EXHIBIT 10.30
TECHNOLOGY TRANSFER AGREEMENT
THIS TECHNOLOGY TRANSFER AGREEMENT (the "Agreement") is entered into
effective as of the 20th day of December 2006 (the "Effective Date"), by and
between Mallinckrodt Inc., a Delaware corporation, with a place of business at
000 XxXxxxxxx Xxxxxxxxx, Xxxxxxxxx, Xxxxxxxx 00000 ("MALLINCKRODT"), and
Molecular Insight Pharmaceuticals, Inc., a Delaware corporation, with an office
at 000 Xxxxxx Xxxxxx, Xxxxxxxxx, Xxxxxxxxxxxxx 00000 ("MIP").
WITNESSETH THAT:
WHEREAS, MIP plans to enter a license agreement with Novartis Pharma AG
("Novartis") for the right to make, use, sell, offer for sale and import the
Product (as defined in Section 1 below); and
WHEREAS, MALLINCKRODT owns or is the licensee of certain Patent Rights (as
defined in Section 1 below), claiming a method of stabilization of
radiopharmaceuticals; and
WHEREAS, MALLINCKRODT has technology and capability to manufacture Vials
(as defined in Section 1 below) and the Product; and
WHEREAS, MIP desires to obtain a license to the Patent Rights and
Technology (as defined in Section 1 below), and to receive a transfer of the
Technology for the Vials and the Product as detailed in EXHIBIT B; and
WHEREAS, MALLINCKRODT is willing to grant the license and to provide the
transfer of the Technology upon the terms and conditions set forth in this
Agreement;
NOW THEREFORE, in consideration of the premises and for other good and
valuable consideration, the receipt and sufficiency of which are hereby
acknowledged, MALLINCKRODT and MIP agree as follows:
1. DEFINITIONS. Wherever used in this Agreement, the following capitalized terms
shall have the meanings set forth below:
1.1 "AFFILIATE" means any entity that directly or indirectly controls or is
controlled by or is under common control with a Party to this Agreement. For
purposes of this definition, "control" or "controlled" means ownership directly
or through one or more Affiliates, of fifty percent (50%) or more of the shares
of stock entitled to vote for the election of directors, in the case of a
corporation, or fifty percent (50%) or more of the equity interest in the case
of any
other type of legal entity, status as a general partner in any partnership, or
any other arrangement whereby a Party controls or has the right to control the
board of directors or equivalent governing body of a corporation or other
entity, or the ability to cause the direction of the management or policies of a
corporation or other entity.
1.2 "AGREEMENT" shall mean this Technology Transfer Agreement together with
all exhibits, schedules and appendices hereto, all as the same may be amended,
modified or supplemented from time-to-time in accordance with the terms of this
Agreement.
1.3 "CHANGE OF CONTROL" shall mean any of the following events: (i) any
Third Party (or group of Third Parties acting in concert) becomes the beneficial
owner, directly or indirectly, of fifty percent (50%) or more of the voting
power of the stock then outstanding of MIP; (ii) MIP consolidates with or merges
into another corporation or entity, or any corporation or entity consolidates
with or merges into MIP, in either event pursuant to a transaction in which
fifty percent (50%) or more of the total voting power of the stock outstanding
of the surviving entity normally entitled to vote is not held by Persons holding
more than fifty percent (50%) of the outstanding shares of MIP prior to such
consolidation or merger; (iii) any Third Party (or group of Third Parties acting
in concert) obtains the power to direct or cause the direction of the management
and policies of MIP by any lawful means whatsoever; or (iv) MIP conveys,
transfers or leases all or substantially all of its assets.
1.4 "COMPOUND" means DOTA-Tyr(3)-Octreotide.
1.5 "EFFECTIVE DATE" shall mean the later to occur of (i) the date upon
which MALLINCKRODT receives written notice from MIP that MIP has executed the
agreement with Novartis as referenced in Section 8 hereof and (ii) the date upon
which the Termination Letter shall have been executed by and between
MALLINCKRODT and Novartis.
1.6 "FDA" means the United States Food and Drug Administration and any
successor agency thereto.
1.7 "GOOD MANUFACTURING PRACTICES" or "GMP" means the then current Good
Manufacturing Practices as such term is defined from time to time by the FDA or
other relevant governmental authority having jurisdiction over the development,
manufacture or sale of the Product in any other country pursuant to its
regulations, guidelines or otherwise.
1.8 "MALLINCKRODT CONFIDENTIAL INFORMATION" means all Technology, data and
other information that is disclosed by MALLINCKRODT to MIP during the course of
providing the technology transfer services under this Agreement to the extent
that such
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information as of the date of disclosure to MIP is not (i) known to MIP other
than by virtue of a prior confidential disclosure to MIP by MALLINCKRODT; or
(ii) disclosed in published literature, or otherwise generally known to the
public through no fault or omission of MIP; or (iii) obtained from a Third Party
free from any obligation of confidentiality to MALLINCKRODT.
1.9 "MIP CONFIDENTIAL INFORMATION" means all information about MIP's
technical requirements with respect to the Product which is disclosed by MIP to
MALLINCKRODT and designated "Confidential" in writing by MIP at the time of
disclosure to MALLINCKRODT to the extent that such information is not (i) as of
the date of disclosure to MALLINCKRODT demonstrably known to MALLINCKRODT other
than by virtue of a prior confidential disclosure to MALLINCKRODT by MIP; or
(ii) as of the date of disclosure or thereafter is disclosed in published
literature, or otherwise generally known to the public through no fault or
omission of MALLINCKRODT; or (iii) obtained from a Third Party free from any
obligation of confidentiality to MIP; or (iv) MALLINCKRODT can demonstrate by
competent evidence was developed by MALLINCKRODT or its Affiliates without
access to or the benefit of MIP Confidential Information. MIP will not disclose
any information to MALLINCKRODT regarding MIP's marketing plans or
commercialization with respect to the Product or to the Indium 111 labelled
Compound for dosimetry planning for OctreoTher therapy delivery and to the
extent disclosed, such information shall not be deemed MIP Confidential
Information for purposes of this Agreement and MALLINCKRODT shall not be under
any limitations with respect thereto.
1.10 "MIP FIELD" means human oncology therapeutic use.
1.11 "OCTREOTHER(R)" means the trademark selected and owned by Novartis for
the Product.
1.12 "PARTY" OR "PARTIES" shall mean MIP or MALLINCKRODT, or MIP and
MALLINCKRODT, whichever the context admits.
1.13 "PATENT RIGHTS" means the patents and patent applications listed in
EXHIBIT A, and patents issuing on them, including any division, continuation,
continuation-in-part, renewal, extension, re-examination, reissue or foreign
counterpart thereof.
1.14 "PERSON" shall mean any individual, corporation, partnership,
association, joint stock company, trust, unincorporated organization or
government or political subdivision thereof.
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1.15 "PRODUCT" means the OctreoTher Hot Liquid which is the radiolabeled
peptide (90)Y DOTA-Tyr(3)-Octreotide (Yttrium ((90)Y) SMT 487) in a solution
prepared from the reconstituted Vials.
1.16 "REGULATORY AUTHORITY" shall mean the FDA or any foreign counterpart
or additional governmental or regulatory agencies in the Territory with
responsibility for marketing approval or authorization of the Product.
1.17 "TECHNOLOGY" means and is limited to the specific materials, technical
information, know-how, expertise, trade secrets and the associated documentation
in MALLINCKRODT's possession and required for:
- the manufacturing and quality control of the Vials; and
- the manufacturing and quality control of the Product.
MIP acknowledges that the term "Technology" does not include any know-how,
expertise or trade secret information, if any, that MALLINCKRODT may have
regarding the labelling of the Compound with Indium-111. Without limiting the
generality of the preceding sentence, MALLINCKRODT shall be under no obligation
whatsoever to provide a Technology transfer to MIP with respect to the labelling
of the Compound with Indium-111.
