EXHIBIT 10.40


 


AMENDED AND RESTATED


MANUFACTURING AND PACKAGING AGREEMENT


 


This Manufacturing and Packaging Agreement (“Agreement”)
is made this    day of March, 2007 by and between Cardinal Health
PTS, LLC, having a place of business at 2725 Scherer Drive, St Petersburg,
Florida 33716 (“Cardinal Health”) and Reliant Pharmaceuticals, Inc. (“Reliant”),
having its principal place of business at 110 Allen Road, Liberty Corner, New
Jersey 07938. (Cardinal Health and Reliant are each a “Party” and shall
collectively be referred to herein as the “Parties.”)


 


BACKGROUND


 


A.            Cardinal
Health provides contract pharmaceutical development, manufacturing, packaging,
analytical, and sales and marketing services to the pharmaceutical industry.


 


B.            Reliant
has rights to market certain pharmaceutical products and wants Cardinal Health
to assist in the formulation, filling, packaging and testing of such products
as provided in this Agreement and the attachments hereto.


 


C.            In
April 2005, Cardinal Health and Reliant entered into that certain
Manufacturing and Packaging Agreement under which Reliant engaged Cardinal
Health to provide certain services to Reliant in connection with the processing
of the Product (defined below) (the “Initial
Agreement”) on a non-exclusive basis.


 


D.            The
Parties wish to amend and restate the Initial Agreement as set forth below.


 


E.             THEREFORE,
in consideration of the mutual conditions and covenants set forth herein, the
Parties hereby agree as follows:


 


ARTICLE 1


DEFINITIONS


 


The
following terms have the following meanings in this Agreement:


 


1.1                                 “Affiliate(s)” means any corporation,
firm, partnership or other entity that controls, is controlled by or is under
common control with a Party. For purposes of this definition, “control” shall
mean the ownership of at least fifty percent (50%) of the voting share capital
of such entity or any other comparable equity or ownership interest.


 


1.2                                 “API” means the active pharmaceutical
ingredient described in the Manufacturing Specifications, which have been
released by Reliant and provided to Cardinal Health as raw material, along with
a certificate of analysis, as provided in this Agreement.


 


1.3                                 “API
Cap” shall have the meaning set forth in Section 15.1.


 

















 


1.4                                 “Applicable Laws” means all laws,
ordinances, rules and regulations within the Territory applicable to the
Manufacturing and Packaging of the Product or any aspect thereof and the
obligations of Cardinal Health or Reliant, as the context requires under this
Agreement, including, without limitation, (A) all applicable federal,
state and local laws and regulations of each Territory; (B) the U.S.
Federal Food, Drug and Cosmetic Act, and (C) the current Good
Manufacturing Practices promulgated by the Regulatory Authorities, as amended
from time to time (“cGMPs”).


 


1.5                                 “Batch” means defined quantity of
finished drug product that has been or is being Manufactured and Packaged in
accordance with the Specifications.


 


1.6                                 “Calendar Quarter” means a period of
three (3) consecutive months commencing on January 1, April 1, July 1
or October 1 of any calendar year.


 


1.7                                 “Cardinal Health Technology” shall have
the meaning set forth in Article 12.


 


1.8                                 “Change Order” shall have the meaning
set forth in Section 4.5(A).


 


1.9                                 “Confidential Information” shall have
the meaning set forth in Section 11.2.


 


1.10                           “Contract Year” means each consecutive
twelve (12) month period beginning on January 1, 2007.


 


1.11                           “Defective Product” shall have the
meaning set forth in Section 5.2.


 


1.12                           “Delivery
Date” shall mean the date on which Cardinal Health tenders the relevant
Batch(es) to the carrier in accordance with Section 6.1. Each Delivery
Date shall be specified by Reliant on the relevant Purchase Order and confirmed
by Cardinal Health as set forth in Section 4.4.


 


1.13                           “Dispute” shall have the meaning set
forth in Section 19.9.


 


1.14                           “Effective Date” means January 1,
2007.


 


1.15                           “Facility
or Facilities” means Cardinal
Health’s facilities located in St. Petersburg, Florida or such other facility
as agreed by the Parties.


 


1.16                           “FDA” means the United States Food and
Drug Administration and any successor agency thereto.


 


1.17                           “Firm Commitment” shall have the
meaning set forth in Section 4.3.


 


1.18                           “Manufacture”
or “Manufacturing” means the compounding, filling, encapsulation, producing
and/or inspection of the API and Raw Materials into Product in accordance with
the Specifications and the terms and conditions set forth in this Agreement.


 

















 


1.19                           “Manufacturing Date” means the day on which the
Product is to be compounded by Cardinal Health, which shall not be more than
forty-five (45) days prior to the Delivery Date.


 


1.20                           “Manufacturing
Related Reference Documents” means (a) all completed production/Batch
records; (b) all quality control test/request forms (result worksheets)
and associated data; (c) dynamic monitoring performed during processing; (d) any
alert/action notifications generated during processing; (e) any planned or
unplanned deviations associated with the Product; (f) any out of
Specification result investigations associated with the Product; (g) the
Certificate of Analysis for the Batch comparing testing to Specifications; (h) the
appropriate disposition notification for the Batch, and (i) a Yield
statement.


 


1.21                           “Manufacturing
Sample” shall have the meaning set forth in Section 5.1.


 


1.22                           “Minimum
Requirement” shall have the meaning set forth in Section 4.1.


 


1.23                           “Package”
or “Packaging” means the labeling and the packaging of the Product onto the
bulk product packaging in accordance with the Specifications and the terms and
conditions of this Agreement.


 


1.24                           “Product” means Omacor® as fully
compounded API Manufactured and Packaged in accordance with the Specifications,
including both Sample Product and Trade Product.


 


1.25                           “Product
Maintenance Fee” shall have the meaning set forth in Section 7.2.


 


1.26                           “Product
Maintenance Services” shall have the meaning set forth in Section 2.3.


 


1.27                           “Purchase Order” shall have the meaning
set forth in Section 4.4.


 


1.28                           “Raw Materials” means all raw
materials, supplies, components and packaging, not including API, necessary to
Manufacture, Package and ship the Product in accordance with the
Specifications.


 


1.29                           “Regulatory Authority” means any
governmental regulatory authority within a Territory involved in regulating any
aspect of the development, manufacture, market approval, sale, distribution,
packaging or use of the Product.


 


1.30                           “Reliant Technology” shall have the
meaning set forth in Article 12.


 


1.31                           “Review Period” shall have the meaning
set forth in Section 5.1.


 


1.32                           “Rolling Forecast” shall have the
meaning set forth in Section 4.3.


 


1.33                           “Sample Product” shall mean Product
supplied to physicians and other permitted recipients without charge in
accordance with all Applicable Laws.


 


1.34                           “Softgel
Technology” means Cardinal Health’s proprietary technology for the manufacture
of softgels for the oral administration of pharmaceutical active ingredients
having 


 

















 


certain solubility
characteristics and includes proprietary know-how including without limitation
know-how relating to (i) the development of fill and shell formulations; (ii) the
design and use of the encapsulation process to enhance stability, solubility,
bioavailability, and manufacturability of active ingredient chemical entities
in softgels; (iii) the selection and preparation of solvents, vehicles,
excipients, surfactants, stabilizers, gelatin, plasticizers and other
components of the liquid fill and the gelatin shell; (iv) certain
encapsulation, drying and related manufacturing techniques and machinery for
making commercial quantities of softgels, and (v) Cardinal Health’s
proprietary [***] technique.


 


1.35                           “Specifications” means the procedures,
requirements, standards, quality control testing and other data and the scope
of services as set forth in Exhibit A, which are hereby
incorporated by reference into this Agreement, along with any valid amendments
or modifications thereto, subject to the terms and conditions of Article 9.


 


1.36                           “Term” shall have the meaning set forth
in Section 15.1.


 


1.37                           “Territory” means the United States of
America, its territories and possessions.


 


1.38                           “Trade
Product” means any Product which has been designated and packaged for
commercial sale in the Territory.


 


1.39                           “Unit”
means each individual unit of Product, as described more fully in the Specifications.


 


1.40                           “Unit Pricing” shall have the meaning
set forth in Section 7.1.


 


1.41                           “Yield”
shall have the meaning set forth in Section 3.4.


 


ARTICLE 2


VALIDATION, MANUFACTURING, PACKAGING &
RELATED SERVICES


 


2.1                                 Validation
Services. During the Term, Cardinal Health shall perform the
qualification and validation services described in Exhibit D of
this Agreement for the prices specified therein.


 


2.2                                 Supply
and Purchase of Product. During the Term, Cardinal Health shall Manufacture
and Package the Products in accordance with the Specifications, Applicable Laws
and the terms and conditions of this Agreement. Reliant shall purchase Product
from Cardinal Health in accordance with the terms and conditions of this
Agreement, including but not limited to the obligations set forth in Section 4.1
and Section 4.2 hereof.


 


2.3                                 Product
Maintenance Services. During the Term and subject to Reliant’s payment of
the Product Maintenance Fee as set forth in Section 7.2, if applicable,
Reliant shall be entitled to the Product maintenance services set forth below
(collectively, the “Product Maintenance Services”). For the avoidance of doubt,
in the event that, in accordance with the terms of Section 7.2, Reliant 


 






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been omitted and filed separately with the Commission. Confidential treatment
has been requested with respect to the omitted portions.


 

















 


is not required to pay
the Product Maintenance Fee, Reliant shall nonetheless be entitled to the
Product Maintenance Services:


 


•                  Administration
of Foreign Trade Zone;


•                  One
annual audit;


•                  Annual
Product review;


•                  Access to document library over and
above the Quality Agreement, including additional copies of batch paperwork or
other batch documentation;


•                  Annual
Drug Master File update;


•                  Preparation of Product licenses or
permits under United States local, state or Federal regulations (in each case
as more fully set forth in Article 10);


•                  Product
Document and Manufacturing Sample Storage relating to cGMP requirements;


•                  Vendor
re-qualification;


•                  Maintenance
and storage of Audit Reports; and


•                  Bulk
stability (6 months, warehouse conditions).


 


ARTICLE 3


MATERIALS


 


3.1           API.


 


A.                                   Reliant
shall supply to Cardinal Health for Manufacturing and Packaging, at Reliant’s
sole cost, the API and applicable reference standards in quantities sufficient
to meet Reliant’s requirements for each Product as further set forth in Article 4.
Prior to delivery of any of the API or reference standard to Cardinal Health
for Manufacturing and Packaging, Reliant shall provide to Cardinal Health a
copy of the API Material Safety Data Sheet (“MSDS”), as amended, and any
subsequent revisions thereto. Reliant shall supply the API, reference
standards, and Certificate of Analysis FOB the Facility no later than thirty
(30) days before the scheduled Manufacture Date upon which such API will be
used by Cardinal Health. Upon receipt of the API, Cardinal Health shall conduct
identification testing of the API. Cardinal Health shall use the API solely and
exclusively for Manufacturing and Packaging under this Agreement. The maximum
volume of API that Reliant supplies to Cardinal Health shall not exceed the
amount reflected in the Firm Commitment and the next six (6) months of the
Rolling Forecast.


 


B.                                     All
API provided by Reliant shall meet applicable Specifications that apply
thereto, and shall be produced in accordance with all applicable federal, state
and local laws and regulations, including, without limitation, cGMPs.


 


C.                                     Cardinal
Health shall inspect API as received to verify its identity and shall give
Reliant oral and written notice of any nonconformity with Specifications within
thirty (30) calendar days of receipt of API by Cardinal Health. Reliant shall
provide a Certificate of Analysis with each delivery of API and such
certificate shall be the basis for drug potency.


 


D.                                    Reliant
shall retain title to API at all times and shall bear the risk of loss thereof;
provided, however, subject to Section 15.1, from the time
API is received at Cardinal Health’s Facility to the time API is returned (or
Product is delivered) to Reliant’s designated carrier at 


 

















 


Cardinal Health’s loading
dock, Cardinal Health shall bear the risk of loss of API arising from Cardinal
Health’s negligence or failure to comply with cGMPs or failure to comply with
all Specifications.


 


3.2                                 Raw
Materials. Cardinal Health shall be responsible for procuring, inspecting
and releasing adequate Raw Materials as necessary to meet the Firm Commitment,
unless otherwise agreed to by the Parties in writing. All Raw Material supplier
changes must be agreed by the Parties by amending the Specifications in
writing.


 


3.3                                 Reimbursement
for Materials. In the event of (A) a Specification change requested by
Reliant or Cardinal Health for Reliant’s benefit and agreed by the Parties, or
to comply with any new requirement of a Regulatory Authority, (B) termination
of this Agreement by Reliant without cause or expiration of this Agreement; or (C) unforeseeable
obsolescence of any Raw Material, Reliant shall bear the cost of any unused Raw
Materials that cannot be used by Cardinal Health or returned for credit,
provided that Cardinal Health purchased such Raw Materials in quantities
consistent with Reliant’s most recent Firm Commitment and the supplier’s
minimum purchase obligations.


 


3.4                                 Yield
and Inventory Reconciliation. Cardinal Health will achieve a minimum Yield
in Manufacturing the Product. “Yield” means the relation between the API
content of the Product Manufactured over a certain time period and the actual
quantity of API used to Manufacture such quantity of Product. The minimum Yield
was determined after the Manufacture of the greater of twenty (20) batches or
the number of batches Manufactured during the first three (3) months of
production and is set forth in Exhibit C. In the event the minimum
yield falls below [***]% at any time during the Term, the Parties agree to
discuss remedies to elevate the minimum yield in good faith and amend the
Agreement as the Parties deem appropriate, provided, however, the
foregoing discussions shall not relieve Cardinal Health of its obligations to
pay for quantities of API consumed in excess of the minimum Yield under this Section 3.4.
In the event the Parties have not agreed on remedies to elevate the Yield to [***]%
within three (3) months of determining the minimum Yield as set forth
above, the Parties expressly agree that for purposes of this Section 3.4
and the obligations set forth herein, the minimum Yield shall be no less than [***]%,
unless the Parties discuss and agree that it is commercially impracticable
under the circumstances. After the Parties have established the minimum Yield,
Cardinal Health shall, after Manufacture of each Batch, compare actual Yield
for such batch with the minimum Yield. Cardinal Health shall prepare a
quarterly report that sets forth all Yields by lot numbers that exceed the
minimum Yield. Cardinal Health will reimburse or credit Reliant an amount that
is equal to the current price that Reliant actually paid for API per kilo in
the Contract Year (currently [***] dollars ($[***])[***]) consumed in excess of
the minimum Yield, as evidenced by written documentation submitted to Cardinal
by Reliant. The Parties agree that for specific written orders Reliant may provide
Cardinal Health with instructions for Manufacturing that result in Yields lower
than the minimum Yield. Reliant will not be entitled to reimbursement or credit
for API to the extent that API loss is attributable solely to Reliant’s
specific instructions. Within three (3) business days of the end of each
quarter Cardinal Health shall notify Reliant of the quantities of API (both raw
material and in-process) in inventory. Upon reasonable advance notice to
Cardinal Health and at mutually agreeable times but not more than twice in any
twelve 


 






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respect to the omitted portions.


 

















 


(12) month period,
Reliant shall be permitted to inspect API inventory at Cardinal Health’s
Facility.


