Exhibit 10.1

Confidential Materials omitted and filed separately with the
Securities and Exchange Commissions. Asterisks denote omissions.

Manufacturing Services Agreement
March 30, 2011

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ARTICLE 1
INTERPRETATION 1

1.1
Definitions.    1

1.2
Currency.    5

1.3
Sections and Headings.    5

1.4
Singular Terms.    5

1.5
Schedules.    5

ARTICLE 2
PATHEON’S MANUFACTURING SERVICES 6

2.1
Technology Transfer and Feasibility Activities.    6

2.2
Manufacturing Services.    6

2.3
Standard of Performance.    7

2.4
Subcontractors.    7

ARTICLE 3
MDCO’S OBLIGATIONS 7

3.1
Payment.    7

3.2
Active Materials.    8

ARTICLE 4
CONVERSION FEES AND COMPONENT COSTS 8

4.1
First Year Pricing.    8

4.2
Price Adjustments.    8

4.2.1 Adjustment due to Volume Changes from Yearly Binding Volumes
9

4.3
Adjustments Due to Technical Changes.    10

ARTICLE 5
ORDERS, SHIPMENT, INVOICING, PAYMENT 10

5.1
Orders and Forecasts.    10

5.2
Reliance by Patheon.    11

5.3
Minimum Orders.    12

5.4
Shipments.    12

5.5
Invoices and Payment.    12

ARTICLE 6
PRODUCT CLAIMS AND RECALLS 12

6.1
Product Claims.    12

6.2
Patheon’s Responsibility for Defective and Recalled Products.    13

6.3
Disposition of Defective or Recalled Products.    14

6.4
Healthcare Provider or Patient Questions and Complaints.    14

6.5
Sole Remedy.    14

ARTICLE 7
CO-OPERATION 14

7.1
Quarterly Review.    14

7.2
Access & Audits.    14

7.3
Reports.    15

7.4
Regulatory Authority Filings.    15

ARTICLE 8
TERM AND TERMINATION 15

8.1
Initial Term.    15

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8.2
Termination for Cause.    15

8.3
Product Discontinuation.    16

8.4
Obligations on Termination.    16

ARTICLE 9
REPRESENTATIONS, WARRANTIES AND COVENANTS 17

9.1
Authority.    17

9.2
MDCO Warranties.    17

9.3
Patheon Warranties.    17

9.4
Debarred Persons.    18

9.5
No Warranty.    19

ARTICLE 10
REMEDIES AND INDEMNITIES 19

10.1
Consequential Damages.    19

10.2
Limitation of Liability-Active Materials.    19

10.3
Patheon.    19

10.4
MDCO.    19

10.5
Reasonable Allocation of Risk.    20

ARTICLE 11
CONFIDENTIALITY 20

11.1
Confidential Information - Disclosing Party’s Property.    20

11.2
Receiving Party’s Obligations.    20

11.3
Allowable Disclosures.    21

11.4
Exclusions.    21

11.5
Continuing Obligations of Confidentiality.    21

ARTICLE 12
DISPUTE RESOLUTION 22

12.1
Commercial Disputes.    22

12.2
Technical Dispute Resolution.    22

ARTICLE 13
MISCELLANEOUS 22

13.1
Inventions.    22

13.2
Intellectual Property.    23

13.3
Insurance.    23

13.4
Independent Contractors.    23

13.5
No Waiver.    24

13.6
Assignment and Subcontracting.    24

13.7
Force Majeure.    24

13.8
Additional Product.    24

13.9
Notices.    24

13.10
Severability.    25

13.11
Entire Agreement.    25

13.12
Other Terms.    26

13.13
No Third Party Benefit or Right.    26

13.14
Execution in Counterparts.    26

13.15
Use of MDCO Name.    26

13.16
Governing Law.    26

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MANUFACTURING SERVICES AGREEMENT
THIS MANUFACTURING SERVICES AGREEMENT (the “Agreement”) made as of the 30th day
of March, 2011 (“Effective Date”)
BETWEEN:
PATHEON INTERNATIONAL A.G.,
Lindenstrasse 14, 6340 Baar, (Switzerland)
a corporation existing under the laws of Switzerland,
(hereinafter referred to as “Patheon”),
- and -
THE MEDICINES COMPANY
8 Sylvan Way, Parsippany, NJ 07054 (U.S.A)
a Delaware corporation, with its principal place of business in Parsippany, New
Jersey, United States of America
(hereinafter referred to as “MDCO”).
RECITALS:
WHEREAS, Patheon and MDCO are Parties to that certain Preliminary Agreement
dated as of October 29, 2010 (the “Preliminary Agreement”), pursuant to which
MDCO is transferring the technology necessary to enable Patheon to manufacture
the Products at Patheon’s Manufacturing Site; and
WHEREAS, MDCO wishes to have the Products manufactured, tested and supplied to
it by Patheon for commercial sales, and Patheon wishes to manufacture, test and
supply to MDCO the Products for commercial sales, in accordance with the terms
and conditions of this Agreement;
WHEREAS, the Parties have agreed to enter into this Agreement to provide the
terms and conditions governing the manufacture, testing and supply of the
Products by Patheon.
NOW, THEREFORE, MDCO and Patheon agree as follows:
ARTICLE 1
INTERPRETATION
1.1    Definitions.
The following terms shall, unless the context otherwise requires, have the
respective meanings set out below and grammatical variations of such terms shall
have corresponding meanings:
“Active Materials”, “Active Pharmaceutical Ingredients” or “API” means the
materials listed on Schedule D hereto;
“Active Materials Credit Value” means the value to be attributed to the Active
Materials for certain purposes of this Agreement, as set forth on Schedule D;
“Affiliate” means:
a business entity which owns, directly or indirectly, a controlling interest in
a party to this

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Agreement, by stock ownership or otherwise; or
a business entity which is controlled by a party to this Agreement, either
directly or indirectly, by stock ownership or otherwise; or
a business entity, the controlling interest of which is directly or indirectly
common to the majority ownership of a party to this Agreement;
For the purposes of this definition, “control” means the ownership of shares
carrying at least a majority of the votes in respect of the election of the
directors of a corporation.
“Annual Report” means the annual report as described in Title 21 of the United
States Code of Federal Regulations, Section 314.81 (b)(2);
“Annual Product Review Report” means the annual product review report as
described in Title 21 of the United States Code of Federal Regulations, Section
211.180(e);
“Applicable Laws” means any statute, law, treaty, rule, code, ordinance,
regulation, that applies, as the context requires to: (i) the Agreement; (ii)
the performance of obligations or other activities related to the Agreement; and
(iii) a party’s Subcontractors (if any).
“Authority” means any governmental or regulatory authority department, body or
agency or any court, tribunal, bureau, commission or other similar body, whether
federal, state, provincial, county or municipal;
“Batch Size” means the estimated batch size of a Product (measured in number of
units of such Product) as set forth in Schedule B;
“Bill Back Items” means the expenses in respect of all third party supplier fees
for the purchase of columns, standards, tooling and supporting equipment and
other project specific items necessary for Patheon to perform the Manufacturing
Services, and which are not included as Components;
“Business Day” means a day other than a Saturday, Sunday or a day that is a
statutory holiday in the Italy, USA and /or Switzerland;
“cGMPs” means current good manufacturing practices as described in:
•
Parts 210 and 211 of Title 21 of the United Slates’ Code of Federal Regulations;
and

•
EC Directive 2003/94/EC;

together with the latest FDA and EMA guidance documents pertaining to
manufacturing and quality control practice, all as updated, amended and revised
from time to time;
“Components” means, collectively, primary packaging components, raw materials
and ingredients, required to be used in order to produce the Products in
accordance with the Specifications, other than the Active Materials;
“Confidential Information” means all information whether commercial, financial,
technical, operational or otherwise in any format, disclosed by one Party or any
of its Affiliates to the other Party or any of its Affiliates in connection with
this Agreement or the Preliminary Agreement which by its nature is clearly
confidential or proprietary (whether

--------------------------------------------------------------------------------

or not that information is marked or designated as confidential or proprietary)
whether disclosed orally, in documentary form, electronically or otherwise and
including the terms of this Agreement;
“Deficiency Notice” shall have the meaning ascribed thereto in Section 6.1 (a);
“Delivery Date” means the date of delivery of Products at the Manufacturing
Site, as stated in the acceptance of the Firm Order by Patheon;
“Disclosing Party” means the Party disclosing Confidential Information;
“Equipment” means the equipment required to be purchased and installed at the
Manufacturing Site in order to manufacture the Product, as detailed in the
Preliminary Agreement;
“Effective Date” means the date set forth in the introductory paragraph that is
the commencement date of this Agreement after execution by both Parties;
“EMA” means the European Medicines Agency;
“FDA” means the United States government agency known as the Food and Drug
Administration;
“Firm Order” means a firm written order in the form of a purchase order or
otherwise that has been accepted by Patheon;
“Intellectual Property” means rights under patent, trademark, copyright, and
trade secret Laws, and any other intellectual property or proprietary rights
recognized in any country or jurisdiction worldwide, including, without
limitation, rights in patents, patent applications, formulae, trade-marks,
trade-mark applications, trade-names, Inventions, copyright, industrial designs,
trade secrets and know-how;
“Invention” means any innovation, improvement, development, discovery, computer
program, device, trade secret, method, know-how, process, technique or the like,
whether or not written or otherwise fixed in any form or medium, regardless of
the media on which it is contained and whether or not patentable or
copyrightable;
“Inventory” means all inventories of Components and work-in-process produced or
held by Patheon in connection with the manufacture of the Products but, for
greater certainty, does not include the Active Materials;
“Law(s)” means all laws, statutes, ordinances, regulations, rules, by-laws,
judgments, decrees or orders of any Authority;
“MA” means Marketing Authorization pursuant to Directive 65/65 EEC (as amended)
or any implementation of it under the laws of a relevant Member State, which for
the Products means the authorisation referred to in the Quality Agreement;
“ML” means Manufacturing License pursuant to Directive 75/319 EEC (as amended)
or any implementation of it under the laws of a relevant Member State, which for
this Agreement means the authorisation referred to in the Quality Agreement;
“Manufacturing Requirements” shall have the meaning ascribed thereto in Section
2.3;
“Manufacturing Services” means the manufacturing, quality control, quality
assurance

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and stability testing, and related services, as contemplated in this Agreement,
required to produce Products from Active Materials and Components;
“Manufacturing Services Based Intellectual Property” means Intellectual Property
generated or derived by Patheon or its Affiliate in the course of performing any
Manufacturing Services or otherwise generated or derived by Patheon or its
Affiliate in connection with the conduct of its business which Intellectual
Property is not specific to, or dependent upon, MDCO’s Active Material or
Product including, without limitation, Inventions and Intellectual Property
which may have application to manufacturing processes or the formulation or
development of drug products, drug product dosage forms or drug delivery systems
beyond the specific requirements of the Product(s);
“Manufacturing Site” means the Patheon’s Affiliate facility, owned and operated
by Patheon Italia S.p.A, that is located at viale G.B. Stucchi n. 110, Monza -
Italy;
“Maximum Credit Value” means the maximum value of Active Materials that may be
credited by Patheon under this Agreement, as set forth on Schedule D;
“Minimum Run Quantity” means !he minimum number of batches of a Product to be
produced during the same cycle of manufacturing as set forth in Schedule B
hereto;
“Party(ies)” means either Patheon or MDCO, or both, as the case may be;
“Price” means the price to be charged by Patheon regarding Product manufactured
and supplied hereunder as delivered to MDCO, and is comprised of the fees for
the Manufacturing Services, and the costs for Components; which Price is fully
described in Schedule B.
“Product(s)” means the product(s) listed on Schedule A hereto;
“Product Quality Review” means the annual product review report as described in
Eudralex Vol. 4 GMP chapter I Quality Management;
“Promptly” means within three (3) business days;
“Quality Agreement” means the agreement to be entered into between the Parties
hereto, required under the laws of the European Union and setting out the
respective liabilities of the Parties and the quality assurance standards in
respect of the Manufacturing Services, which agreement shall be substantially in
the form attached hereto as Schedule F;
“Receiving Party” means the Party to whom Confidential Information is disclosed;
“Regulatory Authority” means the FDA, EMA and any other foreign regulatory
agencies competent lo grant marketing approvals for pharmaceutical products
including the Products in the Territory;
“Specifications” means the file, for each Product, which is provided by MDCO to
Patheon in accordance with the procedures listed in the Quality Agreement hereto
and which contains documents relating to such Product, including, without
limitation:
a)    specifications for Active Materials and Components;
b)    manufacturing specifications, directions and processes;
c)    storage requirements;

