall
provide updates to Nordion on submissions to the FDA and other
21
jurisdictions and regulatory agencies for marketing authorization with
respect to BMIPP.
11.2 MOLECULAR INSIGHT PHARMACEUTICALS RESPONSIBILITIES
It shall be the responsibility of Molecular Insight Pharmaceuticals or its
designee to file, obtain and maintain an IND/NDA, registrations, listings,
authorizations and approvals as the FDA or any other applicable
governmental entity may require to enable use of BMIPP in Clinical Trials
and the Commercial Phase 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 (with
a copy to Molecular Insight Pharmaceuticals purged of Nordion proprietary
technology) 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 IND/NDA submission.
11.3 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 and
prepare for shipment 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 and maintain its existing I-123
bulk chemical Drug Master File ("DMF") with the FDA as may be required for
Molecular Insight Pharmaceuticals' IND/NDA for BMIPP. 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.
11.4 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, Precursor and
Excipients, and (iii) manufacturing, testing, storage and preparation for
shipment of BMIPP, including Process development operations, and auditing
the Facility for compliance with cGMP and/or other applicable
22
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. Notwithstanding the foregoing Molecular
Insight Pharmaceuticals shall be entitled to have a representative in
attendance at the Facility as an observer for the pre-approval inspection.
Nordion agrees to use commercially reasonable efforts promptly to rectify
or resolve any deficiencies noted by a government entity in a report or
correspondence issued to Nordion. Subject to any specific arrangements
agreed upon by the parties, Molecular Insight Pharmaceuticals shall be
responsible for communicating with any governmental authority concerning
the BMIPP or the marketing, distribution or sale of BMIPP, and Nordion
shall, in accordance with the compensation rates set forth in section 5.3,
provide Molecular Insight Pharmaceuticals with whatever assistance
Molecular Insight Pharmaceuticals may reasonably require to assist it in
such communications. Nordion shall have no such communications specifically
related to BMIPP, except to the extent that they relate to Nordion's
manufacturing activities under this Agreement, in which case Nordion shall
be responsible for such communications. Notwithstanding the foregoing and
except to the extent that an immediate communication is necessary under the
circumstances or required by law, Nordion in good faith shall consult in
advance with Molecular Insight Pharmaceuticals regarding all communications
that relate to BMIPP or to Nordion's ability to manufacture BMIPP pursuant
to this Agreement.
11.5 ACCESS TO THE FACILITY
Molecular Insight Pharmaceuticals shall have reasonable access to the
Facility at least once per calendar quarter. 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 12.1 of this
Agreement.
11.6 COMPLAINTS AND ADVERSE REACTIONS
Nordion or Molecular Insight Pharmaceuticals shall provide to each other
prompt notice of any information either of them receives regarding the
safety of the Precursor, Reference Standards, Excipients, BMIPP or Isotope,
including any confirmed or unconfirmed information regarding adverse,
serious or unexpected events associated with BMIPP that may implicate the
manufacture of BMIPP or one of its components; provided,
23
however, that Molecular Insight Pharmaceuticals shall not be required to
provide clinical trial reporting to Nordion. For serious or adverse events,
notice must be given by telephone within one (1) business day after receipt
of the information, followed immediately with written notice, advising the
other of any adverse reaction or safety issues with respect to BMIPP of
which it becomes aware, regardless of the origin of such information. Any
other complaints shall be reported in writing to the other party on a
weekly basis. Nordion agrees to co-operate with Molecular Insight
Pharmaceuticals and any governmental entity in evaluating any complaint,
claim, safety or adverse use report related to BMIPP. Nordion will provide
timely assistance in responding to any complaints, including reviews of
Batch records and retained samples as well as any necessary testing.
11.7 RECALLS
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
agents or employees acts or 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' reasonable
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 employees or
agents, 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.
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11.8 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. The parties shall confer with each other with
respect to the best means to implement and comply with such requirements.
Any modifications or additions to the Facility required as a result of new
regulatory requirements shall be borne by Molecular Insight
Pharmaceuticals.
11.9 RECORDS
Nordion shall maintain all records necessary to evidence compliance in all
material respects with (i) all applicable laws, rules, 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) material obligations under this Agreement. All
such records shall be maintained by 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 within thirty (30) days of receipt of
such notice 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 12 - CONFIDENTIALITY
12.1 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 and not use or
disclose to others for any purpose, other than to its employees or agents
(which agents shall enter into a confidentiality agreement incorporating
similar terms as set forth herein or be otherwise reasonably acceptable to
the other party) with a need to know such information to perform such
party's obligations under this Agreement or other than as expressly
authorized in this Agreement, the content of the transactions contemplated
herein, all technology including Molecular Insight Pharmaceuticals
Background Technology, Nordion Background Technology and improvements
thereto, and other information disclosed to such party by the other party
which is identified as "Confidential Information" by the
25
disclosing party (collectively "Confidential Information"). 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 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, or with the other party's written consent, the other
party's Confidential Information.
All Confidential Information 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 or
expiration of this Agreement.
ARTICLE 13 - DISCLOSURE OF INFORMATION
13.1 AUTHORIZED DISCLOSURE
Notwithstanding section 12.1 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, rules 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, except where impracticable for necessary
disclosure, for example in the event of medical emergency, it will give
reasonable notice to the other party of such disclosure requirement and
will use its reasonable efforts to secure a protective order or limit the
extent of the information to be disclosed.
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ARTICLE 14 - TERM AND TERMINATION
14.1 TERM
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 six (6) years after the Effective
Date (the "Initial Term"). Thereafter, this Agreement shall automatically
be renewed for successive additional two (2) year terms (each a "Renewal
Term"). Either party may terminate this Agreement by providing two (2)
years prior written notice to the other party during the Initial Term such
termination to be effective upon expiry of the Initial Term at the 6th year
anniversary or during any Renewal Term upon two (2) years prior written
notice.
14.2 TERMINATION FOR BREACH
Subject to section 4.8, this Agreement may be terminated by either party in
the event of breach by the other party of a material term or condition
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 therefore. Upon
receipt of such Breach Notice, the breaching party shall have such time as
necessary, but in any event not more than ninety (90) days, to cure such
breach (or thirty (30) days with respect to a failure by Molecular Insight
Pharmaceuticals to pay any undisputed amounts when due which, in the
aggregate, exceed US$100,000 but excluding for this purpose all amounts
which Molecular Insight Pharmaceuticals' in good faith disputes are due to
Nordion which are subject to Section 4.8 herein). 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.
With respect to the supply of Batches of BMIPP by Nordion pursuant to
orders placed pursuant to this Agreement, Nordion's failure to supply
Batches in a timely manner and consistent with such orders and the
Specifications shall not be considered a material breach by Nordion unless
and until Nordion has failed, in any one year period, to fulfill more than
four (4) Batch orders consistent with the Specifications, provided (i) the
failure to supply is not attributable, in whole or in part, directly or
indirectly, to Molecular Insight Pharmaceuticals and (ii) Nordion fails to
supply a replacement Batch meeting the Specifications in accordance with
this Agreement within one (1) week of the delivery date of the originally
scheduled Batch (a "Supply Breach"). In the event of a Supply Breach,
Molecular Insight Pharmaceuticals may terminate this Agreement upon thirty
(30) days prior written notice to Nordion provided it gives written
27
notice of termination to Nordion within sixty (60) days of the Supply
Breach. Any failure by Nordion to manufacture or supply BMIPP due to a
Force Majeure shall not be a material breach under this Agreement.
14.3 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.
14.4 REMEDIES UPON TERMINATION
In the event of termination of this Agreement, in addition to any other
remedies available to either of the parties:
(i) Nordion shall use reasonable efforts to terminate all activities under
this Agreement immediately;
(ii) within forty-five (45) days of such termination, at Molecular Insight
Pharmaceuticals' request and expense, Nordion shall deliver to
Molecular Insight Pharmaceuticals all data, documentation and other
information belonging to Molecular Insight Pharmaceuticals pursuant to
the terms of this Agreement;
(iii) all licenses granted by Molecular Insight Pharmaceuticals to Nordion
under this Agreement shall immediately terminate, and
(iv) within sixty (60) days of such termination all Precursor, Reference
Standards and Excipients remaining in inventory shall at Molecular
Insight Pharmaceuticals' option and expense be disposed of or returned
by Nordion to Molecular Insight Pharmaceuticals.
Molecular Insight Pharmaceuticals shall pay to Nordion any amounts
otherwise due within thirty (30) days of the date of termination.
ARTICLE 15 - SURVIVAL
15.1 CONSEQUENCES OR TERMINATION OR EXPIRATION
All sections which by their nature must survive in order to give effect to
their intent and meaning shall survive termination or expiration of this
28
Agreement, including, without limitation, sections 3.4, 7.2, 10.1 - 10.4,
10.7, 11.9, 12.1, 14.4, 17.1 and 21.1.