 


ARTICLE 4


COMMITMENT OF THE PARTIES, PURCHASE ORDERS &
FORECASTS


 


4.1                                 Minimum
Requirement. During each Contract Year, Reliant shall purchase the minimum
dollar volume of Product (the “Minimum Requirement”) set forth on Exhibit B.
If Reliant does not purchase such Minimum Requirement during any Contract Year,
within thirty (30) days after the end of such Contract Year and upon receipt of
an invoice from Cardinal Health, Reliant shall pay Cardinal Health the
difference between (A) the Minimum Requirement and (B) the sum of all
purchases from Cardinal Health for the Product during the just concluded
Contract Year.


 


4.2                                 Commitment
of the Parties.


 


(a) INTENTIONALLY
OMITTED


 


(b)                                 Reliant
commits to purchase a minimum of 80% of its Manufacturing requirements for Trade
Product in the Territory per Contract Year from Cardinal Health during the Term
of this Agreement, subject to Section 4.2 (c) and (d) below. For
the avoidance of doubt, Reliant may, in its sole discretion, purchase any or
all of its Sample Product from any third party. Further, for the avoidance of
doubt, the pricing for all Product will be at the level assuming that Reliant
purchases 100% of its requirements for Trade Product from Cardinal Health, and,
in the event Reliant purchases less than 100% of its requirements from Cardinal
Health the Parties will conduct a reconciliation of pricing at the conclusion
of that Contract Year.


 


Within
sixty (60)
days following the end of each Contract Year during the Term of this Agreement,
and within sixty
(60) days following the termination or expiration of this Agreement for
any reason, Reliant shall submit to Cardinal Health a written report (each, an “Annual
Report”), certified by an officer of Reliant, setting forth, with respect to
the immediately preceding Contract Year: (i) Reliant’s Manufacturing
requirements for Trade Product in the Territory, (ii) the aggregate Units
of Trade Product purchased from Cardinal Health; (iii) the calculation of
the percentage of its Manufacturing requirements for Trade Product purchased
from Cardinal Health, and (iv) the amount, if any, to be paid to Cardinal
Health in accordance with the terms and conditions set forth in Exhibit B
based on the actual percentage of Reliant’s Manufacturing requirements
purchased from Cardinal Health. In the event that such Annual Report indicates
that Cardinal Health is owed an additional amount for Trade Product purchased
in the immediately preceding Contract Year, Cardinal Health shall invoice
Reliant for such amount, and Reliant shall pay such invoice within thirty (30)
days of the date of receipt of such invoice.


 


(c)                                  In
the event Cardinal Health (i) determines it cannot meet any of Reliant’s
Rolling Forecasts delivered in accordance with Section 4.3 below, or (ii) fails
to deliver any Product within ten (10) days of a respective Delivery Date
for three (3) consecutive months during the Term, such that at the end of
any three month period Cardinal Health has failed to deliver the total number
of lots for which Reliant has issued Purchase Orders, Reliant’s obligations
under 


 






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separately with the Commission. Confidential treatment has been requested with
respect to the omitted portions.


 

















 


4.2(b) shall be
reduced in direct proportion to the percentage such unfulfilled Purchase Orders
represent as measured against Reliant’s obligations in Section 4.2(b), provided,
however, Reliant shall use commercially reasonable efforts to return to
the purchase requirement level set forth in Section 4.2(b) following
resolution of any technical issues.


 


(d)                                 Any
quantity of Product which is not delivered to Reliant by Cardinal Health within
ten (10) days of any Delivery Date, for any reason whatsoever, during the Term
shall give Reliant the option to purchase such quantity of Trade Product, but
only such quantity, from a qualified third-party supplier.


 


(e)                                  In
the event Cardinal Health’s Facility undergoes expansion and subsequent FDA
approval of such expansion, Reliant shall have the option, but not the
obligation, to have its Product Manufactured and Packaged in such new wing,
provided, however, that Reliant shall bear the cost of relocating to such new
wing, up to a cap of $[***].


 


4.3                                 Forecast.
On the Effective Date and on or before the first (1st) day of each
calendar month following the Effective Date, 
Reliant shall furnish to Cardinal Health in writing, an eighteen (18)
month rolling forecast of the quantities of Product that Reliant intends to
order from Cardinal Health during such period (“Rolling Forecast”). The first
three (3) months of such Rolling Forecast shall constitute a binding order
for the quantities of Product specified therein (“Firm Commitment”) and the
following fifteen (15) months of the Rolling Forecast shall be non-binding,
good faith estimates.


 


4.4                                 Purchase
Orders. On or before the first (1st) day of each calendar month,
Reliant shall submit a purchase order for the Firm Commitment, which specifies
the actual number of Batches to be Manufactured and Packaged, the approximate
number of Units in each Batch, and the requested Delivery Dates for each Batch
(“Purchase Order”). Reliant shall submit each Purchase Order to Cardinal Health
at least ninety (90) days in advance of the earliest Delivery Date requested in
the Purchase Order. Cardinal Health shall confirm Delivery Dates to Reliant. In
the event of a conflict between the terms of any Purchase Order and this
Agreement, this Agreement shall control. Notwithstanding the foregoing,
Cardinal Health shall supply Reliant with quantities of Product that exceed by
not more than [***] percent ([***]%)  the
quantities specified in the Firm Commitment (“Excess Quantities”), and shall
use best commercial efforts to supply additional quantities of Product
requested by Reliant (“Additional Quantities”). Cardinal Health’s supply of
Excess Quantities and Additional Quantities are both subject to (i) receipt
of a Purchase Order for such Additional Quantities and Excess Quantities at
least ninety (90) days in advance of the requested Delivery Date for such
Additional Quantities and Excess Quantities, and (ii) Cardinal Health’s
possession of sufficient quantities of API to Manufacture Excess Quantities and
Additional Quantities. Cardinal Health’s failure to supply Reliant with
Additional Quantities shall not constitute a failure to supply under Section 2.2
and 4.2. Should Cardinal Health fail to supply Reliant with its requirements
for the Product, specifically excluding Additional Quantities, for any
particular month hereunder, Cardinal Health shall be required to make up the
difference in the immediately subsequent month.


 






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Certain information on this page has been omitted and filed
separately with the Commission. Confidential treatment has been requested with
respect to the omitted portions.


 

















 


4.5                                 Cardinal
Health’s Cancellation of Purchase Orders. Notwithstanding the terms and
conditions set forth in Section 4.6 below, Cardinal Health reserves the
right to cancel all, or any part of, a Purchase Order upon written notice
to Reliant (and Cardinal Health shall have no further obligations or liability
with respect to such Purchase Order) if Reliant refuses or fails to make
scheduled deliveries of the API.


 


4.6                                 Reliant’s
Modification or Cancellation.


 


A.                                   Reliant
may modify the delivery date, Specifications or quantity of Product in
such Purchase Order only by submitting a written change order (“Change Order”)
to Cardinal Health at least thirty (30) business days in advance of the
earliest scheduled Manufacturing Date for the Manufacturing and Packaging
covered by the change order. Such change order shall be effective and binding
upon Cardinal Health only upon the written acceptance by Cardinal Health and,
notwithstanding the foregoing, Reliant shall remain responsible for the Firm
Commitment portion of the Rolling Forecast.


 


B.                                     Notwithstanding
any amounts due to Cardinal Health under Section 4.1 or Section 4.4,
if Reliant fails to place Purchase Orders sufficient to satisfy the Firm
Commitment, Reliant shall, within thirty (30) days of receipt of invoice, pay
to Cardinal Health the difference between the (i) Unit Price for all Units
that would have been Manufactured and Packaged if Reliant had placed Purchase
Orders sufficient to satisfy the Firm Commitment, and (ii) Cardinal Health’s
cost of any Raw Materials that would have been used in such Units, provided,
however, that Cardinal Health is not in default of any of its supply
obligations hereunder. In the event Cardinal Health has an opportunity to
mitigate its damages hereunder, the Parties shall meet in good faith to discuss
an appropriate reduction.


 


4.7                                 Unplanned
Delay or Elimination of Manufacturing and Packaging. Cardinal Health shall
timely fill each Purchase Order, subject to the terms and conditions of this
Agreement applicable to both Parties. Cardinal Health shall notify Reliant as
soon as possible after the receipt of a Firm Commitment or Purchase Order if
Cardinal Health determines that any Manufacturing or Packaging related to the
Firm Commitment or Purchase Order will be delayed or eliminated for any reason.


 


4.8                                 Inspection
of Manufacturing and Packaging. Reliant may base up to two (2) representatives
at the Facilities to observe the Manufacturing and Packaging provided that
Reliant provide Cardinal Health at least ten (10) days’ advance written
notice of the attendance of such Reliant representatives. Reliant shall
indemnify and hold harmless Cardinal Health for any action or activity of such
representatives while on Cardinal Health’s premises.


 


ARTICLE 5


TESTING; MANUFACTURING SAMPLES; RELEASE


 


5.1                                 Manufacturing
Samples; Testing. Within seven (7) days after Cardinal Health’s
completion of Manufacturing and Packaging of each Batch, Cardinal Health shall
deliver to Reliant, or its designee, a sample of the Product (“Manufacturing
Sample”) and the Manufacturing Related Reference Documents for such Batch. No
later than thirty (30) days after receipt of the Manufacturing Sample and a
complete set of the Manufacturing Related Reference 


 

















 


Documents (“Review Period”),
Reliant or its designee shall review the Manufacturing Related Reference
Documents and notify Cardinal Health whether the Manufacturing Sample conforms
to the warranty set forth in Section 13.1 of this Agreement. Upon receipt
of notice from Reliant that a Batch meets the warranty in Section 13.1, or
upon failure of Reliant to respond by the end of the Review Period, Cardinal
Health will invoice Reliant for such Batch in accordance with Section 7.5
below.


 


5.2                                 Non-Conforming
Product. If Reliant notifies Cardinal Health during the Review Period that
the Manufacturing Sample does not conform to the warranty set forth in Section 13.1
and Cardinal Health agrees with Client’s determination, Client shall not be
responsible to pay for such batch (the “Defective Product”), and Cardinal
Health shall, at Reliant’s option, either (A) replace any Batch of
non-conforming Product, or (B) credit any payments made by Reliant for
such Batch. If Cardinal Health does not agree with Reliant’s determination that
such Product fails to meet the warranty set forth in Section 13.1, then
after reasonable efforts to resolve the disagreement, the Parties shall cause a
mutually acceptable independent third party to review records, test data and to
perform comparative tests and/or analyses on the Manufacturing Sample. The
results of the independent review shall be final and binding. Unless otherwise
agreed to by the Parties in writing, the costs associated with such testing and
review shall be borne by the non-prevailing Party.


 


THE OBLIGATION OF
CARDINAL HEALTH TO (A) REPLACE DEFECTIVE PRODUCT IN ACCORDANCE WITH THE
SPECIFICATIONS OR CREDIT PAYMENTS MADE BY RELIANT FOR DEFECTIVE PRODUCT AND (B) REIMBURSE
RELIANT FOR API LOST IN THE DEFECTIVE BATCH, SUBJECT TO THE LIMITATIONS IN ARTICLE 15.1,
SHALL BE RELIANT’S SOLE AND EXCLUSIVE REMEDY (WITHOUT PREJUDICE TO ANY
INDEMNIFICATION OBLIGATIONS UNDER SECTION 14.1 OR THE OBLIGATIONS OF SECTION 10.6
(RECALL)) UNDER THIS ARTICLE FOR DEFECTIVE PRODUCT AND IS IN LIEU OF ANY
OTHER WARRANTY, EXPRESS OR IMPLIED.


 


5.3                                 Supply
of Material for Defective Product. In the event Cardinal Health is required
to replace Product pursuant to Section 5.2, above, in no instance shall
Cardinal Health be liable for damage in excess of fees paid for Defective
Product and API, subject to the limitation of liability in Section 15.1
and the indemnification obligations under Section 14.1.


 


ARTICLE 6


DELIVERY


 


6.1                                 Delivery.
Cardinal Health shall segregate and store all Product until such Product has
been Manufactured and Packaged to the Product Specifications. Upon such
acceptance, Cardinal Health shall tender the Product for delivery, F.O.B. the
Facility. Reliant shall be responsible for all costs and risk of loss
associated with shipment of the Product. Reliant shall qualify at least one (1) carrier
to ship the Product, and if Reliant qualifies more than one carrier Reliant
shall designate the priority of such qualified carriers to Cardinal Health.


 


6.2                                 Failure
to Take Delivery. If Reliant fails to take delivery within seven (7) days
of any scheduled delivery date solely with respect to Product that has been
deemed acceptable by 


 

















 


Reliant, Reliant shall be
invoiced for such Product pursuant to Section 7.5   On the first day of each subsequent month
Reliant shall be invoiced for the stored Product at a rate of [***] of Batch
price per month for administration and storage costs. For each such batch of
accepted but undelivered Product, Reliant agrees that: (A) Reliant has
made a fixed commitment to purchase such Product, (B) title and risk of
loss for such Product passes to Reliant, (C) such Product shall be on a
bill and hold basis for legitimate business purposes, (D) if no delivery
date is determined at the time of billing, Cardinal Health shall have the right
to ship the Product to Reliant or Reliant’s designee within four months after
billing, and (E) Reliant will be responsible for any decrease in market
value of such Product that relates to factors and circumstances outside of
Cardinal Health’s control. Within five (5) days following a written
request from Cardinal Health, Reliant shall provide Cardinal Health with a
letter confirming items (A) through (E) of this Section for each
Batch of undelivered Product.


 


ARTICLE 7


PRICING AND PAYMENT


 


7.1                                 Unit
Pricing. Reliant shall pay to Cardinal Health the unit pricing set forth on
Exhibit B (“Unit Pricing”) for all Product. When a Purchase Order
is placed, Reliant shall specify in such Purchase Order whether each lot is
designated for Sample Product or Trade Product. For lots designated for Sample
Product, Reliant shall pay the Unit Pricing for Sample Products as set forth on
Exhibit B. For lots designated for Trade Product, Reliant shall pay
the tiered Unit Price based on the number of Units set forth in its Rolling Forecast
for the then-current Contract Year. By way of example, as of the date a
Purchase Order is submitted, if Reliant’s Rolling Forecast for then current
Contract Year estimates a unit volume in excess of One Hundred Million Units,
Reliant shall pay the Unit Pricing for such volume indicated on Exhibit B.
The Parties shall reconcile all accounts annually, no later than thirty (30)
days after the beginning of each Contract Year hereunder, including
verification by Reliant of its sampling program. In the event Reliant shall
desire to make a Sample Product lot out of a lot otherwise forecast and
purchased as Trade Product, the Parties shall reconcile such transfer and
Cardinal Health shall credit the difference to Reliant within thirty (30) days
of such notification. Unit Pricing for Sample Product to be used by Reliant for
physician sampling shall be extended for two (2) years from the Effective
Date. In the event Reliant shall receive FDA approval for a new indication for
the Product, the Parties agree to discuss in good faith an extension of the
Sample Product pricing program at the original sample price. In the event
Reliant requests services other than Manufacturing and Packaging Product,
Cardinal Health shall provide a written quote of the fee for such additional
services and Reliant shall advise Cardinal Health whether it wishes to have
such additional services performed by Cardinal Health.


 


7.2                                 Product
Maintenance Fee. In partial consideration of the Product Maintenance
Services set forth in Section 2.3, Reliant shall pay Cardinal Health an
annual Product Maintenance Fee of [***] dollars ($[***]) for any Contract Year
wherein Reliant purchases less than [***] Units of Product from Cardinal Health.
For any year in which the Product Maintenance Fee is applicable, it shall be
payable by December 31 of such Contract Year. For the avoidance of doubt,
no Maintenance Fees are due and owing as of the Effective Date.