1.18 "TERRITORY" shall mean all of the countries and territories of the
world.
1.19 "TERMINATION LETTER" shall mean an agreement to be entered into by
MALLINCKRODT and Novartis providing for the termination of (i) that certain
agreement, dated December 1, 1992, between Sandoz Pharma Ltd. (now Novartis) and
Mallinckrodt Medical Inc. (now MALLINCKRODT) relating to the development,
manufacture and marketing of molecules for radiodiagnostic and radiotherapeutic
purposes and (ii) that certain agreement, dated October 1996, under which
MALLINCKRODT and Novartis agreed to collaborate in the development, manufacture
and marketing of the Product.
1.20 "THIRD PARTY" shall mean any Person or other entity other than MIP,
MALLINCKRODT or their respective Affiliates.
1.21 "VIAL" means the OctreoTher SMT 487 Reaction Vial which is a vial
containing lyophilized material comprised of DOTA-Tyr(3)- Octreotide, gentisic
acid, inositol, ascorbic acid, and sodium hydroxide that is reconstituted to
make the Product.
2. GRANT OF LICENSE, TERM, RIGHTS AND OBLIGATIONS.
2.1 LICENSE GRANTED TO MIP UNDER THE PATENT RIGHTS AND TECHNOLOGY. Subject
to
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the terms, conditions and limitations of this Agreement, MALLINCKRODT hereby
grants to MIP a non-exclusive, worldwide license under all of MALLINCKRODT's
right, title and interest in the Patent Rights and Technology, to manufacture,
use, sell, offer for sale and import the Product in the MIP Field, as well as to
use the Indium 111 labelled Compound for dosimetry purposes in relation to the
Product therapy administration; provided that MIP can only exercise the
foregoing rights with respect to an Indium 111 labelled Compound to the extent
the FDA or other Regulatory Authority expressly requires the development and use
thereof for dosimetry purposes as a condition to its approval of the Product for
marketing and sale, and provided further that MIP may under no circumstances
market and sell an Indium-111 labelled Compound separately as a diagnostic
imaging agent (i.e., the Indium-labelled Compound can only be marketed and sold
for dosimetry purposes in relation to Product therapy administration). Except as
specifically provided in this Agreement, no licenses are granted by MALLINCKRODT
and MALLINCKRODT retains all other rights under the Patent Rights and the
Technology.
MIP shall have the right to grant sublicenses with respect to the license
rights provided for in this Section 2.1 solely on the following terms and
conditions.
(a) Without MALLINCKRODT'S prior written consent, which MALLINCKRODT
may grant or withhold in its sole and absolute discretion, and notwithstanding
anything to the contrary forth in this Agreement, MIP cannot sublicense any
rights to a direct competitor of MALLINCKRODT, as listed in EXHIBIT G.
(b) In the event MIP intends to grant rights of any nature whatsoever
with respect to the commercialization, including but not limited to the
marketing, promoting, distributing, importing or selling, of the Product to any
Third Party(ies), MIP must first offer any such commercialization rights, in
writing, to MALLINCKRODT. Upon receipt of such offer, MALLINCKRODT shall have
sixty (60) days to inform MIP whether it desires to enter into good faith
negotiations with MIP for a definitive agreement with respect to such rights.
Mallinckrodt's rights under this subsection are subject to MIP's obligation to
first provide Novartis with "rights of first discussions", as set forth in
Section 6.5 of the agreement to be entered into between MIP and Novartis
relating to the Product, as referenced in Section 8 of this Agreement.
(c) MIP shall in all events remain directly responsible to
MALLINCKRODT for the performance by any sublicensee of any and all obligations
and/or responsibilities assumed by such sublicensee under this Agreement.
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(d) The terms and conditions of any Third Party sublicense shall be
consistent in all respects with the terms of this Agreement.
(e) MIP shall cause each sublicensee to execute any and all additional
documents reasonably requested by MALLINCKRODT to reflect the conditions set
forth above.
2.2 TERM OF LICENSE. The term of the license set forth in Section 2.1 shall
commence on the Effective Date and, unless sooner terminated pursuant to Article
9 of this Agreement, shall terminate on a country-by-country basis on the date
when MIP discontinues manufacture and/or sale of the Product, as the case may
be, in such country.
2.3 TRANSFER OF THE TECHNOLOGY.
(a) During the period commencing no later than thirty (30) days after
the Effective Date and terminating not later than one-hundred eighty (180) days
thereafter, MALLINCKRODT shall make available research and development and
production personnel to physically transfer the Technology to MIP personnel.
Such MALLINCKRODT personnel shall be knowledgeable about the Technology, shall
be reasonably capable of transferring the Technology to MIP, and shall use
commercially reasonable efforts to transfer the Technology to MIP personnel. MIP
must at all times during the one-hundred eighty (180) period referenced in the
preceding sentence provide knowledgeable and capable personnel to be the
recipients of the transfer of the Technology. Exhibit B is an all-inclusive list
of the specific services to be provided by MALLINCKRODT personnel hereunder.
MALLINCKRODT shall transfer the Technology to MIP on an "AS IS" basis.
(b) MALLINCKRODT's obligation to provide transfer of the Technology is
in all events limited to ninety (90) work days (i.e., one MALLINCKRODT employee
working ninety (90) days at eight (8) hours per day) or completion by
MALLINCKRODT of the specific services identified in Exhibit B, whichever comes
first.
(c) For purposes of calculating the amount of time devoted by
MALLINCKRODT personnel to the transfer of Technology required under this
Agreement, each response by MALLINCKRODT to a request by MIP or its Affiliates
for assistance, whether in the form of a written communication, oral request, or
otherwise, shall be accounted for as an expenditure of time equal to the greater
of (i) four (4) hours or (ii) the actual time spent by MALLINCKRODT responding
to the request for assistance. For example, if an employee of MIP requests, by
telephone call, assistance with Technology transfer and a MALLINCKRODT employee
devotes two (2) hours responding to the request, MALLINCKRODT shall, for
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purposes of this Agreement, be considered to have provided four (4) hours of
Technology transfer services.
(d) In the event the MALLINCKRODT personnel referenced above are
required to travel away from their regular place of employment, MIP will
reimburse MALLINCKRODT for all reasonable travel and living expenses incurred by
such personnel upon submission by MALLINCKRODT of an itemized account of
expenses for which it seeks reimbursement. Travel time will be considered
working time of MALLINCKRODT employees for purposes of determining
MALLINCKRODT's compliance with its obligations under this Section.
2.4 ADDITIONAL TRANSFER OF THE TECHNOLOGY. If, during the first twelve (12)
months this Agreement is in effect, MIP determines that it requires additional
Technology transfer from MALLINCKRODT, MIP shall provide to MALLINCKRODT a list
of its specific additional requirements for MALLINCKRODT's consideration. If the
request is acceptable to MALLINCKRODT in its reasonable discretion, MALLINCKRODT
shall provide up to an additional ninety (90) work days in thirty (30) work day
increments of Technology transfer during a similar period and in the manner set
forth in Section 2.3. MIP shall make the payment described in Section 3(d) prior
to the commencement of such additional Technology transfer.
2.5 CERTIFICATION BY MALLINCKRODT. Upon completion by MALLINCKRODT of its
obligation(s) to transfer the Technology under Sections 2.3 and/or 2.4 of this
Agreement, MALLINCKRODT shall provide a written certification of completion to
MIP in the form attached to this Agreement as EXHIBIT C. Absent manifest error
demonstrated by MIP, and subject to MIP's rights to additional technical
support, if applicable, as set forth in Section 2.4, such certification shall
for all purposes be deemed conclusive and final evidence of MALLINCKRODT's full
and complete performance of its Technology transfer obligations to MIP.