ARTICLE 16 - NOTICES
16.1 ANY NOTICE TO BE SENT TO A PARTY HEREUNDER SHALL BE FORWARDED TO:
Nordion at: MDS Nordion
000 Xxxxx Xxxx
Xxxxxx, XX
X0X 0X0
Attention: Vice President, Products and Services
Fax: 000-000-0000
Molecular Insight Pharmaceuticals
at:
Molecular Insight Pharmaceuticals, Inc.
000 Xxxxxx Xxxxxx
Xxxxxxxxx, XX
Attention: Chief Operating Officer
Fax: 000-000-0000
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 17 - LIMITED LIABILITY
17.1 DISCLAIMER
EXCEPT IN THE CASE OF THEIR RESPECTIVE INDEMNIFICATION OBLIGATIONS HEREIN,
IN NO EVENT SHALL EITHER PARTY BE LIABLE TO THE OTHER FOR INDIRECT,
CONTINGENT, INCIDENTAL, SPECIAL OR CONSEQUENTIAL DAMAGES, WHETHER IN
CONTRACT, TORT, OR ANY OTHER CAUSE OF ACTION, EVEN IF ADVISED OF THE
POSSIBILITY OF SUCH DAMAGES.
17.2 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
29
OR OTHERWISE INCLUDING, BUT NOT LIMITED TO, ANY IMPLIED WARRANTIES OR
CONDITIONS OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE.
ARTICLE 18 - ASSIGNMENT
18.1 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 or
untimely withheld; provided, however, that Molecular Insight
Pharmaceuticals or Nordion may assign this Agreement without the other's
consent in connection with the sale of all or substantially all of its
assets or the business to which this Agreement pertains, to a third party
or in connection with a merger, consolidation or similar transaction.
ARTICLE 19 - COMPLIANCE
19.1 COMPLIANCE WITH LAWS
This Agreement and Nordion's and Molecular Insight Pharmaceuticals'
obligations hereunder shall be carried out in all material respects in
compliance with all applicable laws, by-laws, rules, regulations and orders
of all applicable Federal, State, Provincial and Municipal governments.
ARTICLE 20 - NON-WAIVER
20.1 NON-WAIVER OF RIGHTS
Failure by either party to enforce at any time any of the provisions of
this Agreement shall not be construed 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.
20.2 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 ninety (90) days
30
the party not subject of the Force Majeure may, upon thirty (30) days
written notice terminate this Agreement. "Force Majeure" shall mean an
occurrence arising from unforeseen circumstances beyond a party's
reasonable control which prevents, delays or interferes with the
performance by such party of any of its obligations hereunder including
without limitation an event that 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, act of terrorism, blockage or
embargo, interruption of or delay in transportation, strike or labor
disruption.
ARTICLE 21 - INSURANCE
21.1 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 eight million United States dollars (US$8,000,000) per occurrence
and in the aggregate. Molecular Insight Pharmaceuticals shall 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 22 - PUBLICATION
22.1 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.
31
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, the FDA, 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.
ARTICLE 23 - DISPUTE RESOLUTION
23.1 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 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 24 - INDEPENDENT CONTRACTOR
24.1 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 25 - SEVERABILITY
25.1 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
32
that the transaction contemplated hereby be consummated as originally
contemplated to the greatest extent possible.
ARTICLE 26 - AGREEMENT
26.1 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, including, without
limitation, the Development Agreement which is terminated upon transition
of the manufacture of BMIPP under this Agreement pursuant to section 4.1.
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.
ARTICLE 27 - LAW
27.1 APPLICABLE LAW
This Agreement shall be governed and construed in accordance with the laws
of the Province of Ontario, 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.
33
IN WITNESS WHEREOF the parties hereto have executed this Agreement as of
the date first above written.
MDS Nordion, a division of MDS (Canada) Inc.
BY: /s/ Xxxx Xxxxxx
------------------------------------
Senior VP, Finance & Operations
Molecular Insight Pharmaceuticals, Inc.
By: /s/ Xxxx X. XxXxxx
------------------------------------
COO
68874
34
SCHEDULE A
DESCRIPTION OF FACILITY PROGRAM, FACILITY MILESTONES AND FACILITY SCHEDULE
FACILITY DESCRIPTION:
BMIPP will be manufactured in two newly constructed cells in a new section of
Nordion's Vancouver Operation building known as the RCA3 building, in basement
rooms 043 and 047. There will be one Class 10,000 cell for formulation with a
connecting cell with HEPA filtered clean zone for dispensing. Air filtration and
radiological containment will be achieved through HEPA filtration of inlet and
exhaust streams under negative pressure. These cells will be capable of holding
at least 10 Ci of I-123 in aggregate.
KEY DELIVERABLES:
1. Two hot cells and related BMIPP production equipment
2. A Class 10,000 clean room
3. A primary anteroom (unclassified) and a gowning anteroom (class 100,000)
4. An unclassified preparatory room adjacent to the clean room suite.
5. A class 10,000 labeling cell with waste storage vault
6. A class 10,000 dispensing cell with autoclave.
7. One dose calibrator in each cell.
8. A visual inspection station in each cell.
9. A pot loading and extraction system for up to six F-335 lead pots at a time
10. A Process Validation Summary Report.
35
COMMERCIAL PRODUCTION FACILITY:
Cell View
(CELL VIEW)
36
FACILITY DIAGRAM:
(FACILITY DIAGRAM)
37
FACILITY MILESTONES AND SCHEDULE
Milestones
The following milestones are critical to the schedule
1) ** after Effective Date FAT (Factory
Acceptance Test) of Cells (fully assembled cells, at manufacturer, are inspected
for functionality and finish according to approved drawings.
2) ** after Effective Date SAT (Site
Acceptance Test) of Cells. The cells are re-inspected after re-assembly at final
site.
3) ** after Effective Date Facility Commissioning Substantially Complete.
4) ** after Effective Date Equipment and Process Validation begins
5) ** after Effective Date Validation executed,
6) ** after Effective Date Project completion, submission
SCHEDULE
(SCHEDULE)
* confidential treatment requested *
38
SCHEDULE B
BMIPP SPECIFICATIONS
MDS NORDION
VANCOUVER OPERATIONS
FINAL PRODUCT SPECIFICATION
Issue No.: 0 iodofiltic acid I-123 SPE-46-200
Effective: 2005.09.09 Page 1 of 2
PRODUCT : iodofiltic acid I-123
SYNONYMS : [I-123] - 15-(p-iodophenyl)-3-methylpentadecanoic
Acid or I-123 BMIPP
VISUAL INSPECTION : Clear, colourless solution, essentially free of
foreign matter visible in the unaided eye.
RADIONUCLIDE IDENTITY : Gamma-Photon emission at 159 +/- 2 keV
RADIONUCLIDIC PURITY : > or = 99.8% I-123
RADIOACTIVITY
CONCENTRATION : 2.25 to 2.75 mCi/mL**
RADIOCHEMICAL IDENTITY : *Rr value between 0.95 to 1.05
RADIOCHEMICAL PURITY : > or = 95% as iodofiltic acid I-123
CHEMICAL PURITY
BMIPP : 0.225 to 0.275 mg/mL
UDCA : 3.15 to 3.85 mg/mL
TOTAL ACTIVITY : 4.5 to 5.5 mCi at TOC**
PH : 8.2 to 9.2
BACTERIAL ENDOTOXIN : < or = 17.5 EU/mL
STERILITY : Meets USP requirements - test initiated on day of
manufacture
EXPIRY : 1200 PT two days after date of manufacture
* Rr is the retention time of the product (iodofiltic acid I-123) divided by
the retention time of the reference standard (non-radioactive Iodofiltic
acid)
** Toc = Time of Calibration; 1500 h PT, one day after date of manufacture.
UNCONTROLLED COPY
39
Issue No.: 0 iodofiltic acid I-123 SPE-46-200
Effective: 2005.09.09 Page 2 of 2
Prepared by /s/ Illegible Date: (Illegible)
----------------------------------------
Approved by /s/ Illegible Date: (Illegible)
----------------------------------------
Production
Approved by /s/ Illegible Date: 2005/8/31
----------------------------------------
Quality
Approved by /s/ Xxxxx Xxxxxxxx Date: 2005 Sept 07
----------------------------------------
Molecular Insight Pharmaceuticals, Inc.