 






 [***]: 
Certain information on this page has been omitted and filed
separately with the Commission. Confidential treatment has been requested with
respect to the omitted portions.


 

















 


7.3                                 Price
Increase. The Unit Pricing may be adjusted on an annual basis,
effective on the first day of each Contract Year beginning January 1,
2008, upon ninety (90) days’ written notice from Cardinal Health to Reliant. Such
adjustment shall be based on actual increases or decreases in Raw Material or
Manufacturing and Packaging costs, subject to the following limitations: The
Unit Pricing for Product shall include only: (a) the cost of Raw Materials
and (b) Cardinal Health’s Manufacturing and Packaging costs, including
without limitation Cardinal Health’s labor, utilities and overhead. Any price
adjustment shall limit the increase in component (b) to [***] ([***]%); provided,
however, Cardinal Health shall use its best commercial efforts to limit
any increases hereunder as much as possible and Cardinal Health agrees to
provide backup documentation for all annual increases, if any, and such costs
and related documentation shall be auditable upon reasonable notice by an
independent third party reasonably acceptable to Cardinal Health and Reliant. Reliant
shall bear all costs associated for such audit, unless such audit reveals that
Cardinal Health exceeded the permitted increase, in which case Cardinal Health
shall bear the costs of the audit and shall credit such overpayment to Reliant.


 


7.4                                 Taxes;
Duty. All taxes, duties and other amounts assessed on the Raw Materials,
API or the Product prior to or upon sale to Reliant are the responsibility of
Reliant, and Reliant shall reimburse Cardinal Health for any such taxes, duties
or other expenses paid by Cardinal Health, upon receipt of reasonable
documentation.


 


7.5                                 Payment
Terms. Cardinal Health shall invoice Reliant for all Product as provided in
Section 7.1, and for any amounts due pursuant to Section 4.1 or Section 4.2
and payment for such undisputed invoices shall be due within thirty (30) days
after the date of such invoice. In the event payment is not received by
Cardinal Health, for any amounts due under this Agreement, on or before the
thirtieth (30th) day after the date of the invoice, or in the case
of the Product Maintenance Fee, upon the date set forth in Sections 7.2, then
such unpaid amounts shall accrue interest at the rate of percent (1.0%) per
month until paid in full.


 


ARTICLE 8


INTENTIONALLY OMITTED


 


ARTICLE 9


CHANGES TO SPECIFICATIONS


 


All
Specifications and any changes thereto agreed to by the Parties from time to
time shall be in writing, dated and signed by the Parties. No change in the
Specifications shall be implemented by Cardinal Health, whether requested by
Reliant or requested or required by any Regulatory Authority, until the Parties
have agreed in writing to such change, the implementation date of such change,
and any increase or decrease in costs, expenses or fees associated with such
change. Cardinal Health shall respond promptly to any request made by Reliant
for a change in the Specifications, and both Parties shall use commercially
reasonable, good faith efforts to agree to the terms of such change in a timely
manner. If after initial Product qualification, Reliant requests a change in
the Specifications for its own benefit or to comply with the requirements of a
Regulatory Authority, the Specifications shall be amended as soon as 


 






 [***]: 
Certain information on this page has been omitted and filed
separately with the Commission. Confidential treatment has been requested with
respect to the omitted portions.


 

















 


possible after a request
is made for any change in Specifications, and Cardinal Health shall notify
Reliant of the costs associated with such change and shall provide such
supporting documentation as Reliant may reasonably require. Reliant shall
pay all costs associated with such Reliant-requested changes or changes
required by a Regulatory Authority as may be agreed upon by the Parties.
Changes, agreed to between the Parties, for the benefit of Cardinal Health,
shall be at the expense of Cardinal Health. If there is a conflict between the
terms of this Agreement and the terms of the Specifications, this Agreement
shall control.


 


ARTICLE 10


RECORDS; REGULATORY MATTERS


 


10.1                           Batch
Records and Data. Within thirty (30) days following the completion of
Manufacturing and Packaging of each batch, Cardinal Health shall provide
Reliant with properly completed copies of Manufacturing Related Reference
Documents prepared in accordance with the Specifications; provided, however,
that if testing reveals an out-of-Specification result, Cardinal Health shall
provide such Batch records within ten (10) days following resolution of
the out-of Specification result.


 


10.2                           Recordkeeping.
Cardinal Health shall maintain true and accurate books, records, test and
laboratory data, reports and all other information relating to Manufacturing
and Packaging under this Agreement, including all information required to be
maintained by all Applicable Laws. Such information shall be maintained in
forms, notebooks and records for a period of at least two (2) years from
the relevant finished Product expiration date or longer if required under
Applicable Laws.


 


10.3                           Regulatory
Compliance. Cardinal Health, with the assistance of Reliant, shall obtain
all permits and licenses required by any United States federal, state or local
regulatory agency with respect to the Product and the Manufacturing and
Packaging under this Agreement, including any product licenses, applications
and amendments in connection therewith. Cardinal Health will be responsible to
maintain all permits and licenses required by any Regulatory Authority with
respect to the Facility. During the Term, Cardinal Health will assist Reliant
with all regulatory matters relating to Manufacturing and Packaging under this
Agreement, at Reliant’s request and at Reliant’s expense. Each Party intends
and commits to cooperate to satisfy all Applicable Laws relating to
Manufacturing and Packaging under this Agreement. Cardinal Health shall provide
a Certificate of Compliance to Reliant annually during the Term.


 


10.4                           Governmental
Inspections and Requests. Cardinal Health shall immediately advise Reliant
if an authorized agent of any Regulatory Authority visits the Facility
concerning the Manufacturing or Packaging of the Product. Cardinal Health shall
furnish to Reliant a copy of the report by such Regulatory Authority, if any,
within ten (10) days of Cardinal Health’s receipt of such report. Further,
upon receipt of a Regulatory Authority request to inspect the Facilities or
audit Cardinal Health’s books and records with respect to Manufacturing or
Packaging under this Agreement, Cardinal Health shall immediately notify
Reliant, and shall provide Reliant with a copy of any written document received
from such Regulatory Authority. Cardinal Health shall permit Reliant to have a
representative present for any such Product-specific Facility inspection unless
such presence would be unreasonable under the circumstances. To the extent
specifically related to the Manufacturing or Packaging hereunder, Cardinal
Health shall provide Reliant with 


 

















 


a copy of any proposed
written response prior to submission and a reasonable opportunity for Reliant
to review and approve, provided such approval is not unreasonably withheld,
conditioned or delayed.


 


10.5                           Reliant
Inspections and Audits.


 


A.                                   Except
for circumstances as set forth in Section 10.4, during the term of this
Agreement, duly-authorized employees, agents and representatives of Reliant
shall be granted access upon at least twenty-four (24) hours prior notice,
unless more time is reasonably requested by Cardinal Health, and at reasonable
times during regular business hours to only the portion of the Facilities where
Cardinal Health Manufactures or Packages API for the purpose of inspecting and
verifying that Cardinal Health is Manufacturing and Packaging API in accordance
with cGMPs, the Specifications and the Product Master Batch Record. For
purposes of this Section 10.5, duly-authorized agents and representatives
shall be required to sign Cardinal Health’s standard Confidential Disclosure
Agreement prior to being allowed access to Cardinal Health’s Facilities.


 


B.                                     With
due regard to information and operations which constitute Proprietary
Information of Cardinal Health, duly-authorized employees, agents and
representatives of Reliant shall have the right to inspect Cardinal Health
Batch Records relating to Product and those portions of Cardinal Health’s
Facilities used for Manufacturing and Packaging Product. Reliant’s Quality
Assurance Manager will arrange audit visits with Cardinal Health Quality
Management.


 


10.6                           Recall.
In the event Cardinal Health believes a recall, field alert, Product withdrawal
or field correction may be necessary with respect to any Product provided
under this Agreement, Cardinal Health shall immediately notify Reliant in
writing. Cardinal Health will not act to initiate a recall, field alert,
Product withdrawal or field correction without the express prior written
approval of Reliant, unless otherwise required by Applicable Laws. In the event
Reliant believes a recall, field alert, Product withdrawal or field correction may be
necessary with respect to any Product provided under this Agreement, Reliant
shall immediately notify Cardinal Health in writing and Cardinal Health shall
provide all necessary cooperation and assistance to Reliant. Reliant shall
solely control the implementation of such recall, filed alert, Product
withdrawal or field correction. The cost of any recall, field alert, Product
withdrawal or field correction shall be borne by Reliant unless such recall, field
alert, Product withdrawal or field correction is caused solely by Cardinal
Health’s breach of its representations, warranties and obligations under this
Agreement or Applicable Laws or its negligence or willful misconduct, then such
cost shall be borne by Cardinal Health. For purposes hereof, such cost shall be
limited to reasonable, actual and documented administrative costs incurred by
Reliant for such recall, withdrawal or correction, and replacement of the
Defective Product to be recalled, in accordance with Article 5.


 


10.7                           Quality
Agreement. Within thirty (30) days following the execution of this
Agreement, the Parties shall execute a Quality Agreement in substantially the form attached
to this Agreement as Exhibit E. The Quality Agreement shall in no
way determine liability or financial responsibility of the Parties for the
responsibilities set forth therein. In the event of a conflict between the
terms of this Agreement and the Quality Agreement, this Agreement shall
control.


 

















 


10.8                           Qualification
of Additional Facilities. In the event Reliant requests that Cardinal
qualify additional Facilities to Manufacture and Package the Product, Reliant
shall be solely responsible for any costs associated therewith which shall be
limited to technology transfer and technology transfer service costs. In the event that Cardinal Health desires to qualify
additional Facilities to Manufacture and Package the Product, Cardinal Health
shall be solely responsible for any costs associated therewith.


 


ARTICLE 11


CONFIDENTIAL INFORMATION


 


11.1                           Confidentiality
Agreement. The use and disclosure of confidential information exchanged
between the Parties shall be governed by the Confidentiality Agreement by and
between Cardinal Health, Reliant and Pronova Biocare, a.s., dated July 29,
2004 (the “Confidentiality Agreement”).


 


11.2                           No
Implied License. Except as otherwise set forth herein, the Party receiving
Confidential Information (as such is defined in the Confidentiality Agreement)
will obtain no right of any kind or license under any patent application or
patent by reason of this Agreement. All Confidential Information will remain
the sole property of the Party disclosing such information or data.


 


11.3                           Return
of Confidential Information. Upon termination or expiration of this
Agreement, the Party to which Confidential Information has been disclosed will,
upon request, promptly return within thirty (30) days, all such Confidential
Information, including any copies thereof, and cease its use or, at the option
of the receiving Party,  promptly
destroy the same and certify such destruction to the disclosing Party, except
for a single copy thereof which may be retained for the sole purpose of
determining the scope of the obligations incurred under this Agreement.


 


11.4                           Disclosure
of Confidential Information. Notwithstanding the terms set forth this Article 11
or the Confidentiality Agreement, each of the Parties shall have the right to
disclose the existence and terms of this Supply Agreement to those of its
directors, managers, officers, employees, accountants, attorneys, advisers,
agents, investment bankers, lenders and potential lenders, financing sources,
acquirers or business combination candidates who need to know such terms for
the purpose of evaluating or entering into a potential business arrangement (“Third
Parties”); provided, that such Third Parties are required to maintain the
confidentiality of this Supply Agreement to the same extent as if they were
Parties hereto Notwithstanding the foregoing, each of the Parties shall have
the right to disclose the existence and terms of this Supply Agreement as may be
required by applicable laws or rules of any stock exchange to which a
Party or any Affiliate of a Party is subject, in which case the disclosing
Party shall provide the non-disclosing Party with prompt advance notice of such
disclosure so that the non-disclosing Party shall have the opportunity if it so
desires to seek a protective order or other appropriate remedy and, in
connection with any disclosure required by the Securities and Exchange
Commission or the rules of any stock exchange to which a Party or any
Affiliate of a Party is subject, the disclosing Party shall use reasonable
efforts to obtain confidential treatment for such disclosure.


 

















 


11.5                           Survival.
The obligations of this Article 11 shall terminate five (5) years
from the expiration or termination of this Agreement.


 


ARTICLE 12


INTELLECTUAL PROPERTY


 


All
Cardinal Health Technology, including, without limitation, all improvements,
developments, derivatives or modifications to the Cardinal Health Technology,
shall be owned exclusively by Cardinal Health and, except as set forth herein
no right or license in Cardinal Health Technology is transferred or granted to
Reliant. All Reliant Technology, including, without limitation, all
improvements, developments, derivatives or modifications to the Reliant
Technology shall be owned exclusively by Reliant. Reliant hereby grants to
Cardinal Health a non-exclusive, royalty-free license for the term of this
Agreement to use Reliant Technology, but solely for the purpose of carrying out
Cardinal Health’s obligations under this Agreement. For purposes hereof, “Cardinal
Health Technology” means all Softgel Technology, Cardinal Health Confidential
Information, intellectual property, and developments (including, all patents,
patent applications, know-how, inventions, designs, concepts, improvements,
technical information, manuals, instructions or specifications), owned,
licensed or used by Cardinal Health in developing, formulating, manufacturing,
filling, processing or packaging of pharmaceuticals and the packaging
equipment, processes or methods of packaging, or any improvements to any of the
foregoing, including any container, pouch, vial, ampoule, blister pack or other
form of container developed by Cardinal Health. For purposes hereof, “Reliant
Technology” means all proprietary information, intellectual property and
developments owned, developed, licensed or used by Reliant relating to the API,
including, without limitation, patents, patent applications, know-how,
inventions, designs, concepts, improvements, technical information, trademarks
or trade names.


 


ARTICLE 13


REPRESENTATIONS AND WARRANTIES


 


13.1                           Cardinal
Health. Cardinal Health represents and warrants to Reliant that:


 


A.                                   At
the time of delivery of the Product as provided in Section 6.1, such
Product will conform to and will have been Manufactured and Packaged in
conformance with the Product Specifications and Applicable Laws;


 


B.                                     Cardinal
Health will be solely responsible for and will obtain all governmental
approvals, permits and licenses necessary or desirable in connection with the
Manufacturing and Packaging of the API in the Territory.


 


C.                                     It
has, and shall have, good, complete and valid rights to utilize the Cardinal
Health Technology utilized in connection with the Product and as contemplated
by this Agreement. There are no patents owned by others related to the Cardinal
Health Technology used with the Product which would be infringed or misused by
Cardinal Health’s performance of the Agreement and, to its knowledge, no trade
secrets or other proprietary rights of others related to the Cardinal Health
Technology used with the Product which would be infringed or misused by
Cardinal Health’s performance of this Agreement.


 

















 


F.                                      THE
LIMITED WARRANTY SET FORTH IN THIS SECTION 13.1 IS IN LIEU OF ALL OTHER
WARRANTIES, EXPRESS OR IMPLIED, INCLUDING ANY WARRANTY OF MERCHANTABILITY AND
ANY WARRANTY OF FITNESS FOR A PARTICULAR PURPOSE. EXCEPT FOR THE WARRANTY
EXPRESSED IN THIS SECTION 13.1, CARDINAL HEALTH MAKES NO OTHER WARRANTY,
EITHER EXPRESS OR IMPLIED, WITH RESPECT TO THE MANUFACTURING AND PACKAGING OR
THE PRODUCT.