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d)    all environmental, health and safety information relating to the Product
including material safety data sheets; and
e)    the finished Product specifications, packaging specifications and shipping
requirements for each Product;
all as updated, amended and revised from time to time by MDCO in accordance with
the terms of this Agreement;
“Subcontractor” means Patheon’s Affiliate named Patheon Italia S.p.A.;
“Technical Dispute” has the meaning specified in Section 12.2;
“Territory” means the geographic areas listed in Schedule G, and any other
territories that may be agreed to in writing between the Parties during the Term
of the Agreement;
“Third-Party Rights” means the Intellectual Properly of any third party;
“Year” means, in the first year of this Agreement, the period from the Effective
Date up to and including December 31 of the same calendar year, and thereafter
shall mean a calendar year;
“Yearly Binding Volume” or “YBV” means the minimum volume of Product to be
manufactured in any Year of this Agreement as set forth in Schedule B hereto.
1.2    Currency.
Unless otherwise indicated, all monetary amounts are expressed in this Agreement
in Euros.
1.3    Sections and Headings.
The division of this Agreement into Articles, sections, subsections and
Schedules and the insertion of headings are for convenience of reference only
and shall not affect the interpretation of this Agreement. Unless otherwise
indicated, any reference in this Agreement to a Section or Schedule refers to
the specified Section or Schedule to this Agreement. In this Agreement, the
terms “this Agreement”, “hereof”, “herein”, “hereunder” and similar expressions
refer to this Agreement and not to any particular part, Section, Schedule or the
provision hereof.
1.4    Singular Terms.
Except as otherwise expressly provided herein or unless the context otherwise
requires, all references to the singular shall include the plural and vice
versa.
1.5    Schedules.
The following Schedules are attached to, incorporated in and form part of this
Agreement:
Schedule A - Product List
Schedule B     - Minimum Run Quantity, Yearly Binding Volume & Price
Schedule C     - Stability Testing Activities
Schedule D     - Active Materials, Active Materials Credit Value & Maximum
Credit Value
Schedule E     - Batch Numbering
Schedule F     - Quality Agreement
Schedule G     - Territory

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ARTICLE 2
PATHEON’S MANUFACTURING SERVICES
2.1    Technology Transfer and Feasibility Activities.
By the Preliminary Agreement, MDCO authorized Patheon to purchase the Equipment
and to begin the Technology Transfer and Feasibility Activities, prior to
commencing the manufacturing of the Product pursuant to Section 2.2. The Parties
hereby agree that the Technology Transfer and Feasibility Activities currently
ongoing shall continue to be controlled by the terms and conditions of the
Preliminary Agreement. Anything not expressly provided therein, shall be
governed by the terms of this Agreement.
2.2    Manufacturing Services.
Patheon shall provide the Manufacturing Services for the Territory for the fees
specified in Schedules B and C in order to produce Products for MDCO. Schedule B
sets forth in detail cost items that are included in the Price for Products and
those cost items excluded from the Price that are subject to additional fees to
be paid by MDCO. Patheon may change the Manufacturing Site for the Products only
with the prior written consent of MDCO, such consent not to be unreasonably
withheld. Patheon will pay, at its own expense, for any Patheon or MDCO
regulatory fees and technical transfer costs from a Patheon-requested change in
Manufacturing Site. Patheon shall be an authorized manufacturer of Products
offered for sale by MDCO in the Territory. In providing the Manufacturing
Services, Patheon and MDCO agree that:
a)
Conversion of Active Materials and Components. Patheon shall convert Active
Materials and Components into Products.

b)
Quality Control and Quality Assurance. Patheon shall perform the quality control
and quality assurance testing specified in the Quality Agreement.

c)
Components. Patheon shall purchase and test all Components (with the exception
of those that are supplied by MDCO) as specified by the Specifications and per
the Quality Agreement.

d)
Stability Testing. Patheon shall conduct stability testing on the Products in
accordance with the protocols set out in the Specifications for the separate
fees and during the time periods specified in Schedule C.

e)
Product Rejection for Finished Product Specification Failure. If Patheon
performs the Manufacturing Services in accordance with the Manufacturing
Requirements and, notwithstanding the foregoing, a batch or portion of batch of
Product does not meet Specification, MDCO shall be obligated to pay Patheon the
applicable fee per unit for such non-conforming Product. However, if the
non-conforming Product results from Patheon’s failure to perform the
Manufacturing Services in accordance with the Manufacturing Requirements, then
MDCO shall not be required to pay Patheon the applicable fee per unit for such
non-conforming product. This absolution of MDCO’s obligation to pay Patheon’s
production fees shall be in addition to Patheon’s compensation to MDCO provided
in section 10.2 for the loss of Active Materials.

f)
Active Materials and MDCO Supplied Components Importing. At least thirty (30)
days prior to the scheduled production date, MDC shall furnish to Patheon, DDP

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(Incoterms 2010) at Manufacturing Site, viale G.B. Stucchi n.110, Monza - Italy,
the Active Materials in such quantities as are necessary to enable Patheon to
manufacture the desired quantities of Product on the requested delivery date. If
such Active Materials are not received thirty (30) days in advance, Patheon will
be entitled to delay shipments of Product caused by the re-scheduling of
production by the same number of days as the delay in receipt of such Active
Materials; provided, however, that in the event Patheon is unable to meet such
scheduling deadline due to prior third party production commitments, Patheon
shall be entitled to delay shipments until such later date as agreed to by the
Parties. All shipment of Active Material shall be accompanied by certificate(s)
of analysis from the Active Material manufacturer confirming the identity,
purity and compliance with the Active Material specifications.
g)
Bill Back Items. Bill Back Items (if any) shall be charged to MDCO at Patheon’s
cost plus the agreed upon handling fee of [**]% subject to a maximum handling
fee of €[**] per item. Should the handling fees exceed the amount of €[**] per
item, the Parties will jointly determine, in good faith, the revised aggregate
amount payable by MDCO.

2.3    Standard of Performance.
Patheon shall provide the Manufacturing Services in accordance with (i) the
Specifications; (ii) any other terms and conditions provided in the Quality
Agreement; (iii) the cGMPs (US/EU) and any other applicable legal requirements
as specified by the Regulatory Authorities. Patheon’s responsibilities and
obligations with respect to the manufacture of the Product as set forth in this
Section 2.3 are hereinafter referred to as the “Manufacturing Requirements”. The
Parties agree that, for the purposes of Article 6 and Section 10.2 of this
Agreement, the Manufacturing Requirements do not include any obligations related
to the cosmetic defects of the Products for the Japanese market (should the
Product be commercialized in such market by MDCO).
2.4    Subcontractors.
MDCO hereby agrees that Patheon will subcontract to its Affiliate, Patheon
Italia S.p.A (“Subcontractor”), any Manufacturing Services under this Agreement.
It is understood that Patheon shall enter into an agreement with its Affiliate
that contains confidentiality and non-use terms similar to and at least as
strict as those set forth in Section 11 of this Agreement, as well as any other
terms necessary to ensure that Patheon meets its obligations under this
Agreement. For the avoidance of doubt, the subcontracting of any Services
hereunder to the Subcontractor by Patheon shall not relieve Patheon of, and
Patheon shall remain solely liable for, its obligations under this Agreement.
ARTICLE 3

MDCO’S OBLIGATIONS
3.1    Payment.
Pursuant to the terms of this Agreement, MDCO shall pay Patheon for the
provision of the Manufacturing Services and related Components according to the
Prices specified in Schedules B and C hereto (such fees being subject to
adjustment in accordance with the terms hereof).
3.2    Active Materials.
MDCO shall at its sole cost and expense, deliver the Active Materials to Patheon
(in

--------------------------------------------------------------------------------

accordance with Section 2.2(f)) in sufficient quantities and at such times to
facilitate the provision of the Manufacturing Services by Patheon. The Active
Materials shall be held by Patheon on behalf of MDCO in accordance with the
Specifications, with any other label and invoice instructions given by MDCO from
time to time in accordance with this Agreement and with the current GMPs. Title
to the Active Materials shall at all times belong to and remain the property of
MDCO. Any Active Materials received by Patheon shall only be used by Patheon to
provide the Manufacturing Services. Patheon’s liability with respect to any lost
or damaged Active Materials shall be as set forth in Section 10.2.
ARTICLE 4

CONVERSION FEES AND COMPONENT COSTS
4.1    First Year Pricing.
The Prices for the Products for the first Year are listed in Schedule B and are
subject to the adjustments set forth in Sections 4.2. and 4.3.
4.2    Price Adjustments.
The Prices for the Products during any Year subsequent to the first Year of this
Agreement shall be determined in accordance with the following:
a)    Manufacturing Costs. Effective at the beginning of March of each Year of
this Agreement, Patheon shall be entitled to an adjustment to the Manufacturing
Services fees in respect of the Products to reflect inflation, which adjustment
shall be based on the annual change in the Consumer Price Index, published by
ISTAT in respect of the immediately prior Year ending December 31 (i.e., the
year over year change from December to December). This index is set forth at the
following web address:
http://www.istat.it/salastampa/comunicati/in_calendaria/precon/20110114_00/
In connection with such Price adjustment, Patheon shall deliver to MDCO on or
about February of each Year, a statement outlining the percentage change in the
Consumer Price Index upon which such price adjustment is based. The adjusted
prices shall be effective as of March 1st of the same Year in which the
adjustment is required and shall be applied to all Firm Orders accepted by
Patheon on or after March 1st. For sake of clarity, the adjusted price shall not
be applied to any Firm Orders accepted by Patheon prior to March 1st, even if
the actual Delivery Date is on or after March 1st.
b)    Extraordinary Increases in Component Costs. If at any time market
conditions result in Patheon’s cost of Components being materially greater than
normal forecasted increases, then Patheon shall be entitled to an adjustment to
the Price in respect of any affected Product to compensate it for such increased
Component costs. For the purposes of this clause (b), changes materially greater
than normal forecasted increases shall be considered to have occurred if: (i)
the cost of a Component increases by [**]% of the cost for that Component upon
which the most recent fee quote was based; or (ii) the aggregate cost for all
Components required to manufacture a Product increases by [**]% of the total
Component costs for such Product upon which the most recent fee quote was based.
To the extent that Component costs have been previously adjusted pursuant to
this clause (b) to reflect an increase in the cost of one or more Components,
the adjustments provided for in (i) and (ii) above shall operate based on the
costs attributed to such Component (or Components) at the time the last of such
adjustments were made.
In connection with a Price adjustment pursuant to this Section 4.2(b), Patheon
shall deliver to MDCO

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a revised Schedule B and such budgetary pricing information, adjusted Component
costs or other documentation reasonably sufficient to demonstrate that a Price
adjustment is justified, provided that Patheon shall have no obligation to
provide any supporting documents to the extent such documents are subject to
obligations of confidentiality between Patheon and its suppliers.
4.2.1
Adjustment due to Volume Changes from Yearly Binding Volumes

(a)
On the execution of this Agreement, MDCO shall provide Patheon with its best
estimate of the volume of Product that MDCO will require Patheon to supply
during the Term of this Agreement (such forecast to be known as the “Long Term
Forecast”), starting from January 1, 2012. This Long Term Forecast is provided
in Schedule B. The volumes of Product forecasted in the Long Term Forecast snail
not be deemed as binding on MDCO.

(b)
Prior to July 1st of each Year during the Term, MDCO will provide Patheon with a
firm volume commitment for the immediately following Year (the “Yearly Binding
Volume” or “YBV”).

During the first Year of this Agreement, MDCO will provide Patheon with the YBV
for the following Year (i.e. 2012) in two (2) separate 6-month volume
commitments. The two (2) 6-month volume commitments will be aggregated to a
single YBV. The first 6-month commitment, concerning the first semester of Year
2012, will be provided to Patheon prior to July 1, 2011. The second 6-month
commitment, concerning the second semester of Year 2012, will be provided to
Patheon prior to January 1, 2012.
(c)
Notwithstanding the foregoing Section 4.2.1(b), the Parties hereby agree that
the Yearly Binding Volume may be reduced yearly during the Term of the Agreement
within the flexibility ranges (hereinafter the “Flexibility Ranges” or “FR”) set
out in the Table below:

YEAR
FLEXIBILITY RANGE ON YEARLY BINDING VOLUME
2012
[**]%
2013
[**]%
2014 and beyond
[**]%

If at the end of each Year, (i) the aggregate actual volume of Product ordered
by MDCO pursuant to Section 5.5 (“Actual Yearly Volume”) during such Year varies
from (ii) the Yearly Binding Volume (“Yearly Binding Volume”), by more than the
Flexibility Ranges as set out in the Table above for such Year, then Patheon
shall be entitled to and may request that MDCO pays to Patheon an amount to be
determined as follows, for the non-absorbed fixed manufacturing costs incurred
by Patheon during such Year:
Amount due to Patheon = [YBV x (1-FR/100) - AYV] *[**]% of the Price
For the purposes of the Agreement, the following terms shall have the respective
meanings set out below:
•
Yearly Binding Volume (or “YBV”): means the aggregate yearly

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binding volume of Product for each relevant Year, as provided by MDCO pursuant
to Section 4.2.1(b) above; and

Actual Yearly Volume (or “AYV”): means the actual total volume of Product
ordered by MDCO and invoiced by Patheon pursuant to Section 5.5 during the
relevant Year.

In any Year in which MDCO’s AYV is less than MDCO’s YBV, Patheon will make every
reasonable effort to mitigate the potential effects of this shortfall and to
avoid any need to require the adjustment payments from MDCO as specified in this
Section 4.2.1.(b). The determination of whether an adjustment payment will be
required by Patheon is subject solely to Patheon’s discretion and determination.
It is an elective payment, and is not mandated by this Agreement.
(d)
If during a Year MDCO requests a volume of Product which exceeds by more than
[**] percent (+[**]%) the YBV for such Year pursuant to Section 4.2.1(b) above,
then the Parties shall evaluate in good faith such request in order to reach an
agreement on Product feasibility in the current Year and Patheon shall use all
commercially reasonable efforts to meet MDCO’s requests.