40
SCHEDULE C
FACILITY CONSTRUCTION FEES
1. FEES
1. Engineering and Documentation **
2. Facility Construction **
3. Cell and Ancillary Equipment **
4. Master Validation Plan program **
5. BMIPP Equipment **
------
Total **
======
Notes: 1. All fees are in United States dollars
2. PAYMENT SCHEDULE
1. ENGINEERING & DOCUMENTATION
** on Effective Date
** on Issuance of Project Status Report at Factory Acceptance Testing of the
cells
** on Facility Commissioning
2. FACILITY CONSTRUCTION
** on Effective Date
** on Commencement of Facility Construction
** on Completion of Facility Construction
3. CELL AND ANCILLARY EQUIPMENT
** on Effective Date
** on Factory Acceptance Testing of the Cells
** on completion of Construction of the Facility
4. VALIDATION PROGRAM
** on Effective Date
** on Facility Commissioning
** on Master Validation Plan program Completion
5. BMIPP PROCESS EQUIPMENT
** on Effective Date
** on Installation of BMIPP Process Equipment
** on Facility Commissioning
* confidential treatment requested *
41
SCHEDULE D
PRICES OF BATCHES FOR CLINICAL TRIAL SUPPLY
A. 1 CI BATCH OF BMIPP
Price: Year 1 supply of BMIPP under this Agreement ** per Batch
Year 2 supply: **
Year 3 supply: **
Year 4 supply: **
Year 5 supply: **
B. 2 CI BATCH OF BMIPP
Price: TBD after development work completed.
Notes:
1. 1 Ci Batch is approximately 30 doses of BMIPP (as defined in Schedule B) of
which 20 are shippable and 10 are retained by Nordion for archival and quality
assurance testing purposes only.
2. The All Items Canadian Consumer Price Index ("CPI") will be based on the
percentage increase in the CPI for the twelve (12) month period ending three (3)
months prior to such anniversary as published in the Canadian Government annual
reports.
* confidential treatment requested *
42
SCHEDULE E
INDICATIVE PRICING OF BMIPP FOR COMMERCIAL PHASE SUPPLY
As per section 4.4 of the Agreement, the indicative price of BMIPP for supply
during the Commercial Phase shall be subject to negotiation and is estimated to
be initially **; provided further that the initial purchase price shall not
exceed **.
This indicative price is based on the following assumptions.
1. Commercial Phase Batch size is ** doses of BMIPP, of which ** doses will be
available for purchase and shipment and 24 doses (including rejects up to
5%) shall be retained by Nordion for archival and quality assurance testing
purposes only.
2. Total doses of BMIPP purchased by Molecular Insight Pharmaceuticals is **
per Commercial Phase Batch of which there shall be at least ** Commercial
Phase Batches produced per week.
3. Overall process yield/efficiencies is **
4. Dose size is 5 mCi and is calibrated to 3 PM PT the day after manufacture.
* confidential treatment requested *
QUALITY AGREEMENT
INTERCOMPANY QUALITY AGREEMENT
MOLECULAR INSIGHT PHARMACEUTICALS, INC.
having a place of business at
000 Xxxxxx Xxxxxx
Xxxxxxxxx Xxxxxxxxxxxxx, 00000 XXX
(hereinafter called "Molecular Insight Pharmaceuticals")
AND
MDS NORDION
Ottawa, Ontario, Canada K2K 1X8
(hereafter called "Nordion")
Approved by: /s/ Illegible Date: 01 FEB 2006
----------------------------------------
Molecular Insight Pharmaceuticals, Inc.
Director of Quality Assurance
Approved by: /s/ Illegible Date: 2006/2/1
----------------------------------------
MDS Nordion
Director, Quality, Safety and Regulatory
Affairs
HISTORY OF REVISIONS
REVISION VERSION REVISION DATE REVISED BY DESCRIPTION
---------------- ------------- ---------- -----------
0 ORIGINAL
Intercompany Quality Agreement Rev.0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 3 of 28
1 QUALITY AGREEMENT
1.1 PURPOSE
This agreement defines how Nordion and Molecular Insight
Pharmaceuticals will interact with each other and describes the
responsibilities of each.
1.2 RELATIONSHIP TO SUPPLY AGREEMENT
1.2.1 This agreement shall be considered a Schedule to the BMIPP
Supply Agreement and all capitalized terms not defined herein
shall have the meaning set forth in the BMIPP Supply Agreement.
1.2.2 In the event of a conflict between any of the provisions of the
Quality Agreement and the BMIPP Supply Agreement, the provisions
of the BMIPP Supply Agreement shall govern.
1.3 GUIDING PRINCIPLES REGARDING WORKING RELATIONSHIPS BETWEEN NORDION AND
MOLECULAR INSIGHT PHARMACEUTICALS.
1.3.1 Molecular Insight Pharmaceuticals has the responsibility to
provide sufficient information to Nordion so that Nordion can
operate within the parameters of the IND/NDA applications.
1.3.2 Nordion has the responsibility to manufacture and test BMIPP in
accordance with the Supply Agreement and the registration
documentation provided by Molecular Insight Pharmaceuticals and
shall supply BMIPP that is manufactured and tested in accordance
with the IND/NDA, which shall include all product specifications
and instructions and cGMPs.
2 PRODUCT
This agreement covers the manufacture of BMIPP in accordance with the
Specifications set out in Nordion's specification #SPE-46-200 iodofiltic
acid I-123 (see Appendix I).
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 3 of 28
3 QUALITY REPRESENTATIVES
The Quality Representatives for each party shall have the responsibility of
ensuring that all actions of their company indicated in this agreement, are
performed as specified.
Molecular Insight Pharmaceuticals Quality Representative:
Xxxx Xxxxx
Director of Quality Assurance
Work: (000) 000-0000
Nordion Quality Representative:
Xxxxx Xxxxxxxxxx
Director, Quality, Safety and Regulatory Affairs
Work: (000) 000-0000
4 DURATION OF AGREEMENT
The agreement will expire concurrently with termination of the BMIPP Supply
Agreement. This agreement can be revised, as needed, with the written approval
of both Quality Representatives.
5 MANUFACTURING CGMP COMPLIANCE
5.1 PREMISES
5.1.1 Nordion will manufacture BMIPP at facilities located at:
Xxxxxxxxx, Xxxxxxx Xxxxxxxx, Xxxxxx
5.1.2 The premises and the equipment used to manufacture and test
BMIPP will be compliant with the then current regulatory
requirements set forth in section 5.2 below and the provisions of
the Supply Agreement.
5.1.3 Nordion will maintain controlled access to the premises. All
visitors must sign-in and shall be escorted during any visit to
the areas of the premises used to manufacture, test, and store
BMIPP. BMIPP shall be manufactured in the Facility referenced in
the Supply Agreement and schedules thereto and such manufacture
shall utilize equipment suitable for the manufacture of-BMIPP.
5.1.4 Nordion will procure all materials and components necessary to
manufacture BMIPP, except that Precursor and Reference Standards
and Excipient (UDCA) shall be supplied by Molecular Insight
Pharmaceuticals.
5.1.5 Nordion is responsible for ensuring that all materials and
components procured for the manufacture of BMIPP meet the written
specifications, including cGMPs, for the materials and
components.
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 4 of 28
5.2 CGMP GUIDELINES
The principles detailed in the United States Current Good Manufacturing
Practices (21 CFR, parts 210 and 211), as amended from time to time, will
cover the standards of manufacture of BMIPP, as well as the product
specifications and any applicable product license.
5.3 BATCH NUMBERS
The convention for the Batch Identification Number will follow Nordion's
system, and will provide a unique identifier to each Batch (BMI-XY-ABC).
The alphanumeric description will be a three letter prefix "BMI" followed
by a two digit year code (i.e., 05 for 2005), and a three digit sequential
number that would be unique for the batch (i.e., 001).
6 QUALITY CONTROL CGMP COMPLIANCE
6.1 GENERAL
The testing activities for BMIPP are defined in the BMIPP Product
Release Forms (see Appendix 2). Nordion is responsible for ensuring
all test samples have been obtained and all required testing
activities have been completed for BMIPP prior to shipment These
activities must ensure that BMIPP meets the requirements as defined in
the approved product Specifications and the Supply Agreement. See
Appendix 2 - PRF-46-001A Product Release Form for [I-123]-BMIPP and
PRF-46-001B Product Release Form for [I-123]-BMIPP.
6.2 BMIPP TESTING
6.2.1 Nordion will perform all required raw material, in-process and
BMIPP testing using approved sampling plans, test methods and
specifications. Sampling plans and test methods shall be jointly
established by Nordion and Molecular Insight Pharmaceuticals and
approved in advance by Molecular Insight Pharmaceuticals.
6.2.2 Nordion-will supply a copy of each completed Batch BMIPP Release
Form, which form shall include product testing data and results
as well as notification of any errors or deviations, to Molecular
Insight Pharmaceuticals within 1 day after such form is
completed.
6.3 RETAIN SAMPLES
Nordion is responsible for retaining and maintaining BMIPP samples per
regulatory requirements.
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 5 of 28
6.4 STABILITY PROGRAM
6.4.1 Nordion is responsible for maintaining the stability program per
regulatory requirements. See Appendix 3 - STM-46-002 Stability
Protocol for iodofiltic acid I-123 and ACR-46-002 Stability
Protocol for iodofiltic acid I-123.