2.6 LIAISON. Each of MIP and MALLINCKRODT shall within ten (10) days of the
execution of this Agreement identify a primary contact person to act as liaison
for the purposes of implementing this Agreement.
3. PAYMENTS. MIP shall make the following payments to MALLINCKRODT by wire
transfer in United States Dollars to an account designated by MALLINCKRODT:
(a) $250,000.00 concurrent with the execution of this Agreement;
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(b) $** upon commencement by MALLINCKRODT of the Technology
transfer as detailed in Exhibit B;
(c) $** upon completion of the Technology transfer as detailed
in Exhibit B; and
(d) $** for each thirty (30) day increment of the additional
Technology Transfer pursuant to Section 2.4, payable upon commencement by
MALLINCKRODT of each such increment.
4. SALE OF OCTREOTHER VIALS.
4.1 MALLINCKRODT hereby sells and MIP buys the 1,800 Vials in
MALLINCKRODT's possession. The purchase price is U.S. $400,000.00, fifty percent
(50%) of which is payable by wire transfer concurrent with the execution of this
Agreement and the balance of which is payable upon confirmation of delivery to
MIP.
4.2 Terms of delivery for the Vials shall be FOB, MALLINCKRODT's facility
in Petten, The Netherlands. MALLINCKRODT shall cause the Vials to be shipped
within thirty (30) days after the later of execution of this Agreement and
receipt by MALLINCKRODT of the fifty percent (50%) installment, as described in
Section 4.1 above, unless directed otherwise by MIP and agreed upon by
MALLINCKRODT in its discretion.
4.3 MALLINCKRODT warrants that the Vials have been manufactured in
accordance with GMP standards and meet the specifications in Section 5.2.1 of
the Yttrium ((90)Y) SMT 487 IND Information Manufacturing Description attached
to this Agreement as EXHIBIT X. XXXXXXXXXXXX MAKES NO OTHER WARRANTY, EXPRESS OR
IMPLIED, WITH RESPECT TO THE VIALS, INCLUDING ANY WARRANTY OF MERCHANTABILITY OR
FITNESS FOR A PARTICULAR PURPOSE, EXCEPT AS SET FORTH IN SECTION 6.
5. MIP RESPONSIBILITIES. Upon the Effective Date, MIP will be solely
responsible, at its own cost, for all regulatory filings, development and
clinical and commercial manufacture of all Product. MALLINCKRODT will have no
responsibilities or obligation of any kind with respect to these activities.
6. REPRESENTATION AND WARRANTY.
6.1 MALLINCKRODT represents and warrants to MIP that, upon execution of the
*Confidential Treatment Requested*
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Termination Agreement by Novartis, it will have the right to grant the license
granted pursuant to Section 2.1 of this Agreement, and that the license so
granted will not conflict with or violate the terms of any agreement between
MALLINCKRODT and any Third Party.
7. TREATMENT OF CONFIDENTIAL INFORMATION.
7.1 CONFIDENTIALITY.
7.1.1 Subject to MIP's rights with respect to the licenses as
specifically provided for in Section 2.1 of this Agreement, MIP and MALLINCKRODT
each agree that during the term of this Agreement and for five (5) years
thereafter, it will keep confidential, and will cause its Affiliates and
sublicensees to keep confidential, all MALLINCKRODT Confidential Information or
MIP Confidential Information, as the case may be, which is disclosed to it or to
any of its Affiliates and sublicensees pursuant to this Agreement. Neither MIP,
its Affiliates or sublicensees, nor MALLINCKRODT shall use Confidential
Information of the other Party except as expressly permitted under this
Agreement.
7.1.2 Each Party agrees that it will disclose the other Party's
Confidential Information to its officers, employees, agents or Affiliates only
if and to the extent necessary to carry out its responsibilities under this
Agreement and shall limit disclosures to the extent possible consistent with
such responsibilities. MALLINCKRODT agrees not to disclose MIP Confidential
Information to any Third Parties under any circumstance without written
permission from MIP. MALLINCKRODT shall take such action, and shall cause its
Affiliates to take such action, to preserve the confidentiality of MIP
Confidential Information as it would customarily take to preserve the
confidentiality of its own Confidential Information. Upon termination of this
Agreement, MALLINCKRODT will, upon MIP's written request, either return or, in
MALLINCKRODT's discretion, destroy all the MIP Confidential Information
disclosed to it by MIP pursuant to this Agreement, including all copies and
extracts of documents, within sixty (60) days of the request except for one (1)
copy which may be kept for the purpose of complying with continuing obligations
under this Agreement.
7.1.3 The Parties represent that all employees who shall have access
to Confidential Information are or will be bound by agreements to maintain such
information in confidence.
7.1.4 Notwithstanding any of the foregoing provisions, MIP
specifically acknowledges and agrees that all confidential and proprietary
information provided by
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MALLINCKRODT to MIP in connection with the negotiation, execution and
performance of this Agreement shall also be and remain subject to the terms of
that certain Confidentiality Agreement, dated November 14, 2005, between the
Parties (the "MALLINCKRODT Confidentiality Agreement.") In the event of any
inconsistencies between the terms of this Agreement and the MALLINCKRODT
Confidentiality Agreement, the terms of the MALLINCKRODT Confidentiality
Agreement shall govern, except that MIP shall, without regard to the terms of
the MALLINCKRODT Confidentiality Agreement, be authorized to communicate
MALLINCKRODT Confidential Information to a permitted sublicensee hereunder (as
provided for in Section 2.1) to the extent required for the performance by such
permitted sublicensee of the obligations that are subject to the sublicense.
7.2 PUBLICITY. Except as required by law, and except for a mutually
approved press release to be issued upon the signing of this Agreement, neither
Party may disclose the terms of this Agreement without the written consent of
the other Party; provided, however, that MIP may disclose the terms, or provide
copies, of this Agreement as necessary in the normal course of business to
bankers, investors and others in order to obtain financing.
7.3 DISCLOSURE REQUIRED BY LAW. If MALLINCKRODT is requested to disclose
MIP Confidential Information in connection with a legal or administrative
proceeding or is otherwise required by law to disclose the Confidential
Information, it will give MIP prompt notice of such request. MIP may seek an
appropriate protective order or other remedy or waive compliance with the
provisions of this Agreement. If MIP seeks a protective order or other remedy,
MALLINCKRODT will cooperate at MIP's sole cost and expense. If MIP fails to
obtain a protective order or waive compliance with the relevant provisions of
this Agreement, MALLINCKRODT will disclose only that portion of MIP Confidential
Information which its legal counsel determines it is required to disclose.
8. NO OTHER AGREEMENTS. Except for the MALLINCKRODT Confidentiality Agreement,
this Agreement is the sole agreement between the Parties with respect to the
subject matter hereof and supersedes all other agreements and understandings
between the Parties with respect to same; provided, however, the execution of
the proposed agreement between MIP and Novartis with respect to the Product
prior to or on even date with this Agreement, together with the execution by
MALLINCKRODT and Novartis of the Termination Agreement, are condition precedents
to the force and effectiveness of this Agreement. If such agreement is not
executed in
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the time described, this Agreement will lapse and the Parties will have no
obligation of any kind to each other; provided that such lapse will have no
effect on the continuing enforceability of the MALLINCKRODT Confidentiality
Agreement in accordance with its terms.
9. TERMINATION AND DISENGAGEMENT.
9.1 MATERIAL BREACH. If either MIP or MALLINCKRODT shall breach any
material obligation contained in this Agreement and, in the case of a breach
capable of remedy, such breach shall not be cured within sixty (60) days (ten
(10) days with respect to a payment default) after written notice to the
breaching Party, the Party not in breach may terminate this Agreement by notice
without prejudice to the accrued rights of either Party.