4.3    Adjustments Due to Technical Changes.
Amendments to the Specifications, the Quality Agreement, or the Product
manufacturing process, requested by either Party, will only be implemented
following a technical and cost review by Patheon and are subject to MDCO and
Patheon’s approval. Once agreement is reached between the Parties as to
revisions, the proposed charges, if any, will be implemented to the Prices
specified in Schedules B or C necessitated by any such amendment. Such approval
not to be unreasonably withheld. If MDCO accepts a proposed Price change, the
proposed change in the Specifications, the Quality Agreement or the Product
manufacturing process shall be implemented, and the Price change shall become
effective only with respect to those orders of Products that are manufactured in
accordance with the revised Specifications, the Quality Agreement or Product
manufacturing process. In addition, MDCO agrees to purchase, at Patheon’s cost
therefore (including all costs incurred by Patheon in connection with the
purchase and handling of such Inventory), all Inventory utilized under the “old”
Specifications or Quality Agreement and purchased or maintained by Patheon in
order to fill Firm Orders or in accordance with Section 5.2, to the extent that
such Inventory can no longer be utilized under the revised Specifications or
Quality Agreement. Open purchase orders for Components no longer required under
any revised Specifications or Quality Agreement that were placed by Patheon with
suppliers in order to fill Firm Orders or in accordance with Section 5.2 shall
be cancelled where possible, and where such orders are not subject to
cancellation without penalty, shall be assigned to and satisfied by MDCO.
ARTICLE 5

ORDERS, SHIPMENT, INVOICING, PAYMENT
5.1    Orders and Forecasts.
a)    Rolling Forecasts. Concurrent with the execution of this Agreement, MDCO
shall provide Patheon with a written non-binding twelve (12) month forecast of
the volume of each Product that MDCO then anticipates will be required to be
produced and delivered to MDCO during each month of that twelve (12) month
period. Such forecast will be updated by MDCO monthly on or

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before the 10th day of each calendar month on a rolling twelve (12) month basis
and updated forthwith upon MDCO determining that the volumes contemplated in the
most recent of such forecasts has changed by more than [**] percent ([**]%). The
most recent 12 month forecast shall prevail.
b)    Firm Orders. The first three (3) months of the initial rolling forecast
shall constitute a Firm Order upon acceptance by Patheon. Thereafter, on or
before the 10th day of each calendar month, MDCO shall issue Firm Orders for
Manufacturing Services in respect of the Products to be produced and delivered
to MDCO on a date not less than three (3) months from the first day of the
calendar month immediately following the date that the Firm Order is submitted.
Such Firm Orders submitted to Patheon shall specify MDCO’s Manufacturing
Services purchase order number, quantities by Product type, monthly delivery
schedule and any other elements necessary to ensure the timely production and
shipment of the Products. The quantities of Products ordered in such written
orders shall be firm and binding on MDCO and shall not be subject to reduction
by MDCO.
c)    Patheon will use commercially reasonable efforts to deliver the ordered
batch(es) of Product by the Delivery Date and shall promptly alert MDCO, in
writing, of any delay that may affect such Delivery Date. Should a delay in
delivery occur, Patheon will develop and carry out a remedial plan with MDCO to
help prevent further possible late deliveries.
d)    Patheon and MDCO will develop, establish and review appropriate key
performance indicators (KPI’s) during the term of this Agreement to assess and
improve the ongoing effectiveness of operations. These KPI’s will be reviewed at
the Quarterly Steering Committee meetings. The KPI’s should be agreed upon by
both Parties, but should, at a minimum, include production yields for drug
product lots, on time delivery and batch record cycle review.
5.2    Reliance by Patheon.
MDCO understands and acknowledges that Patheon will rely on the Firm Orders and
rolling forecasts submitted pursuant to Sections 5.1(a) and (b) in ordering the
Components required to meet such Firm Orders. In addition, MDCO understands that
to ensure an orderly supply of such Components, it may be desirable for Patheon
to purchase such Components in sufficient volumes to meet the production
requirements for Products during part or all of the forecasted periods referred
to in Section 5.1(a) or to meet the production requirements of any longer period
agreed to by Patheon and MDCO. Accordingly, MDCO authorizes Patheon to purchase
Components in order to satisfy the Manufacturing Services requirements for
Products for the first six (6) months contemplated in the most recent forecast
provided by MDCO pursuant to Section 5.1(a) and agrees that Patheon may make
such other purchases of Components to meet Manufacturing Services requirements
during such longer periods as may be agreed to in writing from time to time by
MDCO at the request of Patheon or MDCO. If Components ordered by Patheon
pursuant to Firm Orders or this Section 5.2 are not included in finished
Products manufactured for MDCO within twelve (12) months after the forecasted
month in respect of which such purchases have been made (or such longer period
as the Parties may agree) or if such Components have expired during such period,
then MDCO shall pay to Patheon its costs therefore (including all costs incurred
by Patheon in connection with the purchase and handling of such Components);
provided, however, that in the event such Components are incorporated into
Products subsequently manufactured for MDCO or into third party products
manufactured by Patheon for a third party, MDCO will receive credit for any
costs of such Components previously paid to Patheon by MDCO.
5.3    Minimum Orders.
MDCO may only order Manufacturing Services in respect of batches of Products in
multiples of the Minimum Run Quantities as set out in Schedule B.
5.4    Shipments.

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Shipments of Products shall be made EXW (Incoterms 2010) Manufacturing Site with
Patheon being responsible for loading the carrier’s vehicle, unless otherwise
mutually agreed. Risk of loss or of damage to Products shall remain with Patheon
until Patheon loads the Products onto the carrier’s vehicle for shipment at the
shipping point at which time risk of loss or damage shall transfer to MDCO.
Products shall be transported in accordance with the Specifications. Product not
shipped within [**] days of manufacture and released for shipping by Patheon
will be subject to a [**] Euro €[**] per pallet space per month storage fee
which will be invoiced to MDCO according to the provisions of section 5.5 of
this Agreement.
5.5    Invoices and Payment.
Invoices shall be sent by email to the accounts payable email address provided
by MDCO. Invoices will be sent, by Patheon to MDCO, at the time the Product is
manufactured and released or at the shipping date whichever is earlier. Disputes
regarding the amount of the invoices will not suspend MDCO’s payment
obligations. Each such invoice shall, to the extent applicable, identify MDCO’s
Manufacturing Services purchase order number, Product numbers, names and
quantities, unit price, freight charges and the total amount to be remitted by
MDCO. MDCO shall pay all such invoices within 30 days of the date thereof.
ARTICLE 6
PRODUCT CLAIMS AND RECALLS
6.1    Product Claims.
a)    Product Claims. MDCO has the right to reject any portion of any shipment
of Products that deviates from the Manufacturing Requirements without
invalidating any remainder of such shipment. MDCO shall inspect the Products
manufactured by Patheon upon receipt thereof and shall give Patheon written
notice (a “Deficiency Notice”) of all claims for Products that deviate from the
Manufacturing Requirements within thirty (30) days after MDCO’s receipt thereof
(or, in the case of any defects not reasonably susceptible to discovery upon
receipt of the Product, within thirty (30) days after discovery thereof by MDCO,
but in no event after the expiration date of the Product). Should MDCO fail to
provide Patheon with the Deficiency Notice within the applicable thirty (30) day
period, then the delivery shall be deemed to have been accepted by MDCO on the
thirtieth (30th) day after delivery or discovery, as applicable. Except as set
out in Section 6.2, Patheon shall have no liability for any deviations for which
it has not received notice within the applicable thirty (30) day period.
b)    Determination of Deficiency. Upon receipt of a Deficiency Notice, Patheon
shall have ten (10) days to advise MDCO by notice in writing that it disagrees
with the contents of such Deficiency Notice. If MDCO and Patheon fail to agree
within ten (10) days after Patheon’s notice to MDCO as to whether any Products
identified in the Deficiency Notice deviate from the Manufacturing Requirements,
then the Parties shall mutually select an independent laboratory to evaluate if
the Products deviate from the Manufacturing Requirements. Such evaluation shall
be binding on the Parties, and if such evaluation certifies that any Products
deviate from the Manufacturing Requirements, MDCO may reject those Products in
the manner contemplated in this Section 6.1. In that event the evaluation costs
will be borne by Patheon, otherwise MDCO will be responsible for the evaluation
costs. If such evaluation does not so certify in respect of any such Products,
then MDCO shall be deemed to have accepted delivery of such Products on the
fortieth (40th) day after delivery (or, in the case of any defects not
reasonably susceptible to discovery upon receipt of the Product, on the fortieth
(40th) day after discovery thereof by MDCO, but in no event after the expiration
date of the Product).
c)    Shortages and/or damaged Products. Claims for shortages in the amount of

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Products shipped by Patheon and/or damages to Products delivered by Patheon
shall be dealt with as may be reasonably agreed to by the Parties, consistent
with the circumstances pertaining to the Product shortage or damage.
6.2    Patheon’s Responsibility for Defective and Recalled Products.
a)    Defective Product. In the event MDCO rejects Products in accordance with
Section 6.1 and the deviation is determined to have arisen from Patheon’s
failure to provide the Manufacturing Services in accordance with the
Manufacturing Requirements, Patheon will credit MDCO’s account for Patheon’s
invoice price for such defective Products. If MDCO shall have previously paid
for such defective Products, Patheon shall promptly, at MDCO’s election, either;
(i) refund the invoice price for such defective Products; (ii) offset such
amount against other amounts due to Patheon hereunder; or (iii) replace such
Products with conforming Products without MDCO being liable for payment therefor
under Section 3.1, contingent upon the receipt from MDCO of all Active Materials
required for the manufacture of such replacement Products. For greater
certainty, Patheon’s responsibility for any loss of Active Materials in
connection with defective Product shall be captured under Section 10.2.
b)    Recalled Product. To the extent that a recall or return results from, or
arises out of, a failure by Patheon to provide the Manufacturing Services in
accordance with the Manufacturing Requirements, Patheon shall be responsible for
the documented out-of-pocket expenses of such recall or return and shall use its
commercially reasonable efforts to replace the recalled or returned Products
with new Products, contingent upon the receipt from MDCO of all Active Materials
required for the manufacture of such replacement Products. For greater
certainty, Patheon’s responsibility for any loss of Active Materials in
connection with recalled or returned Product shall be captured under Section
10.2. In the event that Patheon is unable to replace the recalled or returned
Products (except where such inability results from a failure to receive the
required Active Materials), then, upon MDCO’s request, Patheon shall reimburse
MDCO for the price that MDCO paid to Patheon for Manufacturing Services in
respect of the affected Products. In all other circumstances, recalls, returns
or other corrective actions shall be made at MDCO’s cost and expense.
Except as provided in Sections 6.2(a) and (b) above, Patheon shall not be liable
nor have any responsibility for any deficiencies in, or other liabilities
associated with, any Product manufactured by it, (collectively, "Product
Claims"). For greater certainty, Patheon shall have no obligation for any
Product Claims to the extent such Product Claim (i) is caused by deficiencies
with respect to the Specifications, the safety, efficacy or marketability of the
Products or any distribution thereof, (ii) results from a defect in a Component
that is not reasonably discoverable by Patheon using the test methods set forth
in the Specifications, (iii) results from a defect in the Active Materials or
Components supplied by MDCO that is not reasonably discoverable by Patheon using
the test methods set forth in the Specifications, (iv) is caused by actions of
third parties occurring after such Product is shipped by Patheon pursuant to
Section 5.4, (v) is due to packaging or labeling defects or omissions for which
Patheon has no responsibility, (vi) is due to any unascertainable reason despite
Patheon's having met the Manufacturing Requirements, or (vii) is due to any
other breach by MDCO of its obligations under this Agreement.
Notwithstanding anything in this Agreement to the contrary, the Parties agree
that, for the purposes of this Article 6 and Section 10.2, Patheon shall not be
liable vis-à-vis MDCO for any vial of Product manufactured for the Japanese
market and rejected, recalled or returned due to cosmetic defects. For avoidance
of doubt, Patheon will be entitled to invoice MDCO for the Price of the Products
rejected, recalled or returned due to cosmetic defects.
6.3    Disposition of Defective or Recalled Products.
MDCO shall not dispose of any damaged, defective, returned or recalled Products
in relation

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to which it intends to assert a claim against Patheon without Patheon’s prior
written authorization to do so. Alternatively, Patheon may instruct MDCO to
return such Products to Patheon. Patheon shall bear the cost of disposition with
respect to any damaged, defective, returned or recalled Products in relation to
which it bears responsibility under Section 6.2 hereof. In all other
circumstances, MDCO shall bear the cost of disposition, including all applicable
fees for Manufacturing Services, with respect to any damaged, defective,
returned or recalled Products.
6.4    Healthcare Provider or Patient Questions and Complaints.
MDCO shall have the sole responsibility for responding to questions and
complaints from its customers. Questions or complaints received by Patheon from
MDCO’s customers, healthcare providers or patients shall be promptly referred to
MDCO. Patheon shall co-operate as reasonably required to allow MDCO to determine
the cause of and resolve any such questions and complaints. Such assistance
shall include follow-up investigations, including testing. In addition, Patheon
shall provide MDCO with all mutually agreed upon information that will enable
MDCO to respond properly to questions or complaints relating to the Products as
provided in the Quality Agreement. Unless it is determined that the cause of any
such complaint resulted from a failure by Patheon to provide the Manufacturing
Services in accordance with the Manufacturing Requirements, all costs incurred
in respect of this Section 6.4 shall be borne by MDCO. In the event that the
cause of the complaint is attributable to a failure by Patheon to provide the
Manufacturing Services in accordance with the Manufacturing Requirements, such
Product shall be deemed to be Defective Product as defined in Section 6.2(a)
above; and, MDCO shall be entitled to compensation and reimbursement by Patheon
for such Defective Product in accordance with the provisions of Sections 6.2 and
10.2.
6.5    Sole Remedy.
Except for the indemnity provided in Sections 2.2.(e.) and 10.3 and subject to
the limitations set forth in Sections 10.1 and 10.2, the remedies described in
this Article 6 shall be MDCO’s sole remedy for any failure by Patheon to provide
the Manufacturing Services in accordance with the Manufacturing Requirements.
ARTICLE 7