6.4.2 Stability Failures - Any confirmed problems that arise as a
result of the stability program will be immediately communicated
in writing by Nordion to Molecular Insight Pharmaceuticals.
6.5 OUT-OF-SPECIFICATION (OOS) INVESTIGATIONS
Any test result that indicates the requirement(s) detailed in an
approved Nordion material specification is not being met, will be
investigated by Nordion within 24 hours and resolved within 30 days
thereafter. All OOS results that are confirmed or are inconclusive
must be reported to Molecular Insight Pharmaceuticals as detailed
under section 7.1.2 below. Nordion is responsible for carrying out the
OOS investigation that is in accordance with the applicable
regulations and the Supply Agreement. In no case will Nordion release
any BMIPP for shipment with a confirmed out-of-specification result.
7 QUALITY ASSURANCE
7.1 BMIPP MANUFACTURING ERRORS, DEVIATIONS, AND NON-CONFORMANCES
7.1.1 Any error or deviation from specifications in the manufacture or
testing of BMIPP must be carefully explained and documented in
writing. This documentation must be included in the Batch record
for affected BMIPP and retained for 7 years by Nordion.
7.1.2 Nordion shall notify Molecular Insight Pharmaceuticals within 1
days of occurrence in the event of any deviations or significant
problems during manufacturing and when any test reveals
contamination, lack of sterility assurance or BMIPP performance
problems. Any significant deviation must be reviewed and approved
by Molecular Insight Pharmaceuticals. The disposition of any
BMIPP batch(s) implicated in such deviations or significant
problems shall be agreed jointly between Nordion and Molecular
Insight Pharmaceuticals.
7.13 Nordion will notify Molecular Insight Pharmaceuticals in writing
within 24 hours of discovery of any problems that may impact any
Batch previously shipped.
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 6 of 28
7.2 PRODUCT RELEASE
Prior to release, all manufacturing and testing documentation
associated with any Batch is reviewed to ensure all steps were carried
out as described and that all in-process parameters were within
specification. The results of the testing are reviewed to determine if
BMIPP meets Specification. The Batch BMIPP Product Release Form serves
as a checklist to ensure all documentation associated with manufacture
and testing of the Batch is present, and provides the acceptable
limits for test results as derived from BMIPP Specification.
7.3 PRODUCT RECALL
7.3.1 Nordion is responsible for providing any and all data or
information related to BMIPP recalls within an agreed upon time
frame not to exceed 1 day. Molecular Insight Pharmaceuticals and
Nordion will consult and cooperate on any recall decision with
the goal of reaching an agreement; however, Molecular Insight
Pharmaceuticals has the final decision on recalling its product.
Additional provisions pertaining to recalls are set forth in
section 11.7 of the Supply Agreement.
7.3.2 Both parties must forward to the other party a copy of any
regulatory field alerts before or at the time that the alert is
sent to the Regulatory Authorities. Molecular Insight
Pharmaceuticals has final responsibility on the decision to
submit a field alert.
7.4 DOCUMENTATION
7.4.1 Originals of all Batch documents and associated quality control
records including raw materials records will be retained by
Nordion as per Nordion procedure. In any case, Nordion will
consult with Molecular Insight Pharmaceuticals prior to
destruction of any BMIPP related records. See Appendix 4 -
SOP-80-005 Quality Records and XXX-00-000 XXXXX: Batch Records
(Radiopharmaceuticals)
7.4.2 In the case of a specific request from Molecular Insight
Pharmaceuticals, Nordion agrees to provide at a mutually agreed
cost a copy of any of the following Batch documents for BMIPP, by
facsimile or courier:
- Analytical and microbiological test results (finished
product and in-process).
- Deviation Reports
- Executed Batch Record
- Investigation Reports as it relates to a BMIPP batch
- Label Room Samples
- Line Clearances
- Reconciliation Sheets
- Reject Records
- Weighing Records
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 7 of 28
8 REGULATORY CMC COMPLIANCE
8.1 Regulatory Correspondence and Inspections will be governed by section
11.4 of the Supply Agreement.
8.2 REGULATORY ACTIONS
8.2.1 Molecular Insight Pharmaceuticals will promptly notify Nordion
of any regulatory actions related to BMIPP that may impact
Nordion.
8.2.2 Nordion and Molecular Insight Pharmaceuticals agree to supply
each other with any manufacturing, testing, or storage data
within 1 business day, if requested, as the result of a
regulatory inspection, or a potential regulatory exposure such as
a recall or significant product complaint.
8.3 RIGHT OF MOLECULAR INSIGHT PHARMACEUTICALS TO AUDIT
8.3.1 In addition to all audit and inspection rights set forth in the
Supply Agreement, not more often than once per year, except as
set out in 8.3.2 and provided reasonable notice in writing
(minimum of 5 business days) is provided, Nordion will allow
qualified, pre-approved representatives from Molecular Insight
Pharmaceuticals to have access to the manufacturing, warehousing,
laboratory premises and records to perform one standard "cGMP
systems" audit. Molecular Insight Pharmaceuticals representatives
will be escorted at all times by Nordion personnel.
8.3.2 Nordion will permit Molecular Insight Pharmaceuticals
representatives to conduct "for cause" audits as necessary,
provided written notification is provided at least 3 business
days in advance, to address significant product quality or safety
problems and may have access to all related information.
8.3.3 Nordion and Molecular Insight Pharmaceuticals shall agree on a
mutually acceptable course of corrective action and resolution of
the issues, in the event that Molecular Insight Pharmaceuticals
finds any deficiencies during any such audits.
8.4 MOLECULAR INSIGHT PHARMACEUTICALS AUDIT CLOSEOUT
8.4.1 An exit meeting will be held with representatives from Nordion
and Molecular Insight Pharmaceuticals to discuss significant
audit observations.
8.4.2 Molecular Insight Pharmaceuticals will provide a written report
of all observations within 30 days to Nordion. Nordion will
provide a written response to the report. The response will
detail corrective action for each observation, if required. Due
to the potential complexity of the observations and subsequent
planning, Nordion will make every effort to ensure the response
back to Molecular Insight Pharmaceuticals is completed within 30
to 60 days of the audit report receipt. Nordion will follow up to
ensure that all corrective actions are implemented.
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 8 of 28
9 NON-CONFORMITY DISPUTE RESOLUTION
In the event that a dispute arises between Nordion and Molecular Insight
Pharmaceuticals in the non-conformity of a Batch with respect to its
release, the Quality Representatives from both companies shall, in good
faith, promptly attempt to reach an agreement. Whatever the outcome, either
party has the right of veto to reject a BMIPP batch or a portion thereof
based upon a quality issue.
10 CHANGE MANAGEMENT
10.1 Any process changes, including, without limitation, those covering
specifications, manufacturing processes, test methods and their
associated facilities, equipment and utilities proposed by either
Molecular Insight Pharmaceuticals or Nordion will be communicated to
the other party for initial review and written approval of such
changes. This will enable Nordion and Molecular Insight
Pharmaceuticals to assure changes are handled in compliance with
applicable regulatory requirements and will allow Nordion to maintain
adequate control over the quality commitments in the NDA/sNDA
application made to the FDA by Molecular Insight Pharmaceuticals.
10.2 Nordion is responsible for implementing compendial changes of the
ingredients utilized in the manufacture of the product and for
notifying Molecular Insight Pharmaceuticals of any required changes.
10.1 All proposed changes reported to Molecular Insight Pharmaceuticals by
Nordion must go through a technical and regulatory impact assessment
by Molecular Insight Pharmaceuticals. This impact assessment will be
carried out within seven business days. In the event this timeline
cannot be met, Molecular Insight Pharmaceuticals will advise Nordion
and will provide an estimated turnaround time. Any changes that are
identified by Molecular Insight Pharmaceuticals as having a direct
impact on either their regulatory submission or the performance of
BMIPP, must be documented, and notification sent back to Nordion. The
change(s) must receive written approval from the Molecular Insight
Pharmaceuticals Quality and Regulatory representative prior to
implementation. Molecular Insight Pharmaceuticals is responsible for
reporting all changes to FDA.
10.2 Where required, following validation of a process change, Nordion will
supply a copy of the related validation summary report to Molecular
Insight Pharmaceuticals and, if applicable, copies of associated
stability data as it becomes available.
11 VALIDATION OF THE PROCESS
11.1 Nordion is responsible for ensuring that the Process and all testing
associated with the BMIPP is validated pursuant to validation protocol
previously approved in writing by Molecular Insight Pharmaceuticals.
The validation should ensure that the process is capable of
consistently meeting the predetermined release specifications for the
product.
11.2 Nordion will provide Molecular Insight Pharmaceuticals access to all
validation protocols related to the BMIPP (with any proprietary
information redacted) for audit purposes.
