EXHIBIT 10.129
CONFIDENTIAL TREATMENT REQUESTED. CONFIDENTIAL PORTIONS OF THIS DOCUMENT HAVE
BEEN REDACTED AND HAVE BEEN FILED SEPARATELY WITH THE U.S. SECURITIES AND
EXCHANGE COMMISSION
SUPPLY AGREEMENT
between
MADAUS AG
and
INDEVUS PHARMACEUTICALS, INC.
SUPPLY AGREEMENT
This Supply Agreement (the " Agreement") is made as of this 16th day of
December, 2002 ("Effective Date"), by and between Madaus AG, a corporation
organized and existing under the laws of Germany and having its principal office
at Ostmerheimer Stra(beta)e 198, D-51109 Koln, Germany ("Madaus") and Indevus
Pharmaceuticals, Inc., (formerly Interneuron Pharmaceuticals, Inc.), a Delaware
corporation with a place of business at 99 Hayden Avenue, Lexington,
Massachusetts 02421 ("Indevus").
WHEREAS, the Parties have entered into a License Agreement (as defined
herein) under which Madaus granted to Indevus an exclusive license to Licensed
Product (as defined in the License Agreement) in the Territory (as defined
herein);
WHEREAS, the License Agreement provides for Madaus to manufacture and
supply Product (as defined herein) to Indevus under certain conditions;
WHEREAS, Madaus has represented that it is able and willing to manufacture
and supply Indevus with Product on the terms and conditions set forth herein;
and
WHEREAS, Indevus desires to purchase Product from Madaus in accordance with
the terms and conditions of this Agreement;
NOW, THEREFORE, in consideration of the foregoing and the mutual promises
and covenants herein contained, it is hereby agreed as follows:
Article 1 - Definitions
Unless specifically set forth to the contrary herein, the following terms,
whether used in the singular or plural, shall have the respective meanings set
forth below.
1.1. "Act" shall mean the Federal Food Drug and Cosmetic Act of 1934, and the
rules and regulations promulgated thereunder, or any successor act, as the same
shall be in effect from time to time.
1.2. "Affiliate" shall mean (i) any corporation or business entity of which
fifty percent (50%) or more of the securities or other ownership interests
representing the equity, the voting stock or general partnership interest are
owned, controlled or held, directly or indirectly, by Indevus or Madaus, as
applicable; or (ii) any corporation or business entity which, directly or
indirectly, owns, controls or holds fifty percent (50%) or more of the
securities or other ownership interests representing the equity, the voting
stock or, if applicable, the general partnership interest, of Indevus or Madaus,
as applicable.
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1.3. "cGMP" shall mean current good manufacturing practices as applicable to
the Product pursuant to the Act and FDA regulations and guidance documents.
1.4 "Clinical Trial" shall mean any clinical trial conducted under United
States IND Number 61,381 using Compound and/or Product.
1.5. "Compound" shall mean the chemical compound known as trospium chloride,
the active ingredient used in the manufacture of Product.
1.6. "FDA" shall mean the United States Food and Drug Administration and any
successor agency having substantially the same functions.
1.7. "First Commercial Sale" shall mean the first sale by Indevus, its
Affiliates or sublicensees for end use or consumption of Product in the
Territory after all required Regulatory Approvals have been granted by the FDA.
1.8. "Launch Year" shall mean the period commencing on the date of First
Commercial Sale and expiring on the last day of the month that is the twelfth
(12/th/)month following the date of the First Commercial Sale occurs. For
example, if the First Commercial Sale occurs on March 15 of any year, the Launch
Year shall commence on March 15 of such year and expire on March 31 of the
following year.
1.9. "License Agreement" shall mean the License Agreement effective as of
November 26, 1999 by and between Indevus and Madaus.
1.10. "Manufacturing Facility" shall mean Madaus' existing manufacturing
facility in Troisdorf, Germany and/or any manufacturing or testing facility used
by Madaus to perform its obligations hereunder that is approved by the Parties.
1.11. "NDA" shall mean a new drug application filed with the FDA for marketing
authorization of a Product in the United States and any amendments and
supplements thereto.
1.12. "Party" shall mean Madaus or Indevus.
1.13. "Product" shall mean bulk product in final form for commercial sale by
prescription, over- the-counter, or by any other method, or for distribution as
samples and/or, where the context so indicates, the product being tested in a
Clinical Trial, which contains Compound in the formulation set forth in Schedule
1.13 hereto and meeting the Specifications, which product, Compound, its
manufacture, use or sale uses Madaus Know How. This definition of Product shall
not affect the definition of Licensed Product, which shall continue to have the
meaning set forth in the License Agreement.
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1.14. "Regulatory Approval" means all approvals (including pricing and
reimbursement approvals required for marketing authorization), product and/or
establishment licenses, registrations or authorizations of all regional,
federal, state or local regulatory agency, department, bureau or other
governmental entity, necessary for the manufacture, use, storage, import,
export, transport and sale of Product in the Territory.
1.15. "Specifications" shall mean the written methods, formulae, procedures,
specifications, tests (and testing protocols) and standards pertaining to the
manufacture of the Product as attached hereto as Schedule 1.15 hereto and as
such specifications may be modified in accordance with the NDA from time to time
in writing.
1.16. "Supplier Agreement" shall mean the agreement between Madaus and Madaus'
current supplier of Compound (the "Compound Supplier"), effective as of November
13, 2002, relating to manufacture and supply of Compound to Madaus for use in
the manufacture of Product, a copy of which was delivered to Indevus prior to
the Effective Date, or any other agreement to which Madaus is a party, relating
to manufacture of Compound for use in the manufacture of Product, that is
approved by Indevus.
1.17. "Territory" shall mean the United States of America, including the
District of Columbia, and its territories and possessions.
1.18. "Third Party" shall mean a person(s) or entity who or which is neither a
Party nor an Affiliate of a Party.
Article 2 - Supply of Product
2.1. Subject to the terms and conditions of this Agreement and, to the
extent applicable, the License Agreement, Madaus shall supply all of Indevus' or
its designees' requirements of Product for commercial and sample purposes on an
exclusive basis. Subject to the terms and conditions of this Agreement, Madaus
shall convert Compound supplied by Compound Supplier or any other supplier of
Compound approved by the Parties into Product in accordance with the
Specifications. Madaus shall have responsibility for ordering and purchasing all
active ingredient of Compound and all inactive ingredients necessary to perform
its obligations to supply Product in accordance with the terms of this
Agreement.
2.2. Subject to the terms and conditions of this Agreement and, to the
extent applicable, the License Agreement, Indevus shall purchase all of its
requirements of Product for use in the Territory exclusively from Madaus, except
as otherwise set forth in this Agreement or the License Agreement.
2.3. During the Term, Madaus shall obtain and maintain in force all
licenses and authorizations necessary for Madaus to manufacture or have
manufactured and supply Product hereunder. Madaus shall bear the full cost and
expense of so obtaining and maintaining such licenses and authorizations.
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Article 3 - Regulatory Approvals; Inspections; Testing
3.1. Ownership of Regulatory Approvals. Indevus shall, directly or through
its Affiliates, own all necessary Regulatory Approvals in the Territory with
respect to the Product. Madaus shall provide reasonable assistance to Indevus,
from existing information in Madaus' possession, for the purpose of obtaining
Regulatory Approvals in the Territory, including the information set forth in
Section 3.2 below. Madaus shall fulfill and discharge all obligations, using its
best efforts and resources, under any and all U.S. governmental laws, rules or
regulations or otherwise, as well as procedures ensuring timely compliance with
all laws, rules and regulations as are necessary or customary in accordance with
accepted business practices and legal requirements to maintain the authorization
and ability to manufacture, finish, store, mark, label and distribute Compound
and/or Product in each country where it is so manufactured, finished, packaged,
stored, marked, labeled and distributed, including compliance with cGMPs.