CO-OPERATION
7.1    Quarterly Review.
Each Party shall forthwith upon execution of this Agreement appoint one of its
employees to be a relationship manager responsible for liaison between the
Parties. The relationship managers shall meet not less than quarterly to review
the current status of the business relationship and manage any issues that have
arisen.
7.2    Access & Audits.
Patheon will provide MDCO with reasonable access at mutually agreeable times and
during regular business hours to the areas of the Manufacturing Site in which
the Products are manufactured, stored, handled or shipped to permit MDCO to
verify that the Manufacturing Services are being performed in accordance with
the Manufacturing Requirements. But, with the exception of “for-cause” audits,
MDCO will be limited each Year to one cGMP-type audit, lasting no more than two
(2) days, and involving no more than four (4) auditors. MDCO may request
additional cGMP-type audits, additional audit days, or the participation of
additional auditors subject to payment to Patheon of a fee of €[**] for each
additional audit day and €[**] per audit day for each additional auditor. The
right of access provided in this Section 7.2 will not include a right to access
or inspect Patheon’s

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financial records.
7.3    Reports.
Patheon will supply on an annual basis and at MDCO’s expense as outlined in
Schedule B, attached hereto, all Product data in its control, including release
test results, complaint test results, and all investigations (in manufacturing,
testing and storage), that MDCO reasonably requires in order to complete any
filing under any applicable regulatory regime, including any Annual Report that
MDCO is required to file with the FDA, EMA, or other applicable competent
regulatory authority.
7.4    Regulatory Authority Filings.
MDCO is solely responsible for the preparation and filing of the application for
approval by the Regulatory Authorities and any relevant costs shall be borne by
MDCO. The Parties agree to manage such filing before the Regulatory Authorities
in accordance with the provisions set out in the Quality Agreement. The time
taken by Patheon to review the documents will be charged back to MDCO at the
rates detailed in Schedule B.
ARTICLE 8

TERM AND TERMINATION
8.1    Initial Term.
This Agreement shall become effective as of the Effective Date and shall
continue until 31st December 2016 (the “Initial Term”), unless terminated
earlier by one of the Parties in accordance herewith. This Agreement shall
automatically continue after the Initial Term for successive terms of two years
each unless either Party gives written notice to the other Party of its
intention to terminate this Agreement at least 18 months prior to the end of the
then current term.
8.2    Termination for Cause.
a)    Either Party, at its sole option, may terminate this Agreement upon
written notice in circumstances where the other Party has failed to remedy a
material breach of any of its representations, warranties or other obligations
under this Agreement within 60 days following receipt of a written notice (the
“Remediation Period”) of said breach that expressly states that it is a notice
under this Section 8.2(a) (a “Breach Notice”). If the material breach by its
nature is not curable, the non-breaching Party shall have the right to terminate
this Agreement with immediate effect by giving the breaching Party notice of any
such non-curable breach, specifying such non- curable breach in reasonable
detail and stating that it terminates this Agreement, such termination right to
be exercised within a period of thirty (30) days following the date as of which
the terminating Party receives knowledge of any such breach.
b)    Either Party at its sole option may immediately terminate this Agreement
upon written notice, but without prior advance notice, to the other Party in the
event that: (i) the other Party is declared insolvent or bankrupt by a court of
competent jurisdiction; (ii) a voluntary petition of bankruptcy is filed in any
court of competent jurisdiction by such other Party; or (iii) this Agreement is
assigned by such other Party for the benefit of creditors.
c)    MDCO may terminate this Agreement as to any Product upon thirty (30) days’
prior written notice in the event that any governmental agency takes any action,
or raises any objection, that prevents MDCO from importing, exporting,
purchasing or selling such Product.
d)    Patheon may terminate this Agreement upon six (6) months’ prior written
notice

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if MDCO assigns pursuant to Section 13.6 any of its rights under this Agreement
to an assignee that, in the opinion of Patheon acting reasonably, is: (i) not a
credit worthy substitute for MDCO; or (ii) a competitor of Patheon; or (iii) an
entity with whom Patheon has had prior unsatisfactory business relations.
8.3    Product Discontinuation.
MDCO shall provide at least twelve (12) months advance notice if it intends to
no longer order Manufacturing Services for a Product due to that Product’s
discontinuance in the market.
8.4    Obligations on Termination.
If this Agreement is completed, expires or is terminated in whole or in part for
any reason, then (in addition to any other remedies Patheon may have in the
event of default by MDCO):
a)    MDCO shall take delivery of and pay for all undelivered Products that are
manufactured pursuant to a Firm Order, at the price in effect at the time the
Firm Order was placed;
b)    MDCO shall purchase, at Patheon’s cost (including all costs incurred by
Patheon in connection with the purchase and handling of such Inventory), the
Inventory applicable to the Products that cannot reasonably be used for other
products produced by Patheon, that was purchased, produced or maintained by
Patheon in contemplation of filling Firm Orders or in accordance with Section
5.2 prior to notice of termination being given;
c)    MDCO shall satisfy the purchase price payable pursuant to Patheon’s orders
with suppliers of Components, provided such orders were made by Patheon in
reliance on Firm Orders or in accordance with Section 5.2;
d)    Patheon shall return to MDCO all unused Active Materials (with shipping
and related expenses, if any, to be borne by MDCO); and
e)    MDCO acknowledges that no competitor of Patheon shall be permitted access
to the Manufacturing Site;
f)    MDCO shall make commercially reasonable efforts, at its own expense, to
remove from Patheon site(s), within fifteen (15) Business Days, all of MDCO’s
unused Active Materials, Components and Inventory (whether current or obsolete),
supplies, undelivered Product, chattels, Equipment or other moveable property
owned by MDCO, related to the Agreement and located at a Patheon site or that is
otherwise under Patheon’s care and control (“MDCO Property”). MDCO shall pay to
Patheon a thirty Euro (€30.00) per pallet space per month storage fee for all
MDCO Property remaining at Patheon’s site(s) after the fifteenth (15th) Business
Day following the completion, termination or expiration of the Agreement and
will assume any third party storage charges invoiced to Patheon regarding any
such MDCO Property. Patheon will invoice MDCO for such storage charges according
to the provisions of section 5.5 of this Agreement.
Any termination or expiration of this Agreement shall not affect any outstanding
obligations or payments due hereunder prior to such termination or expiration,
nor shall it prejudice any other remedies that the Parties may have under this
Agreement. For greater certainty, termination of this Agreement for any reason
shall not affect the obligations and responsibilities of the Parties pursuant to
Articles 4, 5, 6, 10 and 11 and Sections 7.4, 8.4, 13.1, 13.2, 13.3 and 13.16,
all of which survive any termination.
g)    MDCO shall pay any amounts due under the provisions of this Section 8.4
within 30 days of the date of termination or expiry of this Agreement.

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ARTICLE 9

REPRESENTATIONS, WARRANTIES AND COVENANTS
9.1    Authority.
Each Party covenants, represents and warrants that it has the full right and
authority to enter into this Agreement, and that it is not aware of any
impediment that would inhibit its ability to perform its obligations hereunder.
9.2    MDCO Warranties.
MDCO covenants, represents and warrants that:
(a)
the Specifications for each of the Products are its or its Affiliate’s property
and that MDCO may lawfully disclose the Specifications to Patheon;

(b)
any Intellectual Property, other than Patheon’s Intellectual Property, utilized
by Patheon in connection with the provision of the Manufacturing Services
according to the Specifications (i) is MDCO’s or its Affiliate’s Intellectual
Property, (ii) may be lawfully used as directed by MDCO, and (iii) to MDCO’s
knowledge, such use does not infringe and will not infringe any Third Party
Rights;

(c)
to MDCO’s knowledge, the provision of the Manufacturing Services by Patheon in
respect of any Product pursuant to this Agreement or use or other disposition of
any Product by Patheon as may be required to perform its obligations under this
Agreement does not and will not infringe any Third Party Rights;

(d)
there are no actions or other legal proceedings, the subject of which is the
infringement of Third Party Rights related to: (i.) any of the Specifications,
(ii.) any of the Active Materials, (iii.) any of the Components, or (iv.) the
sale, use or other disposition of any Product made in accordance with the
Specifications;

9.3    Patheon Warranties.
(a)
Patheon covenants, represents and warrants that it shall perform the
Manufacturing Services in accordance with the Manufacturing Requirements.

(b)
Patheon covenants, represents and warrants that any Manufacturing Services Based
Intellectual Property utilized by Patheon in connection with the provision of
the Manufacturing Services (i) is Patheon’s or its Affiliate’s property, (ii)
may be lawfully used as used by Patheon, and (iii) to Patheon’s knowledge, such
use does not infringe and will not infringe any Third Party Rights.

(c)
Anti-Bribery. Patheon represents and warrants that neither Patheon nor its
Affiliates, or any of its or their directors, officers, employees or
representatives will, directly or indirectly, offer or pay, or authorize an
offer or payment of, any money or anything of value to any Public Official

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(defined below) or public entity, with the knowledge or intent that the payment,
promise or gift, in whole or in part, will be made in order to influence an
official act or decision that will assist Patheon or MDCO in securing an
improper advantage or in obtaining or retaining business or in directing
business to any person or entity. Patheon agrees to comply with the MDCO’s
requests for any information and documentation necessary to verify compliance
with this provision and applicable anti-corruption laws.
Patheon represents and warrants that, at the execution date of this Agreement,
neither Patheon nor its Affiliates, or any of its or their directors, officers,
employees or representatives, who perform Manufacturing Services under this
Agreement nor any person or entity acting on Patheon’s behalf is a Public
Official (as defined hereinafter) with the ability to influence an official act.
Patheon will notify MDCO in writing if any of the above captioned individuals,
becomes a Public Official with the ability to influence an official act during
the term of this Agreement.
In addition to other rights or remedies under this Agreement or at Law, MDCO
shall be entitled to terminate this Agreement, pursuant to Section 8.2(a), in
the event that improper payments are being or have been made to Public Officials
by Patheon or by any person or entity acting or its behalf, in order to
influence an official act or decision that will assist Patheon or MDCO in
securing an improper advantage or in obtaining or retaining business or in
directing business to any person or entity.
For the purposes of this Agreement, “Public Official” means any officer or
employee of a government, a public international organization or any department
or agency thereof, or any person acting in an official capacity, including, for
a public agency or enterprise; and any political party or party official, or any
candidate for public office.
9.4    Debarred Persons.
Patheon covenants that it will not in the performance of its obligations under
this Agreement use the services of any person debarred or suspended under 21
U.S.C. §335(a) or (b), or any analogous law or regulation. Patheon represents
that it does not have at the execution date of this Agreement, and covenants
that it will not hire, as an officer or an employee any person who has been
convicted of health care fraud or a felony under the laws of the United States
for conduct relating to the regulation of any drug product under the Federal
Food, Drug, and Cosmetic Act (United States). If any of Patheon or Patheon’s
Affiliate directors, officers, employees, agents, representatives or advisors,
who perform services under this Agreement is debarred or receives notice of an
action or threat of action of debarment, Patheon shall immediately notify MDCO
of same and shall take all the appropriate disciplinary actions against the
individuals responsible for the activity which constitutes cause for debarment.
MDCO shall be entitled to terminate this Agreement pursuant to Section 8.2(a) in
the event of debarment of Patheon or its Affiliates.
9.5    No Warranty.
PATHEON MAKES NO WARRANTY OF ANY KIND, EITHER EXPRESSED OR IMPLIED, BY FACT OR
LAW, OTHER THAN THOSE EXPRESSLY SET FORTH IN THIS AGREEMENT. PATHEON MAKES NO
WARRANTY OF FITNESS FOR A PARTICULAR PURPOSE OR WARRANTY OF MERCHANTABILITY WITH
RESPECT TO THE

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PRODUCTS.
ARTICLE 10

REMEDIES AND INDEMNITIES
10.1    Consequential Damages.
TO THE EXTENT PERMITTED BY THE APPLICABLE LAW, UNDER NO CIRCUMSTANCES WHATSOEVER
SHALL EITHER PARTY BE LIABLE TO THE OTHER IN CONTRACT, TORT, NEGLIGENCE, BREACH
OF STATUTORY DUTY OR OTHERWISE FOR (I) ANY (DIRECT OR INDIRECT) LOSS OF PROFITS,
OF PRODUCTION, OF ANTICIPATED SAVINGS, OF BUSINESS OR GOODWILL OR (II) FOR ANY
OTHER LIABILITY, DAMAGE, COSTS OR EXPENSE OF ANY KIND INCURRED BY THE OTHER
PARTY OF AN INDIRECT OR CONSEQUENTIAL NATURE, REGARDLESS OF ANY NOTICE OF THE
POSSIBILITY OF SUCH DAMAGES.
10.2    Limitation of Liability - Active Materials.
Except in the event the Active Materials are damaged due to the failure of
Patheon to provide the Manufacturing Services in accordance with the
Manufacturing Requirements due to negligence or willful misconduct, under no
circumstances whatsoever shall Patheon be responsible for any loss or damage to
the Active Materials. Patheon’s maximum liability for loss or damage to the
Active Materials shall not exceed the Maximum Credit Value.
10.3    Patheon.
Subject to Section 10.1, Patheon and its Affiliates agree to defend, indemnify
and hold MDCO, its officers, employees and agents harmless against any and all
losses, damages, costs, claims, demands, judgments and liability to, from and in
favour of third parties resulting from, or relating to any claim of personal
injury or property damage, to the extent that such injury or damage is the
result of Patheon’s negligence or willful misconduct in performing the
Manufacturing Services in accordance with the Manufacturing Requirements, except
to the extent that any such losses, damages, costs, claims, demands, judgments
and liability are due to the negligence or wrongful act(s) of MDCO, its
officers, employees or agents or Affiliates.
In the event of a claim, MDCO shall: (a) promptly notify Patheon of any such
claim; (b) use commercially reasonable efforts to mitigate the effects of such
claim; (c) reasonably cooperate with Patheon in the defense of such claim; (d)
permit Patheon to control the defense and settlement of such claim, all at
Patheon’s cost and expense.
10.4    MDCO.
Subject to Section 10.1, MDCO agrees to defend, indemnify and hold Patheon, its
Affiliates, officers, employees and agents harmless against any and all losses,
damages, costs, claims, demands, judgments and liability to, from and in favour
of third parties resulting from, or relating to any claim of infringement or
alleged infringement of any Third Party Rights in respect of the Products, or
any portion thereof, and/or any claim of personal injury or property damage to
the extent that such injury or damage is the result of a breach of this
Agreement by MDCO, including, without limitation, any representation or warranty
contained herein, except to the extent that any such losses, damages, costs,
claims, demands, judgments and liability are due to the negligence or wrongful
act(s) of Patheon, its officers, employees or agents.
In the event of a claim, Patheon shall: (a) promptly notify MDCO of any such
claims; (b)