 


13.2                           Reliant.
Reliant represents, warrants and covenants to Cardinal Health that:


 


A.                                   The
API and any other materials supplied by Reliant to Cardinal Health (“Reliant-supplied
Materials”) will comply with all applicable Specifications, will have been
produced in compliance with the Applicable Laws, and will be provided in
accordance with the terms and conditions of this Agreement;


 


B.                                     It
has all necessary authority and all right, title and interest in and to any
Reliant Technology related to the API or any other Reliant supplied materials;


 


C.                                     No
specific safe handling instructions are applicable to the Product, the API or
any other Reliant supplied materials, except as disclosed to Cardinal Health in
writing by the Reliant in sufficient time for review and training by Cardinal
Health prior to delivery;


 


D.                                    All
Product delivered to Reliant by Cardinal Health will be held, used and/or
disposed of by the Reliant in accordance with all applicable laws, rules and
regulations;


 


E.                                      Reliant
will comply with all laws, rules, regulations and guidelines applicable to
Reliant’s performance under this Agreement and its use of Product provided by
Cardinal Health under this Agreement;


 


F.                                      If
release testing is conducted by Reliant, Reliant will not release any Batch of
Product if the required Certificates of Analysis indicate that the Product does
not comply with the Specifications;


 


G.                                     The
content of all artwork provided to Cardinal Health complies with all Applicable
Laws;


 


H.                                    Reliant
has all necessary authority and right, title and interest in and to any
copyrights, trademarks, trade secrets, patents, inventions and developments
related to the API, the manufacture thereof, and any Product artwork;


 


I.                                         To
the knowledge of Reliant, the work to be performed by Cardinal Health under
this Agreement will not violate or infringe upon any trademark, tradename,
copyright, patent or other rights held by any person or entity; and


 

















 


J.                                        Reliant
will be solely responsible for and will obtain all governmental approvals,
permits and licenses necessary or desirable in connection with the testing,
marketing, sale, advertising or distribution of the Product in the Territory.


 


13.2                           Mutual.
Each Party hereby represents and warrants to the other Party that:


 


A.                                   Such
Party (1) is duly organized, validly existing and in good standing under
the laws of the state in which it is organized, (2) has the power and
authority and the legal right to own and operate its property and assets, and
to carry on its business as it is now being conducted, and (3) is in
compliance with all requirements of applicable law, except to the extent that
any noncompliance would not materially adversely affect such Party’s ability to
perform its obligations under the Agreement;


 


B.                                     Such
Party (1) has the power and authority and the legal right to enter into
this Agreement and to perform its obligations hereunder and thereunder and
(2) has taken all necessary action on its part to authorize the
execution and delivery of the Agreement and the performance of its obligations
hereunder;


 


C.                                     This
Agreement is validly executed and delivered on behalf of such Party, and
constitutes a legal, valid, binding obligation, enforceable against such Party
in accordance with its terms;


 


D.                                    All
necessary consents, approvals and authorizations of all agencies and other
persons required to be obtained by such Party in connection with the Agreement have
been obtained; and


 


E.                                      The
execution and delivery of this Agreement and the performance of such Party’s
obligations hereunder (1) do not conflict with or violate any requirement
of applicable laws or regulations or any material contractual obligation of
such Party and (2) do not materially conflict with, or constitute a
material default or require any consent under, any material contractual
obligation of such Party.


 


ARTICLE 14


INDEMNIFICATION


 


14.1                           Indemnification
by Cardinal Health. Cardinal Health shall indemnify and hold harmless
Reliant, its Affiliates, directors, officers, employees and agents from and
against any and all suits, claims, losses, demands, liabilities, damages, costs
and expenses (including reasonable attorney’s fees) in connection with any
suit, demand or action by any third party (“Losses”) arising out of or
resulting from (A) any breach of its representations, warranties or
obligations under this Agreement; (B) any negligence or willful misconduct
by Cardinal Health, except to the extent that any of the foregoing arises out
of or results from the negligence, willful misconduct or breach of this
Agreement by of Reliant; or (C) any actual or alleged infringement or
violation of any patent, trade secret, copyright, trademark or other proprietary
rights used by Cardinal Health in Manufacturing and Packaging the Product,
except to the extent such was provided by Reliant.


 

















 


14.2                           Indemnification
by Reliant. Reliant shall indemnify and hold harmless Cardinal Health, its
Affiliates, directors, officers, employees and agents from and against all
Losses arising out of or resulting from (A) any breach of its
representations, warranties or obligations under this Agreement; (B) any
manufacture, sale, promotion, distribution, use (other than by Cardinal Health)
of or exposure to the Product, the API or any Reliant-supplied materials,
including, without limitation, product liability or strict liability; (C) Reliant’s
exercise of control over the Manufacturing and Packaging under this Agreement,
to the extent that Reliant’s written instructions or directions violate
applicable law or regulation; (D) any actual or alleged infringement or
violation of any patent, trade secret, copyright, trademark or other
proprietary rights provided by Reliant and used by Cardinal Health in
Manufacturing and Packaging the Product; or (E) any negligence or willful
misconduct by Reliant, except to the extent that any of the foregoing arises
out of or results from the negligence, willful misconduct or breach of this
Agreement by Cardinal Health.


 


14.3                           Indemnification
Procedures. All indemnification obligations in this Agreement are
conditioned upon the Party seeking indemnification (the “Indemnified Party”): (A) promptly
notifying the indemnifying Party (the “Indemnifying Party”) of any claim or
liability of which the Party seeking indemnification becomes aware (including a
copy of any related complaint, summons, notice or other instrument), provided,
however, that failure to provide such notice within a reasonable period of time
shall not relieve the Indemnifying Party of any of its obligations hereunder
except to the extent the Indemnifying Party is materially prejudiced by such
failure; (B) cooperating with the Indemnifying Party in the defense of any
such claim or liability (at the Indemnifying Party’s expense), and (C) not
compromising or settling any claim or liability without prior written consent
of the Indemnifying Party. The liability of an Indemnifying Party under this Article XIV
with respect to Losses arising from claims of any Third Party which are subject
to the indemnification provided for in this Article XIV (“Third Party Claims”) shall be governed by and contingent
upon the following additional terms and conditions. If an Indemnified Party
shall receive notice of any Third Party Claim, the Indemnified Party shall give
the Indemnifying Party notice of such Third Party Claim within thirty (30) days
of the receipt by the Indemnified Party of such notice; provided,
however, that the failure to provide such notice shall not release
the Indemnifying Party from any of its obligations under this Article XIV
except to the extent the Indemnifying Party is materially prejudiced by such
failure. The Indemnifying Party shall be entitled to assume and control the
defense of such Third Party Claim at its expense and through counsel of its
choice if it gives notice of its intention to do so to the Indemnified Party
within thirty (30) days of the receipt of such notice from the Indemnified
Party; provided, however, that if there exists a material conflict of interest that
would make it inappropriate for the same counsel to represent both the
Indemnified Party and the Indemnifying Party, then the Indemnified Party shall
be entitled to retain its own counsel, at the expense of the Indemnifying
Party, provided that the Indemnifying Party shall not be obligated to pay the
reasonable fees and expenses of more than one separate counsel for all
Indemnified Parties, taken together. In the event the Indemnifying Party
exercises the right to undertake any such defense against any such Third Party
Claim as provided above, the Indemnified Party shall cooperate with the
Indemnifying Party in such defense and make available to the Indemnifying
Party, all witnesses, pertinent records, materials and information in the
Indemnified Party’s possession or under the Indemnified Party’s control
relating thereto as is reasonably required by the Indemnifying Party. Similarly,
in the event the Indemnified Party is, directly or indirectly, conducting the
defense against any such Third Party Claim, the 


 

















 


Indemnifying Party shall
cooperate with the Indemnified Party in such defense and make available to the
Indemnified Party, all such witnesses, records, materials and information in
the Indemnifying Party’s possession or under the Indemnifying Party’s control
relating thereto as is reasonably required by the Indemnified Party. The
Indemnifying Party shall not, without the written consent of the Indemnified
Party (which shall not be unreasonably withheld or delayed), (a) settle or
compromise any Third Party Claim or consent to the entry of any judgment which
does not include as an unconditional term thereof the delivery by the claimant
or plaintiff to the Indemnified Party of a written release from all liability
in respect of such Third Party Claim or (b) settle or compromise any Third
Party Claim if the settlement imposes equitable remedies or material
obligations on the Indemnified Party other than financial obligations for which
such Indemnified Party will be indemnified hereunder and which contains no
admission of fault or wrongdoing. No Third Party Claim shall be settled or
compromised by the Indemnified Party without the written consent of the
Indemnifying Party (which shall not be unreasonably withheld or delayed) if
such settlement or compromise would result in an obligation of the Indemnifying
Party to indemnify such Indemnified Party, or would otherwise result in
liability of, or have an adverse impact upon, such Indemnifying Party.


 


ARTICLE 15


LIMITATION OF LIABILITY


 


15.1                           CARDINAL
HEALTH’S LIABILITY UNDER THIS AGREEMENT FOR ANY AND ALL CLAIMS FOR LOST,
DAMAGED OR DESTROYED API OR OTHER RELIANT-SUPPLIED MATERIALS WHETHER OR NOT
SUCH API OR RELIANT-SUPPLIED MATERIALS ARE INCORPORATED INTO PRODUCT IS SET FORTH
IN EXHIBIT B. THE LIMITATION OF LIABILITY, WITH RESPECT TO ANY GIVEN
CONTRACT YEAR, SHALL NOT EXCEED THE APPLICABLE AMOUNTS SET FORTH IN EXHIBIT B
(THE “API CAP”). IN THE EVENT THAT CARDINAL HEALTH LIABILITY FOR LOST API SHALL
EXCEED THE API CAP FOR ANY CONTRACT YEAR DURING THE TERM, THE PARTIES SHALL
MEET WITHIN THIRTY (30) DAYS FROM THE DATE CARDINAL HEALTH’S LIABILITY FOR LOST
API EXCEEDS THE API CAP AND NEGOTIATE IN GOOD FAITH WHETHER (A) CARDINAL
HEALTH INCREASES THE API CAP FOR SUCH CONTRACT YEAR, OR (B) WHETHER
RELIANT’S OBLIGATIONS UNDER SECTION 4.2(B) SHALL BECOME NULL AND VOID.
IN THE EVENT THAT THE PARTIES CANNOT REACH AN AGREEMENT WITH REGARD TO THE
FOREGOING SENTENCE WITHIN SUCH THIRTY (30) DAY PERIOD, RELIANT SHALL HAVE THE
SOLE OPTION TO (X) CONTINUE WITH THE AGREEMENT WITH CARDINAL HEALTH HAVING NO
LIABILITY IN EXCESS OF THE API CAP FOR LOST, DAMAGED OR DESTROYED API FOR THE
THEN CURRENT CONTRACT YEAR, OR (Y) HAVE PRODUCT MANUFACTURED AND PACKAGED BY A
QUALIFIED THIRD-PARTY SUPPLIER WITHOUT REGARD TO ITS OBLIGATIONS UNDER SECTION 4.2(B).
ANY AMOUNTS OWING BY CARDINAL HEALTH HEREUNDER SHALL NOT COUNT AGAINST THE
LIABILITY CAP SET FORTH IN SECTION 15.2 BELOW.


 


15.2                           NOTWITHSTANDING,
AND SPECIFICALLY EXCLUDING, ANY AMOUNTS OWED BY CARDINAL HEALTH TO RELIANT
UNDER SECTION 15.1 ABOVE, AND SPECIFICALLY EXCLUDING LOSSES RESULTING FROM
CARDINAL HEALTH’S GROSS NEGLIGENCE, FRAUD OR WILLFUL MISCONDUCT, CARDINAL
HEALTH’S 


 


 

















 


TOTAL LIABILITY UNDER
THIS AGREEMENT OTHER THAN FOR LOST, DAMAGED OR DESTROYED API, SHALL IN NO EVENT
EXCEED FIVE MILLION DOLLARS ($5,000,000).


 


15.3                           NEITHER
PARTY SHALL BE LIABLE TO THE OTHER PARTY FOR INDIRECT, INCIDENTAL, SPECIAL OR
CONSEQUENTIAL DAMAGES (EXCEPT FOR THOSE INDEMNITY OBLIGATIONS UNDER ARTICLE 14
THAT ARE DEEMED CONSEQUENTIAL DAMAGES) ARISING OUT OF PERFORMANCE UNDER THIS
AGREEMENT, INCLUDING WITHOUT LIMITATION, LOSS OF REVENUES, PROFITS OR DATA,
WHETHER IN CONTRACT OR TORT, EVEN IF SUCH PARTY HAS BEEN ADVISED OF THE
POSSIBILITY OF SUCH DAMAGES.


 


15.4                           Limitation
of Liability for Operation of Foreign Trade Subzone. Cardinal Health has
been granted a special purpose subzone (the “FTZ”) that includes the main plant of Cardinal Health’s US
Facility. Reliant may recognize a number of economic benefits resulting
from Cardinal Health’s operation of the FTZ. However, notwithstanding anything
to the contrary contained herein, including but not limited to the provisions
of Section 14.1, Cardinal Health’s liability to the Reliant, if any, as a
result of any and all liabilities, losses, claims, demands, damages, costs,
expenses, settlements made or reasonably approved by Cardinal Health, and money
judgments (including attorneys’ fees and other costs of litigation), related to
Cardinal Health’s operation of the FTZ, including, but not limited to: (A) Cardinal
Health acting as Reliant’s agent for duty drawback purposes pursuant to 19 CFR
§191.9 with respect to the Product; and (B) the suspension or closing of
the FTZ (whether voluntary or not)), incurred by or rendered against the Reliant
for personal injury, sickness, disease or death and other damages shall in no
event exceed Fifty Thousand United States Dollars ($50,000).


 


ARTICLE 16


INSURANCE


 


16.1                           Cardinal
Health. Cardinal Health shall, at its own cost and expense, obtain and maintain
in full force and effect the following insurance during the term of this
Agreement: (A) Commercial General Liability insurance with per-occurrence
and general aggregate limits of not less than $1,000,000; (B) Products and
Completed Operations Liability Insurance with per-occurrence and general
aggregate limits of not less than $5,000,000; (C) Workers’ Compensation
and Employer’s Liability Insurance with statutory limits for Workers’
Compensation and Employer’s Liability insurance limits of not less than
$1,000,000; and (D) Professional Services Errors & Omissions
Liability Insurance with per claim and aggregate limits of not less than
$1,000,000 covering sums that Cardinal Health becomes legally obligated to pay
as damages resulting from claims made by Reliant for errors or omissions
committed in the conduct of the services outlined in the Agreements. In lieu of
insurance, Cardinal Health may self-insure any or a portion of the above
required insurance. In the event that any of the required policies of insurance
are written on a claims made basis, then such policies shall be maintained
during the entire Term and for a period of not less than three (3) years
following the termination or expiration of this Agreement. Cardinal Health
shall obtain a waiver from any insurance carrier with whom Cardinal Health
carries Workers’ Compensation insurance releasing its subrogation rights
against Reliant. Reliant shall be named as an additional insured under the
Commercial 


 

















 


General Liability and
Products and Completed Operations Liability insurance policies as respects the
manufacturing services outlined in this Agreement. Cardinal Health shall
furnish certificates of insurance for all of the above noted policies and
required additional insured status to Reliant as soon as practicable after the
Effective Date of the Agreement and upon renewal of any such policies. Each
insurance policy that is required under this Section shall be obtained
from an insurance carrier with an A.M. Best rating of at least A- VII.