9.2 TERMINATION FOR INSOLVENCY. Either Party may terminate this Agreement
immediately upon delivery of written notice to the other Party: (i) upon the
institution by or against the other Party of insolvency, receivership or
bankruptcy proceedings or any other proceedings for the settlement of the other
Party's debts; provided, however, with respect to involuntary proceedings, that
such proceedings are not dismissed within one hundred and twenty (120) days;
(ii) upon the other Party's making an assignment for the benefit of creditors;
or (iii) upon the other Party's dissolution or ceasing to do business.
9.3 CHANGE OF CONTROL. MALLINCKRODT may terminate this Agreement
immediately in the event there is a Change in Control, provided such Change in
Control results in MIP being owned by a direct competitor of MALLINCKRODT, as
listed on Exhibit G hereto.
9.4 EFFECT OF TERMINATION.
(a) The expiration of termination of this Agreement for any reason
shall not relieve the Parties from any obligations that accrued prior to such
expiration or termination, including without limitation MALLINCKRODT's right to
receive all payments accrued hereunder as of the effective date of expiration or
termination. In addition, except where explicitly elsewhere provided herein,
termination of this Agreement for any reason, or expiration of this Agreement,
will not affect any rights or obligations which, from the context thereof, are
intended to survive termination or expiration of this Agreement.
(b) In the event this Agreement is rightfully terminated by
MALLINCKRODT pursuant to Sections 9.1, 9.2 or 9.3, (i) all of MIP's rights to
the Patent Rights and the Technology shall immediately revert to MALLINCKRODT,
including but not limited to all rights under the license conveyed pursuant to
Section 2.1 of this Agreement, and
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(ii) MALLINCKRODT shall be entitled to immediately cease all Technology transfer
activities otherwise remaining to be performed under this Agreement.
(c) In the event this Agreement is rightfully terminated by MIP
pursuant to Sections 9.1 or 9.2, MIP's license rights in and to the Patent
Rights and the Technology shall nevertheless continue in full force and effect
in accordance with the terms of this Agreement.
10. INDEMNIFICATION. MIP hereby agrees to indemnify, defend and hold harmless
MALLINCKRODT (and all officers, directors, employees, agents and other
Affiliates of MALLINCKRODT) for any and all claims, liabilities, damages,
losses, costs or expenses (including but not limited to reasonable attorneys'
fees) arising from or in connection with (i) any breach by MIP of a material
obligation under this Agreement, (ii) clinical trials pursued by MIP, its
Affiliates or sublicensees with respect to the Product or the Compound or (iii)
the development, manufacture, marketing and/or sale of the Product by MIP, its
Affiliates or sublicensees. MIP shall choose legal counsel, shall control the
defense of such claim or action and shall have the right to settle same on such
terms and conditions it deems advisable.
11. LIMITATION OF DAMAGES. Neither Party nor their respective Affiliates shall
have any liability for any special, incidental or consequential damages,
including but not limited to loss of opportunity, revenue or profit, in
connection with or arising out of this Agreement, even if it shall have been
advised of the possibility of such damages.
12. NOTICES. All notices shall be in writing mailed via certified mail, return
receipt requested, courier, or facsimile or other e-mail transmission addressed
as follows, or to such other address as may be designated from time to time:
IF TO MIP: Molecular Insight Pharmaceuticals, Inc.
000 Xxxxxx Xxxxxx
Xxxxxxxxx, Xxxxxxxxxxxxx 00000
Attn: Vice President, Commercial and Business Development
WITH COPY TO: Xxxxxx X. Xxxxxxxxx, Esq.
Xxxxxxxx & Xxxx LLP
00
Xxx Xxxxxx Xxxxx
Xxxxxx, XX 00000
IF TO MALLINCKRODT: Mallinckrodt Inc.
000 XxXxxxxxx Xxxx.
Xx. Xxxxx, XX 00000
Attn: President, Imaging Division
WITH COPY TO: Mallinckrodt Inc.
000 XxXxxxxxx Xxxx.
Xx. Xxxxx, XX 00000
Attn: Vice President Legal, Imaging Division
Notices shall be deemed given as of the date received.
13. GOVERNING LAW. This Agreement shall be governed by and construed in
accordance with the laws of the State of Delaware without giving effect to the
principles of conflicts of laws thereof or any other law that would apply the
law of another jurisdiction.
14. MISCELLANEOUS.
14.1 BINDING EFFECT. This Agreement shall be binding upon and inure to the
benefit of the Parties and their respective legal representatives, heirs,
successors and permitted assigns.
14.2 HEADINGS. Paragraph headings are inserted for convenience of reference
only and do not form a part of this Agreement.
14.3 COUNTERPARTS. This Agreement may be executed simultaneously in two or
more counterparts, each of which shall be deemed an original. Signatures may be
transmitted via facsimile, thereby constituting the valid signature and delivery
of this Agreement.
14.4 AMENDMENT; WAIVER; ETC. This Agreement may be amended, modified,
superseded or cancelled, and any of the terms may be waived, only by a written
instrument executed by each Party or, in the case of waiver, by the Party or
Parties waiving compliance. The delay or failure of any Party at any time or
times to require performance of any provisions shall in no manner affect the
rights at a later time to enforce the same. No waiver by any Party
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of any condition or of the breach of any term contained in this Agreement,
whether by conduct, or otherwise, in any one or more instances, shall be deemed
to be, or considered as, a further or continuing waiver of any such condition or
of the breach of such term or any other term of this Agreement.
14.5 NO THIRD PARTY BENEFICIARIES. No Third Party including any employee of
any Party to this Agreement, shall have or acquire any rights by reason of this
Agreement. Nothing contained in this Agreement shall be deemed to constitute the
Parties as partners with each other or any Third Party.
14.6 ASSIGNMENT AND SUCCESSORS. MALLINCKRODT may not assign its Technology
transfer obligations under this Agreement to any Third Party without MIP's
consent, which will not be unreasonably withheld, other than to an Affiliate,
any purchaser of all or substantially all of MALLINCKRODT's assets, or to any
successor corporation resulting from any merger or consolidation of MALLINCKRODT
with or into such corporation. MIP may not transfer or assign any of its rights
or obligations under this Agreement without the express, prior written consent
of MALLINCKRODT, which MALLINCKRODT may withhold in its sole discretion in the
event the proposed assignee is a MALLINCKRODT competitor as listed on Exhibit G
hereto. With respect to any other assignee (i.e., an assignee not listed on
Exhibit G), MALLINCKRODT will not unreasonably withhold its consent to the
proposed transfer or assignment. Any attempted assignment or transfer in
contravention of this Section shall, at the option of the non-assigning Party,
be null and void and of no effect. No assignment shall release either Party from
responsibility for the performance of any accrued obligation of such Party
hereunder.
14.7 FORCE MAJEURE. Neither MIP nor MALLINCKRODT shall be liable for
failure of or delay in performing obligations (other than payment obligations)
set forth in this Agreement, and neither shall be deemed in breach of its
obligations, if such failure or delay is due to natural disasters or any causes
reasonably beyond the control of MIP or MALLINCKRODT.
14.8 SEVERABILITY. If any provision of this Agreement is or becomes invalid
or is ruled invalid by any court of competent jurisdiction or is deemed
unenforceable, it is the intention of the Parties that the remainder of the
Agreement shall not be affected so long as the essential benefits of this
Agreement remains enforceable and obtainable.
14
IN WITNESS WHEREOF, the Parties have caused this Agreement to be executed
by their duly authorized representatives as of the date first above written.
MOLECULAR INSIGHT MALLINCKRODT INC.
PHARMACEUTICALS, INC.
By: /s/ Xxxxx Xxxxxx By: /s/ Xxxxx Xxxxxx
--------------------------------- ------------------------------------
Xxxxx Xxxxxx Xxxxx Xxxxxx
Title: ----------------------------- Title: ---------------------------------
Chairman and CEO, Molecular President, Imaging Division
Insight Pharmaceuticals, Inc.