3.2. Manufacturing Process; Drug Master File. With respect to Product
supplied by it, Madaus shall be responsible for all process and equipment
validation and quality control tests and procedures required by the FDA and
shall take all steps necessary to pass inspection by the FDA or other
governmental agency. Madaus shall also assist Indevus in preparing and updating
any required regulatory submission and all other documents required for
Regulatory Approvals of the Product, including providing Indevus with all
information required to be included in the NDA relating to manufacture of
Product, including a right of reference to any Drug Master File owned by Madaus,
the Compound Supplier or any of Madaus' other suppliers. Madaus shall ensure
that such Drug Master File shall be updated by Madaus, the Compound Supplier or
any other applicable supplier to Madaus, according to applicable regulations and
Madaus shall provide Indevus with a written notice of any such proposed update
prior to submitting such update to the FDA. Madaus will make no change, and will
take all reasonable measures to ensure that no change is made by Compound
Supplier or any of Madaus' other suppliers, to the manufacturing process,
equipment or analytical protocols/procedures (i) without notification to Indevus
(for purposes of this provision, notice shall be given to Greg Lerch or to such
other person as Indevus designates) and, (ii) if such change, in Indevus'
judgment, could potentially conflict with the NDA or require any supplement to
the NDA, without Indevus' approval. Madaus shall notify Indevus within
forty-eight (48) hours of any deviation of the specified manufacturing or
testing process. Madaus shall maintain, and shall require Compound Supplier and
any of its other suppliers to maintain, all appropriate original regulatory
documents, reserve samples and records relating to its responsibilities with
respect to the manufacturing of Compound and/or Product according to cGMPs for
such periods as required by applicable laws and regulations. Copies of all such
documents, samples and records,
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including manufacturing and packaging batch records of Product, will be
available for review by Indevus or its designee upon request.
3.3. Inspections or Inquiries by Government Agencies. Madaus shall provide
Indevus, within forty-eight (48) hours, copies of any correspondence to or from
the FDA or other regulatory authority relating to Product. Madaus shall be
responsible for responding to any inquiry from the FDA or any other health or
government authority regarding the manufacture of Product and Indevus shall give
reasonable assistance. Madaus shall, within forty-eight (48) hours, inform
Indevus of any such inquiries or any requests for inspections of Madaus
Manufacturing Facility(ies), Compound Supplier's facilities or Madaus' other
suppliers' facilities of which it becomes aware and shall without delay make
available to Indevus a copy of any inspection report received by Madaus
resulting from any inspection of any of such facilities by such health or
government authority to the extent such report relates to the Compound or
Product, the formulation, manufacture, testing, storage and delivery of the
Compound or Product or any premises used by Madaus or Madaus' supplier(s) in
performing Madaus' obligations under this Agreement. Madaus shall also provide
Indevus with a written copy of any proposed response(s) thereto at least three
Business Days prior to submitting such response to the FDA or any other health
or government authority as well as a copy of the response actually submitted.
Representatives of Indevus or its designee shall have the right to be present
during the inspection and/or during the close-out session with the inspectors.
Any Form 483 observations or warning letter related to the Product shall be
provided promptly to Indevus. Indevus shall have the right to review and discuss
with Madaus Madaus' proposed written response to such 483 observations or
warning letter, and a copy of the response actually submitted shall be promptly
provided to Indevus.
3.4. Inspections by Indevus. Representatives of Indevus or its designee
shall have the right to (i) review Madaus' licenses and permits relating to the
Manufacturing Facility and licenses and permits of the Compound Supplier and
(ii) inspect the manufacturing, laboratory, packaging and warehouse facilities
used by Madaus in the manufacture, packaging, testing, storage, shipping and
receiving of Compound or Product, as applicable, or its components, its methods
of manufacturing and all related records for the same at the Manufacturing
Facility and all premises used by Madaus during normal business hours, provided
tha such inspection is related to production or quality issues of the product ]
Such inspection right may be exercised by Indevus one time each year without
Cause upon fifteen (15) Business Days' notice and at any time with Cause upon
five (5) Business Day's notice. Cause shall be defined as an issue reasonably
relating to compliance with the terms of this Agreement or with cGMPs.
3.5. Testing and Certificates of Analysis.
(a) Compound. Madaus shall obtain from Compound Supplier or any other
supplier of Compound approved by the Parties a written certificate of analysis
with each shipment Madaus receives of Compound. Upon receipt of such Compound in
bulk form,
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Madaus shall inspect such active ingredient and test samples thereof in
accordance with cGMPs and with the same procedures provided by and used by
Compound Supplier, in accordance with the NDA's requirements and commitments and
as set forth in Exhibit 3.5 attached hereto, as such may be modified from time
to time by agreement of the Parties. Before releasing any lot of the Compound
for use under this Agreement, Madaus shall check the compliance of such lot with
the Specifications. Such inspection and compliance check shall be performed by
Madaus Quality Assurance/Quality Control department and shall be certified by
the head of such department (or his/her designee).
(b) Product. Madaus shall test samples of Product manufactured hereunder
in accordance with cGMPs and with the NDA's requirements and commitments and as
set forth in Exhibit 3.5 hereto, as such may be modified from time to time.
Before releasing any lot of the Product, Madaus shall check the compliance of
such lot with the Specifications. Such inspection and compliance check shall be
performed by Madaus Quality Assurance/Quality Control department and shall be
certified by the head of such department (or his/her designee).
(c) Certificate of Analysis. Copies of the certificates of analysis
incorporating certification of the manufacturing and analytical/microbiological
records and certifying compliance with the manufacturing and testing
requirements of Compound and Product respectively, shall be sent to Indevus with
each shipment of Product containing material from such lot. All such copies
shall be sent to the addressees specified by Indevus or, if no addressee is
specified, to the place of shipment of the Product. In addition, copies of all
batch records relating to Product shall be sent to Indevus or its designee upon
request.
3.6. Preservation Samples/Retained Samples. Pursuant to all applicable
laws, rules and regulations and to the Specifications, Madaus shall assign and
apply lot numbers and shall take from each lot of (i) the Compound used to
manufacture Product pursuant to this Agreement; (ii) inactive ingredients used
in the manufacture of Product pursuant to this Agreement; and (iii) the Product
shipped to Indevus or its designee pursuant to this Agreement, preservation
samples/retained samples. Madaus shall retain and store the particular lot of
Compound, other ingredients or Product, as applicable, in accordance with FDA
and other applicable regulations, which currently provide for a period expiring
no earlier than two (2) years after the expiration of the shelf life of the
particular lot of Product shipped to Indevus or its designee pursuant to this
Agreement. Preservation samples/retained samples, as referred to herein, do not
include samples retained for purposes of stability testing.