 


16.2                           Reliant
Insurance. Reliant shall, at its own cost and expense, obtain and maintain
in full force and effect the following insurance during the term of this
Agreement: (A) Products and Completed Operations Liability Insurance with
per-occurrence and general aggregate limits of not less than $10,000,000; (B) Workers’
Compensation and Employer’s Liability Insurance with statutory limits for
Workers’ Compensation and Employer’s Liability insurance limits of not less
than $1,000,000; (C) All Risk Property Insurance in an amount equal to
full replacement value covering Reliant’s property while it is at Cardinal
Health’s facility; and (D) transit coverage in an amount not less than
$1,000,000 while Reliant’s property is in transit to or from Cardinal Health’s
facility. In the event that any of the required policies of insurance are
written on a claims made basis, then such policies shall be maintained during
the entire Term and for a period of not less than three (3) years
following the termination or expiration of this Agreement. Reliant shall obtain
a waiver from any insurance carrier with whom Reliant carries Workers’
Compensation insurance releasing its subrogation rights against Cardinal
Health. Reliant shall obtain a waiver from any insurance carrier with whom Reliant
carries Property Insurance releasing its subrogation rights against Cardinal
Health. Reliant shall not seek reimbursement for any property claim, or portion
thereof, which is not fully recovered from Reliant’s Property Insurance policy.
Cardinal Health and its Subsidiaries and Parent Corporation shall be named as
additional insureds under the Products and Completed Operations Liability
insurance policies as respects the products and completed operations outlined
in this Agreement. Reliant shall furnish certificates of insurance for all of
the above noted policies and required additional insured status to Cardinal
Health as soon as practicable after the Effective Date of the Agreement and
upon renewal of any such policies. Each insurance policy that is required under
this Section shall be obtained from an insurance carrier with an A.M.
Best rating of at least A- VII.


 


ARTICLE 17


TERM AND TERMINATION


 


17.1                           Term.
This Agreement shall commence on the Effective Date and shall continue for a
period of five (5) Contract Years (January 1, 2007 through December 31,
2011), unless earlier terminated under Section 17.2 (the “Initial Term”). After
the Initial Term, this Agreement may be automatically extended for further
periods of one (1) year each (the “Renewal Term”), unless terminated by
either Party upon written notice given to the other Party at least twelve (12)
months prior to the end of the Initial Term. The Initial Term and any Renewal
Term shall constitute the Term.


 


17.2                           Termination
by Either Party.


 


A.                                   Material
Breach. Either Party may terminate this Agreement effective upon sixty
(60) days prior written notice to the other Party, if the other Party commits a
material breach of this Agreement and fails to cure such breach by the end of
such sixty (60) day period; provided, 


 

















 


however, that failure to
pay amounts due under this Agreement within thirty (30) days after such
payments are due (as set forth in Section 7.5) more than two (2) times
in any Contract Year shall constitute cause for immediate termination of this
Agreement, provided, however, that Reliant’s Chief Operating
Officer, or his designee, and Cardinal’s Facility General Manager from each
Party shall discuss such nonpayment in advance of termination.


 


B.                                     Bankruptcy.
Either Party may terminate this Agreement effective upon written notice to
the other Party, if the other Party becomes insolvent or admits in writing its
inability to pay its debts as they become due, files a petition for bankruptcy,
makes an assignment for the benefit of its creditors or has a receiver, trustee
or other court officer appointed for its properties or assets.


 


17.3                           Without
Cause. Either Party may terminate this Agreement without cause upon
thirty-six (36) months’ written notice to the other Party, following the date
which is twenty-four (24) months from the Effective Date.


 


17.4                           Effect
of Termination.


 


A.                                   Expiration
or termination of this Agreement shall be without prejudice to any rights or
obligations that accrued to the benefit of either Party prior to such expiration
or termination.


 


B.                                     In
the event of any termination, Cardinal Health shall promptly return (1) any
remaining inventory of materials received from Reliant, (2) all remaining
inventories of API and Product, and (3) any other Product, or API being
stored for Reliant, to Reliant at Reliant’s expense. Cardinal Health shall have
no obligation to return the foregoing until all outstanding undisputed invoices
sent by Cardinal Health to Reliant have been paid in full. For termination
initiated by Reliant, Reliant shall also be required to pay for (Y) completed
but not yet shipped Product and (Z) Product in process and Product shipped but
not yet invoiced in the event that this Agreement is terminated for reasons
other than Cardinal Health’s default. In the event Reliant breaches or
terminates this Agreement (other than as a result of a breach of this Agreement
by Cardinal Health) or if Cardinal Health terminates this Agreement under Section 17.2
hereof, Reliant will also be required to pay Cardinal Health for its direct
cost of all materials purchased by Cardinal Health for Processing. Reliant
shall specify the location in the continental United States to which delivery,
at Reliant’s expense, of the foregoing is to be made.


 


ARTICLE 18


NOTICE


 


All
notices and other communications hereunder shall be in writing and shall be
deemed given:    (A) when delivered
personally; (B) when delivered by facsimile transmission (receipt
verified);   (C) when received or
refused, if mailed by registered or certified mail (return receipt requested),
postage prepaid; or (D) when delivered if sent by express courier service,
to the Parties at the following addresses (or at such other address for a Party
as shall be specified by like notice; provided, that notices of a change of
address shall be effective only upon receipt thereof):


 

















 


	
  To Reliant:

  	
  Reliant
  Pharmaceuticals, Inc.

  
	
   

  	
  110 Allen Road

  
	
   

  	
  Liberty Corner,
  NJ 07938

  
	
   

  	
  Attention:
  Robert Polster, Ph.D., Vice President,

  
	
   

  	
  Commercial
  Operations

  
	
   

  	
  Facsimile:
  908.542.9405

  
	
   

  	
   

  
	
  With a copy to:

  	
  Reliant
  Pharmaceuticals, Inc.

  
	
   

  	
  110 Allen Road

  
	
   

  	
  Liberty Corner,
  NJ 07938

  
	
   

  	
  Attention: Legal
  Department

  
	
   

  	
  Facsimile:
  908.542.9405

  
	
   

  	
   

  
	
  To Cardinal
  Health:

  	
  Cardinal Health
  PTS, LLC

  
	
   

  	
  2725 Scherer
  Drive

  
	
   

  	
  St. Petersburg,
  Florida 33716

  
	
   

  	
  Attention:
  General Manager, Encapsulation,

  
	
   

  	
  North America

  
	
   

  	
  Facsimile: (727)
  803-1632

  
	
   

  	
   

  
	
  With a copy to:

  	
  Cardinal Health, Inc.

  
	
   

  	
  14 Schoolhouse
  Road

  
	
   

  	
  Somerset, New
  Jersey 08873

  
	
   

  	
  Attn: General
  Counsel

  
	
   

  	
  Facsimile: (732)
  537-6491

  



 


ARTICLE 19


MISCELLANEOUS


 


19.1                           Entire
Agreement; Amendments. This Agreement including the attachments, as well as
the Confidentiality Agreement dated July 29, 2004, constitute the entire
understanding between the Parties and supersedes any contracts, agreements or
understanding (oral or written) of the Parties with respect to the subject
matter hereof; provided, however, that this Agreement does not supersede the
Initial Agreement with respect to events that happened prior to January 1,
2007. For the avoidance of doubt, as of January 1, 2007, other than
payments due and owing of which both parties are aware, there are no payments
of any kind due and owing to either party. No term of this Agreement may be
amended except upon written agreement of both Parties, unless otherwise
provided in this Agreement.


 


19.2                           Captions.
The captions in this Agreement are for convenience only and are not to be
interpreted or construed as a substantive part of this Agreement.


 


19.3                           Further
Assurances. The Parties agree to execute, acknowledge and deliver such
further instruments and to take all such other incidental acts as may be
reasonably necessary or appropriate to carry out the purpose and intent of this
Agreement.


 

















 


19.4                           No
Waiver. Failure by either Party to insist upon strict compliance with any
term of this Agreement in any one or more instances will not be deemed to be a
waiver of its rights to insist upon such strict compliance with respect to any
subsequent failure.


 


19.5                           Severability.
If any term of this Agreement is declared invalid or unenforceable by a court
or other body of competent jurisdiction, the remaining terms of this Agreement
will continue in full force and effect.


 


19.6                           Independent
Contractors. The relationship of the Parties is that of independent
contractors, and neither Party will incur any debts or make any commitments for
the other Party except to the extent expressly provided in this Agreement. Nothing
in this Agreement is intended to create or will be construed as creating
between the Parties the relationship of joint ventures, co-partners,
employer/employee or principal and agent.


 


19.7                           Successors
and Assigns. This Agreement will be binding upon and inure to the benefit
of the Parties, their successors and permitted assigns. Neither Party may assign
this Agreement, in whole or in part, without the prior written consent of the
other Party (which consent shall not be unreasonably withheld, conditioned or
delayed), except that either Party may, without the other Party’s consent,
assign this Agreement to an Affiliate or to a successor to substantially all of
the business or assets of the assigning company (or the assigning company’s
business unit responsible for the performance of this Agreement), or, in the
case of Reliant, to a successor to all of the assets relating to the Product.


 


19.8                           Governing
Law. This Agreement shall be governed by and construed under the laws of
the State of New York, excluding its conflicts of law provisions.


 


19.9                           Alternative Dispute Resolution. If a dispute, controversy or disagreement (“Dispute”)
arises between the Parties in connection with this Agreement, then the Dispute
shall be presented to the respective presidents or senior executives of
Cardinal Health and Reliant for their consideration and resolution. If such
Parties cannot reach a resolution of the Dispute, then such Dispute shall be
resolved by binding alternative dispute resolution in accordance with the then
existing commercial arbitration rules of The CPR Institute for Dispute
Resolution (“CPR”), 366 Madison Avenue, New York, NY 10017. Arbitration shall be
conducted in New York, New York.


 


19.10                     Counterparts.
This Agreement may be executed in one or more counterparts, each of which
will be deemed an original but all of which together will constitute one and
the same instrument.


 


19.11                     Publicity.
Neither Party will make any press release or other public disclosure regarding
this Agreement or the transactions contemplated hereby without the other Party’s
express prior written consent (which shall not be unreasonably withheld,
conditioned or delayed), except as required under applicable law or by any
governmental agency, in which case the Party required to make the press release
or public disclosure shall use commercially reasonable efforts to obtain the
approval of the other Party (which shall not be unreasonably withheld,
conditioned or delayed) as to the form, nature and extent of the press release
or public disclosure prior to issuing the press release or making the public
disclosure.


 

















 


19.12                     Survival.
The rights and obligations of the Parties shall continue under Articles 5
(Testing; Manufacturing Samples; Release), 7 (Payment Terms), , 10 (Records;
Regulatory Matters), 11 (Confidential Information), 12 (Intellectual Property),
14 (Indemnification), 15 (Limitations of Liability), 16 (Insurance) to the extent
expressly stated therein, 18 (Notice), 19 (Miscellaneous), and Sections 4.2, 6.2
and 17.4 (Effect of Termination), notwithstanding expiration or termination of
this Agreement.


 


19.13                     Force
Majeure. Except as to payments required under this Agreement, neither Party
shall be liable in damages for, nor shall this Agreement be terminable or
cancelable by reason of, any delay or default in such Party’s performance
hereunder if such default or delay is caused by events beyond such Party’s
reasonable control including, but not limited to, acts of God, regulation or
law or other action or failure to act of any government or agency thereof, war
or insurrection, civil commotion, destruction of production facilities or
materials by earthquake, fire, flood or storm, labor disturbances, epidemic, or
failure of suppliers, public utilities or common carriers;  provided however, that the Party seeking
relief hereunder shall immediately notify the other Party of such cause(s)
beyond such Party’s reasonable control. The Party that may invoke this section shall
use all reasonable endeavors to reinstate its ongoing obligations to the other.
If the cause(s) shall continue unabated for sixty (60) days, then both Parties
shall meet to discuss and negotiate in good faith what modifications to this
Agreement should result from this force majeure.


 


The
Parties are executing this Agreement on the date stated in the introductory
clause.


 


	
  CARDINAL
  HEALTH PTS, LLC

  	
  RELIANT
  PHARMACEUTICALS, INC.

  
	
   

  	
   

  
	
  By:

  	
   

  	
   

  	
  By:

  	
   

  	
   

  
	
  Name: David J.
  Heyens

  	
  Name: Joseph S.
  Zakrzewski

  
	
  Its: President,
  Encapsulation North America

  	
  Its: Chief
  Operating Officer

  
						



 

















 


EXHIBIT A


SPECIFICATIONS


 


	
  Finished Product Release Specification

  

  

  Omacor Capsules

  	
  OMA-RSP

  

  

  Version: 03

  	
  

  



 


	
  Test

  	
   

  	
  Acceptance Criteria

  	
   

  	
  Method

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  *

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  *

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  *

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  *

  	
   

  
	
  [***]

  	
   

  	
  [***]

  	
   

  	
  *

  	
   

  







*Microbial limit tests are
performed by qualified laboratories, typically bulk capsule manufacturers.


History:


•      Version
01:  Approved on 6/14/05.


•      Version
02:  Removed unit for anisidine value
(typographical error), modified microbial limit test method numbers and other
minor typographical errors.  Approved on
8/31/05.


•      Version
03:  Changed capsule logo to “REL900” and
other editorial changes.


 


 


	
  Prepared by:

  	
   

  	
     Date:

  	
  8/11/06

  	
     Prepared by:

  	
   

  	
     Date:

  	
  8/11/06

  
	
   

  	
  Cindy Wu

  Manager

  QA/QC

  	
   

  	
   

  	
   

  	
  Goff Baker

  Director

  QA/QC

  	
   

  	
   

  



 






[***]:  Certain information on this page has been
omitted and filed separately with the Commission. Confidential treatment has
been requested with respect to the omitted portions.


 


 

















 


EXHIBIT B


UNIT PRICING, LIMITS OF LIABILITY, AND MINIMUM
REQUIREMENT


 


UNIT PRICING FOR TRADE PRODUCT– [***]% Requirements Level


 


	
  Units
  (millions)

  	
   

  	
  Price per thousand Units

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  



 


UNIT PRICING FOR TRADE PRODUCT– [***]% Requirements Level


 


	
  Units
  (millions)

  	
   

  	
  Price per thousand Units

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  



 


In the event Reliant
purchases less than [***] percent ([***]%) but more than [***] ([***]%) of its [***]
from Cardinal in any given Contract Year, an additional [***] dollars ($[***])
shall be added to the amounts set forth in the “Price per thousand Units”
column, in accordance with the first chart above i.e., if Reliant purchases up
to [***] units in a Contract Year, and such [***] Units amount represents less
than [***]% of Reliant’s commercial requirement for that given Contract Year,
the price shall be $[***] per [***] Units ([***]).


 


This is a “tiered”
pricing system. Therefore, for example, if Reliant purchases [***] Units from
Cardinal Health in a given Contract Year, and this represents [***] percent ([***]%)
of Reliant’s Manufacturing requirement levels for Trade Product for that
Contract Year, the price for the first [***] Units shall be $[***] per [***] Units,
the price for [***] Units through [***] Units shall be $[***] per [***] Units,
the price for [***]Units through [***] Units shall be $[***] per [***] Units,
and the price for [***] Units through [***] Units shall be $[***]. In the event
the [***] Units purchased from Cardinal Health does not represent [***] percent
([***]%) of Reliant’s Manufacturing requirement levels for Trade Product for
that Contract Year, the Unit Pricing shall be modified in accordance with the
paragraph and applicable chart above.


 


The price for Sample
Product shall be $[***] per [***] Units for any Contract Year wherein Reliant
purchases less than [***] percent ([***]%) of its Manufacturing requirement
levels for Trade Product from Cardinal Health. For any Contract Year wherein
Reliant purchases [***] percent ([***]%) of its Manufacturing requirement
levels for Trade Product from Cardinal Health, the price of the Sample Product
shall be the same as the price for the Trade Product for that Contract Year as
reflected in the applicable above chart.