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use commercially reasonable efforts to mitigate the effects of such claim; (c)
reasonably cooperate with MDCO in the defence of such claim; (d) permit MDCO to
control the defense and settlement of such claim, all at MDCO’s cost and
expense.
10.5    Reasonable Allocation of Risk.
The provisions of this Agreement (including, without limitation, this Article
10) are reasonable and create a reasonable allocation of risk having regard to
the relative profits the Parties respectively expect to derive from the
Products, and that Patheon, in its fees for the provision of the Manufacturing
Services, has not accepted a greater degree of the risks arising from the
manufacture, distribution and use of the Products, based on the fact that MDCO
has developed and holds the marketing approval for the Products and requires
Patheon to manufacture the Products strictly in accordance with the
Specifications, and that MDCO and not Patheon is in a position to inform and
advise potential users of the Products as to the circumstances and manner of use
of the Products.
ARTICLE 11

CONFIDENTIALITY
11.1    Confidential Information - Disclosing Party’s Property.
Except as otherwise provided in this Agreement, any Confidential Information
that is disclosed by or on behalf of a Disclosing Party lo the Receiving Party
will remain the property of the Disclosing Party.
11.2    Receiving Party’s Obligations.
The Receiving Party undertakes to:
(a)
use the Confidential Information solely and exclusively for the purposes of this
Agreement (or such other purpose as is agreed in writing between the Parties at
the time of disclosure), and not to use the Confidential Information for any
other purpose whatsoever, including the development, manufacture, marketing,
sale or licensing of any process or product or any other commercial purpose
anywhere in the world, unless the Parties enter into an agreement specifying
otherwise; and

(b)
maintain the confidentiality of the Confidential Information and not to disclose
it directly or indirectly to any other company, organization, individual or
third party, except as expressly permitted; and

(c)
at the request of the Disclosing Party, to return, delete or destroy all copies
of the Confidential Information, in whatever form it is held, except one (1)
copy which may be kept by the Receiving Party in its secured files for evidence
purposes only.

11.3    Allowable Disclosures.
(a)
Notwithstanding Section 11.2, the Receiving Party may disclose Confidential
Information to any of its Affiliates, and its Affiliates’ directors, employees
and professional advisers who need to know the Confidential Information in order
to fulfill the purpose of this Agreement, provided that the Receiving Party
ensures that prior to such disclosure,

--------------------------------------------------------------------------------

each such Person to whom Confidential Information is to be disclosed is made
aware of the obligations contained in this Agreement, and adheres to these terms
as if it were a party to this Agreement.
(b)
Nothing in Section 11.2 will preclude disclosure of any Confidential Information
required by any governmental, quasi-governmental or regulatory agency or
authority or court entitled by Law to disclosure of the same, or which is
required by Law or the requirements of a national securities exchange or another
similar regulatory body to be disclosed, provided that the Receiving Party
promptly notifies the Disclosing Party when such requirement to disclose has
arisen to enable the Disclosing Party to seek an appropriate protective order,
to make known to the relevant agency, authority, court or securities exchange
the proprietary nature of the Confidential Information, and to make any
applicable claim of confidentiality. The Receiving Party agrees to co-operate in
any action that the Disclosing Party may decide to take. If the Receiving Party
is required to make a disclosure in accordance with this clause, it will only
make a disclosure to the extent to which it is obliged.

11.4    Exclusions.
The provisions of Section 11.2 will not apply to any Confidential Information
which the Receiving Party can demonstrate, to the reasonable satisfaction of the
Disclosing Party:
(a)
was already in the possession of the Receiving Party or any of its Affiliates
(through no fault of the Receiving Party or any of its Affiliates and no breach
of this Agreement by the Receiving Party) prior to its disclosure by the
Disclosing Party under this Agreement;

(b)
is purchased or otherwise legally acquired by the Receiving Party or any of its
Affiliates at any time from a third party having the right to disclose it;

(c)
comes into the public domain, other than through the fault of the Receiving
Party or any of its Affiliates; or

(d)
is independently generated by the Receiving Party or any of its Affiliates
without any recourse or reference to the Confidential Information.

11.5    Continuing Obligations of Confidentiality.
The obligations of each Party in this Section will survive for a period of five
(5) years after the date of expiration or termination of this Agreement.
ARTICLE 12

DISPUTE RESOLUTION
12.1    Commercial Disputes.
In the event of any dispute arising out of or in connection with this Agreement
(other than a dispute determined in accordance with Section 6.1(b) or a
Technical Dispute), the Parties shall first try to solve it amicably. In this
regard, either Party may send a notice of dispute to the other, and

--------------------------------------------------------------------------------

each Party shall appoint, within ten (10) Business Days from receipt of such
notice of dispute, a single representative to handle the dispute. The
representatives so designated shall confer as necessary in order to solve such
dispute. If these representatives fail to solve the matter within one month from
their appointment, or if a Party fails to appoint a representative within the
ten (10) Business Day period set forth above, such dispute shall immediately be
referred to the Chief Operating Officer (or such other officer as he/she may
designate) of each Party who will meet and discuss as necessary in order to try
to solve the dispute amicably. Should the Parties fail to reach a resolution
under this Section 12.1, the dispute will be referred to a court of competent
jurisdiction in accordance with Section 13.16.
12.2    Technical Dispute Resolution.
In the event of a dispute (other than disputes in relation to the matters set
out in Sections 6.1(b) and 12.1) between the Parties that is exclusively related
to technical aspects of the manufacturing, quality control testing, handling,
storage or other activities under this Agreement (a “Technical Dispute”), the
Parties shall make all reasonable efforts to resolve the dispute by amicable
negotiations. In this regard, senior representatives of each Party shall, as
soon as practicable and in any event no later than ten (10) Business Days after
a written request from either Party to the other, confer in good faith to
resolve any Technical Dispute. If, despite such efforts, the Parties are unable
to resolve a Technical Dispute within a reasonable time, and in any event within
thirty (30) Business Days of such written request, the Technical Dispute shall,
at the request of either Party, be referred for determination to a mutually
acceptable expert with experience and expertise in the subject matter of the
dispute. The costs and expenses of the expert shall be shared equally by the
Parties. In the event that the Parties cannot agree whether a dispute is a
Technical Dispute, Section 12.1 shall prevail. For greater certainty, the
Parties agree that the release of the Products for sale or distribution pursuant
to the applicable marketing approval for such Products shall not by itself
indicate compliance by Patheon with its obligations in respect of the
Manufacturing Services and further that nothing in this Agreement shall remove
or limit the authority of the relevant qualified person (as specified by the
Quality Agreement) to determine whether the Products are to be released for sale
or distribution.
ARTICLE 13
MISCELLANEOUS
13.1    Inventions.
(a)
For the term of this Agreement, MDCO hereby grants to Patheon and to the
Subcontractor a non-exclusive, paid-up, royalty-free, non-transferable license
of MDCO’s Intellectual Property which Patheon and the Subcontractor must use
solely for the purpose of performing the Manufacturing Services.

(b)
All Intellectual Property generated or derived by Patheon and/or by the
Subcontractor in the course of performing the Manufacturing Services, to the
extent it is specific to the development, manufacture, use and sale of MDCO’s
Product that is the subject of the Manufacturing Services, shall be the
exclusive property of MDCO.

(c)
All Manufacturing Services Based Intellectual Property generated or derived by
Patheon and/or by the Subcontractor in the course of performing the
Manufacturing Services shall be the exclusive property of Patheon or of its
Subcontractor (as the case may be); Patheon hereby grants to MDCO and (if it is
the case) will cause the Subcontractor to grant, a perpetual, irrevocable,
non-exclusive, paid-up, royalty-free,

--------------------------------------------------------------------------------

transferable license of the Manufacturing Services Based Intellectual Property
used to manufacture the Product(s) which MDCO may use for the Manufacturing
Services and in connection with the offer for sale and for the sale of the
Product.
(d)
Each Party shall be solely responsible for the costs of filing, prosecution and
maintenance of patents and patent applications on its own Inventions.

(e)
Either Party shall give the other Party written notice, as promptly as
practicable, of all Inventions which can reasonably be deemed to constitute
improvements or other modifications of the Products or processes or technology
owned or otherwise controlled by such Party.

13.2    Intellectual Property.
Subject to Section 13.1, all Intellectual Property of MDCO shall be owned by
MDCO and all Intellectual Property of Patheon or its Affiliates shall be owned
by Patheon. Neither Party has, nor shall it acquire, any interest in any of the
other Party’s Intellectual Property unless otherwise expressly agreed to in
writing signed by an authorized representative of each Party. Each Party agrees
not to use any prior Intellectual Property of the other Party, except as
specifically authorized by the other Party or as required for the performance of
its obligations under this Agreement.
13.3    Insurance.
Each Party shall maintain commercial general liability insurance, including
blanket contractual liability insurance covering the obligations of that Party
under this Agreement through the term of this Agreement and for a period of 1
(one) year thereafter, which insurance shall afford limits of not less than (i)
€[**] for each occurrence for personal injury or property damage liability; and
(ii) €[**] in the aggregate per annum with respect to product and completed
operations liability. If requested each Party will provide the other with a
certificate of insurance evidencing the above and showing the name of the
issuing company, the policy number, the effective date, the expiration date and
the limits of liability. The insurance certificate shall further provide for a
minimum of thirty (30) days’ written notice to the insured of a cancellation of,
or material change in, the insurance. If a Party is unable to maintain the
insurance policies required under this Agreement through no fault on the part of
such Party, then such Party shall forthwith notify the other Party in writing
and the Parties shall in good faith negotiate appropriate amendments to the
insurance provision of this Agreement in order to provide adequate assurances.
13.4    Independent Contractors.
The Parties are independent contractors and this Agreement shall not be
construed to create between Patheon and MDCO any other relationship such as, by
way of example only, that of employer-employee, principal agent, joint-venturer,
co-partners or any similar relationship, the existence of which is expressly
denied by the Parties hereto.
13.5    No Waiver.
Either Party’s failure to require the other Party to comply with any provision
of this Agreement shall not be deemed a waiver of such provision or any other
provision of this Agreement, with the exception of Sections 6.1 and 8.2.
13.6    Assignment and Subcontracting.
(a)
Neither Party may assign this Agreement or any of its rights or obligations

--------------------------------------------------------------------------------

hereunder except with the written consent of the other Party, such consent not
to be unreasonably withheld. It is agreed upon between the Parties that Patheon
may arrange for the Manufacturing Services to be performed by the aforementioned
Subcontractor.
(b)
Notwithstanding the foregoing provisions of this Section 13.6, either Party may
assign this Agreement to any of its Affiliates or to a successor to or purchaser
of all or substantially all of its business, provided that such assignee
executes an agreement with the non-assigning Party hereto whereby it agrees to
be bound hereunder.