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 9 of 28
APPENDIX 1
FINAL PRODUCT SPECIFICATION
MDS NORDION
VANCOUVER OPERATIONS
FINAL PRODUCT SPECIFICATION
Issue No.: 0 iodofiltic acid I-123 SPE-46-200
Effective: 2005.09.09 Page 1 of 2
Product : iodofiltic acid I-123
Synonyms : [I-123] - 15-(p-iodophenyl)-3-
methylpentadecanoic Acid or I-123 BMIPP
Visual Inspection : Clear, colourless solution, essentially free of
foreign matter visible to the unaided eye.
Radionuclide Identity : Gamma-Photon emission at 159 +/- 2 keV
Radionuclidic Purity : > or = 99.8% I-123
Radioactivity Concentration : 2.25 to 2.75 mCi/mL**
Radiochemical Identity : *Rr value between 0.95 to 1.05
Radiochemical Purity : > or = 95% as iodofiltic acid I-123
Chemical Purity
BMIPP : 0.225 to 0.275 mg/mL
UDCA : 3.15 to 3.85 mg/mL
Total Activity : 4.5 to 5.5 mCi at TOC**
pH : 8.2 to 9.2
Bacterial Endotoxin : < or = 17.5 EU/mL
Sterility : Meets USP requirements - test initiated on day
of manufacture
Expiry : 1200 PT two days after date of manufacture
* Rr is the retention time of the product (iodofiltic acid I-123) divided
by the retention time of the reference standard (non-radioactive
iodofiltic acid)
** TOC = Time of Calibration; 1500 h PT, one day after date of manufacture.
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 10 of 28
APPENDIX 1 - CONT.
FINAL PRODUCT SPECIFICATION
Issue No.: 0 iodofiltic acid I-123 SPE-46-200
Effective: 2005.09.09 Page 2 of 2
Prepared by: /s/ Illegible Date: 2005. 08.30
---------------------------------------
Approved by: /s/ Illegible Date: (Illegible)
---------------------------------------
Production
Approved by: /s/ Illegible Date: 2005/8/31
---------------------------------------
Quality
Approved by: /s/ Illegible Date: 2005 Sept 07
---------------------------------------
Molecular Insight Pharmaceuticals, Inc.
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 11 of 28
APPENDIX 2
PRODUCT RELEASE FORMS
Each page of the document
has been checked against
MDS NORDION the master copy for
VANCOUVER OPERATIONS accuracy
PRODUCT RELEASE FORM
(Illegible)
Date: ___________________
Issue No.: 1 Product Release Form PRF-16-001A
Effective: 2005.09.14 for iodofiltic acid I-123 Page 1 of 2
LOT NO.: _______ BMI- ___ - _________ QC Lab No.: __________________
Production Date: ________________ [ ] Release [ ] Reject
Calibration Date: 1500 PT ___________________ _______________
Expiry Date: 1200 PT Quality Control Date
QUALITY CONTROL RESULTS
TESTS RESULTS SPECIFICATIONS DOCUMENT
----- ------- -------------- --------
Visual Inspection Conform: Clear, colourless ACR-16-003
[ ] Y [ ] N solution, essentially
free of foreign matter
visible to the
unaided eye.
pH 8.2 - 9.2 ACR-16-006
Activity Concentration** mCi/mL 2.25 - 2.75 mCi/mL ACR-16-005
Total Activity** mCi 4.5 - 5.5 mCi XXX-00-000
Xxxxxxxx (iodofiltic acid I-123) Rr* = 0.95 - 1.05 ACR-16-024A
Radionuclidic Identity keV 157 - 161 keV
Radionuclidic Purity** % I-123 > or = 99.8% X-000 XXX-00-000
Xxxxxxxxxxxxx Xxxxxx % as iodofiltic > or = 95% as ACR-16-024B
acid I-123 iodofiltic acid I-123
CHEMICAL PURITY
BMIPP mg/mL 0.225 to 0.275 mg/mL ACR-16-024A
UDCA mg/mL 3.15 to 3.85 mg/mL
Endotoxin Limit Test (LAL) EU/mL < or = 17.5 EU/mL ACR-10-003
Sterility Test initiated on Meet USP requirements ACR-78-001
day of Manufacture
by: ______________
Autocalve Results Reviewed by: _____ Autoclave printout PCR-73-001
reviewed by QC
* Rr is the retention time of the product (iodofiltic acid I-123) divided by
the retention time of the reference standard (non-radioactive iodofiltic
acid I-123)
** At calibration time, 1500 h PT, one day after date of manufacture.
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 12 of 28
APPENDIX 2 - CONT.
PRODUCT RELEASE FORMS
Issue No.: 1 Product Release Form PRF-16-001A
Effective: 2005.09.14 for iodofiltic acid I-123 Page 2 of 2
DOCUMENTS REQUIRED FOR BATCH RELEASE X
---------------------------------------------------------------------------- ---
SOP-16-301 Sodium Iodide-123 (I-123) Radiochemical for iodofiltic acid
I-123 Production (Certificate of Analysis)
SOP-16-300 Sodium Iodide-123 (I-123) Radiochemical for iodofiltic acid
I-123 Production (Certificate of Compliance)
PCR-16-001 Production of iodofiltic acid I-123
PCR-16-030 Capintee Calibration and Total Activity Measurement of
Dispensed Vials of iodofiltic acid I-123
ACR-16-005 Activity Concentration of iodofiltic acid I-123
ACR-16-007 High Resolution Gamma Measurement of iodofiltic acid I-123
Radionuclidic Identity and Purity
ACR-16-006 pH Determination of iodofiltic acid I-123
ACR-16-011 Preparation of Mobile Phase Solvents for High Performance
Liquid (Illegible) (HPLC) Quality Control Assay of iodofiltic
acid I-123
ACR-16-012 iodofiltic acid I-123 Quality Control Assay HPLC System
Preparation
ACR-16-013 iodofiltic acid I-123 Quality Control HPLC System Clean-up
and Storage
ACR-16-010 Reconciliation of Dispensed Vials of iodofiltic acid I-123
ACR-16-003 Visual Inspection of Dispensed Vials of iodofiltic acid
I-123
PCR-73-001 Operation of Radiopharmaceutical Autoclave (Illegible)
PCR-16-017 Preparation of iodofiltic acid I-123 Component Kits
PCR-16-018 Printing and Control of Vial Labels for iodofiltic acid
I-123
PCR-16-019 Printing and Control of Outer Lead Pot Labels for iodofiltic
acid I-123
PCR-16-032 iodofiltic acid I-123 Purification HPLC System Preparation
PCR-16-033 Preparation of Mobile Phase Solvents for High Performance
Liquid Chromatography (HPLC) Purification of iodofiltic
acid I-123
PCR-16-011 Dispensing of iodofiltic acid I-123
ACR-16-024A High Performance Liquid Chromatography (HPLC) Quality Control
Assay of iodofiltic acid I-123
ACR-16-024B High Performance Liquid Chromatography (HPLC) Quality Control
Assay of iodofiltic acid I-123
PCR-16-034 iodofiltic acid I-123 Purification HPLC System Clean-up and
Storage
PCR-16-043 iodofiltic acid I-123 Pre-process Preparation
PCR-16-101A Nonviable Environmental Monitoring for iodofiltic acid I-123
ACR-10-003 Bacterial Endotoxin Test (LAL Test)
SOP-70-002 Deviation (as required): DN-155-______________________
SOP-80-001 Positive Recall (as required), Ctrl No.: _____________
Prepared by: Xxxxxx Xxx Date: 2005.07.28
Revised by: /s/ Illegible Date: (Illegible)
----------------------------------------
Approved by: /s/ Illegible Date: (Illegible)
---------------------------------------
Quality
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 13 of 28
APPENDIX 2-CONT.
PRODUCT RELEASE FORMS
Each page of this document
has been checked against
the transfer copy of
accuracy.
Verified __________________
Date ______________________
MDS NORDION
VANCOUVER OPERATIONS
PRODUCT RELEASE FORM
Issue No.: 1 Product Release Form For iodofiltic Acid I-123 PRF-16-001B
Effective: 2005.09.14 Page 1 Of 1
DOCUMENTS REQUIRED FOR COMPLETE BATCH RECORD (POST RELEASE) X
---------------------------------------------------------------------------- ---
PCR-16-039 Cleaning of the Xxxxxxxx Syringe Pump
PCR-16-100 Viable Environmental Monitoring for iodofiltic acid I-123
ACR-78-001 Sterility Testing of Radiopharmaceutical Products
SOP-80-011 OOSI (as required): Ctrl No.: ______________________
PCR-70-005 A/B NCMR (as required): Ctrl No.: ______________________
SOP-80-008 PAFI (as required): PAFI-155-_______________________
QUALITY CONTROL POST RELEASE - MICROBIOLOGICAL TESTS
TESTS RESULTS SPECIFICATIONS DOCUMENT
----- ------- -------------------------------------- ----------
Biological - Negative growth of the exposed
Indicator ampoule PCN-73-001
for Autoclave
- Positive growth of the unexposed
positive control (#0 - ___)
Sterility Negative growth STM-78-001
(#0 - ___)
Bacteriostasis/ Positive growth STM-78-001
Fungistasis
(#0 - ___)
Approved by: Date:
--------------------------------------- -------------------
Quality Control
Prepared by: Xxxxxx Xxx Date: 2005.07.25
Revised by: /s/ Illegible Date: (Illegible)
----------------------------------------
Approved by: /s/ Illegible Date: (Illegible)
---------------------------------------
Quality
________________________________________________________________________________
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 14 of 28
APPENDIX 3
STABILITY PROCEDURES
MDS NORDION.
