Exhibit 10.40
***Text Omitted and Filed
Separately
with the Securities and Exchange Commission
Confidential Treatment Requested
Under 17 C.F.R. Sections 200.80(b)(4) and 240.24b-2.
C
O N F
I D E N T I A
L
COMMERCIAL SUPPLY
AGREEMENT
THIS SUPPLY AGREEMENT
(the
“Agreement” ) is entered into as of
October 12, 2006 (the “Effective Date” ),
by and between AMYLIN PHARMACEUTICALS, INC. (
“Company” ), having its principal place
of business located at 9360 Towne Centre Drive, Suite 110, San
Diego, CA 92121, U.S.A., and Wockhardt UK (Holdings) Ltd. (
“Manufacturer” ), having its registered
office at Ash Road North, Wrexham Industrial Estate, Wrexham LL13
9UF, United Kingdom.
RECITALS
WHEREAS, Manufacturer is in the business of manufacturing
pharmaceutical products;
WHEREAS, Company is engaged in research, development, and
commercialization of pharmaceutical products; and
WHEREAS, Company and Manufacturer (then CP
Pharmaceuticals Ltd) having previously entered into a Manufacturing
Agreement, effective from 28 th April 1999 and now mutually wish to
supercede such agreement with the terms and conditions set forth
herein; and
WHEREAS, Company wishes to purchase from Manufacturer,
and Manufacturer is willing to manufacture and supply to Company,
the Product (as defined below) in commercial quantities for
commercial sale on the terms and conditions set forth
herein.
NOW, THEREFORE,
in consideration of the foregoing
and the mutual covenants and premises contained in this Agreement,
the parties hereto agree as follows:
1.
Definitions.
1.1
“Affiliate ” shall mean an entity that, directly or
indirectly, controls, is controlled by or is under common control
with a party, where “control” means the possession,
direct or indirect, or the power to direct or cause the direction
of the management or policies of an entity, whether by ownership of
at least 50% of the common stock or voting ownership interest of an
entity, by contract or otherwise.
CONFIDENTIAL
1.2
“Applicable Laws ” shall mean all United States and
European jurisdiction’s federal, state, local and other laws,
statutes, rules, regulations, ordinances, (including any amendments
thereto), applicable to the manufacture and shipment of Product,
including, without limitation, the applicable regulations and
guidance of the FDA, all applicable EU cGMPs. Extensions to the
aforementioned defined territories shall be the subject of side
letters to this Agreement which may be jointly agreed in good faith
from time to time between the parties.
1.3
“Batch ” shall mean that quantity of units of
Product produced from a single homogeneous mix in a single cycle of
manufacture.
1.4
“Batch Record ” shall mean Manufacturer’s
documented procedures for compounding, filling, testing, labeling,
and packaging Pramlintide Acetate Drug Substance and/or inactive
excipients into Product as agreed upon by the parties in writing in
advance of manufacture of the applicable Batch.
1.5
“Business Day” shall mean any Monday, Tuesday, Wednesday,
Thursday or Friday which is not a bank holiday in San Diego,
California or the United Kingdom.
1.6
“Certificate of Analysis”
shall mean a signed certificate,
issued by the party providing a pharmaceutical compound or product,
attesting to the nature and/or content, as applicable, of such
compound or product.
1.7
“cGMP” shall mean current good manufacturing practices
as defined from time to time (a) in regulations promulgated
under the FDCA; (b) the principles and guidelines specified in
Chapter II of European Commission Directive 91/356/EEC, including
“the rules governing medicinal products” in the
European Union Volume 4; and (c) laws, rules, or regulations
of an applicable Regulatory Authority at the time of manufacture
equivalent to those in (a) and (b) above.
1.8
“Confidential Information”
of a party shall mean all data and
information, tangible or intangible, whether in written, graphic,
verbal or electronic form, disclosed by such party to the other
party, its employees or representatives, or developed for or on
behalf of such party by the other party under this
Agreement.
1.9
“Contaminant” means a substance contained in Product that (i)
causes Product to fail to meet any Product Requirements or (ii)
causes Product to be adulterated within the meaning of the
FDCA.
1.10
“Control” shall mean, with respect to certain rights,
possessing ownership of or possessing the right to grant a license
to such rights.