13.7    Force Majeure.
Neither Party shall be liable for the failure to perform its obligations under
this Agreement if such failure is occasioned by a cause or contingency beyond
such Party’s reasonable control, including, but not limited to, strikes or other
labour disturbances, lockouts, riots, quarantines, communicable disease
outbreaks, wars, acts of terrorism, fires, floods, storms, interruption of or
delay in transportation, defective equipment, lack of or inability to obtain
fuel, power or components or compliance with any order or regulation of any
government entity acting within colour of right (a “Force Majeure Event”). A
Party claiming a right to excused performance under this Section 13.7 shall
immediately notify that other Party in writing of the extent of its inability to
perform, which notice shall specify the occurrence beyond its reasonable control
that prevents such performance. Neither Party shall be entitled to rely on a
Force Majeure Event to relieve it from an obligation to pay money (including any
interest for delayed payment) which would otherwise be due and payable under
this Agreement.
13.8    Additional Product.
Additional products may be added to this Agreement and such additional products
shall be governed by the general conditions hereof with any special terms
(including, without limitation, price) governed by amendments to the Schedules
attached hereto as applicable.
13.9    Notices.
Any notice, approval, instruction or other written communication required or
permitted hereunder shall be sufficient if made or given to the other Party by
personal delivery, by facsimile (fax) communication, or confirmed receipt email
or by sending the same by first class mail, postage prepaid to the respective
addresses or facsimile (fax) numbers or electronic mail addresses set forth
below:
If to MDCO:
The Medicines Company
8 Sylvan Way
Parsippany, NJ 07054
Attention: Mr. Paul Antinori
Senior Vice President and General Counsel
Facsimile (fax) number: 862-207-6062
Email address: Paul.Antinori@themedco.com
If to MDCO (for accounting purposes):
The Medicines Company
8 Sylvan Way
Parsippany, NJ 07054
Attention: Mr. Bill O’Connor

--------------------------------------------------------------------------------

Chief Accounting Officer
Facsimile (fax) number: 862-207-6094
Email address: Bill.O’Connor@themedco.corn
If to Patheon International A.G:
Patheon International A.G
Lindenstrasse 14, 6340 Baar, (Switzerland)
Attention: General Counsel Europe
Facsimile (fax) number: +41 417104229
With a copy to Patheon Italia S.p.A:
Patheon Italia S.p.A
Viale G.B. Stucchin. 110
Monza, Italia
Attention: Department of Legal Services
Facsimile (fax) number: +39 039 2047219
or to such other addresses, facsimile numbers or electronic mail addresses
provided to the other Party in accordance with the terms of this Section 13.9.
Notices or written communications made or given by personal delivery, facsimile
or electronic mail shall be deemed to have been sufficiently made or given when
sent (receipt acknowledged), or if mailed, five (5) days after being deposited
in the European Union mail, postage prepaid or upon receipt, whichever is
sooner.
13.10    Severability.
If any provision of this Agreement is determined by a court of competent
jurisdiction to be invalid, illegal or unenforceable in any respect, such
determination shall not impair or affect the validity, legality or
enforceability of the remaining provisions hereof, and each provision is hereby
declared to be separate, severable and distinct. The Parties shall endeavor, in
due form, to replace the invalid or void provision with a new provision or to
fill the gap with a provision which best enables the economic purpose pursued to
be achieved.
13.11    Entire Agreement.
This Agreement, together with the Quality Agreement, constitutes the full,
complete, final and integrated agreement between the Parties hereto relating to
the subject matter hereof and supersedes all previous written or oral
negotiations, commitments, agreements, transactions or understandings with
respect to the subject matter hereof. Any modification, amendment or supplement
to this Agreement must be in writing and signed by authorized representatives of
both Parties. In case of conflict, the prevailing order of documents shall be
this Agreement and then the Quality Agreement except in matters pertaining to
product quality, GMP and regulatory responsibilities, in which case the Quality
Agreement will prevail. THE TERMS OF ANY PURCHASE ORDER, ACKNOWLEDGMENT OR
SIMILAR STANDARDIZED FORM GIVEN OR RECEIVED IN THE CONTEXT OF THE SUBJECT MATTER
OF THIS AGREEMENT WHICH ARE IN ADDITION TO OR INCONSISTENT WITH THE TERMS OF
THIS AGREEMENT WILL HAVE NO EFFECT AND SUCH TERMS AND CONDITIONS ARE HEREBY
EXPRESSLY EXCLUDED.
13.12    Other Terms.
No terms, provisions or conditions of any purchase order or other business form
or written authorization used by MDCO or Patheon will have any effect on the
rights, duties or obligations of the Parties under or otherwise modify this
Agreement, regardless of any failure of MDCO or Patheon to object to such terms,
provisions, or conditions unless such document specifically refers to this

--------------------------------------------------------------------------------

Agreement and is signed by both Parties.
13.13    No Third Party Benefit or Right.
For greater certainty, nothing in this Agreement shall confer or be construed as
conferring on any third party any benefit or the right to enforce any express or
implied term of this Agreement.
13.14    Execution in Counterparts.
This Agreement may be executed in two or more counterparts, by original or
facsimile signature, each of which shall be deemed an original, but all of which
together shall constitute one and the same instrument.
13.15    Use of MDCO Name.
Patheon shall not make any use of MDCO’s name, trademarks or logo or any
variations thereof, alone or in connection with any other word or words, without
the prior written consent of MDCO, which consent shall not be unreasonably
withheld.
13.16    Governing Law.
This Agreement shall be construed and enforced in accordance with the laws of
Delaware, USA and subject to the exclusive jurisdiction of the courts of
Delaware, USA. The UN Convention on Contracts for the International Sale of
Goods shall not apply to this Agreement.

--------------------------------------------------------------------------------

IN WITNESS WHEREOF, the duly authorized representatives of the Parties have
executed this Agreement as of the date first written above.
PATHEON INTERNATIONAL A.G.
by /s/ A.J. Kelley    12-05-11
by     
THE MEDICINES COMPANY
by /s/ Anthony Norman    May 20, 2011
by     

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SCHEDULE A

PRODUCT LIST
Product List
Angiomax® for injection(name in U.S., Canada and other markets)
10 ml vials containing 250 mg of lyophilized bivalirudin
Angiox® for injection (name in the EU, Russian and Swiss markets)
10 ml vials containing 250 mg of lyophilized bivalirudin

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SCHEDULE B

MINIMUM RUN QUANTITY, YEARLY BINDING VOLUME AND PRICE
A) MINIMUM RUN QUANTITY

PRODUCTS
MINIMUM RUN QUANTITY
Angiomax®/ Angiox®
2 Batches

B) LONG TERM FORECAST

PRODUCTS
2012
2013
2014
2015
2016
Angiomax®/ Angiox®
[**] vials
[**] vials
[**]vials
[**] vials
[**] vials

C) PRICE
Scenario 1 - Batch size: 30,000 vials (current filed)
Product
Fill
Volume
Vial Size
Lyo
cycle
Batch
size
proposed
Annual
Volume
Unit
Conversion Price(1)
Unit Total
Price (1)
Angiomax®/
Angiox®
5.5 ml
ext.Ø
~105 hours
30,000
vials
From 1 vial to 400k vials
[**] €/vial
[**] €/vial
23.75 mm
More than 400k vials
[**] €/vial
[**] €/vial

Scenario 2 – Batch sixe: 48,000 vials (maximum lyo capacity)
Product
Fill
Volume
Vial Size
Lyo
cycle
Batch
size
proposed
Annual
Volume
Unit
Conversion Price(1)
Unit Total
Price (1)
Angiomax®/
Angiox®
5.5 ml
ext.Ø
~105 hours
~48,000
vials
From 1 vial to 400k vials
[**] €/vial
[**] €/vial
23.75 mm
More than 400k vials
[**] €/vial
[**] €/vial

Notes:
(1) Conversion Pricing includes only the costs for manufacturing, Identification
(ID) testing of the API (ID), in-process testing and controls (IPC) and finished
Product release, according to the Specifications. Pricing assumes production on
a campaign basis (2 batches back to back). The total Price includes components
(stopper, vial, seal) and excipients. Based on offers from component suppliers,
Patheon estimates a component cost at [**] €/vial.
Component costs will be confirmed after confirmation that the Suppliers
recommended and selected

--------------------------------------------------------------------------------

by Patheon are acceptable to MDCO. The cost will be passed without any fee to
MDCO and evidence of the costs will be provided by Patheon to MDCO upon request.
Notes:
Should Patheon become responsible for full testing of API, then a fee of [**]
€/API batch will be applied. This responsibility does not include the management
of the supplier from a Quality perspective (audits etc).
For sake of clarity, the Total Unit Price does not include the costs of any
additional visual inspection of the Products for the Japanese’s market that it
will be charged to MDCO separately.
REGULATORY SUPPORT WORK
In accordance with Section 7.4 of the Agreement, the Regulatory works performed
by Patheon on behalf of MDCOs will be charged at €[**]/hr.
In addition to the above, the Annual Product Review (APR)/Product Quality Review
(PQR) work shall be charged at €[**]/hr.

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SCHEDULE C

STABILITY TESTING ACTIVITIES
Patheon and MDCO shall agree in writing on any stability testing to be performed
by Patheon in connection with the Products. Such agreement shall specify the
commercial and Product stability protocols applicable to the stability testing.
Charge per time point per storage condition is € [**].

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SCHEDULE D

ACTIVE MATERIALS
Active Materials
Supplier
Bivalirudin
Lonza

ACTIVE MATERIALS CREDIT VALUE
The Active Materials Credit Value shall be as follows:

PRODUCT
ACTIVE MATERIALS
ACTIVE MATERIALS CREDIT VALUE
Angiomax® / Angiox®
Bivalirudin
€ [**] per vial, if loss is to Product or in-process materials in vials
€ [**] per gram, if loss is directly to Active Materials or to in-process
production

MAXIMUM CREDIT VALUE
Patheon’s liability for Active Materials in accordance with Section 10.2 of the
Agreement will not exceed in any one year, in the aggregate, the maximum credit
value set forth below:

PRODUCT
MAXIMUM CREDIT VALUE
Angiomax® / Angiox®
[**]% of the annual conversion costs invoiced by Patheon and paid by MDCO for
the manufacture of Product. during the Year in which the API’s loss occurs.
Final calculation of the Maximum Credit Value will be made following the end of
the applicable Year.

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SCHEDULE E

BATCH NUMBERING
Each batch of the Product manufactured by Patheon will bear a unique lot number
using Patheon’s batch numbering system. This number will appear on all documents
relating to the particular batch of Product and shall identify the date of
manufacture for the batch of Product.

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SCHEDULE F
QUALITY AGREEMENT

Quality Agreement
Commercial Product
Between
THE MEDICINES COMPANY
8 Sylvan Way
Parsippany, NJ
a corporation existing under the laws of Delaware
(hereinafter referred to as “MDCO”)
-and-
PATHEON ITALIA S.P.A.
a corporation existing under the laws of ●,
Specific sites covered by this Agreement:
Monza facility, Viale G.B. Stucchi 110, 20900 Monza (MB), Italy,
(hereinafter referred to as “Patheon”)
Effective Date: ●

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SCHEDULE F
QUALITY AGREEMENT
TABLE OF CONTENTS
SECTION 1: PREMISES AND AGREEMENT 1
SECTION 2: RESPONSIBILITIES TABLE 2
SECTION 3: GENERAL 4
SECTION 4: DESCRIPTION OF RESPONSIBILITIES 5
SECTION 5: APPENDICES 15
APPENDIX A: PRODUCT(S)
APPENDIX B: QUALITY CONTACTS
APPENDIX C: PATHEON APPROVED VENDOR LIST
APPENDIX D: MDCO APPROVED VENDOR LIST
APPENDIX E: PATHEON APPROVED CONTRACT
LABORATORIES LIST

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SCHEDULE F
QUALITY AGREEMENT
SECTION 1: PREMISES AND AGREEMENT

--------------------------------------------------------------------------------

PREMISES. Under a manufacturing services agreement dated ● between Patheon and
MDCO (the “MSA”), Patheon agrees to perform pharmaceutical manufacturing
services (the “Manufacturing Services”) for certain Products (as described in
Appendix A hereto) and MDCO is required to give certain information to Patheon
in order for Patheon to perform the Manufacturing Services (the
“Specifications”). Under the MSA, Patheon is required to operate within the
Specifications.
The parties desire to assign and allocate the responsibility for procedures and
Specifications impacting on the identity, strength, quality and purity of the
Products.
In the event of any conflict between the terms of this Quality Agreement and the
MSA, the MSA shall take precedence except with respect to any specific quality
issue.
AGREEMENT. NOW THEREFORE in consideration of the Premises and rights conferred
and the obligations assumed under the MSA and herein, and for other good and
valuable consideration (the receipt and sufficiency of which are acknowledged by
each party), and intending to be legally bound, the parties agree as follows:
SCHEDULE F
QUALITY AGREEMENT
SECTION 2: RESPONSIBILITIES TABLE
Patheon will be responsible for all the operations that are marked with “X” in
the column titled “Patheon” and MDCO will be responsible for all the operations
that are marked with “X” in the column titled “MDCO”. If marked with “(X)”,
cooperation is required from the designated party.