VANCOUVER OPERATIONS
STANDARD TEST METHOD
Issue No.: 0 Product Release Form For Iodofiltic Acid I-123 STM-16-002
Effective: 2005.O8.25 Page 1 of 6
1. PURPOSE
1.1 The purpose of the stability protocol is to validate the assigned
shelf-life of the iodofiltic acid I-123 under recommended storage
conditions (20-25 degrees C).
2. POLICY
2.1 The information provided by the stability protocol remains valid only
as long as the source and the standard of the raw materials, the
manufacturing process and equipment, and the standard for the drug
product and its packaging components remain constant. Any significant
change in any of these factors should lead to a review of the
stability study.
2.2 The stability of the product is revalidated after any significant
changes in formulation, manufacturing procedures or packaging
materials that may affect the shelf life of the product.
2.3 Deviations from this STM will be immediately brought to the attention
of the Quality Director or designate, and the protocol SOP-70-002,
Deviations from Approved Procedures will be followed.
2.4 Any action arising as a result of deviations will be recorded.
2.5 This STM is to be followed for the first three validation runs and on
one representative production lot per year.
3. RESPONSIBILITIES
3.1 The QC technician shall rigidly adhere to this protocol, to promptly
record all dain and to report any and all deviations.
3.2 The QC technician shall promptly report all results falling to meet
specifications to the Director, Quality, Safety, and Regulatory
Affairs or designate. Such actions shall be recorded.
3.3 The QC department shall compile and maintain ACR-46-002 and all
Quality Records relevant to the Stability Validation.
4. STABILITY STUDIES
4.1 Stability studies on iodofiltic acid I-123 final product are to be
done at the time of manufacture (the normal time of QC analyses for
final product release), on the calibration date and on the day after
expiry date.
Ensure Expiry Date study is performed on or after 1200 h PT on the day
of expiry so as to validate the entire shelf life.
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 15 of 28
APPENDIX 3 - CONT.
STABILITY PROCEDURES
Issue No.: 0 Stability Protocol for Iodofiltic acid I-123 STM-16-002
Effective: 2005.08.25 Page 2 of 6
4.2 In order to represent the "worst case" scenario, vials of Iodofiltic
acid I-123 are placed upside down at 20 degrees - 25 degrees C to
maximize the time the teflon lined rubber stopper is in contact with
the production solution, for the day after manufacture and two days
after manufacture tests.
4.3 THE FOLLOWING PARAMETERS ARE MONITORED:
PARAMETER DOCUMENT
--------- -----------
4.3.1 Visual Inspection ACR-46-003
4.3.2 pH ACR-46-006
4.3.3 Activity Concentration ACR-46-005
4.3.4 Total Activity PCR-46-030
4.3.5 Identity (Iodofiltic acid I-123) ACR-46-024A
4.3.6 Radionuclidic Identity ACR-46-007
4.3.7 Radionuclidic Purity ACR-46-007
4.3.8 Radiochemical Purity ACR-46-024B
4.3.9 Chemical Purity
4.3.9.1 BMIPP ACR-46-024A
4.3.9.2 UDCA ACR-46-024A
4.3.9.3 Ethanol ACR-46-031
4.3.10 Endotoxin Limit Xxxx(XXX) XXX-00-000
4.3.11 Sterility ACR-78-001
4.4 IODOFILTIC ACID I-123 SAMPLE SIZE
4.4.1 Visual Inspection
4.4.1.1 All dispensed vials of iodofiltic acid I-123 are visually
inspected for particles, labels and container closure system
integrity on the day of manufacture prior to final product
release.
Note: In a regular manufacturing run, one vial for Endotoxin
test and one vial for HPLC are taken prior to visual
inspection due to time constraints.
4.4.1.2 Vials of iodofiltic acid I-123 for QC samples are
visually inspected at subsequent stability time points.
4.4.2 Chemical tests for the First Three Validation Lots
Each set of chemical tests requires two vials (one for HPLC and
one for other chemical tests) which is based on the above test
parameters in section 4.3.1 to 4.3.9.2.
Intercompany Quality Agreement Rev.0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 16 of 28
APPENDIX 3 - CONT.
STABILITY PROCEDURES
Issue No.: 0 Stability Protocol for iodofiltic acid I-123 STM-16-002
Effective: 2005.08.25 Page 3 of 6
4.4.2.1 On the day of iodofiltic acid I-123 manufacture, collect
six vials, two vials from the beginning, two vials from the
middle and two vials from the end of the iodofiltic acid
I-123 dispensed vials.
4.4.2.1.1 With reference to Section 4.3.1 to 4.3.9.2,
perform HPLC and other chemical tests on each of the
three vials collected (one from the beginning, one from
the middle, and one from the end) of the dispensed
vial.
4.4.2.1.2 Report each set of test results (HPLC and chemical
tests) in VCR-16-009 for manufacturing process
validation of iodofiltic acid I-123.
4.4.2.1.3 Report one set of test results from Section
4.4.2.1.2 (HPLC and chemical tests) in ACR-46-002 in
the column "on the day of manufacture"
4.4.2.2 On the day of iodofiltic acid I-123 manufacture, five
additional iodofiltic acid I-123 vials are to be collected
randomly and placed upside down at 20-25 degrees C.
4.4.2.2.1 On the day of calibration date of iodofiltic acid
I-123 product, use one upside down vial for HPLC
analysis and use one upside down vial for chemical
tests (Section 4.3.1 to 4.3.9.2). Report the test
results in ACR-46-002.
4.4.2.2.2 Similarly on the day of expiry date, use one
upside down vial for HPLC analysis and one upside down
vial for chemical tests. Report the test results in
ACR-46-002.
4.4.2.2.3 Ethanol content is analyzed at post expiry date
and the test result is recorded in the post expiry date
column on VCR-46-009 Manufacturing Process Validation
of Iodofiltic acid I-123 and ACR-46-002 Stability
Protocol for iodofiltic acid I-123.
4.4.3 Chemical Tests for Annual Product Stability Lot
Each set of chemical tests requires two vials (one for HPLC and
one for other chemical tests) which are based on section 4.3.1 to
4.3.9.2.
4.4.3.1 On the day of iodofiltic acid I-123 manufacture, collect
two random vials from Production.
4.4.3.1.1 Perform HPLC analysis on one vial and other
chemical tests on the second vial as described in
Section 4.3.1 to 4.3.9.
4.4.3.1.2 Report the test results in ACR-46-002 in the
column "On the Day of Manufacture".
4.4.3.2 On the day of manufacture, five additional iodofiltic
acid I-123 vials are to be collected randomly and placed
upside down at 20-25 degrees C.
Intercompany Quality Agreement Rev.0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 17 of 28
APPENDIX 3 -CONT.
STABILITY PROCEDURES
Issue No.: 0 Stability Protocol for iodofiltic acid I-123 STM-16-002
Effective: 2005.08.25 Page 4 of 6
4.4.3.2.1 On the day of calibration date of iodofiltic acid
I-123 product, use one upside down vial for HPLC
analysis and use one upside down vial for other
chemical tests (Section 4.3.1 to 4.3.9.2). Report the
test results in ACR-46-002.
4.4.3.2.2 Similarly on the day of expiry date, use one
upside down vial for HPLC and use one upside down vial
for other chemical tests (section 4.3.1 to 4.3.9.2).
Report the test results in ACR-46-002.
4.4.3.2.3 Perform Ethanol content analysis on post
iodofiltic acid I-123 expiry date.
4.4.3.2.4 Report test results in ACR-46-002 in the column
"Post Expiry Date".
4.4.4 Microbiological Tests (Sterility and Endotoxin) for the first
Three Validation Lots and for Annual Product Stability Lot
4.4.4.1 On the day of iodofiltic acid I-123 manufacture, five
vials are collected, with three vials being collected in a
manner similar to Section 4.4.2.1 (i.e., one from the
beginning, one from the middle, and one from the end). These
are pooled with a fourth vial (selected randomly) and all
four are used for sterility testing. One extra vial is
collected randomly for Endotoxin testing.