1.11
“Drug Approval Application”
shall mean an application and/or
supplemental application for Regulatory Approval required before
commercial sale or use of Product as a drug in a regulatory
jurisdiction.
1.12
“Facilities” shall mean the manufacturing plant and offices
owned by Manufacturer and located at Ash Road North, Wrexham
Industrial Estate, Wrexham LL13 9UF,
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United Kingdom and a storage and
distribution facility owned by Manufacturer and located at Unit B,
Spectrum Business Park, Bridge Road South, Wrexham Industrial
Estate, Wrexham LL13 9QA, United Kingdom.
1.13
“FDA” shall mean United States Food and Drug
Administration or any successor agency.
1.14
“FDCA” shall mean the United States Federal Food Drug
and Cosmetics Act, as amended, and all regulations promulgated
thereunder, or any successor laws and regulations
thereto
1.15
“Fill Date” shall mean that date on which the manufacture of
a Batch is actually completed, notwithstanding the date on which
the Batch manufacture begins.
1.16
“Hidden Defect” shall mean a defect that causes Product to fail
to conform to the Specifications or to the warranties provided by
Manufacturer hereunder, which defect is not discoverable upon
reasonable physical inspection and testing performed pursuant to
Section 5.3 but is discovered at a later time ( e.g. ,
in the course or as a result of long-term stability
studies).
1.17
“Launch Date” shall mean the date of the first commercial sale
of Product manufactured using Manufacturer Technology under this
Agreement, in a country after approval by appropriate regulatory
authorities for market and sale in such country.
1.18
“Manufacturing Process” shall mean any and all specifications,
compositions, identities and quantities of materials, formulas,
methods, techniques, processes, procedures and quality control
necessary or relevant for manufacture of Product.
1.19
“Manufacturer’s Technology”
shall mean the specific and
confidential technology which has been developed by Manufacturer
for the siliconisation of glass cartridges used in the production
of the Product as defined herein and is described further in
related standard operating procedures (“SOPs”)
.
1.20
“Materials” shall mean raw materials, components, excipients
and other ingredients and packaging materials used in the
manufacture and packaging of Product.
1.21
“OUS Country” shall mean any country outside of the United
States and its territories.
1.22
“Pramlintide Acetate or Pramlintide Acetate Drug
Substance” shall mean a dry bulk powder preparation
containing pramlintide acetate peptide as provided by Company for
further manufacture into Product by Manufacturer.
1.23
“Product” shall mean the finished dosage form of
Pramlintide Acetate, for injection in cartridge presentation as
described in Exhibit B to this Agreement.
1.24
“Product Price” shall mean the price for Product set forth in
Exhibit A .
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CONFIDENTIAL
1.25
“Product Requirements” shall mean all of the requirements referenced
in Section 8.3 of this Agreement.
1.26
“Quality Agreement” shall mean the (Technical) Quality Agreement
between Company and Manufacturer dated as of October 16, 2002, or
that agreed in writing on any subsequent date between the parties,
which is incorporated into this Agreement by reference and made a
part hereof.
1.27
“ Recall
Action ” shall have the meaning ascribed to it
in Section
5.4 hereof.
1.28
“Regulatory Approval” shall mean any approvals (including supplements,
amendments, pre-marketing and post-marketing approvals, labeling
approval, and pricing and reimbursement approvals), licenses,
registrations or authorizations of any national, supra-national (
e.g. , the European Commission or the Council of the
European Union), regional, state or local regulatory agency,
department, bureau, commission, council or other governmental
entity, necessary for the manufacture, distribution, use or sale of
Product in a regulatory jurisdiction.
1.29
“Regulatory Authority” shall mean the FDA in the United States or the
MHRA, EMEA or any other applicable regulatory agency or entity
having the responsibility, jurisdiction, and authority to approve
the manufacture, use, importation, packaging, labeling, marketing,
and sale of Product in any additional country, or any successor
body to any of them.
1.30
“Specifications” shall mean the regulatory, manufacturing,
quality control and quality assurance procedures, processes,
practices, standards, instructions and any other attributes that
the parties agree upon, or that are otherwise required, in
connection with the manufacture of Product, as set forth on
Exhibit B, as amended from time to time by written agreement
of the parties pursuant to Section 4.3.