Section No.
Subject/Terms
MDCO
Patheon
4.1 Quality Management
4/1/2001
GMP, Health and Safety Compliance
 
X
4/1/2002
MDCO Audit Rights
X
 
4/1/2003
Subcontracting
(X)
X
4/1/2004
Self-Inspection
 
X
4.2 Regulatory Requirements
4/2/2001
Licenses, Marketing Authorizations and Permits
X
X
4/2/2002
Regulatory Filing / Registration Change Control
X
(X)
4/2/2003
Regulatory Compliance
 
X
4/2/2004
Government Agency Inspections, Communications and Requisitions
(X)
X
4.3 Material Control
4/3/2001
Test Methods and Specifications
X
 
4/3/2002
Material Destruction
(X)
X
4/3/2003
Vendor Audit Responsibility
X
X
4/3/2004
Material Certifications
X
X
4/3/2005
Incoming Material Release
 
X
4.4 Building, Facilities, Utilities and Equipment
4/4/2001
General
 
X
4/4/2002
Equipment, Calibration and Preventative Maintenance
 
X
4/4/2003
Environmental Monitoring Program
 
X
4.5 Product Controls
4/5/2001
Master Batch Record
(X)
X
4/5/2002
Reprocessing and Rework
N/A
N/A
4/5/2003
Personnel Training
 
X
4.7 Exception Reports (Deviations / Investigations)
4/7/2001
Manufacturing Instruction Deviations
(X)
X
4/7/2002
Packaging Instructions Deviations
(X)
X
4/7/2003
Notification of Deviations
 
X

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Section No.
Subject /Terms
MDCO
Patheon
4.8 Release of Product
4/8/2001
Test Methods and Specifications
X
X
4/8/2002
Batch Release for Shipment
 
X
4/8/2003
Certificate of Analysis & Certificate of Compliance
 
X
4/8/2004
Product Release
X
 
4.9 Validation
4/9/2001
Master Validation Plan
(X)
X
4/9/2002
Cleaning & Cleaning Validation Program
(X)
X
4/9/2003
Analytical Method and Procedure Validation
X
 
4.10 Change Control
4.10.1
General
X
X
4.11 Documentation
4.11.1
Record Retention
 
X
4.11.2
Batch Document Requisition
 
X
4.12 Laboratory Controls
4.12.1
Specifications and Test Methods
X
X
4.12.2
Out of Specifications (OOS)
 
X
4.12.3
Supply of Reference Standards
X
 
4.13 Stability
 
 
4.13.1
Sample Storage
 
X
4.13.2
Stability Studies and Protocol
X
X
4.13.3
Stability Failures
(X)
X
4.13.4
Termination of MSA
 
X
4.14 Annual Product Review & Product Quality Review
4.14.1
General
 
(X)
4.15 Storage and Distribution
 
 
4.15.1
General
(X)
X
4.15.2
Product Storage and Shipment Changes
X
(X)
4.15.3
Product Quarantine
 
X
4.15.4
Shipment and Distribution
X
(X)
4.16 Product Complaints
4.16.1
Complaint Investigation
X
(X)
4.17 Product Recall
4.17.1
Product Recall Notification
X
(X)
4.17.2
Government Agency Notification
X
X
4.18 Reference and Retention Samples
4.18J
Excipient, Active Pharmaceutical Ingredient, and Product Reference Sample
 
X
4.18.2
API and Product Retention Sample
X
 

SCHEDULE F
QUALITY AGREEMENT
SECTION 3: GENERAL

3.1
Any communications about the subject matter of this Agreement will be directed,
in the first instance, to the person(s) identified in Appendix B.

3.2
Capitalized terms not otherwise defined herein will have the meaning specified
in the MSA.

3.3
If any provision of this Agreement should be or found invalid, or unenforceable
by law, the rest of the Agreement will remain valid and binding and the parties
will negotiate a valid provision which meets as close as possible the objective
of the invalid provision.

3.4
If this Agreement requires modification to comply with regulatory or legal
requirements, such that either party affected cannot be reasonably expected to
continue to perform under this Agreement, then the parties will negotiate and
revise the Agreement accordingly

3.5
Any amendment of this Agreement will be made in writing and signed by both
parties.

3.6
This Agreement will start on the Effective Date that is set forth on the cover
page of this Agreement and will remain in force until the latest of: (i) the
expiration date of the last batch of Product produced by Patheon for commercial
distribution; (ii) completion of any ongoing stability studies; (iii) two years
after the termination of the last effective MSA; or (iv) all Quality obligations
under all applicable MSA’s have been fulfilled.

3.7
Despite the termination of this Quality Agreement all regulatory obligations
contained herein that are required of either Party or both Parties by an
applicable regulatory authority or agency shall survive termination of this
Quality Agreement.

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SCHEDULE F
QUALITY AGREEMENT
SECTION 4: DESCRIPTION OF RESPONSIBILITIES
4.1
Quality Management

4.1.1
GMP, Health and Safety Compliance

Patheon will conduct operations in compliance with applicable environmental,
occupational health and safety laws, and cGMP regulations.
4.1.2
MDCO Audit Rights

Patheon will provide MDCO with reasonable access at mutually agreeable times and
during regular business hours to the areas of the Manufacturing Site in which
the Products are manufactured, stored, handled or shipped to permit MDCO to
verify that the Manufacturing Services are being performed in accordance with
the Manufacturing Requirements. But, with the exception of “for-cause” audits,
MDCO will be limited each Year to one cGMP-type audit, lasting no more than two
(2) days, and involving no more than four (4) auditors.
4.1.3
Subcontracting

Patheon will not subcontract any tasks or services to a third party without
MDCO’s consent.
4.1.4
Self-Inspection

Patheon will perform self-inspections of its premises, facilities, and processes
used to manufacture, package, test, and store MDCO’s starting, intermediate,
and/or finished products in accordance with Patheon’s written standard operating
procedures (“SOP’s”) to ensure compliance with cGMP and this Quality Agreement.
4.2
Regulatory Requirements

4.2.1
Licenses, Marketing Authorizations and Permits

MDCO will be solely responsible for obtaining and/or maintaining, on a timely
basis, any permits or other regulatory approvals for the Products or the
Specifications, including, without limitation, all marketing and post-marketing
approvals.
Patheon will obtain and maintain the appropriate manufacturing license(s) to
allow for the Manufacturing services.
MDCO shall provide Patheon with a copy of the draft CMC section, as well as, all
supporting documents which have been relied upon to prepare the CMC section at
least twenty-one (21) days prior to filing any Marketing Authorization, such as
a New Drug Application or Abbreviated New Drug Application with any Regulatory
Authority.
Patheon will verify that the CMC section accurately describes the manufacturing
processes that Patheon will perform.
Patheon and MDCO shall work together to resolve any deficiencies in the
documentation

--------------------------------------------------------------------------------

prior to submission to any regulatory agency.
MDCO shall provide Patheon with final copies of all CMC filings at the time of
submission.
If MDCO does not provide Patheon with the documents requested within the time
stipulated and if Patheon reasonably believes that Patheon’s standing with a
regulatory authority may be jeopardized, Patheon may, in its sole discretion,
delay or postpone any inspection by the regulatory authority until such time as
Patheon has reviewed the requested documents and is satisfied with their
contents.
4.2.2
Regulatory Filing / Registration Change Control

MDCO will determine whether changes to the Product or related to the Product
will impact a regulatory filing and will apply for and receive approval for any
required manufacturing amendment, change or addition to their Product marketing
authorization. Upon request, Patheon will provide assistance in the preparation
of pertinent sections of new or supplemental regulatory applications before
filing. Patheon will also have the right to review the new or supplemental
sections that apply to Patheon’s areas of responsibility before filing. MDCO
will provide Patheon copies of sections of product registration/regulatory
submissions that are relevant to the manufacture of the Product. MDCO is
responsible for all communications with Regulatory Authorities as well as for
the approval, maintenance, and updating of marketing approval in a timely
manner.
4.2.3
Regulatory Compliance

Patheon will ensure that Product(s) are manufactured and tested in strict
compliance with current US Federal and EC regulatory and statutory requirements
relating to Good Manufacturing Practices (GMP) (US 21 CFR parts 210 and 211 and
EU Directive 2003/94/EC for the manufacture of finished medicinal product) as
applicable, regulatory approvals and local laws and regulations applicable at
the site(s) of manufacture and/or testing.
4.2.4
Government Agency Inspections, Communication and Requisitions

Patheon will permit all relevant inspections by regulatory authorities of
premises, procedures, and documentation.
Patheon will notify MDCO within one (1) Business Day of receipt of any notice of
inspection from a regulatory authority and within one (1) Business Day of any
regulatory authority request for Product samples, batch documentation, or other
information related to the Product.
Patheon will notify MDCO within one (1) Business Day of receipt of any Form
483’s warning letter or the like from any regulatory agency that relates to the
Product; or if the supply of Product will be affected, or if the facilities used
to produce, test or package the Product will be affected.
The responses from Patheon related to the Product will be reviewed and approved
by MDCO prior to submission to the regulatory agency. Notwithstanding, Patheon
reserves the right to respond to the regulatory agency without approval, if, in
the reasonable opinion of Patheon’s Legal counsel, it is required to do so.

--------------------------------------------------------------------------------

4.3
Material Control

4.3.1
Test Methods and Specifications

MDCO will provide Patheon with a copy of the Specifications and test methods
used for Active Pharmaceutical Ingredients and Materials if MDCO issues raw
material Specifications.
4.3.2
Destruction of Active Pharmaceutical Ingredient or Product

Patheon has the right to either return to MDCO or dispose of any outdated or
rejected Active Pharmaceutical Ingredients or Product. If the Active
Pharmaceutical Ingredient or Product is disposed of, disposal will be consistent
with the nature of the Active Pharmaceutical Ingredient or Product and will be
sent to a permitted waste disposal facility.
Prior to such disposal Patheon will send notice to MDCO about Patheon’s intent
to dispose of the Active Pharmaceutical Ingredient or Product. If no direction
is received from MDCO, Patheon will dispose of the Active Pharmaceutical
Ingredient or Product no sooner than ninety (90) days after the date of the
notice.
The Active Pharmaceutical Ingredient or Product will be disposed and destroyed
in compliance with local environmental regulations and performed in a secure and
legal manner that prevents unauthorized use or diversion.
Upon completion of destruction of Active Pharmaceutical Ingredient or Product,
Patheon will provide to MDCO a Certificate of Destruction issued by Patheon or
by the licensed third party that destroyed the Active Materials or bulk Product.
Patheon will maintain destruction records in accordance with Patheon SOP’s.
4.3.3
Vendor Audit Responsibility

4.3.3.1
Excipient, Component and API Vendors:

(i.)
MDCO is responsible for the API vendor. MDCO will approve the API manufacturer/s
and will inform Patheon about the approval status. MDCO will be also responsible
for providing PATHEON with a proof of API manufacturer/s compliance with EU GMP
Part II and will ensure the API cGMP compliance in accordance with Section 4.3.4
of this Agreement. The MDCO stipulated vendor(s) will be included on MDCO’s
approved vendor list (attached hereto as Appendix D).

(ii.)
PATHEON is responsible for Components and excipient vendors. PATHEON will be
responsible for approving the manufacturers and for ensuring their cGMP
compliance in accordance with Patheon SOP. The PATHEON stipulated vendor(s) will
be included on PATHEON’s approved vendor list (attached hereto as Appendix C).

4.3.4
Material Certifications

MDCO and PATHEON are each responsible for providing a certificate of compliance
for each of its respective vendors confirming the following:
(i.)
That the materials are compliant with the provisions outlined in the “Note for
Guidance on minimizing the risk of transmitting spongiform encephalopathy agents

--------------------------------------------------------------------------------

via human and veterinary medicinal products” (EMEA/410/01, Rev.2 or update) and
(ii.)
A residual solvent certificate confirming that there is no potential for
specific toxic solvents listed in the EP / USP / ICH residual solvents Class I,
Class II or Class III to be present and the material, if tested, will comply
with established EP / USP / ICH requirements. If any of the solvents listed in
the EP / USP / ICH residual solvents Class I, Class II or Class III are used in
the manufacture or are generated in the manufacturing process, solvents of
concern will be indicated.

4.3.5
Incoming Material Release

Prior to its use in the manufacture of any Product all Material(s) will be
inspected, tested and released by Patheon against the Specification approved by
MDCO. Patheon will perform only an Assay and Identification test on the Active
Pharmaceutical Ingredient.
4.4
Building, Facilities, Utilities and Equipment

4.4.1
General

All buildings and facilities used in the manufacturing, packaging, testing and
storage of any materials and/or Product will be of suitable size, construction
and location to facilitate cleaning, and will be maintained in a good state of
repair. Maintenance and cleaning records will be kept in accordance with
Patheon’s SOP’s.
4.4.2
Equipment, Calibration and Preventative Maintenance

All equipment used in the manufacturing, packaging, testing and storage of any
materials and/or Product will be suitable for its intended use and appropriately
located to allow for cleaning and maintenance. Calibration and maintenance
records will be kept according to Patheon SOP’s for all critical equipment.
Patheon will calibrate instrumentation and qualify computer systems used in the
manufacture and testing of the Product in accordance with Patheon’s SOP’s.
4.4.3
Environmental Monitoring Program

Patheon will perform and maintain an environmental monitoring program. The
collected data will be reviewed and interpreted by the responsible person within
Patheon’s quality unit. Any out of limit results will be managed appropriately
in accordance with Patheon SOP’s.
4.5
Production Controls

4.5.1
Master Batch Record

MDCO will provide the Specifications to Patheon and Patheon will manufacture
Product in accordance with the Specifications.
Patheon is responsible for preparing the master batch records for the Product,
however, MDCO is responsible to review and approve such master batch records
prior to the manufacture of the Product.
Patheon will not make changes to master batch records except through the
established Patheon change control system, and all master document revisions
will be provided in Italian and English and will be approved by MDCO’s quality
unit All proposed changes to the

--------------------------------------------------------------------------------

master batch records will be provided by Patheon in the change control, which
will be issued in English.
4.5.2
Reprocessing and Rework

Reprocessing and Rework is not permitted for Product(s) covered in this Quality
Agreement or the associated MSA.
4.5.3
Personnel Training

Patheon will provide appropriate training for all employees. Each person engaged
in the manufacture, packaging, testing, storage, and shipping of the Product
will have the education, training, and experience necessary, consistent with
current GMP and safety training requirements.
4.6
Exception Reports (Deviations / Investigations)

4.6.1
Manufacturing Instruction Deviations

Patheon will document, investigate and resolve deviations from approved
manufacturing instructions or Specifications in accordance with Patheon’s SOP’s.
Patheon will report and obtain approval from MDCO’s responsible person for all
deviations to its Product. Such MDCO approval will not be unreasonably withheld.
Patheon will provide MDCO with a list of the deviations in the Certificate of
Compliance.
4.6.2
Primary Packaging Instructions Deviations

Patheon will document, investigate, and resolve any deviation from approved
primary packaging instructions or Specifications according to Patheon SOP’s.
Patheon will report and obtain approval from MDCO’s responsible person for all
deviations to its Product. Such MDCO approval will not be unreasonably withheld.
Patheon will provide copies of all deviation reports to MDCO as part of the
executed batch packaging record.
4.7.3    Notification of Deviations
Patheon will notify MDCO within one (1) Business Day if any deviation occurs
during manufacture of the Product, where such deviation may affect the quality,
efficacy or availability of the Product.
4.1
Release of Product