 






 [***]: 
Certain information on this page has been omitted and filed
separately with the Commission. Confidential treatment has been requested with
respect to the omitted portions.


 

















 


For the avoidance of
doubt, the price for all Product purchased by Reliant from Cardinal Health from
July 1, 2006 through and including December 31, 2006 shall be [***]dollars
($[***]) per [***] Units.


 


LIMITATIONS OF LIABILITY


 


	
  Units

  	
   

  	
  Liability Limit per Each Contract Year

  
	
  Up to and
  including 200 million

  	
   

  	
  $ 1 million

  
	
  201 million up
  to and including 500 million

  	
   

  	
  $ 2 million

  
	
  501 million up
  to and including 750 million

  	
   

  	
  $ 3 million

  
	
  751 million up
  to and including 1 billion

  	
   

  	
  $ 4 million

  
	
  1 billion up to
  and including 1.25 billion

  	
   

  	
  $ 5 million

  
	
  1.251 billion up
  to and including 1.50 billion

  	
   

  	
  $6 million

  
	
  1.51 billion up
  to and including 1.750 billion

  	
   

  	
  $7 million

  
	
  1.751 billion
  and above

  	
   

  	
  $8 million

  



 


MINIMUM REQUIREMENT


 


	
  Contract
  Year

  	
   

  	
  Product / Dosage Form

  	
   

  	
  Minimum Requirement

  
	
  Contract Year 1

  	
   

  	
   

  	
   

  	
  $250,000

  
	
  Contract Years 2
  through 5

  	
   

  	
   

  	
   

  	
  $250,000
  adjusted for inflation and indexes

  



 






 [***]: 
Certain information on this page has been omitted and filed
separately with the Commission. Confidential treatment has been requested with
respect to the omitted portions.


 

















 


EXHIBIT C


 


MINIMUM YIELD SCHEDULE


 


[Reliant Pharmaceuticals
Letterhead]


 


May 23, 2006                                                


VIA
FACSIMILE (727) 803-2224


Cardinal Health PTS, LLC

2725 Scherer Drive

St. Petersburg, Florida  33716

Attention:  President, Encapsulation,

North America Oral Technologies


Re:          Minimum Yield


Dear Mr. Heyens:


                Reference is made hereby to the Manufacturing and
Packaging Agreement dated as of April 14, 2005 (the “Agreement”) between
Reliant Pharmaceuticals, Inc. (“Reliant”) and Cardinal Health PTS, LLC
(“Cardinal Health”).  All capitalized
terms in this letter that are not otherwise defined herein shall have the
meaning set forth in the Agreement.


By this letter Reliant and
Cardinal Health hereby acknowledge and agree that for purposes of Section 3.4,
the parties have established the Minimum Yield to be [***] Percent ([***]%).  This letter shall serve as Exhibit C
to the Agreement.  In all other respects
the Agreement shall remain in full force and effect.


To confirm your agreement
with the foregoing, please execute a copy of this letter in the place indicated
below.


	
   

  	
  Reliant
  Pharmaceuticals, Inc.

  
	
   

  	
   

  
	
   

  	
   

  
	
   

  	
  By:

  	
   

  
	
   

  	
   

  	
  Robert
  Polster

  
	
   

  	
   

  	
  Vice
  President, Manufacturing

  



 


 


 


Agreed
and acknowledged this 23 day


of
May, 2006


 


 


	
  By:

  	
   

  	
   

  
	
   

  	
  David Heyens

  
	
   

  	
  President,
  Encapsulation — North America

  
	
   

  	
   

  
	
  cc:

  	
  Cardinal Health, Inc.
  Associate General Counsel, Pharmaceutical Technologies and Services (via
  facsimile — (614) 757-5051)

  



 






[***]:  Certain information on this page has been
omitted and filed separately with the Commission. Confidential treatment has
been requested with respect to the omitted portions.


 


 

















 


EXHIBIT D


 


QUALIFICATION, VALIDATION AND STABILITY SERVICES


 


Quotation


Process Validation of 1000 mg
Omacor

Softgels at the St. Petersburg, FL

Facility


 


QTE-RLD-0025.00


 


 


 


Confidential for Reliant Pharmaceuticals


 


Prepared for Abdel Fawzy, Ph.D

100 Allen Road

Liberty Corner, NJ 07938

908-542-4488


Cardinal Health Contact: Jack Wright

Phone: 609-654-4524


February
15, 2005


 




	
  

   CardinalHealth

  	
  BioPharmaceutical
  Product Development

  Pharmaceutical Product Development

  Clinical Packaging Services

  Analytical Chemistry Services

  Scientific and Regulatory Consulting

  Pulmonary and Nasal Product Development

  Clinical and Small Scale Commercial Manufacturing

  






 

















 


	
  QTE-RLD-0025.00

  	
   

  	
  CONFIDENTIAL

  



 


 


Executive Summary


 


Reliant Pharmaceuticals (Reliant) has requested Cardinal Health,
Pharmaceutical Development (Cardinal Health) to perform process validation for
the Omacor 1000 mg softgels at Cardinal Health’s facility in St. Petersburg,
FL. The estimated cost for this project is $[***] plus cost of softgels, over a
period of approximately [***].


 


Section 1.  Scope of Work


 


Cardinal Health, Somerset has developed and scaled up Omacor 1000 mg
softgels to commercial scale in Cardinal Health, St. Petersburg. Cardinal
Health will manufacture three (3) process validation batches and generate
validation report prior final commercial launch. All clinical batch manufacture
activities will be conducted according to cGMP guidelines.


 


Section 2.  Activities/Specifications


 


2.1          Project Activities


 


2.1.1                     Cardinal
Health’s Responsibilities


 


2.1.1.1           Preliminary Activities


 


Cardinal Health
will conduct preliminary activities to include the following:


 


•                  Provide project
management and timelines.


•                  Identify
project team members and outline expectations.


•                  Finalize
initial protocols.


•                  Identify and
receive necessary Reference Standards, API lots, and excipients for
development.


Estimated Cost


	
  Estimated Duration (Weeks)

  	
   

  	
  Estimated Cost ($)

  
	
  1

  	
   

  	
  No Charge

  



 


2.1.1.2           Omacor Development Report


 


Cardinal Health will
carry out project-related activities to include the following:


 


•                  Compile listing
of all batches made in St. Petersburg, FL.


•                  Gather all
information related to any research and development conduct in the St.
Petersburg, FL facility.


•                  Issue a
development report summarizing all work completed in the St. Petersburg,
FL facility.


14 Schoolhouse
Road • Somerset, NJ 08873

Direct: (732) 537-6200 • Facsimile: (732) 537-6480 • www.cardinal.com/pts


 






[***]:  Certain information on this page has been
omitted and filed separately with the Commission. Confidential treatment has
been requested with respect to the omitted portions.


 


2





















Estimated Cost


	
  Estimated Duration (Weeks)

  	
   

  	
  Estimated
  Cost ($)

  
	
  [***]

  	
   

  	
  [***]

  



 


2.1.1.3           Omacor 1000 mg Softgel Process Validation


 


Cardinal Health
will perform the following activities in order to validate Omacor 1000 mg
softgel manufacturing process at commercial scale:


 


•                  Generate a
process validation protocol and obtain approval from Reliant.


•                  Obtain drug
substance from Reliant and complete ID test for release (included in analytical
support section).


•                  Order raw
materials and sample for release.


•                  Generate
product masters.


•                  Perform as
customer liaison and supervise batches.


•                  Complete
peroxide test on drug prior to encapsulation (included in analytical support
section).


•                  Manufacture and
validate manufacturing process of three full-scale in-line printed
batches at production site.


•                  Monitor batches
and collect fill and softgel samples for in-process testing as required in the
validation protocol.


•                  Monitor
hardness of softgels during drying.


•                  Wash and bulk
package softgels for shipping to Reliant.


•                  Perform
in-process seal thickness, fill and shell weight measurement.


•                  Clean equipment
as per validated method.


•                  Release
finished product.


•                  Perform QA
review of all documentation.


Estimated Cost


	
  Estimated Duration (Weeks)

  	
   

  	
  Estimated
  Cost ($)

  
	
  [***]

  	
   

  	
  [***]

  



 


2.1.1.4           DMF Update


 


Cardinal Health will
update the DMF to reflect all changes made from the original DMF filing.


Estimated Cost


	
  Estimated Duration (Weeks)

  	
   

  	
  Estimated
  Cost ($)

  
	
  [***]

  	
   

  	
  [***]

  



 






[***]:  Certain information on this page has been
omitted and filed separately with the Commission. Confidential treatment has
been requested with respect to the omitted portions.


 


3

















 


2.1.1.5           In-Process and Release Testing of
Softgels for Process Validation


 


Cardinal Health will
carry out project-related activities for three process validation batches as
follows:


 


•                  Perform appropriate
in-process fill weight and content uniformity testing and release testing for
three batches of active: appearance, identification (HPLC), assay/related
substances, fill weight, disintegration, content uniformity, moisture, and
microbial limits testing (MLT).


•                  Perform
peroxide test and AQL on three batches.


•                  Issue CoA.


Estimated Cost


	
  Activity and Estimated Duration
  (Weeks)

  	
   

  	
  Estimated Cost ($)

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  
	
  [***]

  	
   

  	
  [***]

  







* Additional
cost may be incurred for more then three samples ($[***] per sample requiring assay). Content uniformity will be charged at $[***] per set of samples.


2.1.2                     Reliant
Responsibilities


 


Reliant will sign the
protocol and provide a technical contact who will be available for technical
discussions and make decisions that are needed in reference to this project.
Reliant will not use any samples/materials shipped from Cardinal Health for
this project in a manner that is inconsistent with the scope of this project.


 


2.2          Specifications


 


2.2.1                     Cardinal
Health’s Responsibilities


 


Cardinal Health will
propose and document the specifications, as applicable, in the Protocol(s).


 






[***]:  Certain information on this page has been
omitted and filed separately with the Commission. Confidential treatment has
been requested with respect to the omitted portions.


 


4

















 


2.2.2                     Reliant’s
Responsibilities


 


Reliant will provide all
specifications necessary to perform this project.


 


Section 3.  Cost Proposal


 


3.1          Project Costs


Total Estimated Project Cost


	
  Section

  Reference

  	
   

  	
  Activity

  	
   

  	
  Estimated Duration

  (Weeks)

  	
   

  	
  Estimated Cost

  ($)

  	
   

  
	
  2.1.1.1.

  	
   

  	
  Preliminary Activities

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  2.1.1.2.

  	
   

  	
  Omacor Development
  Report

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  2.1.1.3.

  	
   

  	
  Omacor 1000 mg Softgel
  Process Validation

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  2.1.1.4.

  	
   

  	
  DMF Update

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  2.1.1.5.

  	
   

  	
  In-Process and Release
  Testing of Softgels for Process Validation

  	
   

  	
  [***]

  	
   

  	
  [***]

  	
   

  
	
  Total
  Estimated Project Cost

  	
   

  	
  [***]

  	
   

  



 


3.2          Additional
Fees


 


If copies of raw data are requested in the course of an active project,
Reliant will be invoiced at $[***] for time required to generate and compile
the data packet. If copies of raw data are requested after a final report has
been issued, Reliant will be invoiced at the current laboratory rate for the
hours required to generate and compile the data packet.


 


3.3          Revisions
to Pricing


 


Cardinal Health reserves the right to revise quoted costs for any
project as a result of initial scope change, revisions in Protocols,
modifications of test methods, final review of test methods, undocumented
requirements, retesting or resynthesis, or any unforeseen difficulty in
executing the project. The additional work will be performed based on written
agreement from Reliant and will be documented on a Cardinal Health Quotation
Amendment Record (QAR).


 


All required investigational work (such as OOS investigations, trouble
shooting chromatographic methods, etc.) may be conducted without prior approval
from Reliant, for up to 16 scientist hours per occurrence. If the additional
work requires going beyond [***] hours, Reliant will be contacted prior to
continuation. All investigational retesting performed that is not directly due
to a Cardinal Health error will be invoiced to Reliant.


 


 






[***]:  Certain information on this page has been
omitted and filed separately with the Commission. Confidential treatment has
been requested with respect to the omitted portions.


 


 


5

















Section 4.  Invoicing and Payment Terms


 


4.1          Invoicing


 


Upon request from Reliant, Cardinal Health will
purchase all samples/materials necessary to perform the project and will
invoice Reliant monthly at cost plus reasonable and customary acquisition and
handling costs.


 


Non-standard or special instrumentation or equipment
required solely for this project will be invoiced to Reliant following Reliant
approval.


 


4.2          Additional Invoicing Terms


 


Cardinal Health will issue invoices based on
milestones identified in Section 2.1.1. If a draft report is issued, Reliant
will have 10 business days to return comments to Cardinal Health. If no
comments are received, Cardinal Health will finalize the report and issue the
invoice. If comments are received after issuance of the final report, Reliant
will be billed at the current standard hourly rate for the time required to
complete changes and reissue the report.


 


4.3          Payment Terms


 


Payments toward all invoices are due within 30 days of
receipt of invoice and are non-refundable. Any applicable wire transfer fees
must be included in the payment issued to Cardinal Health. All shipments are
FOB Somerset, New Jersey. Remit all payments to:


 


Cardinal Health, Pharmaceutical Development, Somerset 

P.O. Box 827389

Philadelphia, PA 19182-7389


 


Section 5.  Scheduling/Deliverables


 


5.1          Scheduling


 


Cardinal Health must receive a signed Quotation with a
Purchase Order number (if applicable), a signed Protocol, and all raw
materials/intermediates/final product samples in order for this project to be
scheduled. Once scheduled, Reliant will be notified by Cardinal Health of the
anticipated start and completion date of the project activities.


 


5.2          Deliverables


 


5.2.1                     Reports
and Certificates of Analysis


 


A report and/or
Certificate of Analysis will be issued upon completion of each project phase.


 


6

















5.2.2                     Communication


 


In order to establish a
collaborative relationship between Reliant and Cardinal Health, both parties
will appoint a Project Manager to serve as a point of contact to oversee
progress on this project. Upon initiation of the project, Cardinal Health and
Reliant will establish a communication plan, if requested, that may include
conference calls, visits, and timelines.


 


Section 6.  Additional Project Terms


 


6.1          Safety


 


6.1.1                     Cardinal
Health’s Responsibilities


 


Cardinal Health will
assess all vendor and Reliant MSDS and all handling data for the
samples/materials associated with this project. If categorized as a CDS and/or
Category 3 or above, the samples/materials will require special handling
precautions and will be subject to a Hazardous Material Fee for all handling
and testing directly associated with the samples/materials. If applicable, this
Hazardous Materials Handling Surcharge will be included in the project costs.


 


6.1.2                     Reliant’s
Responsibilities


 


Reliant will provide MSDS
and all sample/material handling data for the samples/materials associated with
this project. If any sample/material has any special handling considerations,
Reliant will notify Cardinal Health prior to the initiation of the project.


 


6.2          Methods/Documentation


 


6.2.1                     Cardinal
Health’s Responsibilities


 


Cardinal Health will
review all project-related documentation and methods received from Reliant
associated with this project.


 


6.2.2                     Reliant’s
Responsibilities


 


Reliant will provide all
available project-related documentation and methods to be used for this
project.