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3.7. Inspection Upon Delivery. Upon receipt of the Product in any shipment,
Indevus or its designee may inspect such Product and assay samples thereof. If
Indevus finds that any Product delivered to Indevus or its designee hereunder
fails to conform to the Specifications and the other requirements of this
Agreement upon delivery to Indevus, then Indevus or its designee shall provide
Madaus with a written notice (the "Non-conformance Notice") within two (2) days
of determination of non-conformance and within sixty (60) days of receipt of
such Product by Indevus or its designee. Notwithstanding the foregoing, it is
understood and agreed by the Parties that Indevus or its designee shall have no
obligation to inspect each lot of Product. Indevus shall retain the
non-conforming Product and Madaus shall have the right to inspect such Product.
In the event Madaus does not respond in writing, within thirty (30) days of the
date of the Non-conformance Notice, Madaus shall be deemed to be in agreement
with Indevus' or Indevus' designee's determination of non-conformance
(a) Undisputed Claims. Madaus shall, if it agrees or is deemed to
agree with Indevus' determination of non-conformance, replace any such
non-conforming Product with an equal quantity of Product complying with the
Specifications at no additional cost to Indevus and without undue delay.
Indevus shall dispose of any Product that is not in compliance with the
Specifications at Madaus' cost, except that Indevus shall follow any
reasonable instructions from Madaus to return to Madaus or otherwise
dispose of such non-conforming Product in another manner at Madaus' cost.
Within thirty (30) days from the date of the Non-conformance Notice, Madaus
will, if in agreement or deemed to be in agreement with the determination
of non-conformance, issue a credit to Indevus representing any charges
relating to such non-conforming and replacement Product.
(b) Disputed Claims. If Madaus does not agree with Indevus's
determination of non-conformance, then Madaus shall provide Indevus with a
written notice of such disagreement within thirty (30) days of receipt of
the Non-Conformance Notice, responding to Indevus' claim. The Parties shall
use commercially reasonable efforts to resolve such disagreement within ten
(10) Business Days of Indevus' receipt of Madaus' notice of disagreement.
Until such time as the disagreement is resolved, no Product from the lot
tested shall be released. Any related expense shall be borne by the Party
whose analysis was in error.
3.8. Stability Testing. Madaus shall, at its own cost and expense, conduct
stability testing programs for Product in accordance with the NDA's requirements
and commitments, including (i) stability testing of Product stored as in-process
or final bulk material, and (ii) stability testing of Product stored in the
shipping containers used to ship Product hereunder, to ensure Product meets
Product Specifications as included in the NDA and is evaluated in accordance
with International Conference of
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Harmonization guidances and other applicable regulations, and showing not less
than six (6) months stability. The results of the testing programs shall be made
available as soon as practicable upon completion of testing to Indevus without
charge. Any results not meeting the Specifications or other requirements of this
Section 3.8 will be reported to Indevus within two (2) Business Days. Indevus
may, at its own discretion and at its own cost and expense, conduct its own
stability testing program on Product in final packaging.
3.9. Customer Complaints. Indevus shall be responsible for investigating
and responding to all customer complaints relating to the Product delivered to
Indevus hereunder. Each Party shall without delay notify the other of any such
complaints of which it becomes aware and the Parties shall cooperate in
resolving any such complaints. Madaus shall provide Indevus with all reasonable
assistance in investigating and responding to complaints that are alleged to
have arisen from the manufacturing or supply of the Product hereunder. Indevus
shall keep and maintain a record of all customer complaints and any resolution
of such complaints and provide Madaus with a current copy of the record on a
monthly basis.
Article 4 - Forecasts and Ordering; Shipments
4.1 Forecasts. The total quantity of Product forecasted for commercial use
and for samples for any year shall be the "Annual Forecast Amount". The total
quantity of Product purchased for commercial use and for samples for any year
shall be the "Annual Purchased Amount".
(a) Launch Year. Within six (6) months prior to the anticipated date of
First Commercial Sale, Indevus shall provide Madaus with a three year forecast
(broken down by quarter for the Launch Year) of Indevus' estimated requirements
of commercial supplies and samples of Product. Subject to the provisions of
subsection 4.1 (c) below, the Annual Purchased Amount for the Launch Year shall
be at least [*] percent ([*]%) of the Annual Forecast Amount for the Launch
Year and Madaus will be obligated to supply up to [*] percent ([*])% of the
Annual Forecast Amount for the Launch Year, provided, however, that Madaus shall
use its best efforts to satisfy any purchase orders exceeding [*] percent ([*]%)
of the Annual Forecast Amount. For the Launch Year, quantities of Product
ordered for delivery in advance of the date of First Commercial Sale shall be
included in the Annual Purchased Amount for Launch Year. For the Launch Year,
Indevus shall on a quarterly basis update and, if necessary, revise the Annual
Forecast Amount provided that such revisions shall not alter or effect the [*]
percent ([*]%) requirement of the initial Launch Year forecast.
*CONFIDENTIAL TREATMENT REQUESTED
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(b) Subsequent Years. For all years during the Term subsequent to the
Launch Year ("Subsequent Years"), Indevus shall provide Madaus with a non
binding rolling three year forecast (broken down by month for the initial 12
months of each such forecast). Except for the first 12 months of such three year
forecast, it will not be binding in any way on the parties. Each forecast shall
supercede any previous forecast of the Annual Forecast Amount for each of such
Subsequent Years, and shall update the forecast on a rolling monthly basis,
except that it shall not alter or effect the [*] percent minimum purchase
requirement of earlier forecasts. The Annual Purchased Amount for each
Subsequent Year shall, accordingly, be at least [*] % of the Annual Forecast
Amount set forth in each Indevus forecast for each initial 12 month period set
out in each forecast.
(c) General. Such forecasts shall not be deemed to be firm orders. After
receiving Indevus' forecasts, Madaus shall notify Indevus within ten (10) days,
if Madaus will be unable to supply Indevus' forecasted requirements of Product.
If Madaus advises that it cannot meet such forecasted requirements, the
provisions of Article VII of this Agreement shall be applicable. In the event
that the Annual Purchased Amount in any 12 month period does not equal or exceed
[*]% of the Annual Forecast Amount for the first 12 month period, Indevus shall
pay to Madaus a fee (the "Minimum Fee") as set forth in Schedule 4.1 hereto,
provided, however, that Indevus shall not be obligated to pay the Minimum Fee in
the event that Indevus' failure to meet such [*]% requirement is attributable to
the fault of Madaus or to any regulatory or safety issue relating to Product.
4.2 Firm Orders. Indevus or its designee shall provide Madaus with
purchase orders on the standard purchase order forms of Indevus or its designee
of its requirements of commercial supplies and samples of the Product at least
[*] days before it requires each delivery of Product during the Launch Year and
[*] days before it requires each delivery of Product for each Subsequent Year,
specifying the required delivery date in each purchase order and specifying the
quantity of Product for commercial use and the quantity of Product for sample
use. Madaus will promptly confirm receipt and acceptance of each such purchase
order. Madaus shall fulfill orders made hereunder by delivering the Product on
or prior to the specified delivery date. The terms of the purchase orders shall
conform to the terms of this Agreement.
(a) Full Batch Quantities. Indevus' firm orders for Product shall be
in Madaus' ordinary production batch quantities, which are [*] tablets per
batch (a "Batch"), or multiples thereof.
(b) Shortages. Madaus agrees that it will use its best efforts to
prevent an interruption of supply to Indevus and shall immediately notify
Indevus of any problems or unusual production situations which may
adversely affect production or quality of Product or its Specifications or
its timely delivery to Indevus or its designee. If, at any time during the
term of this Agreement, Madaus becomes
*CONFIDENTIAL TREATMENT REQUESTED
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aware that it will not be able to satisfy Indevus' forecasts or ordered
requirements for Product, then Madaus shall: (i) give Indevus immediate
notice thereof, (ii) take all commercially reasonable steps to procure
adequate quantities of Product from another Manufacturing Facility in
accordance with the applicable provisions of Section 3.7 of the License
Agreement and (iii) continue to use its best efforts to fulfill orders made
pursuant to this Section 4.2.