Date: December 19, 2006 Date: 12/20/06
------------------------------- -----------------------------------
15
EXHIBIT A
US 5,384,113
EP 600 992B1
AT 196428T
BE 000 000
XX 000 000
DE 692231469T
DK 600 992
ES 2150916T
FR 600 992
GB 600 000
XX 3035067T
IT 600 992
LU 600 992
NL 000 000
XX 000 000
CA 2113995C
JP 6510539T
16
EXHIBIT B
Below are the services to be provided by MALLINCKRODT for the transfer of
the Technology for the Vials and the Product to MIP. The objective of this
technology transfer is for MALLINCKRODT to provide MIP with sufficient
information and training to enable MIP to manufacture and quality control the
Vials and the Product. A timeline of activities described below appears in
EXHIBIT E.
B.1. Documentation for Vials (OctreoTher Reaction Vial) and Product (OctreoTher
Hot Liquid)
The following documents will be provided by MALLINCKRODT to MIP at least 10
business days prior to the commencement of the Transfer of Technology as
described in Section 2.3, unless otherwise agreed upon by MALLINCKRODT and MIP:
- R&D Reports as per Table 1, in English and in both hard copy and
electronic pdf document format.
- Standard Operating Procedures as per Table 2, in the original Dutch
and in English and in both hard copy and electronic Word document
format.
- Regulatory Information Documents as per Table 3, in English and in
both hard copy and electronic Word document format.
- Documents pertaining to the lyophilization process or the equipment
necessary for the manufacturing and quality control of the Vials and
the Product as per Table 4, in English or in Dutch and in either hard
copy or electronic format.
- In addition to the items listed in Tables 1, 2, 3 and 4, MALLINCKRODT
will provide to MIP any additional documents identified during the
Transfer of Technology that already exist and are readily available to
MALLINCKRODT, are required for the manufacturing and quality control
of the Vials and the Product, and are requested by MIP.
17
TABLE 1. R&D REPORTS
Number Title Report No.