4.1.5
Test Methods and Specifications

MDCO will provide to Patheon the in-process and finished Product Specifications
and will develop and supply validated analytical test methods to Patheon for
these methods.
4.1.6
Batch Release for Shipment

Batch review and release for shipment to MDCO will be the responsibility of
Patheon’s Quality Assurance department who will act in accordance with Patheon’s
SOP’s.
4.1.7
Certificate of Analysis & Certificate of Compliance

For each batch released by Patheon for shipment to MDCO, Patheon will deliver to
MDCO

--------------------------------------------------------------------------------

a copy of the batch record (with attachments) in Italian in electronic (pdf)
format; and, a Certificate of Analysis detailing the results of final product
testing against the test specifications. Patheon will also provide a Certificate
of Compliance that will include a statement that the batch has been manufactured
in accordance with cGMPs and the Specifications. The Certificate of Analysis and
the Certificate of Compliance will be provided in English.
4.1.8
Product Release to Market

MDCO will have sole responsibility for release of the Product to the market.
4.2
Validation

4.2.5
Master Validation Plan

Patheon will establish applicable master validation plans and maintain a
validation program for the Product. MDCO will review and approve the,
performance qualification and process validation protocols and reports relevant
to the introduction of Product in the facility.
4.2.6
Cleaning & Cleaning Validation Programs

MDCO will provide to Patheon toxicological information to be used in the
development of a cleaning program. Patheon will maintain an appropriate cleaning
program and cleaning validation program.
4.2.7
4.9.3 Analytical Method and Procedure Validation

MDCO must ensure that its analytical methods and manufacturing procedures are
validated. If the methods and procedures are not validated by MDCO, then Patheon
may assist in validation development with the costs being borne by MDCO.
4.3
CHANGE CONTROL

4.3.6
General

Patheon will notify and obtain approval from MDCO before implementing any
proposed changes to the Specifications, process, Active Materials, Materials,
testing, that are involved in the manufacture of the Product. This MDCO approval
will not be unreasonably withheld.
MDCO will be responsible for determining whether or not to initiate registration
variation procedures and for maintaining adequate control over the quality
commitments of the marketing authorization made to the regulatory authorities by
MDCO for the Products.
Following validation of a process change, Patheon will deliver a copy of the
related validation report to MDCO and the associated stability data, if
applicable, as it becomes available.
4.4
Documentation

4.4.4
Record Retention

Patheon wilt maintain all batch records for a minimum of one (1) year past
Product expiry date and will supply all these records to MDCO upon request.
Patheon will maintain records and evidence on the testing of raw materials for
five (5) years

--------------------------------------------------------------------------------

after the materials were last used in the manufacture of the Product.
At the end of the above noted retention period, MDCO will be contacted
concerning the future storage or destruction of the documents.
4.5
Laboratory Controls

4.5.4
Specifications and Test Methods

Patheon will test and approve starting material, in-process materials, and the
Product in accordance with the approved Specifications, analytical methods, and
Patheon’s SOP’s.
MDCO will provide Patheon with the API Specifications including the
manufacturer’s Certificate of Analysis. Patheon will be responsible for
performing only an assay and ID testing on the API.
MDCO will provide Patheon with test methods for API and excipients (if
non-compendial). Patheon is responsible for validating non-compendial testing
methods.
4.5.5
Out of Specifications (OOS)

Patheon will manage OOS in accordance with Patheon in-house SOP. Patheon will
generate a deviation report as per Patheon SOP’s.
4.5.6
Supply of Reference Standards

MDCO will provide Patheon with the API Reference Standards.
4.6
Stability

4.6.3
Sample Storage

Patheon will store stability samples as required.
4.6.4
Stability Studies and Protocol

MDCO will develop and validate stability indicating assay(s) prior to process
validation. If required, Patheon may assist, with the cost being borne by MDCO.
Patheon will conduct stability studies in accordance with the agreed and
validated stability testing analytical methods at the agreed upon testing points
in accordance with the approved stability protocol.
Patheon will perform the stability testing described in accordance with the
stability protocol developed by MDCO. Stability data will be provided by Patheon
to MDCO on an ongoing basis as agreed to by both parties.
4.6.5
Stability Failures

Stability failures will be managed in accordance with Patheon OOS SOP. If a
result indicates that a Product has failed to remain within stability
Specifications, Patheon will notify MDCO within one (1) Business Day.
Patheon shall promptly prepare a deviation report for any and all stability
failures generated

--------------------------------------------------------------------------------

during follow-up studies that will be reviewed and approved by both Patheon and
MDCO.
4.6.6
Termination of MSA

If the MSA is terminated, Patheon will continue to provide MDCO with stability
data supporting the acceptability of the Product until all Product distributed
by MDCO has reached the end of its shelf-life.
4.7
Annual Product Review & Product Quality Review

Patheon shall prepare an Annual Product Review (APR)/Product Quality Review
(PQR) for the Products covering the activities executed during the review period
January 1 through December 31. The report shall be prepared according to cGMP
and it shall be in English. Patheon shall provide a copy of the APR/PQR to MDCO
within 60 days of the review period.
4.8
Storage and Distribution

4.8.1
General

Patheon will ship Product in accordance with the agreed qualified transportation
requirements provided by MDCO to Patheon.
4.8.2
Product Storage and Shipment Changes

Each Party will inform the other Party about any proposed changes in storage and
shipping conditions.
4.8.3
Product Quarantine

Patheon will have a system in place for assuring that Product is not shipped
unless authorized by MDCO’s quality unit.
4.8.4
Shipment and Distribution

MDCO will be responsible for shipping and distribution of the Product.
4.9
Product Complaints

4.9.1
Complaint Investigation

MDCO will investigate and resolve all medical and non-medical Product
complaints.
MDCO shall inform Patheon within 5 business days, or sooner as required, of
complaints involving potential Product issues that may be related to
Manufacturing.
Patheon will investigate all Patheon manufacturing and packaging type Product
complaints related to the Manufacturing Services provided and will provide a
written report within 30 days, or sooner if mutually agreed and/or if required
to meet regulatory reporting requirements.
MDCO will retrieve complaint sample(s) and forward them to Patheon in a timely
manner to facilitate a complete and comprehensive investigation.
MDCO will inform Patheon if the sample is not available.

--------------------------------------------------------------------------------

MDCO shall maintain a record of all complaints, and notify health authorities
and/or regulatory agencies as required.
4.10
Product Recall

4.10.1
Product Recall Notification

MDCO will notify Patheon about a Product recall or other regulatory type product
notification (e.g. field alert) as soon as possible. MDCO will be responsible
for all related field alert and/or recall activities.
Patheon and MDCO shall each maintain such records as may be necessary to permit
a Recall of any Products delivered to MDCO or customers of MDCO. Each Party
shall promptly notify the other by telephone (to be confirmed in writing) of any
information that might affect the marketability, safety or effectiveness of the
Products and/or which might result in the Recall or seizure of the Products.
Upon receiving any such notice or upon any such discover, each Party shall cease
and desist from further shipments of such Products in its possession or control
until a decision has been made whether a Recall or some other corrective action
is necessary. The decision to initiate a Recall or to take some other corrective
action, if any, shall be made and implemented by MDCO.
MDCO shall have the responsibility for handling customer returns of the
Products. Patheon shall provide MDCO with such assistance as MDCO may reasonably
require to handle such returns.
4.10.2
Government Agency Notification

MDCO will perform the Product recall and will inform the appropriate regulatory
authorities. Where required by legislation and/or regulation, Patheon reserves
the right to notify regulatory authorities of Product quality issues. Patheon
will inform MDCO prior to any notification to the regulatory authorities.
4.11
Reference and retention Samples

4.11.1
Excipient, Active Pharmaceutical Ingredient, and Product Reference Samples

Patheon will keep a reference sample of each excipient, and Active
Pharmaceutical Ingredient received by Patheon and used to manufacture the
Product. The reference sample will consist of at least two (2) times the
quantity required for all Quality Control tests required to determine whether
the materials meet required Specifications.
Patheon will store the reference samples under controlled conditions in
accordance with GMP storage requirements for one (1) year beyond the expiration
date of the last batch of the product containing the materials. The reference
samples will be made available by Patheon to MDCO, if requested.
Patheon will retain retention samples of finished Product under controlled
conditions in accordance with GMP storage requirements for one (1) year past
Product expiry or such longer period as required by taw. Each retention sample
will consist of at least two (2) times the quantity required for all Quality
Control tests required to determine whether the materials meet required
Specifications plus one (1) times the quantity required for sterility testing.
4.11.2
Active Pharmaceutical Ingredient and Product Retention Sample

MDCO will retain samples of API and Product at MDCO approved storage facility.
Each

--------------------------------------------------------------------------------

retention sample will consist of at least (2) times the quantity required for
all Quality Control tests required to determine whether the materials meet
required Specifications plus (1) times the quantity required for sterility
testing.
* * *
IN WITNESS WHEREOF, the parties have caused their duly authorized officer to
execute and deliver this Quality Agreement as of the Effective Date identified
on the first page:
The Medicines Company
 
By:     (Signature)    
(insert Name/Title)
Date:            
By:     (Signature)    
(Insert Name/Title)
Date:            
PATHEON ITALIA S.P.A.
Date:            
By:     (Signature)    
Maria Di Cillo (QA/QC-QP)

 

--------------------------------------------------------------------------------

SCHEDULE F
QUALITY AGREEMENT
SECTION 5: APPENDICES
•
Appendix A: Product(s)

•
Appendix B: Quality Contacts

•
Appendix C: Patheon Approved Supplier List

•
Appendix D: MDCO Approved Supplier List

•
Appendix E: Patheon Approved Contract Laboratories List

APPENDIX A: PRODUCTS
Products (s)
Galenic Form
Dosage (Strength)
Bivalirudin (Angiomax & Angiox
lyophilized
250mg/mL

--------------------------------------------------------------------------------

APPENDIX B: QUALITY CONTACTS

 
Patheon
MDCO
Responsibility
Quality Assurance
Quality Assurance
Name
Maria Di Cillo
Batsheva Bain
Title
QA/QC Manager-QP
Director, Supplier Quality and Regulatory Compliance
Phone
390,292,047,509
973-290-6326
Fax
390,292,047,314
862-207-6326
E-mail
maria.dicillo(3)pa theon.com
Batsheva.bain@themedco.com
Address
Viale G.B. Stucchi, 110 20900 Monza (MB)
The Medicines Company
8 Sylvan Way
Parsippany, NJ 07054
Responsibility
Regulatory Affairs
Regulatory Affairs
Name
Isabella Scrocchi
Batsheva Bain
Title
Regulatory Affairs Manager
Director, Supplier Quality and Regulatory Compliance
Phone
390,292,047,270
973-290-6326
Fax
390,292,047,314
862-207-6326
E-mail
isabella.scrocchi@patheon.com
Batsheva.bain@themedco.com
Address
Viale G.B. Stucchi, 110 20900 Monza (MB)
The Medicines Company
8 Sylvan Way
Parsippany, NJ 07054
Responsibility
Product Complaints
Product Complaints
Name
Francesco Boschi
Jamal Brown
Title
Complaints & Self audits
Director, Quality
Phone
390,292,047,271
973-290-6145
Fax
390,292,047,314
862-207-6145
E-mail
francesco.boschi@patheon.
Jamal.brown@themedco.com
com
 
Address
Viale G.B. Stucchi, 110 20900 Monza (MB)
The Medicines Company
8 Sylvan Way
Parsippany, NJ 07054

--------------------------------------------------------------------------------

Responsibility
Product Release
Product Release
Name
Maria Di Cillo
Batsheva Bain
Title
QA/QC Manager-QP
Director, Supplier Quality and
Regulatory Compliance
Phone
390,292,047,509
973-290-6326
Fax
390,292,047,314
862-207-6326
E-mail
maria.dicillo@patheon.com
Batsheva.bain@themedco.com
Address
Viale G.B. Stucchi, 110
20900 Monza (MB)
The Medicines Company
8 Sylvan Way
Parsippany, NJ 07054
Responsibility
Account Manager
Business Manager
Name
Andrea Como
Angie Green
Title
Technical Business
Manager
Vice President, Manufacturing
Outsourcing Operations
Phone
0039.039.2047.433
973-290-6042
Fax
 
862-207-6042
E-mail
andrea.como@patheon.com
Angie.green@themedco.com
Address
Viale G.B. Stucchi, 110
20900 Monza (MB)
The Medicines Company
8 Sylvan Way
Parsippany, NJ 07054

*Deputy QPs can be responsible for Product Release, in accordance with PATHEON
SOP

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APPENDIX C: PATHEON APPROVED VENDOR LIST
Sodium hydroxide
Supplier: [**]
Mannitol
Supplier: [**]

--------------------------------------------------------------------------------

APPENDIX D: MDCO APPROVED VENDOR LIST
Lonza Braine SA
Chaussée de Tubize 297
BE – 1420 Braine – L’Alleud

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APPENDIX E: PATHEON APPROVED CONTRACT LABORATORIES LIST

Eurofins Biolab S.r.l.
Via B. Buozzi, 2
20090 Vimodrone (MI), Italy

SCHEDULE G
QUALITY AGREEMENT

TERRITORY
All member states of the European Economic Area (EEA), the United States of
America and:
Argentina
Israel
Australia
New Zealand
Brazil
Peru
Canada
Russia
Chile
Switzerland
China
Turkey
India
Venezuela