4.3. Shipment. At the time of delivery, the Product shall conform to the
Specifications. Madaus shall test the Product against the Specifications prior
to shipment and shall provide Indevus with the information required by Section
3.5 hereto. Delivery shall be made no later than the date of delivery specified
in Indevus' purchase order. The Product will be shipped in appropriate packaging
for transport in accordance with applicable regulatory requirements and Schedule
4.3 to this Agreement. All Product delivered hereunder shall have a shelf life
to be determined by an appropriate stability evaluation to be performed in
accordance with U.S. and International Conference of Harmonization Guidances,
and shall in any event have a shelf life of at least [*] months on the date of
delivery to Indevus or its designee. With respect to pre-launch build up, the
Parties will agree on a date for start of manufacturing and, based on production
lead times, determine an acceptable shelf life for pre-launch shipment of launch
inventories. The terms of delivery of the Product by Madaus shall be FOB point
of delivery at, and title and risk of loss shall pass to Indevus upon delivery
to the regional distribution facility in the Territory to be designated by
Indevus or its designees.
Article 5 - Prices and Payment Terms
5.1 Price for Commercial Product. With respect to Product intended for
commercial sale, Madaus agrees to sell Product and Indevus agrees to purchase
Product manufactured by Madaus at the prices (in Euros) set forth in Schedule
5.1 attached hereto, which price includes the cost of all Compound and other
ingredients used in the manufacture of Product, as well as packaging, packing,
handling, freight, insurance and any other direct costs as well as the Madaus
profit margin (the "Commercial Product Prices"). The Parties agree that the Base
Price initially set forth on Schedule 5.1 shall remain in effect through the
Launch Year. Thereafter, the Base Price used in calculating the Commercial
Product Prices shall be subject to increase or decrease [*]. The increase or
decrease can be applied not more often than [*]. In no event shall any increase
or decrease in the Base Price used to calculate Commercial Product Prices
changes under this Section 5.1 exceed [*] percent ([*]%) during any [*] period.
Any agreed to changes to the Commercial Product Prices shall be reflected on an
updated Schedule 5.1 to be signed by each Party.
*CONFIDENTIAL TREATMENT REQUESTED
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5.2 Samples.
(a) With respect to Product intended for distribution as samples, Madaus
agrees to manufacture and sell such Product to Indevus at prices (the "Sample
Product Prices") as a percentage of the Commercial Product Prices as set forth
on Schedule 5.2 attached hereto. Indevus shall be responsible for packaging such
Product in a matter consistent with packaging of samples.
(b) With the exception of Section 5.2 (a) and the applicable terms of
Section 5.3, supply of Product intended for distribution as samples shall be in
accordance with all other terms and conditions of this Agreement.
5.3 Payment Terms.
(a) Indevus shall settle invoices received from Madaus within thirty (30)
days from the date of receipt of the Product by Indevus or Indevus' designee or,
for amounts in dispute pursuant to Section 9.4, within ten (10) days from the
date the dispute is resolved. Payments hereunder shall be in Euros. The price
for all Product delivered to Indevus hereunder shall be FOB point of delivery to
[*], or such other facility designated by Indevus or its designees, provided
that if delivery to such other facility increases the delivery cost, the Parties
will negotiate in good faith the payment of such increased cost.
(b) For purchase orders and invoices during any particular year, the
Sample Product Price and Commercial Product Prices and related payment terms
shall be calculated on a cumulative basis based on the quantity of Product
purchased (and giving effect to the designation of Product purchased as samples
or for commercial use) during that year up to and including Product purchased
under the purchase order for which the calculation is being made, provided,
however, that within ninety (90) days after the end of the Launch Year and each
Subsequent Year during the term of this Agreement, Indevus shall provide to
Madaus a summary analysis of the quantity of samples distributed during the
preceding year and a reconciliation, if necessary, of payments or refunds due
under this Agreement, based on a year-end calculation of the quantity of Product
purchased as samples for that year as a percentage of the Annual Purchased
Amount for that year.
(c) Notwithstanding and in addition to any other remedy set forth in this
Agreement, within fourteen (14) days of the date of any Non-conformance Notice
under Section 3.7, Madaus shall refund to Indevus the purchase price paid for
the Product subject to the Non-conformance Notice, subject to reconciliation in
the event the claim is disputed and the analysis of Indevus was determined to be
in error, in accordance with the provisions of Section 3.7
*CONFIDENTIAL TREATMENT REQUESTED
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Article 6 - Warranty, Indemnification and Insurance: Recalls
6.1 Warranties. Madaus hereby represents and warrants to Indevus that:
(a) at the time of delivery, the Product supplied by Madaus hereunder
including for any Clinical Trial conformed and shall conform to the
Specifications; the Product and Compound was and shall be manufactured,
tested and stored in accordance with the Specifications and with cGMPs, and
other applicable laws and regulations governing manufacture, formulation,
storage, testing, packaging or labeling, and shall be of merchantable
quality and fit for the purposes for which it is intended;
(b) for the purpose of Section 303(c) of the Act, all Product shipped
by Madaus hereunder including for any Clinical Trial was not and will not,
on the date of shipment be, adulterated or misbranded within the meaning of
the Act and the regulations issued thereunder or within the meaning of any
other applicable law, rules or regulations, the provisions of which are in
effect at the time of such shipment, and will not be an article (Product)
which may not, under the provisions of Section 404 or 505 of the Act, be
introduced into interstate commerce;
(c) Madaus has all required manufacturing facilities and equipment
necessary to manufacture Product pursuant to Specifications and otherwise
perform its obligations hereunder, and Madaus', Compound Supplier's and
Madaus' other suppliers' manufacturing facilities, processes and equipment
validation used and to be used in the manufacture of Compound and Product
comply with cGMPs and other applicable laws and regulations;
(d) the manufacture, use or sale of Product does not infringe any
patents owned or controlled by any Third Party in the Territory or any
country outside the Territory in which the Product is or will be
manufactured for use in the Territory; and
(e) it has full corporate power and authority under the laws of the
jurisdiction of its incorporation to enter into this Agreement and to carry
out the provisions hereunder; it has secured or obtained all corporate and
governmental approvals needed by it to enter into and to perform this
Agreement; this Agreement is a legal and valid obligation binding upon it
and is enforceable in accordance with its terms; and the execution,
delivery and performance of this Agreement by it does not conflict with any
agreement, oral or written, to which it is a party or by which it may be
bound, nor violate any law or regulation of any court, governmental body or
administrative or other agency having authority over it.
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6.2 Indemnity. As used herein, the phrase "under this Agreement" includes
but is not limited to references to actions under or pursuant to Article 6 of
this Agreement, which might otherwise be post termination of this Agreement.
(a) Madaus Indemnity. Madaus shall indemnify, hold harmless and
defend Indevus and its Affiliates and their respective directors, officers,
employees, successors, assignees and agents from and against any and all
claims, demands, suits or proceedings, damages and costs (including
reasonable attorneys' fees), expenses and losses arising out of (i) Madaus'
manufacture, formulation, testing, use, storage, handling, packaging,
distribution, delivery or sale of Compound and/or Product; (ii) the breach
or violation of this Agreement by Madaus or (iii) the negligence or willful
misconduct of Madaus in the performance of its duties under this Agreement.