------ ----- ----------
1 Suitability test for a new crimp capsule for OctreoTher bottles
(Helvoet code 1C325-3-C39) 01ewe03r
2 IN-PROCESS-CONTROL OF 90Y INCORPORATION DURING OCTREOTHERTM PRODUCTION. 01WGO01R
APPROPRIATE OR INAPPROPRIATE
3 OCTREOTHER CONSISTENCY RUNS STABILITY STUDY 05WGO00R
4 MEASUREMENT OF YTTRIUM (90Y) BREMMSSTRAHLUNG 03MJ098R
5 Water content in OctreoTher reaction mixture. 03mpa02R (version
Validation of the method. 2) + memo
6 Stability of NaCl 0.9% purged with Nitrogen for OctreoTher production 04mpa01r
7 Quality testing of Reaction Mixture for OctreoTher PO: 70190 05mjo03R
8 Stability of NaCl 0.9% purged with Nitrogen for OctreoTher production.
FM 257 stopper vs. FM 259 Stopper 05mpa02r
9 OctreoTher consistency runs. Stability Study. 05wgo00r
10 Scale up production process OctreoTher Novartis B220x clinical studies 06evw02r
11 STABILITY STUDY OCTREOTHERTM REACTION MIXTURES INTERIM REPORT 06WGO00R
12 Annual Overview OctreoTherTM Productions 2003 07mjo04r
13 Bone marrow dosimetry consequences by widening the specification for
free 90Y in therapy with OctreoTher 07MKO00R
14 JUSTIFICATION FOR THE OF ACID INTRODUCTION OF ASCORBIC ACID IN THE
FORMULATION OF OCTREOTHER BULKSOLUTION 08MJO02R
15 PRODUCTION AND QUALITY CONTROL OF SMT487 08MJO97R
FORMULATION FOR USE IN THE SUB-ACUTE TOXICITY STUDY
16 PRODUCTION AND QUALITY CONTROL OF SMT487 FORMULATION FOR USE IN THE
ACUTE TOXICITY STUDY 09MJ097R
17 Feasibility of heat sterilization of Octreother (Y90) 09MJ098R
18 OCTREOTHER CONSISTENCY RUNS and STABILITY STUDY OF VIALS CONTAINING
3330 RESPECTIVELY 4440 MBq Y-90 OCTREOTHER 09WGO01R
19 Overview OctreoTher(TM) productions 2002 10ewe03r
20 Stability Study OctreoTher Reaction Mixtures 11mjo02r
21 Annual Overview OctreoTher(TM) Productions 2004 10mjo05r
22 Non-radioactive Testing of OctreoTher Production Process in the
Hot Liquid Facility 12mjo99r
23 OCTREOTHER CONSISTENCY RUNS OF ADAPTED PRODUCTION PROCESS.
STABILITY STUDY 14WGO00R
24 Identification of an impurity visible in HPLC analysis of Yttrium
labelled DOTA-Tyr3-octreotide 16MJ098R
25 DETERMINATION OF EXCIPIENTS IN REACTION VIALS FOR OCTREOTHER
VALIDATION OF THE METHOD 17MJO97R
18
26 Integrity testing of container/closure system to be used in the
Octreother hot liquid production 17MJO99R
27 DETERMINATION OF EXCIPIENTS IN REACTION VIALS FOR OCTREOTHER
VALIDATION OF THE METHOD Addendum 19MJO00R
28 OCTREOTHER CONSISTENCY RUNS OF ADAPTED PRODUCTION PROCESS.
MICROBIOLOGICAL DATA 24WGO00R
29 Preliminary Stability Results SMT487 (90Y) Liquid 27mjo97r
30 Radiochemical Purity Determination of OctreoTher Using Different
Integration Events 32MJ099R
31 OCTREOTHER FORMULATION REPORT 5061/14/1996
32 DEVELOPMENT OF OCTREOTHER-90 KIT 5061/15/1995
33 DOTA-TYR3-OCTREOTIDE ASSAY BY HPLC.
VALIDATION OF METHOD 5061/21/1996
34 RADIOCHEMICAL PURITY OF 90Y-DOTA-TYR3-OCTREOTIDE.
VALIDATION OF THE METHOD 5061/22/1996
35 INCORPORATION OF 90Y-DOTA-TYR3-OCTREOTIDE VALIDATION OF THE METHOD 5061/24/1996
36 STABILITY 90Y-SMT487 FOR HOT-TOXICITY STUDY 07MJO97R
37 Quality testing of Yttrium (90Y) chloride by means of incorporation
assay into DOTA-Tyr3-Octreotide 12mjo02R
38 Influence of the Alltech 1.0 ml Minivial 20/4000 on the incorporation
capability of Y-90 to SMT 487 peptide 18ewe03r
39 Close out report B220X project, validation status of OctreoTher
facility 2465201001
40 Extension of the OctreoTher production Memo to File, X.
xxx Xxxxxxxx
41 Identification of Impurities in gentisic acid and peroxide cured
silicon tubing 13MJO02R
42 Air-tightness testing mepal container for Yttrium-OctreoTher
solution shipments 2132701003
43 testing box 33 Multipack containing Yttrium-OctreoTher solution 2132701001
19
TABLE 2. STANDARD OPERATING PROCEDURES
Title document code
-------------- --------
Octreother D3-03925
Reactionmixture for Octreother bulk D6-03925
Reactiemixture for Octreother D7-03925
Dispensing set, solutions and dilutions, 10 - 25 ml, sterilized E2-10504
Fiterset, Millipak 60, sterilized E2-10561
tubingset Octreother, cel 0902.000 Compudil A, sterilized E2-11326
tubingset Octreother, cel 0902.000 diluter, sterilized E2-11328
tubingset Octreother, cel 0903.000, sterilized E2-11331
Filter, Pall, NOVASIP, C2PFRP1, E2-11375
Tubingset, diluter Octreother, 3 flasks, sterilized E2-11407
tubingset, verdunner Octreother, sterilized E2-11412
Pumping set Octreother, cel 0903.000 E2-11413
Needle, pencilpoint, diam 1,2mm E2-11418
Z-needle, pencilpoint, lengte 20x20x78mm E2-11419
Curved needle, pencilpoint, diam 1,2mm, lengte 20x54mm E2-11421
Tubing set, bulkfluidreactionmixture, sterile E2-11441
Curved needle,pencilpoint, diam 1,2 mm, lengte 20x87 mm E2-11445
Curved needle,pencilpoint, diam 1,2 mm, lengte 28x57 mm E2-11446
Z-needle, pencilpoint, 20x20x78mm, passivated E2-11447
Curved needle, pencilpoint, 20x54mm, passivated E2-11448
Curved needle,pencilpoint, diam 1,2 mm, lengte 20x50 mm E2-11449
Dispensing set, sofiumchloride for octreother, gesteriliseerd E2-11450
Curved needle, pencilpoint, 28x57mm, gepassiveerd E2-11456
Curved needle, pencilpoint, 20x87mm, gepassiveerd E2-11457
Dispensing set Octreother forunit cel 0903.000, gesteriliseerd E2-11467
Filterset A Millipak 60, Pt-netted tubing E2-11490
filterset B Millipak 60, Pt-netted tubing E2-11491
Dispensing set, Pt-netted tubing E2-11492
dispensingset, Pt-netted tubing E2-11492
flask 2, assembleerd, Millipak 60, Pt-netted tubing E2-11493
flask 2, assembleerd, Millipak 60, Pt-netted tubing E2-11493
Dispensing set for kits, Pt-netted tubing E2-12007
Lyophilization vial 10 ml, stopper FM157, clean E2-12198
Wing needle, diam 2,0mm, lengte 20x280mm E2-12336
transportcontainer Octreother E3-11472
Certificate of analysis: Octreother E4-11335
SPC Yttrium (Y90) SMT487, i.v. E4-11373
Rubberstopper E6-10030
Rubberstopper X0-00000
Xxxxx for injecties, in bulk E5-10114
Purified water E5-12300
Materials for the productie of octreother E5-11408
Lyophilization vial 10 ml, E6-10009
Lyophilization stopper, DIAM 20 mm, FM157, E6-10018
vial 100 ml, clean gesteriliseerd E6-11303
vial 100ml, filled with nitrogen E6-11304
Rubberstop, diam 32 mm, FM257, clean, sterile E6-11308
Needleprotector, rubber, 14 mm E6-11394
Elution needle protector E6-10130
Octreother F3-03925
Reactiemixture for octreother, bulk F6-03925
20
TABLE 2. STANDARD OPERATING PROCEDURES
Title document code
-------------- --------
Reactiemixture for voor Octreother F7-03925
ring glassvial Octreother-Lab G0-00095
ring Nensure P-2 flacon Octreotherlab G0-00102
ring 10 ml lyophilization vial Octreotherlab G0-00105
ring for 100 ml flacon octreotherlab G0-00114
Testset for visual inspection of vials in octreotherlab en radiopharmacy G0-00147
Vial 500 ml Vacuum steriel N1-12015
Tubing, siliconubber, diam 6,0 x 10,0 mm N2-10044
Tubing, siliconrubber, diam 4,0x7,0mm N2-10459
Tubing, siliconrubber, diam 4,0 x 7,0 mm N2-10459
Tubing, siliconrubber, diam 1,0x3,0mm N2-10460
Filter millex N2-10825
Tubing, siliconrubber, diam 4,0 x 10,0 mm N2-10462
Injection needle 18G, lengte 19 mm N2-10561
Filter millipore, millipak 60 MPGL 06GH2 N2-10811
Filter hydrofoob ACRO 50 N2-10826
Vail 250 ml N2-11429
Tubing, siliconrubber, 1,6 x 6,4 mm N2-11435
Tubing, siliconrubber, 3,2 x 8,0 mm N2-11436
Tubing 1,02 mm, diam 2,69 mm, lengte 3 m N2-11476
Filter, Whatman, Polycap 36 SPF N2-11508
Double tubingsett, 3,2 mm N2-11515
Double tubingset, 4,8 mm N2-11516
Curved needle, diam 0,9 x 1,2 mm, lengte 20 x 200 mm X0-00000
Xxxxxxxx xxxxx X0-00000
Tubing, siliconrubber, 2,38 x 4,0 mm N2-11743
Tubing siliconrubber, 2,29x0,85x900mm N2-11744
capsule, diam 32,5 mm, N2-11745
Filter, Pall, Novasip, C2PFRP1 N2-11775
Tubing, siliconrubber, diam. 1,6 x 4,8 mm N2-11785
Vial 500ml N2-11820
dispensingset octreother, cel 0903.000 N2-11852
Filter, Millex 0,22 ugm, SLGP 033 RS N2-11855
Tubing, siliconrubber, diam 4,8 x 9,6 mm N2-11858
Tubing, siliconrubber, diam 6,4 x 9,6 mm X0-00000
Xxxxxxx N2-11925
Tubing, PTFE, capilaire tubing N2-11926
Wing needle, 18G x 1,5 N2-11927
Syringe 1 ml luerlock H804 N2-12035
Neo labbinders N2-12041
Tubing siliconenrubber 10 x 14 N2-12075
T-piece Diam, 6 MM P.P. N2-12081
Filter Millex SLFG 025 LS N2-12098
Connector Luer 0,8 female N2-12111
Connector Luer 1.6 male N2-12112
Connector luer 0,8 male N2-12113
Connector Luer 1,6 female N2-12115
Connector luer 3.2 Female N2-12117
Connector Luer 3.2 MALE N2-12118
Naald vleugel/beluchting 1.6 MM N2-12119
T-part, polupropylene N2-11915
Beaker, plastic N3-11854
21
TABLE 2. STANDARD OPERATING PROCEDURES
Title document code
-------------- --------
Demineralized water N5-70362
Ascorbic acid N5-70001
sodiumhydroxide, N5-70016
nitrogenf 99,98 % fluid X0-00000
XXXXXXXx acid N5-70128
Inositol N5-70135
Water forr injections in vial, 1000 ml N5-70261
sodiumchloride-solution 0,9% in vial 1000 ml N5-70267
DOTA-TYR3-octreotide N5-70415
Connector N6-10158
lyophilizationstopper diam 20mm grey FM157 N6-10159
Needle, Z-vormig UTK N6-10177
Venapunction needle X0-00000
Xxxxxxxxxxxxxx vial 10 ml N6-10217
Needle steel 316, diam 0,83x1,2mm, lengte 173mm N6-10247
Elution needle protector N6-10006
vail 100 ml, N6-11736
Rubberstopper, diam 32 mm, , FM257 N6-11737
capsule, aluminium, diam 20 mm N6-11884
capsule, diam 32,5 mm, N6-11887
Yttrium chloride (Y90) N7-70429
Needle N6-10248
Tubing set P5-11407
dispensinglset, solutions, 10 - 25 ml, gesteriliseerd P2-10504
Filterrset, Millipak 60, gesteriliseerd P2-10561
tubingset Octreother, cel 0902.000, Compudil A, gesteriliseerd P2-11326
tubingset Octreother, cel 0902.000, diluter, gesteriliseerd P2-11328
tubingset Octreother, cel 0903.000, gesteriliseerd P2-11331
tubingset, diluter octreother, 3 flasks, gesteriliseerd P2-11407
Tubingset diluetr octreother, gesteriliseerd P2-11412
Pumptubingset octreother, cel 0903.000 P2-11413
tubingset, bulk reactionmixture octreother, gesteriliseerd P2-11441
Z-needle, pencilpoint, 20x20x78mm, gepassiveerd P2-11447
Curved needle, pencilpoint, 20x54mm, gepassiveerd P2-11448
dispensingset sodiumchloride for octreother gesteriliseerd P2-11450
Curved needle, pencilpoint, 28x57mm, gepassiveerd P2-11456
Curved needle, pencilpoint, 20x87mm, gepassiveerd P2-11457
Materials for the production of octreother P5-11408
Lyophilization stopper, DIAM 20 mm, FM157,sterilized P6-10018
vial 100ml filled with nitrogen P6-11304
Rubberstop, diam 32 mm, , FM257, P6-11308
Visual inspection of octreother vials W0-10364
Procedure to calculate the yttrium-90 amount to order W0-10436
Measurement of radioactivity with an ionisatiecahmber with picoammeter W1-10001
22
TABLE 3. REGULATORY INFORMATION DOCUMENTS
Number Title
------ -----
1 Yttrium (90Y) SMT 487 Clinical Trial Application Information
Chemical and Pharmaceutical Data
2 Yttrium (90Y) SMT 487 IND Information
Manufacturing Description
23
TABLE 4. ADDITIONAL DOCUMENTS
Number Title
------ -----
1 Description of the lyophilization process
2 Description of the equipment used in the manufacturing process
for the Product
3 Description of the Quality Control equipment used in the
quality control methods of the Vials
4 Description of the Quality Control equipment used in the
quality controls methods of the Product
24
B.2. Manufacture and Quality Control of the Vials (OctreoTher Reaction Vial)
Prior to commencing the manufacturing and quality control technology transfer at
the Petten Facility, MIP personnel must successfully complete Laboratory and
Radiation Safety Training conducted by Safety Personnel at the MALLINCKRODT
Petten site.