4.4.4.2 On the day of manufacture, ten additional iodofiltic acid
I-123 vials are collected randomly and placed upside down at
20-25 degrees C
4.4.4.2.1 On the day of calibration date of iodofiltic acid
I-123 product, four upside down vials are used for
sterility test. One vial is tested for Endotoxin.
4.4.4.2.2 On the day of expiry date of the iodofiltic acid
I-123 product, four remaining upside down vials are
used for sterility test. One vial is tested for
Endotoxin.
4.4.5 Testing Schedule
4.4.5.1 ACR-46-002 shows the testing schedule for the various QC
analysis at the different stability time points. Report all
the test results in the ACR.
Intercompany Quality Agreement Rev.0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 18 of 28
APPENDIX 3 - CONT.
STABILITY PROCEDURES
Issue No.: 0 Stability Protocol for iodofiltic acid I-123 STM-16-002
Effective: 2005.08.25 Page 5 of 6
5. CRITERIA FOR ACCEPTABLE LEVELS OF STABILITY
CONDITION MAINTAINED THROUGHOUT THE
TYPE OF STABILITY SHELF-LIFE OF THE DRUG PRODUCT
----------------- ------------------------------------------------------------
Chemical Each active ingredient retains its chemical integrity and
labelled potency, within the specified limits.
Physical The original physical properties, including appearance,
uniformity, and solubility are retained.
Microbiological The product meets the specified limits for endotoxin and
sterility at the beginning and at the end of its assigned
shelf life.
6. DOCUMENTATION
Document
---------------------------------------------------------
6.1 ACR-46-002 Stability Protocol for iodofiltic acid I-123
7. APPENDICES
7.1 Appendix I: Sampling Plan on Dispensed Vials for Manufacturing Process
Validation of iodofiltic acid I-123
7.2 Appendix II: Sampling Plan on Dispensed Vials for Annual Stability
Study of iodofiltic acid I-123
Prepared by: /s/ Illegible Date: (Illegible)
----------------------------------------
Approved by: /s/ Illegible Date: (Illegible)
----------------------------------------
Quality
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 19 of 28
APPENDIX 3 - CONT.
STABILITY PROCEDURES
Issue No.: 0 Stability Protocol for Iodofiltic acid I-123 STM-16-002
Effective: 2005.08.25 Page 6 of 6
Appendix I
Sampling Plan on Dispensed Vials for Manufacturing Process
Validation of iodofiltic acid I-123
On the day of On On Post
manufacture Calibration Date Expiry Date Expiry Date
------------- ---------------- ----------- -----------
HPLC Analysis 3 B,M,E 1* R 1* R
Chemical tests 0 X,X,X 0* X 0* X
Xxxxxxx Analysis 1* R
Endotoxin test (LAL) 1 R 1* R 1* R
Sterility test 4 B,M,E,R 4* R 4* R
Total Vials Required: 26
Appendix II
Sampling Plan on Dispensed Vials for Annual Stability Study of iodofiltic
acid I-123
On the day of On On Post
manufacture Calibration Date Expiry Date Expiry Date
------------- ---------------- ----------- -----------
HPLC Analysis 1 R 1* R 1* R
Chemical tests 1 R 1* R 1* R
Ethanol Analysis 1* R
Endotoxin test (LAL) 1 R 1* R 1* R
Sterility test 4 B,M,E,R 4* R 4* R
Total vials required: 22
B = Beginning of dispensed vials
M = Middle of the dispensed vials
E = End of the dispensed vials
R = Random dispensed vials
* Vials are collected on the day of manufacture and are store upside down at
20-25 degrees C prior to performing the required tests.
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 20 of 28
APPENDIX 3 - CONT.
STABILITY PROCEDURES
Each page of this document
has been checked against the
master copy for accuracy
Verified
Date
MDS NORDION
VANCOUVER OPERATIONS
STANDARD TEST METHOD
Issue No.: 0 Stability Protocol for iodofiltic acid I-123 ACR-16-002
Effective: 2005.08.25 Page 1 of 2
IODOFILTIC ACID I-123 LOT NUMBER
PRODUCT STABILITY STUDY BMI - _____________
Date of Manufacture __________________________ Date of Expiry ________________
Conditions: iodofiltic acid I-123 vials were stored upside down at 20-25
degrees C. The product solution was in contact with the teflon
lined rubber slippers.
Day of Calibration Post
Specification Manufacture Date Expiry Date Expiry Date
--------------------- ----------- ----------- ----------- -----------
Visual Inspection Clear colourless
solution, essentially
free of foreign
matter visible to the
unaided eye.
pH 8.2-9.2
Activity Concentration* 2.25-2.75 mCi/mL
Total Activity* 4.5-5.5 mCi
Identity Iodofiltic acid I-123 Rr=0.95-1.05
Radionuclidic Identity 157-161 keV
Radionuclidic Purity* > or = 99.8% I-123
Radiochemical Purity > or = 95% as
iodofiltic acid I-123
Chemical Purity
BMIPP 0.225-0.275mg/mL
UDCA 3.15-3.85 mg/mL
Ethanol 2-10% v/v
Endotoxin Limit Test (LAL) < or = 17.5 EU/mL
Sterility Meets USP
requirements
* Term of (Illegible)
* (Illegible)
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 21 of 28
APPENDIX 3 - CONT.
STABILITY PROCEDURES
Issue No.: 0 Stability Protocol for iodofiltic acid I-123 ACR-16-002
Effective: 2005.08.25 Page 2 of 2
Comments
________________________________________________________________________________
________________________________________________________________________________
________________________________________________________________________________
________________________________________________________________________________
________________________________________________________________________________
________________________________________________________________________________
________________________________________________________________________________
Compiled by: Date:
---------------------------------------- ------------------
Approved by: Date:
---------------------------------------- ------------------
Prepared by: /s/ Illegible Date: 2005/08/22
----------------------------------------
Approved by: /s/ Illegible Date: 2005/8/24
----------------------------------------
Quality
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 22 of 28
APPENDIX 4
QUALITY RECORDS
MDS NORDION
VANCOUVER OPERATIONS
STANDARD OPERATING PROCEDURE
Issue No.: 6 Quality Records SOP-80-005
Effective: 2003.12.02 Page: 1 of 5
1 INTRODUCTION
1.1 PURPOSE
1.1.1 This procedure identifies Nordion's Vancouver Operations Quality
Records and describes their collection, indexing, access, filing,
storage, maintenance and disposition requirements.
1.2 POLICY
1.2.1 This procedure applies to Quality Records at Nordion's Vancouver
Operations as they pertain to ISO 9001:2000.
1.2.2 Procedures describing the upkeep of the records systems are
current and effective.
1.2.3 Records are stored under conditions that allow rapid retrieval,
ensure safekeeping and protect proprietary information.
1.2.4 Records are reviewed and approved by the designated personnel.
1.2.5 All Quality Records shall be legible and identifiable to the
product involved.
1.3 RESPONSIBILITIES
1.3.1 Management shall determine record requirements and ensure that
adequate systems for records are implemented and maintained.
1.3.2 Each functional group shall assure a Quality Records
Responsibility and Maintenance Form (QRRMF, Appendix I) is
completed.
1.3.3 Individuals identified on the QRRMF shall manage the record for
its entire stipulated life cycle.
1.3.4 The Quality Director or designate shall handle, maintain and
dispose of off-site records as per SOP-80-015 Control of Records
Stored Off-Site.
1.3.5 The Quality Department shall maintain Internal storage, truck
retention times and issue disposition instructions, where
applicable.
1.3.6 Onsite records retrieved from their storage area shall require
the approval of the Director, Quality, Safety, and Regulatory
Affairs or designate. A logbook shall be maintained to record
such activities.
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 23 of 28
APPENDIX 4 - CONT.
QUALITY RECORDS
Issue No.: 6 Quality Records SOP-80-005
Effective: 2003.12.02 Page: 2 of 5
2 PREPARATION
2.1 DOCUMENTS
2.1.1 All documents pertaining to the Quality Records described herein
are identified in the individual QRRMF.
2.1.2 Quality Manual
2.2 APPENDICES
2.1.1 Appendix I: Quality Records Responsibility and Maintenance Form
(QRRMF).
2.1.2 Appendix II: Description of the Elements on the QRRMF.
3 DEFINITIONS
3.1 QUALITY RECORDS: For each Quality Record identified, a Quality Record
Responsibility and Maintenance Form (Appendix I) will be issued
describing responsibility, location and retention periods.
3.2 SUPPLIER RECORDS: Where contractual agreements have been for a
supplier to maintain records, details are indicated in the Purchase
Order or contract. Access by Nordion to these records is part of the
terms and conditions.