(b) Indevus Indemnity. Indevus shall indemnify, hold harmless and
defend Madaus and its Affiliates and their respective directors, officers,
employees, successors, assignees and agents from and against any and all
claims, demands, suits or proceedings, damages and costs (including
reasonable attorneys' fees), expenses and losses arising out of (i) Indevus
representations, advertising, claims, handling, storage, distribution,
delivery or sale of Compound and/or Product; or (ii) the negligence or
willful misconduct of Indevus in the performance of its duties under this
Agreement.
(c) Cooperation of the Parties. Any party claiming indemnification
pursuant to this Article 6 (the "Claiming Party") shall give prompt written
notice to the other party (the "Indemnifying Party") of the commencement of
any action, suit or proceeding for which indemnification may be sought.
Upon receipt of such notice, the Indemnifying Party shall assume the
defense thereof; provided, however, that the Claiming Party shall be
entitled to participate in any such action, suit or proceeding with counsel
of its own choice, but at its own expense. If the Indemnifying Party fails
to assume the defense within a reasonable time, the Claiming Party may
assume such defense and the fees and expenses of its attorneys will be
covered by the Indemnifying Party pursuant to the indemnity provisions
provided for herein. The Claiming Party will cooperate with the
Indemnifying Party at the Indemnifying Party's expense in the defense of
any suit. Neither Party shall be liable for any costs resulting from any
settlement made by a Party without the consent of the other Party to such
settlement, which consent shall not be unreasonably withheld.
6.3 Insurance. At all times during the term of this Agreement and for a
period of not less than five (5) years thereafter, each of Madaus and Indevus
shall maintain in full force and effect commercial general liability insurance
issued by a reputable
-13-
insurance company having a Best's rating of [*], insuring against all liability,
including product liability, personal injury, physical injury and property
damage in an amount equal to a minimum of $[*] per occurrence and per year and
shall furnish the other Party at its request with a certificate of insurance
showing the above coverage, signed by an authorized agent of the insurance
company. Each Party shall be named as an additional insured on the other Party's
insurance policy.
6.4 Recall. In the event of any recall, seizure, stop sale or governmental
action, direction or withdrawal (all or any of which is referred to herein as a
"Recall") of Product arising from any Party's breach of any representation,
warranty or covenant contained in this Agreement or failure to perform any
provision hereof, the Party in breach shall reimburse the other Party for any
costs, expenses or damages incurred by the other Party in connection with such
Recall. If the Recall resulted from a Madaus breach, and if requested by
Indevus, Madaus shall supply Product in an amount sufficient to replace the
recalled or seized Product without charge to Indevus with all transportation
charges and import duties prepaid. Any Product returned to Indevus shall be
shipped to Madaus' nearest facility, or to such other destination as Madaus may
require in writing, with any shipping or other related costs to be paid by the
party in breach, and the other party shall incur no liability of any nature in
handling any such Recalls or returns. If Recall resulted from an Indevus breach,
then all costs associated with the Recall shall be born by Indevus.
Article 7 - Shortages; Second Source
7.1. Continuity. Madaus shall use its best efforts to prevent an
interruption of supply to Indevus and shall immediately notify Indevus of any
problems or unusual production situations which may adversely affect production
or quality of Product or its Specifications or the timely delivery of Product to
Indevus or its designee.
7.2. Second Source Supplier. Upon the Effective Date, Madaus shall take all
necessary actions to ensure that Madaus is able to meet requirements of Indevus
for Product, including compliance with cGMPs and all other regulatory
requirements for manufacturing and testing Product. Any second source supplier
shalI demonstrate capability to meet Indevus' manufacturing requirements
including compliance with cGMPs and all other regulatory requirements. If at any
time during the Term for any reason Madaus shall be unable to manufacture and
deliver Product in accordance with the terms of this Agreement or in sufficient
quantities to satisfy Indevus' forecasted requirements for Product on the
requested delivery date, Madaus shall immediately so notify Indevus in writing,
advising as to the period for which such inability to manufacture and deliver
shall continue. In the event such inability is anticipated to or shall continue
for [*] days or more, Indevus may use another manufacturer/supplier of Product
and Madaus will transfer Compound and know how to such manufacturer/supplier so
that such nominated manufacturer/supplier can supply
*CONFIDENTIAL TREATMENT REQUESTED
-14-
Indevus for that period of time Madaus is unable to supply Product in accordance
with the terms of this Agreement and with Indevus' requirements. In such event,
Indevus may cancel all outstanding Madaus purchase orders and purchase any or
all of its requirements of Product from such other manufacturer/supplier,
limited to the period in which Madaus is unable to supply Product in accordance
with the terms of this Agreement and with Indevus' requirements, and provided
that Indevus shall reinstate Madaus as exclusive supplier of Product within [*]
of notification by Madaus to Indevus of Madaus' ability to meet Indevus'
forecasted requirements of Product in accordance with the terms of this
Agreement. To the extent not otherwise set forth in this Section 7.2, issues
relating to a second source of supply shall be governed by the provisions of
Section 3.7 of the License Agreement
Article 8 - Term and Termination
8.1 Term. Unless terminated earlier as provided herein, the Term of this
Agreement shall commence on the Effective Date and shall expire on the tenth
anniversary of the First Commercial Sale, provided that Indevus shall have the
right to extend the term of this Agreement for one year periods by giving Madaus
notice of its intention to renew within one hundred and eighty (180) days prior
to the expiration of the then term.
8.2 Termination. Notwithstanding anything contained herein to the
contrary, either Party shall have the right to terminate this Agreement by
written notice to the other Party at any time during the term of this Agreement
for cause as follows:
(a) by either Party if the other Party is in breach of its material
obligations hereunder by causes and reasons within its control or has
breached any of its representations or warranties set forth in Section 6.1
hereto and has not cured such breach within sixty (60) days after notice
requesting cure of the breach;
(b) by Indevus on thirty (30) days' notice if the FDA or any other
regulatory agency takes any action which would prohibit or materially
restrict the manufacture, sale or use of Product; or
(c) by either Party on thirty (30) days' notice if the NDA is not
approved by the FDA within five (5) years from the Effective Date.
8.3 Effect of Expiration or Termination. Expiration or termination of this
Agreement shall not relieve the Parties of any obligation accrued or accruing
under this Agreement prior to such expiration or termination, including the
obligation to supply Product under orders made prior to such termination or to
make payment for Product
*CONFIDENTIAL TREATMENT REQUESTED
-15-
delivered pursuant to such orders and the provisions of Article 6 shall survive
the expiration or termination of this Agreement and shall continue in effect for
seven (7) years from the date of expiration or termination. Except as expressly
set forth herein, the rights to terminate as set forth herein shall be in
addition to all other rights and remedies available under this Agreement, at
law, or in equity, or otherwise
8.4 Survival. Notwithstanding anything herein to the contrary, the
provisions of Articles 6 and 9 as well as those portions of Section 8.3, or any
other provisions which relate to post termination rights and obligations, shall
survive any termination of this Agreement.