B.2.1. Manufacturing of the Vials
MALLINCKRODT personnel will describe and demonstrate to MIP personnel the
manufacturing process for the OctreoTher Reaction Vial consistent with or
equivalent to GMPs at the MALLINCKRODT facility in Petten, The Netherlands. The
following services will be provided:
- a review of the Process Flow Sheet describing the manufacturing,
ingredients, and materials needed in the manufacturing process;
- a review of the packaging;
- one demonstration of the preparation of the matrix solution, without
the addition of the peptide SMT 487, by MALLINCKRODT personnel during
the initial visit to Petten by MIP personnel. MIP has the right to
request that MALLINCKRODT personnel perform one additional
demonstration of the preparation of the matrix solution, without the
addition of the peptide SMT 487, at a date and site to be determined
after the initial visit to Petten by MIP personnel. In the event that
this additional demonstration occurs, MIP shall pay MALLINKRODT'S
expenses pursuant to Section 2.3;
- at least one but not more than two preparations of the matrix solution
by MIP personnel with MALLINCKRODT personnel supervision during the
initial visit to Petten by MIP personnel. MIP has the right to perform
at least one but not more than two preparations of the matrix solution
by MIP personnel with MALLINCKRODT
25
personnel supervision at a date and site to be determined after the
initial visit to Petten by MIP personnel. In the event that such
additional activities occur, MIP shall pay MALLINKRODT'S expenses
pursuant to Section 2.3;
- the parameters for the lyophilization cycle;
- discussion of the documents provided in Tables 1, 2, and 3 as they
pertain to the OctreoTher Reaction Vial manufacturing, such as product
specifications, batch records, stability studies, fill-finish, and the
lyophilization cycle.
B.2.2. Quality Control of Vials
MALLINCKRODT personnel will describe and demonstrate to MIP personnel the
quality control (QC) methods for the OctreoTher Reaction Vial consistent with or
equivalent to GMPs at the MALLINCKRODT facility in Petten, The Netherlands.
OctreoTher Reaction Vials from lot number 220930 will be used for this testing.
The following services will be provided:
- one demonstration of the QC methods for the ingredients by
MALLINCKRODT personnel during the initial visit to Petten by MIP
personnel. MIP has the right to request that MALLINCKRODT personnel
perform one additional demonstration of the QC methods at a date and
site to be determined after the initial visit to Petten by MIP
personnel. In the event that this additional demonstration occurs, MIP
shall pay MALLINKRODT'S expenses pursuant to Section 2.3;
- one demonstration of in-process testing by MALLINCKRODT personnel
during the initial visit to Petten by MIP personnel. MIP has the right
to request that MALLINCKRODT personnel perform one additional
demonstration of in-process testing at a date and site to be
determined after the initial visit to Petten by MIP personnel. In the
event that this additional demonstration occurs, MIP shall pay
MALLINKRODT'S expenses pursuant to Section 2.3;
26
- one demonstration of the QC methods for the Vial by MALLINCKRODT
personnel during the initial visit to Petten by MIP personnel. MIP has
the right to request that MALLINCKRODT personnel perform one
additional demonstration of the QC methods for the Vial at a date and
site to be determined after the initial visit to Petten by MIP
personnel. In the event that this additional demonstration occurs, MIP
shall pay MALLINKRODT'S expenses pursuant to Section 2.3;
- at least one but not more than two completions by MIP personnel of the
QC methods for the ingredients, in-process testing, and the Vial with
MALLINCKRODT personnel supervision during the initial visit to Petten
by MIP personnel. MIP has the right to perform at least one but not
more than two completions of the QC methods for the ingredients,
in-process testing, and the Vial with MALLINCKRODT personnel
supervision at a date and site to be determined after the initial
visit to Petten by MIP personnel. In the event that such additional
activities occur, MIP shall pay MALLINKRODT'S expenses pursuant to
Section 2.3;
- discussion of the documents provided in Tables 1, 2, and 3 as they
pertain to OctreoTher Reaction Vial quality control.
B.3. Manufacture and Quality Control of the Product (OctreoTher Hot Liquid)
B.3.1. Manufacturing of the Product
MALLINCKRODT personnel will describe and demonstrate to MIP personnel the
manufacturing process for the Product consistent with or equivalent to GMPs at
the MALLINCKRODT facility in Petten, The Netherlands. OctreoTher Reaction Vials
from lot number 220930 will be used for the manufacturing of the Product. The
following services will be provided:
27
- a review of the Process Flow Sheet describing the manufacturing,
ingredients, and materials needed in the manufacturing process;
- a review of the packaging;
- one demonstration of the preparation of the OctreoTher Hot Liquid
without Y-90 by MALLINCKRODT personnel during the initial visit to
Petten by MIP personnel. MIP has the right to request that
MALLINCKRODT personnel perform one demonstration of the OctreoTher Hot
Liquid without Y-90 at a date and site to be determined after the
initial visit to Petten by MIP personnel. In the event that this
additional demonstration occurs, MIP shall pay MALLINKRODT'S expenses
pursuant to Section 2.3;
- one demonstration of the preparation of the OctreoTher Hot Liquid with
Y-90 by MALLINCKRODT personnel during the initial visit to Petten by
MIP personnel. MIP has the right to request that MALLINCKRODT
personnel perform one additional demonstration of the OctreoTher Hot
Liquid with Y-90 at a date and site to be determined after the initial
visit to Petten by MIP personnel. In the event that this additional
demonstrations occur, MIP shall pay MALLINKRODT'S expenses pursuant to
Section 2.3;
- one preparation of the OctreoTher Hot Liquid without Y-90 by MIP
personnel with MALLINCKRODT personnel supervision during the initial
visit to Petten by MIP personnel. MIP has the right to perform one
preparation of the OctreoTher Hot Liquid without Y-90 by MIP personnel
with MALLINCKRODT personnel supervision at a date and site to be
determined after the initial visit to Petten by MIP personnel. In the
event that such additional activities occur, MIP shall pay
MALLINKRODT'S expenses pursuant to Section 2.3;
28
- one preparation of the OctreoTher Hot Liquid with Y-90 by MIP
personnel with MALLINCKRODT personnel supervision during the initial
visit to Petten by MIP personnel. MIP has the right to perform one
preparation of the OctreoTher Hot Liquid with Y-90 by MIP personnel
with MALLINCKRODT personnel supervision at a date and site to be
determined after the initial visit to Petten by MIP personnel. In the
event that such additional demonstrations occur, MIP shall pay
MALLINKRODT'S expenses pursuant to Section 2.3;
- discussion of the documents provided in Tables 1, 2, and 3 as they
pertain to the OctreoTher Hot Liquid manufacturing, such as product
specifications, batch records, and stability studies.