1.31
“Term” shall have the meaning provided in Section
9.1.
2.
Purchase and Supply.
2.1
Purchase and Supply Agreement. During the Term, Company agrees to buy
from Manufacturer, and Manufacturer agrees to sell to Company, such
quantities of the Product as may be set forth on purchase orders
placed by Company in accordance with the provisions
hereof.
2.2
Minimum Orders.
For the time frame beginning on the Effective Date and ending on
the first day of the calendar month after the date of the one year
anniversary of the date of the first Regulatory Approval of the
Product (the “Initial Period” ), Company
shall only be obligated to purchase, and Manufacturer shall only be
obligated to supply, that quantity of Product ordered by Company,
which is submitted to Manufacturer via purchase order and
Manufacturer accepts via a confirmation. For the time
frame beginning on the date the Initial Period ends and ending on
the one year anniversary thereof (the “Second
Period” ), Company agrees to purchase Product from
Manufacturer in an amount equal to or greater than [***]
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TREATMENT REQUESTED
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cartridges. For the time frame
beginning on the date the Second Period ends and ending on the one
year anniversary thereof (the “Third
Period” ), Company agrees to purchase Product from
Manufacturer in an amount equal to or greater than [***]
cartridges. For the time frame beginning on the date the Third
Period ends and ending on the one year anniversary thereof (the
“Fourth Period” ), Company agrees to
purchase Product from Manufacturer in an amount equal to or greater
than [***] cartridges. For the time frame beginning on the date the
Fourth Period ends and ending on the one year anniversary thereof
(the “Fifth Period,” and together with
the Initial Period, the Second Period, the Third Period, and the
Fourth Period, the “Purchase Periods” ),
Company agrees to purchase Product from Manufacturer in an amount
equal to or greater than [***] cartridges. Not withstanding
the foregoing, however, the Parties agree that upon completion of
the Initial Period, the Parties shall meet for the purpose of
reconsidering each of the foregoing quantities specified for the
Third, Fourth and Fifth Periods and shall, prior to the
commencement of the Third Period, adjust such quantities, if
necessary, upon mutual written agreement. In the event that
during any Purchase Period the Company’s actual purchases of
the Product from Manufacturer are less than the minimum amount
specified above for said Purchase Period, Company will pay to
Manufacturer the difference between the amount invoiced to Company
for its actual purchases during the Purchase Period and the amount
that would have been invoiced had Company purchased the minimum
amount agreed to for such Purchase Period; provided ,
however , (i) Company shall not be obligated to make
any such payments if the Agreement has been terminated, and (ii)
the Company shall only be obligated to pay for Product supplied to
the Company pursuant to this Agreement. In any given calendar
quarter, Company shall order [***]% of the minimum quantity, plus
or minus [***]%, for the Purchase Period in which the calendar
quarter occurs. Following the Fifth Period, Manufacturer may
bid, in competition with Company’s other manufacturers of the
Product, to provide a greater percentage of Company’s
requirements of the Product. For purposes of this Section
2.2, a “purchase” shall mean the submission by Company
of a firm purchase order.
2.3
Forecasts.
Beginning within seven (7) days after the Effective Date and at the
commencement of every calendar month thereafter, Company shall
furnish Manufacturer with non-binding forecasts of [***] Product
requirements under this Agreement for the ensuing [***] calendar
[***].
2.4
Purchase Orders.
Company shall order the Product by submitting written purchase
orders, in Company’s standard form in effect from time to
time, to Manufacturer. Each purchase order shall specify the
quantities of the Product ordered which shall be in Batch
quantities or multiples thereof, the cartridge size thereof, the
desired shipment date for such Product, the pricing, and any
special shipping instructions. Company shall submit each
purchase order to Manufacturer at least [***] Business Days in
advance of the desired shipment date specified in such purchase
order. No more than ten (10) Business Days following receipt of
each purchase order Manufacturer shall confirm in writing its
acceptance of same and shall advise Company of its planned shipment
date and its designated lot numbers for the Product.
Manufacturer shall make each shipment of the Product in the
quantity, cartridge size and on the shipment date specified for it
on Company’s purchase order, via the mode(s) of
transportation and to the party and destination specified on such
purchase order. Release samples representing the
Manufacturing Process and meeting the requirements set forth in the
Batch Record will be shipped within [***] Business Days after the
actual Fill Date.