Article 9 - Confidentiality and Dispute Resolution
9.1 Non-disclosure and Non-Use Obligations. All proprietary information
disclosed by one Party to the other Party hereunder shall be maintained in
confidence and shall not be disclosed to any nonparty or used for any purpose
except as expressly permitted herein without the prior written consent of the
other Party to this Agreement. The foregoing nondisclosure and nonuse
obligations shall not apply to the extent that such proprietary information:
(a) is known by the receiving party at the time of its receipt, and
not through a prior disclosure by the disclosing party, as documented by
business records;
(b) is properly in the public domain;
(c) is subsequently disclosed to a receiving party by a third party
who may lawfully do so and is not under an obligation of confidentiality to the
disclosing party; or
(d) is developed by the receiving party independently of proprietary
information received from the other party, as documented by research and
development records.
9.2 Permitted Disclosure of Proprietary Information. Indevus grants to
Madaus the right to use Indevus' clinical and preclinical data relating to
Compound or Licensed Product for Madaus' own regulatory filings relating to
development and marketing of Compound or Product in countries outside of the
Territory, as set forth in Section 2.2 of the License Agreement. Notwithstanding
Section 9.1, a Party receiving proprietary information of the other Party may
disclose such proprietary information:
(a) to governmental or other regulatory agencies in order to obtain
patents or to gain approval to conduct clinical trials or to market Product, but
such
-16-
disclosure may be only to the extent reasonably necessary to obtain patents or
authorizations;
(b) to its sublicensees, agents, consultants, Affiliates and/or other
Third Parties for the research and development, manufacturing and/or marketing
of the Product (or to such Third Parties to determine their interest in
performing such activities) on the condition that such Third Parties agree to be
bound by the confidentiality obligations contained in this Agreement, provided
that the term of confidentiality for such Third Parties shall be no less than
seven (7) years; or
(c) when required to be disclosed by law or court order, provided
that notice is promptly delivered to the other Party in order to provide an
opportunity to challenge or limit the disclosure obligations; provided, however,
without limiting any of the foregoing, it is understood that either Party
hereto, including any Affiliate, may make reasonable disclosure of this
Agreement, and the terms hereof in any filings required by the Securities and
Exchange Commission, subject to requests for confidential treatment for certain
provisions of this Agreement, as agreed to by the Parties.
9.3 Applicable Law. The Agreement shall be governed by and construed in
accordance with the laws of the State of Delaware and the United States, without
reference to any rules of conflict of laws or renvoi.
9.4 Dispute Resolution. (a) The Parties agree to attempt initially to
solve all claims, disputes, or controversies arising under, out of, or in
connection with this Agreement (a "Dispute") by conducting good faith
negotiations. Any Disputes which cannot be resolved by good faith negotiation
within twenty (20) Business Days, shall be referred, by written notice from
either Party to the other, to the Chief Executive Officer of each Party. Such
Chief Executive Officers shall negotiate in good faith to achieve a resolution
of the Dispute referred to them within twenty (20) Business Days after such
notice is received by the Party to whom the notice was sent. If the Chief
Executive Officers are unable to settle the Dispute between themselves within
twenty (20) Business Days, they shall so report to the Parties in writing. The
Dispute shall then be referred to mediation as set forth in the following
subsection (b).
(b) Upon the Parties receiving the Chief Executive Officers' report that
the Dispute referred to them pursuant to subsection (a) has not been resolved,
the Dispute shall be referred to mediation by written notice from either Party
to the other. The mediation shall be conducted pursuant to the LCIA Mediation
Procedure. The place of the mediation shall be London, England and the language
of the mediation shall be English. If the Parties have not reached a settlement
within twenty (20) Business Days of the date of the notice of mediation, the
Dispute shall be referred to arbitration pursuant to subsection (c) below.
(c) If after the procedures set forth in subsections (a) and (b) above,
the Dispute
-17-
has not been resolved, a Party shall decide to institute arbitration
proceedings, it shall give written notice to that effect to the other Party. The
Parties shall refrain from instituting the arbitration proceedings for a period
of sixty (60) days following such notice. During such period, the Parties shall
continue to make good faith efforts to amicably resolve the dispute without
arbitration. If the Parties have not reached a settlement during that period the
arbitration proceedings shall go forward and be governed by the LCIA Arbitration
Rules then in force. Each such arbitration shall be conducted by a panel of
three arbitrators: one arbitrator shall be appointed by each of Indevus and
Madaus and the third arbitrator, who shall be the Chairman of the tribunal,
shall be appointed by the two-Party appointed arbitrators. Any such arbitration
shall be held in London, England.
The tribunal shall issue its award within forty-five (45) days after the
date on which the arbitration proceedings have closed. The arbitrators shall
have the authority to grant specific performance. Judgment upon the award so
rendered may be entered in any court having jurisdiction or application may be
made to such court for judicial acceptance of any award and an order of
enforcement, as the case may be. In no event shall a demand for arbitration be
made after the date when institution of a legal or equitable proceeding based on
such claim, dispute or other matter in question would be barred by the
applicable statute of limitations. Each Party shall bear its own costs and
expenses incurred in connection with any arbitration proceeding and the Parties
shall equally share the cost of the mediation and arbitration levied by the
LCIA.
Any mediation or arbitration proceeding entered into pursuant to this
Section 9.4 shall be conducted in the English language.
Article 10 - General Provisions
10.1 Force Majeure. Neither Party shall be liable for non-performance or
delay in the fulfillment of its obligations when any such non-performance or
delay shall be occasioned by any cause beyond the reasonable control of Indevus
or Madaus, as the case may be, including without limitation fire, flood,
earthquakes, accidents, explosions, sabotage, strikes, or labor disturbances
(regardless of the reasonableness of the demands of the labor force), civil
commotions, riots, invasions, wars, acts of war (whether declared or not) acts,
restraints, requisitions, regulations, or directions of government authorities,
or acts of God ("Force Majeure Events"). The affected Party shall notify the
other Party of such force majeure circumstances as soon as reasonably
practicable and the affected Party shall use all reasonable efforts to avoid or
remove such causes of non-performance as promptly as practicable and shall
continue performance with the utmost dispatch whenever such causes are removed.
When such circumstances arise, the Parties shall discuss what, if any,
modification of the terms of this Agreement may be required in order to arrive
at an equitable solution. In the event that a Force Majeure Event continues for
a period in excess of ninety (90) days, the Party not relying on the Force
Majeure Event shall have the right with immediate effect to terminate this
Agreement by written notice to the other party.
-18-
10.2 Notices. All notices, requests, reports, demands and other
communications made or given under the terms of this Agreement or in connection
herewith shall be in writing and shall be either personally delivered,
transmitted by postage prepaid registered mail, by courier providing
documentation of receipt or by telecopy (confirmed in writing by postage prepaid
registered mail or by such courier), and shall be addressed to the appropriate
Party at the addresses set forth in Schedule 10.2 hereto or to such other
address or place as such Party may from time to time designate. Any notice,
request, demand or other communication given or made pursuant to this section
shall be deemed effective on the date which is the confirmed date of receipt by
the registered mail or courier service.
10.3 Non-Waiver of Rights. The failure by either Party at any time to
enforce any of the provisions of this Agreement shall not be construed as a
waiver of such provisions or any other provisions hereof. The exercise by either
Party of any of its rights herein or at law or in equity shall not preclude or
prejudice such Party from exercising any other rights provided herein or at law
or in equity.