 


7

















6.3          Samples/Materials


 


6.3.1                     Cardinal
Health’s Responsibilities


 


Cardinal Health will, as
necessary, log in all samples/materials according to current Standard Operating
Procedures. The sample/material lot numbers will be recorded in the laboratory
notebooks at the time of use.


Upon issuance of the
final report or Certificate of Analysis, samples/materials will be stored in
quarantine at Cardinal Health for a period of 30 days. After the 30-day
quarantine period, samples/materials will be disposed of at Cardinal Health
unless requested otherwise by Reliant. If additional storage is requested,
Cardinal Health will issue a QAR for the additional cost.


 


6.3.2                     
Reliant’s Responsibilities


 


If available, Reliant
will provide all samples/materials necessary to perform this project. The
samples/materials should arrive at Cardinal Health with all proper
documentation. If samples/materials are not available, Reliant will request
that Cardinal Health purchase all necessary samples/materials needed to perform
this project.  If return shipment is
requested, Reliant will notify Cardinal Health prior to the disposition of
samples/materials.


 


6.4          Cancellation


 


If this project is cancelled by Reliant for purposes
within their control, Cardinal Health will invoice Reliant the cost of any
sample/materials, work performed before cancellation, reference materials,
equipment, and supplies purchased by Cardinal Health specifically for this
project.  In addition, Cardinal Health
reserves the right to invoice project cancellation fees according to the following
schedule: acceptance of quotation but no approved protocol, $[***]; acceptance
of protocol but no laboratory work, $[***]; and after laboratory work has
begun, [***]%.


 


For pilot plant manufacture, Cardinal Health reserves
the right to invoice project cancellation fees according to the following
calendar day schedule: [***].


 


6.5          Project Notes


 


Reliant communication is encouraged.  To foster project planning, reviews/updates,
and coordination meetings, Cardinal Health will provide four person-hours a
month of communication free of charge. 
Additional communication hours beyond this amount will be invoiced at
the standard hourly rate.


 






[***]:  Certain information on this page has been
omitted and filed separately with the Commission. Confidential treatment has
been requested with respect to the omitted portions.


 


8

















Reliant shall pay for all product batches, including
batches that do not conform to applicable specifications, unless all methods
and processes associated with the manufacture, testing, and storage of that
product have been fully validated in accordance with generally accepted
standards of the pharmaceutical industry.


 


The costs associated with optional testing have not
been included in the total estimated project cost.


 


The summary of costs detailed above does not include
any extra reformulation activities, any post submission activities, and/or any
activities required for commercial batch manufacture.  Additionally, it does not include any post
approval tasks such as annual stability testing or storage.  If requested by Reliant, these costs will be
quoted separately.


 


Section 7.   Version History


 


 


Revisions


 


	
  Version

  	
   

  	
  Revisions

  
	
  00

  	
   

  	
  New Issue

  



 


Section 8. 
Terms and Conditions


All work performed under this quotation is subject to the
Supply Agreement to be executed between Cardinal Health and Reliant
Pharmaceuticals.  Upon receipt of an
executed Term Sheet and Purchase Order from Reliant, Cardinal Health shall
commence the validation process activities and manufacture the validation lots,
while the parties negotiate the supply agreement.  In the event that the supply agreement has
not been executed as of the date of the completion of the manufacture of the
validation lots, Cardinal Health shall release the validation lots to Reliant
upon payment of the amounts due Cardinal Health as set forth in the Purchase
Order and agreement by the parties as to responsibility for any liabilities
(i.e. recall, product liability etc) associated with the manufacture or sale of
the validation lots.


 


9

















Section 9.  Project Approval and Authorization


 


By signing below, Reliant agrees to the project
details as set forth in this Quotation.


 


	
  Reliant Pharmaceuticals.



  	
   

  	
  Cardinal Health PTS, LLC



  
	
   

  	
   

  	
  /s/

  
	
  Signature

  	
   

  	
  Signature

   

  
	
   

  	
   

  	
  Kent Payne, Ph.D.

  
	
  Printed Name



  	
   

  	
  Printed Name



  
	
   

  	
   

  	
  Vice President, Research and Development

  
	
  Title



  	
   

  	
  Title



  
	
   

  	
   

  	
  16 Feb 2005

  
	
  Date



  	
   

  	
  Date

  
	
   

  	
   

  	
   

  
	
  PO Number

  	
   

  	
   

  



 


Please sign and return a copy of the Quotation Approval Page via fax to

Denise McGraw at (732) 537-6480 or email to denise.mcgraw@cardinal.com.


 

















EXHIBIT E


 


FORM OF QUALITY AGREEMENT


 


 


COMMERCIAL

QUALITY AGREEMENT


Between





And





For the manufacture of:



OmaCor Capsules


 

















	
  Commercial Quality Agreement

  	
   

  	
  OmaCor Capsules

  
	
  Between Reliant Pharmaceuticals,
  Inc. and Cardinal Health

  	
   

  	
   

  



TABLE OF CONTENTS


	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  Page

  	
   

  
	
  I

  	
   

  	
  QUALITY AGREEMENT AND TERM 

  	
   

  	
  1

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  II

  	
   

  	
  PRODUCTS 

  	
   

  	
  1

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  III

  	
   

  	
  CONTACT INFORMATION 

  	
   

  	
  2

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  IV

  	
   

  	
  MANUFACTURING COMPLIANCE

  	
   

  	
   

  	
   

  	
  3

  	
   

  
	
   

  	
   

  	
  1.

  	
   

  	
  Premises

  	
   

  	
  3

  	
   

  
	
   

  	
   

  	
  2.

  	
   

  	
  Equipment

  	
   

  	
  3

  	
   

  
	
   

  	
   

  	
  3.

  	
   

  	
  Personnel

  	
   

  	
  3

  	
   

  
	
   

  	
   

  	
  4.

  	
   

  	
  Materials

  	
   

  	
  4

  	
   

  
	
   

  	
   

  	
  5.

  	
   

  	
  Documentation

  	
   

  	
  4

  	
   

  
	
   

  	
   

  	
  6.

  	
   

  	
  Lot Numbers and Expiration

  	
   

  	
  5

  	
   

  
	
   

  	
   

  	
  7.

  	
   

  	
  Bulk Product Storage and Shipment

  	
   

  	
  5

  	
   

  
	
   

  	
   

  	
  8.

  	
   

  	
  Processing of Intermediates (Bulk
  Hold)

  	
   

  	
  5

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  V

  	
   

  	
  QUALITY CONTROL 

  	
   

  	
  6

  	
   

  
	
   

  	
   

  	
  1.

  	
   

  	
  Premises

  	
   

  	
  6

  	
   

  
	
   

  	
   

  	
  2.

  	
   

  	
  Equipment

  	
   

  	
  6

  	
   

  
	
   

  	
   

  	
  3.

  	
   

  	
  Vendor Approval

  	
   

  	
  6

  	
   

  
	
   

  	
   

  	
  4.

  	
   

  	
  Personnel

  	
   

  	
  6

  	
   

  
	
   

  	
   

  	
  5.

  	
   

  	
  Out-of-Specification (OOS
  Investigations)

  	
   

  	
  6

  	
   

  
	
   

  	
   

  	
  6.

  	
   

  	
  Reference Standards

  	
   

  	
  7

  	
   

  
	
   

  	
   

  	
  7.

  	
   

  	
  Product Release

  	
   

  	
  7

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  VI

  	
   

  	
  QUALITY ASSURANCE 

  	
   

  	
  8

  	
   

  
	
   

  	
   

  	
  1.

  	
   

  	
  Documentation

  	
   

  	
  8

  	
   

  
	
   

  	
   

  	
  2.

  	
   

  	
  Samples

  	
   

  	
  8

  	
   

  
	
   

  	
   

  	
  3.

  	
   

  	
  Investigations/Deviations

  	
   

  	
  9

  	
   

  
	
   

  	
   

  	
  4.

  	
   

  	
  Product Complaints or Adverse
  Events

  	
   

  	
  10

  	
   

  
	
   

  	
   

  	
  5.

  	
   

  	
  Annual Product Review

  	
   

  	
  10

  	
   

  
	
   

  	
   

  	
  6.

  	
   

  	
  Product Recalls

  	
   

  	
  11

  	
   

  
	
   

  	
   

  	
  7.

  	
   

  	
  Audits by Reliant Pharmaceuticals

  	
   

  	
  11

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  VII

  	
   

  	
  REGULATORY 

  	
   

  	
  12

  	
   

  
	
   

  	
   

  	
  1.

  	
   

  	
  Inspections by Regulatory Agencies

  	
   

  	
  12

  	
   

  
	
   

  	
   

  	
  2.

  	
   

  	
  Annual Reports

  	
   

  	
  12

  	
   

  
	
   

  	
   

  	
  3.

  	
   

  	
  Drug Listing

  	
   

  	
  12

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  VIII

  	
   

  	
  VALIDATION 

  	
   

  	
  13

  	
   

  
	
   

  	
   

  	
  1.

  	
   

  	
  Process

  	
   

  	
  13

  	
   

  
	
   

  	
   

  	
  2.

  	
   

  	
  Equipment Cleaning Validation

  	
   

  	
  13

  	
   

  
	
   

  	
   

  	
  3.

  	
   

  	
  Computer

  	
   

  	
  13

  	
   

  
	
   

  	
   

  	
  4.

  	
   

  	
  Analytical Test Methods

  	
   

  	
  13

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  REVISION HISTORY AND APPROVAL 

  	
   

  	
  14

  	
   

  
										



 


i

















 


This Quality Agreement does
not supercede or amend any provisions in the Supply Agreement between Reliant
Pharmaceutical (Reliant) and Cardinal Health (Cardinal) dated April 14, 2005
(as may be amended from time to time, the “Agreement”).  In the event of a conflict between the terms
of the Agreement and this Quality Agreement, the Agreement shall be
controlling.


I               QUALITY AGREEMENT AND TERM


 


1.             It is deemed
necessary by Reliant and Cardinal to allocate the responsibilities of current
good manufacturing practice (cGMP), as defined in 21 CFR part 210-211, by which
OmaCor Capsules shall be manufactured and provided to Reliant.


2.             This Quality
Agreement, in conjunction with the Agreement, shall define the responsibilities
of the parties involved, and the levels of interaction necessary for the
delivery of a compliant drug product.


3.             This Quality
Agreement shall expire with the termination of the Agreement.  This Quality Agreement can be modified with
the written approval of Reliant and Cardinal Quality Departments.  A revision history shall be maintained as
part of the Quality Agreement.


II             PRODUCTS


 


Cardinal has agreed to
manufacture OmaCor Capsules in accordance with all cGMP’s, Product
Specifications and all applicable federal, state, and local laws and
regulations.


 


1

















 


III            CONTACT INFORMATION


 


Communication pertaining to the manufacture of the
Drug Product shall flow between the established channels detailed below.


 


	
  DEPARTMENT

  	
   

  	
  RELIANT CONTACT

  	
   

  	
  CARDINAL CONTACT

  
	
  QUALITY
  ASSURANCE

  	
   

  	
  Name: 

  Phone: 

  Fax: 

  e-mail: 

  	
  Keith Bowen

  (908) 542-4432

  (908) 542-4460

  kbowen@reliantrx.com

  	
   

  	
  Name: 

  Phone: 

  Fax: 

  e-mail:

  	
  Leandra Mollanazar

  (727) 803-2263

  (727) 803-2315

  leandra.mollanazar@cardinal.com

  
	
  MANUFACTURING OPERATION

  	
   

  	
  Name: 

  Phone: 

  Fax: 

  e-mail: 

  	
  Christopher Campbell

  (908) 542-4425

  (908) 542-9405

  ccampbell@reliantrx.com

  	
   

  	
  Name: 

  Phone: 

  Fax: 

  e-mail: 

  	
  Michael Stanco

  (727) 803-2373

  (727) 803-1632

  michael.stanco@cardinal.com

  
	
  REGULATORY

  	
   

  	
  Name: 

  Phone: 

  Fax: 

  e-mail: 

  	
  Mary Chin

  (908) 542-4461

  (908) 542-4460

  mchin@greliantrx.com

  	
   

  	
  Name: 

  Phone: 

  Fax: 

  e-mail: 

  	
  Gloria Kulcheski

  (727) 803-2454

  (727) 803-2315

  gloria.kulcheski@cardinal.com

  
	
  PRODUCTION PLANNING

  	
   

  	
  Name: 

  Phone: 

  Fax: 

  e-mail: 

  	
  Tanya Quinn

  (908) 860-4654

  (908) 542-9405

  tquinn@reliantrx.com

  	
   

  	
  Name: 

  Phone: 

  Fax: 

  e-mail: 

  	
  Lee Kelly

  727-803-2209

  727-572-9577

  lee.kelly@cardinal.com

  



 


2

















 


IV            MANUFACTURING COMPLIANCE


OmaCor will be manufactured by Cardinal according to the Agreement at
their facility located at 2725 Scherer Drive, St. Petersburg, FL  33716 as detailed in the NDA and
Agreement.  The FDA facility number for
this location is 1811396.


1.             Premises


1.1           The manufacturing facility shall
comply with all aspects of 21 CFR Part 210 and 211 Subpart C, as well as all
additional requirements detailed in the Agreement,


2.             Equipment


2.1           Equipment used to manufacture the
Product shall comply with 21 CFR part 211 Subpart D, as well as all additional
requirements detailed in the original DMF and subsequent updates.


2.2           Cardinal shall maintain written
records for equipment usage, cleaning, maintenance and calibration of all
equipment used in the processing of the Drug Product to ensure that cleaning
and maintenance records are readily identifiable with equipment usage in the
event of a drug product problem that may be investigated.  Cardinal shall maintain approved written
procedures including, but not limited to, specifications for cleaning,
assignment of responsibility for cleaning and maintaining equipment.


2.3           Installation qualification (IQ)/
operational qualification (OQ)/ performance qualification (PQ) shall be
performed on all equipment used in the manufacture and analysis of the product,
and the same equipment shall be placed on a calibration and/or preventive
maintenance schedule, as appropriate.


2.4           Cardinal shall only use the major
equipment detailed in the Master Batch Records thereto for the processing and
manufacture of the product.  Use of
equipment other than that stipulated in the mutually agreed to Master Batch production
records shall not be permitted without prior written consent from Reliant
Quality and Regulatory, irrespective of FDA guidance’s detailing equipment
class and subclass equivalencies.


3.             Personnel


3.1           Cardinal shall maintain quality
control and quality assurance units to be responsible for the duties relating
to quality control and quality assurance. 
The responsibilities of these units shall be defined in written
procedures.


3.2           Personnel used to process the drug
product shall be appropriately trained in cGMP’s, as well as the processes they
perform.  Training shall be


 


3

















 


                documented and available for review.  Training shall be conducted on a continuing
basis by qualified individuals.


3.3           There shall be an adequate number of
qualified personnel to perform and supervise the processing and manufacture of
the drug product.


4.             Materials


4.1           Cardinal shall use only those
excipients, Active Pharmaceutical Ingredients (“API”), components, and bulk
capsule packaging materials as detailed in the DMF.


4.2           Cardinal shall sample all materials
according to approved procedures, and shall test and release those materials
according to approved analytical methodology and specifications as filled in
the DMF.


4.3           Cardinal shall store all packaging
materials, excipients, API, and finished product in a suitable environment so
as not to impact the materials’ quality. 
A suitable retest program shall be used to demonstrate the quality of
the stored material versus approved specifications.  Certificates of Analysis or analytical test
sheets, as defined by Cardinal, shall be generated and reviewed by quality
control to release all materials used to process and manufacture the Product.