3.3 SECURITY: Quality records are maintained in locked rooms or cabinets
located in a suitable environment to minimize deterioration or damage
to the records. Usually the storage areas are sprinklered or suitable
fire resistance containment is used. Record release is strictly
controlled and limited to authorized Nordion personnel, customers, or
regulatory bodies. Copies may be sent or used as necessary. See
Section 1.3.4 for more information on the security of offsite quality
records.
3.4 MAINTENANCE AND CHANGES TO RECORDS: Records are identified, indexed
and filed for easy retrieval. Each document is filed under a unique
code and records are maintained of revisions. Records of all revisions
remain as records for reference.
3.5 RECORD RETENTION PERIODS: Each record or group of records has a
retention period. This period is established in consultation with the
cognizant line management and the Director, Quality, Safety and
Regulatory Affairs. Where a retention period is indicated as "minimum
one year", this implies that records from the previous calendar year
and year to date are maintained prior to the disposition being
considered. A "minimum of five years" Implies that records from the
previous five years and year to date are maintained prior to
disposition being considered. Onsite Retention Periods and Offsite
Retention Periods are recorded on the Quality Records Responsibility
and Maintenance Forms (QRRMF) (see Appendix I).
3.6 ALL RECORDS MUST BE LEGIBLE. This is to include no pencil entries and
proper reproduction equipment so as to provide clear copies.
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 24 of 28
APPENDIX 4 - CONT.
QUALITY RECORDS
Issue No.: 6 Quality Records SOP-80-005
Effective: 2003.12.02 Page: 3 of 5
3.7 All records are to be clearly identifiable to the product involved by
proper indication on each record of specific identifiers.
4 PROCEDURE
4.1 Upon identification of a Quality Record, the originator shall use the
format as provided for QRRMF (Appendix I). The originator shall
complete the following actions and obtained approval from their
respective line manager.
Section 1. Quality Record
Section 2 Reference Document
Section 3 Responsible Person(s) Job Title
Section 4 Location of On-Site Storage
Section 5 Location of Off-Site Storage
Section 6 Method for Indexing and Storage
Section 9 Media
4.2 The line manager in consultation with the Manager, Quality, Safety,
and Regulatory Affairs shall complete the following sections:
Section 7 On-Site Retention Time
Section 8 Off-Site Retention Time
Section 10 Disposition
4.3 Upon receipt of a QRRMF, the Document Coordinator shall create a Data
Control Sheet and update DCS-76-001 QRRMF Master list.
4.4 In order to ensure that QRRMF are up-to-date, such documents shall be
included as part of the Annual Review of documents as per SOP-70-017
Annual Review of Control Documents.
Document Approval
Prepared by: Xxxxxxx Xxxx Date: 1997.06.23
Revised by: /s/ Illegible Date: (Illegible)
---------------------------------------
Approved by: /s/ Illegible Date: (Illegible)
--------------------------------------
Quality
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 25 of 28
APPENDIX 4 - CONT.
QUALITY RECORDS
Issue No.: 6 Quality Records SOP-80-005
Effective: 2003.12.02 Page: 4 of 5
APPENDIX I - QUALITY RECORDS RESPONSIBILITY AND MAINTENANCE FORM
1. Quality Record
2. Reference Document
3. Responsible Person(s) Job Title
4. Location of On-Site Storage
5. Location of Off-Site Storage
6. Method for Indexing and Storage
7. On-Site Retention Time
8. Off-Site Retention Time
9. Media:
10 Disposition
Prepared by: Date:
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Approved by: Date:
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Line Manager
Approved by: Date:
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Manager, Quality, Safety, and
Regulatory Affairs
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 26 of 28
APPENDIX 4 - CONT.
QUALITY RECORDS
Issue No.: 6 Quality Records SOP-80-005
Effective: 2003.12.02 Page: 5 of 5
APPENDIX II - ELEMENT DESCRIPTION
1. Quality Record The title of the Quality Record.
2. Reference Document Document or procedure describing the
Quality Record.
3. Responsible Person(s) Job Title Title of designated responsible
individual(s).
4. Location of On-Site Storage A general description of the physical area
within the Vancouver facility in which the
records are stored.
5. Location of Off-Site Storage A general description of the physical area
off the Vancouver premises in which the
records are stored.
6. Method for Indexing and Storage This describes how the records are indexed
and store, i.e., by part number, date, P.O.
number, unique identifiers, etc.
7. On-Site Retention Time This minimum duration for on-side record
retention.
8. Off-Site Retention Time The minimum duration for off-site record
retention.
9. Media: Describes the physical record type, i.e.,
paper, microfilm, computer records, etc.
10 Disposition Means of disposing of records.
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 27 of 28
APPENDIX 4 - CONT.
QUALITY RECORDS
MDS NORDION
VANCOUVER OPERATIONS
DATA CONTROL SHEET
Issue No.: 3 QRRMF: Batch Records (Radiopharmaceuticals) DCS-76-004
Effective: 2005.07.18 Page: 1 of 1
QUALITY RECORDS RESPONSIBILITY AND MAINTENANCE FORM
1. Quality Record Batch Records (Radiopharmaceuticals)
2. Reference Document Product SOPs, PCRs, STMs, ACRs, PRFs
3. Responsible Person(s) Job Title QA Designate
4. Location of On-Site Storage QC Administration Office or QA Records Room
5. Location of Off-Site Storage Iron Mountain
6. Method for Indexing and Storage By product and sequentially by batch
7. On-Site Retention Time Minimum 1 month, except rejected batches,
which are kept on-site permanently
8. Off-Site Retention Time Permanent
9. Media: Paper
10 Disposition N/A
Prepared by: Xxxxxxx Xxxx Date: 2000.03.23
Revised by: /s/ Illegible Date: (Illegible)
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Approved by: /s/ Illegible Date: (Illegible)
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Quality
Intercompany Quality Agreement Rev. 0
MDS Nordion and Molecular Insight Pharmaceuticals, Inc. Page 28 of 28
72
SCHEDULE G
SPECIFICATIONS FOR PRECURSOR, REFERENCE STANDARDS AND EXCIPIENTS
PRECURSOR AND REFERENCE STANDARDS:
MDS NORDION
VANCOUVER OPERATIONS
RAW MATERIALS SPECIFICATION
Issue No.: 0 15-(p-Iodophenyl)-3-methylpentadecanoic SPE-46-007
Effective: 2005.07.11 Acid (BMIPP) Page 1 of 1
PRODUCT : 15-(p-Iodophenyl)-3-methylpentadecanoic Acid (BMIPP)
DESCRIPTION : White crystalline powder
VISUAL INSPECTION : Each lot or every shipment shall be visually inspected
for appropriate labelling and contents, Materials,
packaging, product and package integrity or damage.
Materials should be essentially free of foreign matter
visible to the unaided eye.
IDENTIFICATION : Melting range 53.5 to 55.0 degrees C
SUPPLIER : TCI America
CATALOGUE NUMBER : Z3398
SIZE* : Variable
STORAGE CONDITIONS : Containers shall be identified with proper distinct
labelling for each lot and each shipment received. All
containers shall be stored off the floor at all times in
a manner to prevent contamination. Refer to cGMP 211.80.
Material shall be stored at 2 TO 8 degrees C in the dark.
CERTIFICATE : Certificate of Analysis
EXPIRY DATE : One year After receipt.
* Based on Manufacturer's claim
Prepared by: /s/ Illegible Date: (Illegible)
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Approved by: /s/ Illegible Date: 2005/7/8
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Quality
UNCONTROLLED COPY
73
SCHEDULE G (CONT.)
EXCIPIENTS:
MDS NORDION
VANCOUVER OPERATIONS
RAW MATERIALS SPECIFICATION
Issue No.: 0 Ursodeoxycholic Acid (Ursodiol or UDCA) SPE-46-008
Effective: 2005.07.11 Page 1 of 1
PRODUCT : Ursodeoxycholic Acid (Ursodiol OR UDCA)
DESCRIPTION : White crystalline powder
VISUAL INSPECTION : Each lot of every shipment shall be visually inspected
for appropriate labelling and contents, materials,
packaging, product and package integrity or damage.
Materials should be essentially free of foreign matter
visible to the unaided eye.
IDENTIFICATION : Melting range between 200 to 2O5 degrees C
GRADE* : Eur. Ph.
SUPPLIER : Diapharma Xxxxxxx, Xxxxxxxxxx S.p.A.
CATALOGUE NUMBER : Material Code 500346, Code 110
SIZE* : Variable
STORAGE CONDITIONS : Containers shall be identified with proper distinct
labelling for each lot and each shipment received. All
containers shall be stored off the floor at all times in
a manner to prevent contamination. Refer to cGMP 211.80.
Material shall be stored at 2 to 8 degrees C in the dark.
CERTIFICATE : Certificate of Analysis
EXPIRY DATE : Manufacturer's expiry date.
* Based On manufacturer's claim
Prepared by: /s/ Illegible Date: (Illegible)
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Approved by: /s/ Illegible Date: 2005/7/8
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Quality