B.3.2. Quality Control of Product
MALLINCKRODT personnel will describe and demonstrate to MIP personnel the
quality control (QC) methods for the OctreoTher Hot Liquid consistent with or
equivalent to GMPs at the MALLINCKRODT facility in Petten, The Netherlands. The
following services will be provided:
- one demonstration of in-process testing by MALLINCKRODT personnel
during the initial visit to Petten by MIP personnel. MIP has the right
to request that MALLINCKRODT personnel perform one additional
demonstration of in-process testing at a date and site to be
determined after the initial visit to Petten by MIP personnel. In the
event that this additional demonstration occurs, MIP shall pay
MALLINKRODT'S expenses pursuant to Section 2.3;
- one demonstration of the QC methods for the Product by MALLINCKRODT
personnel, preferably on the Product manufactured by MALLINCKRODT in
Section B.3.1 during the initial visit to Petten by MIP personnel. MIP
has the right to request
29
that MALLINCKRODT personnel perform one additional demonstration of
the QC methods for the Product at a date and site to be determined
after the initial visit to Petten by MIP personnel. In the event that
this additional demonstration occurs, MIP shall pay MALLINKRODT'S
expenses pursuant to Section 2.3;
- at least one but not more than two completions by MIP personnel of the
QC methods for in-process testing and the Product, preferably on the
Product produced by MIP in Section B.3.1, with MALLINCKRODT personnel
supervision during the initial visit to Petten by MIP personnel. MIP
has the right to perform at least one but not more than two
completions by MIP personnel of the QC methods for in-process testing
and the Product with MALLINCKRODT personnel supervision at a date and
site to be determined after the initial visit to Petten by MIP
personnel. In the event that such additional activities occur, MIP
shall pay MALLINKRODT'S expenses pursuant to Section 2.3;
- discussion of the documents provided in Tables 1, 2, and 3 as they
pertain to OctreoTher Hot Liquid quality control.
B.4. Response to Inquires Concerning the Technology
MALLINCKRODT personnel will be available to provide responses or clarification
to inquiries from MIP concerning the Technology during the course of the
transfer of the Technology as described in Section 2.3.
B.5. Equivalency Testing of the Product (OctreoTher Hot Liquid)
MALLINCKRODT and MIP personnel will conduct equivalency testing on the
OctreoTher Hot Liquid. Equivalency testing will consist of MALLINCKRODT and MIP
independently conducting quality control (QC) testing of the Product as defined
by the specifications in Section
30
5.3.1 of the Yttrium ((90)Y) SMT 487 IND Information Manufacturing Description
attached to this Agreement as EXHIBIT F. The OctreoTher Hot Liquid will be
manufactured consistent with or equivalent to GMPs by either MALLINCKRODT or MIP
as specified below. The following services will be provided:
- MALLINCKRODT will prepare one manufacturing preparation of the
OctreoTher Hot Liquid sufficient to provide finished Product for QC
testing by both MALLINCKRODT and MIP;
- MALLINCKRODT will ship to MIP the required vials of Product necessary
to perform the QC testing;
- On the same date, MALLINCKRODT and MIP will independently perform the
QC tests and MALLINCKRODT will inform MIP of its results.
- MALLINCKRODT will receive from MIP one but not more than two
manufacturing preparations of the OctreoTher Hot Liquid manufactured
by MIP;
- On the same date, MALLINCKRODT and MIP will independently perform the
QC tests and MALLINCKRODT will inform MIP of its results.
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EXHIBIT C
CERTIFICATION OF COMPLETION OF TECHNOLOGY TRANSFER
MALLINCKRODT INC. hereby certifies that it has completed its Technology transfer
obligations under that certain Agreement, dated as of ____________, 2006,
between MALLINCKRODT INC. and MOLECULAR INSIGHT PHARMACEUTICALS, INC.
MALLINCKRODT INC.
By:
---------------------------------
Title:
------------------------------
Date:
-------------------------------
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EXHIBIT D
Specifications for the OctreoTher SMT 487 Reaction Vial are as follows:
TEST LIMIT
---- -----
Appearance clear and no visual impurities
pH 4.0 - 5.0
Sterility sterile
Endotoxins < or = 20 EU/vial
Ascorbic acid 64.0 - 78.2 mg/vial
Inositol 36.0 - 44.0 mg/vial
Radiochemical purity, 15 min > or = 90%
Radiochemical purity, 6 h > or = 90%
(90)Y-Incorporation > or = 99.5%
SMT 487 72.0 - 88.0 ug/vial
Uniformity SMT 487 content 10 vials within 85 - 115% (n=10) or
< or = 1 of 30 out of 85 - 115%, but all
within 75 - 125%
Gentisic acid 14.4 - 17.6 mg/vial
Water content < or = 5%
Identity comply with test
33
EXHIBIT E
The overall work plan and timeline for the Transfer of Technology is as follows:
Month 1 Month 2 Month 3 Month 4 Month 5 Month 6
Days Days Days Days Days Days
TASK NAME 1 - 30 31 - 60 61 - 90 91 - 120 121 - 150 151 - 180
--------- ------- ------- ------- -------- --------- ---------
CONTRACT EXECUTION
Mallinckrodt & MIP Execute Contract
Mallinckrodt Receives Initial Payment at Contract Execution
Mallinckrodt Invoices MIP and Receives 50% Payment for
OctreoTher Vials
Mallinckrodt Initiates SOP Translation per MIP Instructions
COMMENCEMENT OF TECHNOLOGY TRANSFER
Mallinckrodt Transmits R&D and Regulatory Documents to MIP
Mallinckrodt Transmits First Set of Translated SOPs to MIP
Mallinckrodt Invoices MIP for Payment due upon Commencement
of Technology transfer
Mallinckrodt Ships OctreoTher Vials to MIP per Their
Instructions
Mallinckrodt Invoices MIP for Remaining 50% Payment due for
OctreoTher Vials
Mallinckrodt Receives Above Two Payments Prior to On-Site
Technology Transfer
TRANSFER OF TECHNOLOGY AT MALLINCKRODT PETTEN FACILITY
Mallinckrodt Provides Services per Exhibit B
MALLINCKRODT TECHNICAL AVAILABILITY
Mallinckrodt Provides Services per Exhibit B
TRANSFER OF TECHNOLOGY AT MIP DESIGNATED FACILITY (IF
REQUESTED)
Mallinckrodt Provides Services per Exhibit B
EQUIVALENCY TESTING
Mallinckrodt Provides Services per Exhibit B
TECHNOLOGY TRANSFER COMPLETION
Mallinckrodt Sign-Off of Certificate of Completion
Mallinckrodt Invoices for and Receives Payment for
Completion of Technology Transfer
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EXHIBIT F
Specifications for Yttrium (90Y) SMT 487 (OctreoTher Hot Liquid) are as follows:
TEST LIMIT
---- -----
Appearance Clear, colourless, or slightly yellow solution
(90)Y-Incorporation > or = 99.3%
Radiochemical purity > or = 90%
Radioactive concentration 51.6 Bq/ml +/- 10% (1.4 mCi/ml +/- 10%)
pH 4.0 - 5.0
Endotoxins < or = 0.2 EU/vial (parametric release)
Sterility sterile (parametric release)
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EXHIBIT G
Below is a list of MALLINCKRODT competitors.
Bracco
Xxxxxxx-Xxxxx Squibb
Cardinal Health, Inc.
GE Healthcare Division of the General Electric Company
Schering AG
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