5.             Documentation


5.1           Cardinal shall provide written
documentation in the form of a master batch record for all processes used in
the manufacture of the Product.


5.2           Cardinal shall maintain and follow
Standard Operating Procedures (SOP) required to manufacture, package, analyze,
release, and store in-process materials as well as the Product as detailed in
the DMF, and required by cGMP.


5.3           Cardinal shall follow a suitable
change control procedure for all documentation. 
All changes to controlled documents such as, batch records,
manufacturing specifications, test methods, and raw materials supplied by
Reliant and product specifications must be submitted to Reliant QA for review
and approval prior to final approval and implementation.  Any documentation necessary to support the
change request shall be provided as necessary.


5.4           Labeling of bulk finished product
will be executed per Cardinal’s in-house labeling program.  Bulk shipper labels shall contain a minimum
of the following information:  product
name, strength, container number, storage statement, package by date, Cardinal
shall follow written procedures for 


 


4

















 


label control for the
receipt, release, dispensing, and reconciliation of all labels, as appropriate.


6.             Lot Numbers and Expiration


6.1           Cardinal shall assign unique lot
numbers to bulk finished product to ensure complete product traceability.


7.             Bulk Product Storage and
Shipment


7.1           Cardinal shall store all finished
product in suitable containers, labeled with lot specific information, and in a
controlled environment to remove possibility of tampering, theft, adulteration,
or contamination.


7.2           Product shall be labeled with all
D.O.T. and O.S.H.A. information, as required, and suitably packaged to minimize
damage during transit.


7.3           Bulk product container shall be
sealed with tamper evident closures or seals to remove the possibility of
tampering, theft, adulteration, or contamination.


7.4           Bulk finished product may be shipped
by Cardinal to a Reliant specified address once all site specific testing
requirements are approved all deviations and investigations are closed, and the
batch record is approved..  Materials may
be shipped under Quarantine only with the prior written consent from the
Quality Department from Reliant and Cardinal.


7.5           Product should be segregated by lot
number prior to shipment.


8.             Processing of Intermediates
(Bulk Hold)


8.1           Each process intermediate for each
step of the manufacturing process may be held for a period of up to 30
days.  Holding a process intermediate for
a period of longer than 30 days must be supported by stability data, generated
per an approved protocol that supports a longer storage interval.


 


5

















 


V             QUALITY
CONTROL


Cardinal shall maintain a cGMP quality control laboratory suitable to
test and release all materials; API, components, in-process test samples, and
finished product according to the analytical methods and specifications
detailed in the DMF and subsequent updates or NDA or approved Supplement.  This laboratory is the only qualified
laboratory to perform analytical testing in support of the materials, API,
components, and drug products, unless otherwise specified in the DMF.  Use of any other laboratory for release
testing is not permitted.


1.             Premises


1.1           The quality control laboratory shall
comply with all aspects of 21 CFR Part 210 and 211.


2.             Equipment


2.1           Installation qualification/
operational qualification/ performance qualification shall be performed on all
equipment used in analysis of excipients, components, and the product and the
same equipment shall be placed on a calibration schedule, as appropriate.


2.2           Cardinal shall maintain written
records for equipment usage, maintenance and calibration.


3.             Vendor Approval


3.1           Cardinal shall suitably qualify all
vendors from which materials are sourced for use in the finished drag
product.  This includes, but is not
limited to excipients, container closure systems, printed commodities, etc.


4.             Personnel


4.1           Personnel used to test and release
the Product shall be appropriately trained in cGMP’s, as well as the methods
and techniques they utilize.  Training
shall be documented and available for review. 
Training shall be conducted on a continuing basis by qualified individuals.


5.             Out-of-Specification (OOS)
Investigations


5.1           Cardinal is responsible for following
its SOP to investigate any test results that fail to meet specifications.  A confirmed OOS failure should be conveyed to
Reliant Quality within 2 business days. 
These OOS investigations are open to review by Reliant during an audit.


 


6

















 


6.             Reference Standards


6.1           All testing shall use primary
reference standards, or appropriately qualified secondary reference
standards.  Qualification of secondary
reference standards must comply with current ICH guidelines.


7.             Product Release


7.1           Reliant is responsible for assessing
final product disposition and release. 
Cardinal shall provide a COA/COC and product yield page for each lot
manufactured.


 


7

















 


VI            QUALITY
ASSURANCE


Cardinal’s Quality Department shall assure that the drug product was
manufactured, tested, released, and stored in accordance with cGMP’s, and all
requirements as detailed in the in the approved master batch
record/specifications.


1.             Documentation


1.1           Cardinal will provide both a
Certificate of Analysis indicating all Cardinal test results and their
specifications, and a Certificate of Compliance indicating the Drug Product has
been manufactured, packaged, tested, released and stored according to cGMP’s
and all requirements as detailed in the master batch record/specifications.


1.2           Cardinal shall provide written
certification for cGMP Compliance and Debarment annually upon request.


1.3           Cardinal shall retain all Batch
Production Records for the Drug Product for a period of not less than one year
past the finished product expiration date.


1.4           Deviations to the manufacturing
process or analytical test methods must be documented, reviewed versus the
respective validation, and approved by both Reliant and Cardinal Quality
Assurance department s prior to release of the Drug Product.


1.5           Cardinal is responsible for
maintaining all documentation supporting all manufacturing processes,
analytical testing, and storage of the Drug Product for a period of not less
than one year past the expiration date of any finished product lot containing
it.


1.6           Cardinal shall follow a suitable
Change Control Procedure for all documentation. 
All changes to batch records, manufacturing specifications, or test
methods must be submitted to Reliant Quality Assurance for review and approval
prior to implementation.


1.7           Validation records shall be
maintained by Cardinal until the NDA is retired.


2.             Samples


2.1           Cardinal’s Quality Control Unit shall
assure that all test samples are taken in accordance with approved SOP’s.


2.2           Cardinal shall maintain bulk product
reserved samples for a period of not less than one year past the expiration
date of finished products.  At least
twice as much material shall be retained as is needed to conduct testing if
necessary.


 


8

















 


2.3           Cardinal shall retain API reserve
samples for one year after the expiration date on the last finished product lot
containing it.  At least twice as much
material shall be retained as is needed to conduct all specification release
testing.


2.4           Manufacturer shall perform annual
inspection of the bulk product retained samples as per 21 CFR 211.170, and will
perform an investigation of deterioration, if necessary, as per 21 CFR 211.170.


3.             Investigations/Deviations


3.1           Cardinal shall notify Reliant Quality
in writing within two business day after confirmation of any situation that
impacts product that has already been released. 
Cardinal shall also provide Reliant with verbal communication of any
such investigation prior to the confirmation so that appropriate action can be
implemented to restrict continued distribution of product until the
investigation can be finalized.


3.2           All major and minor manufacturing
deviations shall be investigated and approved by both Cardinal and Reliant QA
departments.  Copies of the final
approves investigations shall be conveyed to Reliant Quality with the issuance
of the bulk product certificate of analysis. 
In addition, Cardinal shall inform Reliant QA of any confirmed Out of
Specification result.


A Major Deviation is defined as:  A departure from normal operating conditions
that is determined to have a significant or unknown
impact on the identity, strength, quality, and purity of the drug product.  Examples include, but are not limited
to:  failure of a batch or lot to meet
any analytical specification that is not determined to be a laboratory error;
or, compounding errors such as dispensing incorrect quantities of material; or
processing errors such as using equipment that is outside of approved
calibration dating or processing a batch outside the tolerances set forth in
the batch record; or observation of foreign materials in a batch; or packaging
or labeling errors.


A Minor Deviation is defined as:  A departure from normal operating conditions
that is determined to have no impact on the identity, strength, quality, and
purity of the drug product.  Examples
include, but are not limited to:  low
gross yields; or calculation or rounding errors that have no impact on the
batch.


3.3           Rework/Reinspections:  Cardinal shall obtain approval from Reliant
QA before performing any rework or reinspection of intermediates or finished
product.


 


9

















 


4.             Product Complaints or Adverse
Events


4.1           All individuals reporting a product
related complaint shall be immediately directed to contact Reliant
Pharmaceuticals’ Customer Complaints Group at telephone number:  908.580.1200.


4.2           All individuals reporting an Adverse
Event shall be immediately directed to contact Reliant Pharmaceuticals’ Medical
Affairs Department at telephone number: 
908.580.1200.


4.3           Reliant Pharmaceutical’s Quality
Department shall evaluate all complaints and determine if product retain
analysis is required.  A written request
shall be forwarded to Cardinal detailing any product retain investigation that
is required.  Cardinal shall provide a
written report of the investigation within 20 business days.


4.4           Cardinal shall maintain a system for
logging, tracking, and responding to complaints.


4.5           Reliant shall be the only authorized
group to provide product related responses to the public.


4.6           Should Reliant discover a product
related problem, Reliant Quality Department shall provide a written complaint
notification to Manufacturer within 2 business days of the occurrence.


4.7           Should Cardinal, through routine
product review, discover a product related issues that causes an investigation,
Cardinal shall provide written notification to Reliant’s Quality Department
within 3 business days.


5.             Annual Product Review


5.1           Cardinal shall perform an annual
product review for the Product detailing all product lots manufactured, product
investigations, lots released or rejected, specification changes (to excipient,
in-process controls, or finished product), and process or method revisions
(including validation reports) for all Product lots manufactured in the
previous calendar year.  All critical
release data shall be trended to evaluate the process.


5.2           The written annual product review
report for a given year shall be sent to Reliant Quality Department.  The reporting period shall commence with the
first day of the month in which the validation campaign started, and shall
close 365 days later (i.e. April 1, 2005 through March 31, 2006).  This period will be the established reporting
period for the product.


 


10

















 


5.3           The written annual product review
report for a given year shall be sent to Reliant Quality Department within 90 days
of the close of the reporting period.


6.             Product Recalls


6.1           It shall be the sole responsibility
of Reliant to issue a FDA Field Alert Notification pertaining to a product
quality issue discovered by Cardinal or Reliant.  An alert shall only be issued with
substantive evidence of a quality issue, for which Cardinal shall have 5
business days from obtaining knowledge of the substantial evidence of a quality
issue to provide a full investigation report to Reliant Pharmaceuticals.


6.2           It shall be the sole responsibility
of Reliant to issue a product recall, and discuss with FDA the extent or type
of action that should occur.  Decisions
to initiate a product recall shall be based on product medical reviews and the
investigation report used to support the FDA Field Alert.


7.             Audits by Reliant
Pharmaceuticals


7.1           Routine Audits may be performed by
Reliant or its agent upon prior notification, and not more than once a
year.  CGMP compliance audits of
Cardinal’s facilities may be conducted during regular business hours, and may
cover any system or area, plus associated documentation, used to support
receiving, sampling, testing, releasing and holding of raw materials, or
manufacturing, sampling, testing, releasing, labeling, holding, and
distribution of the drug product.


7.2           Reliant Quality shall provide 180
days notification for a routine audit, and 7 days notification for a ‘for
cause’ audit pertaining to a specific product quality and safety issue.  A ‘for cause’ audit does not constitute a
routine audit.


7.3           An exit meeting shall be held to
provide significant audit observations. 
A written report of observations shall be issued.


7.4           Cardinal shall provide a written
response to the audit observations within 30 business days of receipt of
written observations from Reliant.  The
response shall include details of the corrective actions to the observations,
and the expected completion date of the action. 
Reliant Quality shall follow-up on the progress of the corrective
actions based on the expected completion dates provided.


7.5           Reliant shall have the right to be
present during the manufacture of any product validation lots, or during the
manufacture of a lot in which a CAPA issue is being implemented.  These visits shall not go against Reliant’s
right to an annual audit.


 


11

















 


VII          REGULATORY


All final, Regulatory assessments pertaining to the manufacture,
release, and distribution of the Product shall be the responsibility of
Reliant’s Regulatory Affairs group. 
Cardinal shall provide a cGMP compliant facility in order to supply the
Product to Reliant Pharmaceuticals.


1.             Inspections by Regulatory
Agencies


1.1           Cardinal shall inform Reliant
Pharmaceuticals of any Regulatory Agency performing an inspection relating to
the Product, or a facilities inspection affecting the Product within the same
business day of notification.  Reliant
Quality Department may be present at any Product specific inspections and exit
meetings with prior approval from Cardinal’s Quality Department.


1.2           All Product specific regulatory
correspondence, or facilities correspondence affecting the manufacturing of the
Product shall be conveyed to Reliant Quality Department within 2 business days
of receipt.  Cardinal shall provide
written responses to all Product related observations for Reliant review prior
to commitment to any regulatory authority.


1.3           Cardinal shall provide copies of all
regulatory agency inspection documentation (i.e. 483’s, EIR’s, etc.) or any
other regulatory correspondence pertaining to the Product to Reliant Quality
Department within seven business days of receipt.  A redacted copy will be provided to protect
other customer’s products.


2.             Annual Reports


2.1           It shall be the sole responsibility
of Reliant Pharmaceuticals to maintain all regulatory communication and updates
(Supplements, CBE, Annual Reports, etc.) pertaining to the Product as outlined
in ICH and FDA regulatory guidance documents. 
All necessary CMC documentation updates will be conveyed to Cardinal,
who shall provide the necessary documentation to Reliant Regulatory not less
than 45 days prior to filing date.


3.             Drug Listing


3.1           It shall be the responsibility of
Reliant Regulatory to submit FDA Form #2657 every June and December updating
the Drug Product Listing.  When no changes
have occurred since the previously submitted list, no report is required.


 


12

















 


VIII         VALIDATION


Cardinal shall assure that all systems used to manufacture, test,
release, and distribute the Product shall have been appropriately transferred,
qualified, and/or validated prior to using that system to process the Product
for commercial product.


1.             Process


1.1           Cardinal shall be responsible for
performing and documenting process validation to comply with cGMP’s and to
ensure consistency of quality Product.  A
process validation protocol shall be forwarded to Reliant for review and
approval prior to carrying out the validation. 
A final report will be issued and a copy will be provided to Reliant
Quality.


2.             Equipment Cleaning Validation


2.1           Cardinal is responsible for reviewing
toxicity and safety information for all products they manufacture to set
appropriate cleaning limits to ensure there are no cross contamination issues
between products.  Cardinal shall demonstrate,
through approved protocol and final report, that cleaning validation has been
performed.


3.             Computer


3.1           Cardinal is responsible for
compliance as it pertains to systems validation, electronic records, electronic
records retention, and electronic signatures for those systems used in the
control of the manufacturing processes, analytical testing, receipt, release
and distribution of materials, API, components, and the Product as prescribed
by 21 CFR part 11, and any other current, approved FDA Guidance requirements..


4.             Analytical Test Methods


4.1           Cardinal shall be responsible for
demonstrating the suitability (methods transfer or validation, as appropriate)
of all methodology used to release raw materials, components, and the finished
product, as appropriate.


 


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REVISION HISTORY


	
  Revision

  Date

  	
   

  	
  Revision
  Description

  
	
  June 2005

  	
   

  	
  New Document

  



 


	
  APPROVALS

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  Reliant Pharmaceuticals, Inc.

  	
   

  	
  Cardinal Health

  
	
   

  	
   

  	
   

  
	
   

  	
  June 1, 2005

  	
   

  	
   

  	
  06-06-05

  
	
  Signature

  	
  Date

  	
   

  	
  Signature

  	
  Date

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  Godfrey Baker

  	
   

  	
  Dina Kostakis

  
	
  Director, QA/QC

  	
   

  	
  Quality and Regulatory Affairs Director