10.4 Entire Agreement - Modifications. This Agreement supersedes all prior
agreements, oral or written, between the Parties hereto with respect to the
subject matter hereof and contains the entire and only agreement between the
Parties regarding the subject matter hereof (except as otherwise expressly
provided herein with respect to the License Agreement), and any representation,
terms or conditions relating thereto or in connection therewith, oral or in
writing, not incorporated herein will not be binding upon either Party. No
modification or discharge of this Agreement or any of the provisions hereof nor
any representation, promise or condition relating to this Agreement nor any
terms or conditions of any purchase order, invoice, shipping document or other
document shall be binding unless made in writing with express reference to this
Agreement and signed by authorized representatives of both Parties.
Notwithstanding anything herein to the contrary, the Parties may mutually amend
any of the Schedules hereto at any time during the Term by executing a version
thereof dated after the then-current version. All of the Schedules, and any
amendments thereto made pursuant to this section, are a part of this Agreement
and are hereby incorporated herein.
10.5 Assignment. Neither Party may assign or delegate any of its rights or
obligations hereunder without the prior written approval of the other except
that Indevus may assign this Agreement and its rights and obligations hereunder
without the consent of Madaus to an Affiliate or in connection with the transfer
or sale of all or substantially all of its assets related to Product or its
business, or in the event of its merger or consolidation or change in control or
similar transaction. Except as otherwise set forth herein, any permitted
assignee shall assume all obligations of its assignor under this
-19-
Agreement. Any assignment or attempted assignment contrary to the provisions
hereof shall be null and void.
10.6 Severability. If one or more of the provisions contained in this
Agreement shall be invalid, illegal or unenforceable in any respect under any
applicable law, the remaining portions hereof shall remain in full force and
effect. If any of the terms or provisions of this Agreement are in conflict with
any applicable statute or rule of law, then such terms or provisions shall be
deemed inoperative to the extent that they may conflict therewith and shall be
deemed to be modified to conform with such statute or rule of law. If the terms
and conditions of this Agreement are materially altered as a result of the
preceding two sentences, the Parties shall negotiate in good faith the terms and
conditions of this Agreement to resolve any inequities.
10.7 Interpretation. Unless expressly set forth, the use of the singular
form of terms herein shall include the plural and the use of the plural form of
terms herein shall include the singular. The word "including" shall be deemed to
be followed by the words "without limitation." Headings are for reference only
and shall not be used to interpret this Agreement.
10.8 Independent Contractors. It is expressly agreed that Indevus and
Madaus are independent contractors and that the relationship between the two
Parties shall not constitute a partnership, joint venture or agency. Neither
Madaus nor Indevus shall have the authority to make any statements,
representations or commitments, or to take any action, which shall be binding on
the other, without the prior consent of the other Party to do so.
-20-
IN WITNESS WHEREOF, the Parties hereto have executed this Agreement as
of the date first set forth above.
Madaus AG
By: /s/ Chris P. Thomas B: /s/ Marc Trube
-------------------- ----------------
Name: Chris P. Thomas Name: Marc Trube
Title: C E O Title: C F O
Indevus Pharmaceuticals, Inc.
By: /s/ Glenn L. Cooper
--------------------
Name: Glenn L. Cooper
Title: CEO
-21-
SCHEDULES AND EXHIBITS
Schedule 1.13
-------------
Product Formulation
- -------------------
Core:
- -----
1 [*] [*] [*]
2 [*] [*] [*]
3 [*] [*] [*]
4 [*] [*] [*]
5 [*] [*] [*]
6 [*] [*] [*]
7 [*] [*] [*]
8 [*] [*] [*]
9 [*] [*] [*]
10 [*] [*]
------------------
Total Core weight [*] [*]
Sugar coating (including polish and ink):
- -----------------------------------------
10 [*] [*] [*]
11 [*] [*] [*]
12 [*] [*] [*]
13 [*] [*] [*]
14 [*] [*] [*]
15 [*] [*] [*]
16 [*] [*] [*]
17 [*] [*] [*]
18 [*] [*] [*]
19 [*] [*] [*]
20 [*] [*]
21 [*] [*]
------------------
Total coated tablet weight [*] [*]
[*]
[*]
*CONFIDENTIAL TREATMENT REQUESTED
Schedule 1.15
-------------
Specifications
--------------
Trospium Chloride:
Specifications:
Characters [*]
Identification [*]
[*]
Tests [*]
*CONFIDENTIAL TREATMENT REQUESTED
Assay [*]
[*]
Trospium Chloride, [*] Coated Tablets:
Specifications:
[*]
Characters
Identification [*]
Tests [*]
Assay [*]
Quality [*]
*CONFIDENTIAL TREATMENT REQUESTED
Exhibit 3.5
-----------
Testing Procedures
------------------
Refer to attached testing procedures for Trospium Chloride and Trospium
Chloride, [*] Tablet.
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 1 of 21
- ---------------------
Determination
- ---------------------
Synonyms [*]
Graphic formula: [*]
Molecular formula: [*]
Relative molecular mass: [*]
Properties: [*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 2 of 21
Amount of test sample for complete [*]
testing:
1. Characters
1.1 Physical characters: [*]
2. Identification
2.1 Chloride:
[*]
2.2 Infrared absorption:
[*]
Compact: [*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 3 of 21
3. Test
3.1 pH: [*]
[*]
Number of determinations: [*]
Number of measurements: [*]
Test solution: [*]
3.2 Appearance of solution
3.2.1 Clearness: [*]
3.2.2 Colouring: [*]
3.3 Loss on drying: [*]
[*]
Number of determinations: [*]
Number of measurements: [*]
3.4 [*]: [*]
[*]
[*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 4 of 21
3.5 [*]: [*]
Number of determinations: [*]
Number of measurements: [*]
Solvent mixture C: [*]
Reference substance: [*]
[*]
Reference solution: [*]
Test solution: [*]
Measuring programme:
Column: [*]
Mobile phase: [*]
Temperature: [*]
Detector wavelength: [*]
Flow rate: [*]
Time of flow: [*]
Volume applied: [*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 5 of 21
Retention time: [*]
Calculation: [*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 6 of 21
Figure for para. 3.5
[*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 7 of 21
3.6 [*]
3.6.1 [*]: [*]
3.6.2 [*]: [*]
3.6.3 [*]: [*]
3.6.4 [*]: [*]
3.6.5 [*]: [*]
Number of determinations: [*]
Number of measurements: [*]
Test solution (TS): [*]
Reference solutions (RS):
1. RS: [*]
2. RS: [*]
3. RS: [*]
4. RS: [*]
5. RS: [*]
Quantity applied: [*]
Adsorbent: [*]
Mobile phase: [*]
Distance of migration: [*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 8 of 21
Removal of mobile phase: [*]
Detection: [*]
Identity: [*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 9 of 21
Purity: [*]
Densitometric measurement:
Measuring conditions:
[*]
Path length: [*]
Measuring rate: [*]
Wavelength: [*]
Sensitivity: [*]
Span: [*]
Offset: [*]
Light slit: [*]
Band width: [*]
Abs/fluorine: [*]
Trans/refl: [*]
Limits of detection and determination:
[*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 10 of 21
Calculation: [*]
3.6.1 [*]
[*]
3.6.2 [*]
[*]
3.6.3 [*]
[*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 11 of 21
3.7 Residual solvents
3.7.1 [*]: [*]
3.7.2 [*]: [*]
3.7.3 [*]: [*]
3.7.4 [*]: [*]
Number of determinations: [*]
Number of measurements: [*]
Test solution A: [*]
Reference solution A: [*]
Reference solution B: [*]
Reference solution C: [*]
Reference solution D: [*]
Reference solution E: [*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 12 of 21
Test solution 1: [*]
Test solution 2: [*]
Reference solution 1: [*]
Reference solution 2: [*]
Reference solution 3: [*]
Blank value: [*]
Conditions for chromatography:
Instruments: [*]
Column: [*]
Carrier gas: [*]
Split: [*]
Detector: [*]
Temperatures: [*]
[*]:
Sample temperature: [*]
Needle temperature: [*]
Transfer duct: [*]
GC cycle time: [*]
Thermostatting time: [*]
Pressure build-up time: [*]
Injection duration: [*]
Withdrawal time: [*]
Identity: [*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 13 of 21
Figure for para. 3.7
[*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 14 of 21
Limits of determination: [*]
Calculation:
1. [*]
2. [*]
3. Calibration line:
[*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 15 of 21
3.8 [*], total: [*]
Total of the values determined from:
[*]
3.9 [*]: [*]
[*]
[*]
Assay
4.1 Trospium chloride, [*]
calculated relative to the dried
substance
Number of determinations: [*]
Number of measurements: [*]
Main test: [*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 16 of 21
Blank test: [*]
Volumetric solution: [*]
Equivalent mass: [*]
Instrument: [*]
Method: [*]
Electrode: [*]
Calculation:
[*]
Standard [*] substance: [*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 17 of 21
Adjustment: [*]
Equivalent mass: [*]
Calculation: [*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 18 of 21
Reagent:
Para. 2.1 [*]
Para. 2.2 [*]
Para. 3.5 [*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 19 of 21
Para. 3.6 [*]
Reference substances: [*]
Para. 3.7
Reference substances: [*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 20 of 21
Solvent: [*]
Para. 3.9 [*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE
Page 21 of 21
Para. 4.1 [*]
Volumetric solution: [*]
Standard titrimetric substance: [*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE, [*] TABLET
Page 1 of 13
- -------------
Determination
- -------------
Amount of test sample for [*] coated tablets.
complete testing:
1. Characters
Physical characters: [*]
1.1
[*]
The test is carried out on [*] coated
tablets.
2. Identification
2.1 Trospium chloride:
[*]
Test solution: [*]
Reference solution: [*]
Quantity applied: [*]
[*]
[*]
Adsorbent: [*]
Mobile phase: [*]
Distance of migration: [*]
Removal of mobile phase: [*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE, [*] TABLET
Page 2 of 13
Detection: [*]
Evaluation: [*]
Detection limit: [*]
[*]
*CONFIDENTIAL TREATMENT REQUESTED
TESTING PROCEDURE: TROSPIUM CHLORIDE, [*] TABLET
Page 3 of 13
2.2 Trospium chloride:
[*]
2.3 Chloride: [*]
3. Tests
3.1 Impurities:
3.1.1 [*]: [*]
3.1.3 [*]: [*]
3.1.5 [*]: [*]
3.1.7 [*]: [*]
3.1.9 Sum of all impurities: [*]
[*]
Number of determinations: [*]
Number of measurements: [*]
[*]
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Page 4 of 13
3.2 Microbiological purity
[*]
3.2.1 [*]: [*]
3.2.2 Fungi: [*]
3.2.3 Escherichia coli: [*]
4. Assay
4.1.1 Assay trospium chloride: [*]
Number of determinations: [*]
Number of measurements: [*]
[*]
Solvent mixture C: [*]
Reference substance: [*]
[*]
[*]
[*]
Reference solution (RL) A: [*]
Reference solution (RL) B: [*]
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Page 5 of 13
Reference solution (RL) C: [*]
Test solution (UL): [*]
Measuring programme:
Precolum: [*]
Column: [*]
Mobile phase: [*]
Temperature: [*]
Detector wavelength: [*]
Flow rate: [*]
Time of flow: [*]
Volume applied: [*]
System suitability test:
Reference solution (RL) B: [*]
Reference solution (RL) C: [*]
Identification: [*]
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Page 6 of 13
1. Calculation [*]:
[*]
2. Calculation [*] (para. 3.1.1):
[*]
3. Calculation of [*] (3.1.3)
[*]
4. Calculation [*] (para. 3.1.5):
[*]
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Page 7 of 13
Figure for para. 4.1.1
[*]
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TESTING PROCEDURE: TROSPIUM CHLORIDE, [*] TABLET
Page 8 of 13
5. Quality
5.1 Dissolution test of trospium chloride:
5.1 Dissolution test at 40 min: [*]
Number of determinations: [*]
Number of measurements: [*]
Specification: [*]
Acceptance Table
Stage Number Tested Acceptance Criteria
---------------------------------------------------------------------------
[*] [*] [*]
[*] [*] [*]
[*] [*] [*]
[*]
Method: [*]
Apparatus: [*]
Number of revolutions: [*]
Test medium: [*]
Temperature: [*]
Test volume: [*]
Sampling volume: [*]
Time interval: [*]
Number of samples: [*]
Assay: [*]
Test solution: [*]
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Page 9 of 13
Filter: [*]
Standard substance: [*]
[*]
Standard solution: [*]
Measuring programme: [*]
Calculation: [*]
5.2 Content uniformity: [*]
Test solution: [*]
[*]
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TESTING PROCEDURE: TROSPIUM CHLORIDE, [*] TABLET
Page 10 of 13
Criteria: [*]
*CONFIDENTIAL TREATMENT REQUESTED
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Page 11 of 13
Reagents:
Para. 2.1 [*]
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Page 12 of 13
Para. 2.3 [*]
Para. 4.1 [*]
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Page 13 of 13
Para. 5.1 [*]
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Schedule 4.1
Minimum Fee
Annual Purchased Amount as % of
Annual Forecast Amount Minimum Fee
- --------------------------------------------------------------------------------
[*] % - [*] % [*] % of Base Price
** [*] % [*] % of Base Price
Note: Minimum Fee will be assessed for each year in which the [*] % minimum
requirement was not satisfied and must be paid within [*] days of assessment
notice.
** Less than
*CONFIDENTIAL TREATMENT REQUESTED
Schedule 4.3
------------
Packaging
---------
[*]
*CONFIDENTIAL TREATMENT REQUESTED
Schedule 5.1
Commercial Product Price [Euros]
Quantity of Batches purchased
- -----------------------------
per year: Commercial Product Prices:
- -------- -------------------------
First [*] Batches: [*] Euros per [*] tablets (Base Price)
[*] to [*]
Batches: [*] Euros per [*]
Above [*]
Batches: [*] Euros per [*]
*CONFIDENTIAL TREATMENT REQUESTED
Schedule 5.2
Sample Product Price*
Quantity of Samples Purchased as
Percentage of Annual Purchased
Amount: Sample Product Price:
- --------------------------------------------------------------------------------
Launch Year and Year 2:
Not to exceed [*] %: [*] % of Base Price
All Subsequent Years:
Not to exceed [*] % [*] % of Base Price
*Subject to year-end reconciliation pursuant to Section 5.3 (b) of this
Agreement.
*CONFIDENTIAL TREATMENT REQUESTED
Schedule 10.2
Notice Addresses
1. If to Indevus:
Indevus Pharmaceuticals, Inc.
99 Hayden Avenue
Lexington, Massachusetts 02421
Attention: President
Fax No: 781.861.0253
2. If to Madaus AG
Madaus AG
Ostmerheimer Stra(beta)e 198
D-51109 Koln, Germany
Attention: CEO
Fax No: 011.49.221.8998.733