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Manufacturer shall ship the Product
which is the subject of the purchase order, subject to Section 5.1,
and shall supply copies of the associated documentation as
described in the Quality (Technical) Agreement, including the
signed Certificate of Analysis and signed certificate of compliance
for the Product. Any purchase orders for the Product submitted by
Company to Manufacturer shall reference this Agreement and shall be
governed exclusively by the terms contained herein except to the
extent set forth in the following sentence. The terms and
conditions of this Agreement shall supersede any term or condition
in any order, confirmation or other document furnished by Company
or Manufacturer that is inconsistent with these terms and
conditions, except to the extent that any term, provision or
condition set forth in a purchase order expressly states that it
supersedes any term, provision or condition of this Agreement,
unless it is mutually agreed between the parties hereto. If
purchase orders are issued less than [***] Business Days in advance
of the desired shipment date, Manufacturer shall make commercially
reasonable efforts to meet Company’s requirements, however
Manufacturer’s failure to meet such requirements shall not be
deemed to be a breach of this Agreement. In the event a
purchase order is issued less than [***] Business Days in advance
of the desired shipment date, Manufacturer shall advise Company
within [***] Business Days whether such purchase order can be
fulfilled by the date requested in the purchase order and the
parties shall agree upon a delivery date of the requested
Product.
3.
Prices and Payment.
3.1
Product Price. The
Product Price shall be fixed for the Initial Period of this
Agreement as specified in Exhibit A .
3.2
Purchase Price Adjustment. Upon expiration of the Initial Period,
Manufacturer may adjust the Purchase Price of Product to reflect
changes in [***], subject to Section 4.1(b). Any such adjustment by
Manufacturer shall be notified to Company no less than [***] prior
to expiration of the Initial Period. Upon commencement of the
Second Period Company and Manufacturer agree to meet [***] to
formally review continuous improvement activities and other
improvements resulting from experience in operating the
Manufacturing Process including [***]. Company and Manufacturer
shall work together to obtain process improvements. Net
savings or increases in the [***] shall result in reductions or
increases respectively in the Purchase Price. [***] resulting from
Manufacturer’s efficient management of the Manufacturing
Process shall not result in reductions in the Purchase Price. Net
increases in the cost of the Manufacturing Process due to [***]
shall result in increases in the Purchase Price. Net savings in the
product cost per unit achieved due to increases in the [***] shall
result in corresponding reductions in the Purchase Price. If
the parties cannot in good faith agree on the proposed Purchase
Price adjustment, the dispute will be discussed between the senior
management of both Company and Manufacturer. In no event may
Manufacturer increase the Purchase Price following the Initial
Period by [***]. The increase will be applicable on [***] of
every calendar year.
3.3
Invoices. Upon
acceptance by Manufacturer of a purchase order, Manufacturer shall
invoice Company for [***]%) of the estimated aggregate Product
Price for the purchase order (the “Reservation
Fee”). Not withstanding the foregoing, however, the
Parties agree that prior to completion of the Initial Period, the
Parties shall meet for the purpose of reconsidering the percentage
used to determine the Reservation Fee and shall, prior to
the
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commencement of the Second Period,
adjust such percentage, if necessary, upon mutual written
agreement. Upon completion of the manufacture of each purchase
order and the submission of a Certificate of Analysis and
Certificate of Compliance duly approved by Manufacturer to Company
for the batches of Product manufactured for such purchase order
Manufacturer shall refund Company the Reservation Fee and invoice
Company the Product Price for the quantity of Product
manufactured.
3.4
Cancellation Fee. If,
after issuing a Purchase Order to the Manufacturer for quantities
which are in excess of the minimum order quantities defined
in Section 2.2 for that Purchase Period and acceptance by the
Manufacturer of such Purchase Order, but before Manufacturer starts
work to manufacture for that Purchase Order, the Company
subsequently cancels or postpones its order, then Manufacturer
shall have the right but not the obligation to charge to Company
[***]%) of the product price (“Cancellation Fee”). If,
after issuing a Purchase Order to the Manufacturer, the Company
subsequently cancels or postpones its order after the Manufacturer
has started work to manufacture for that Purchase Order, the
Manufacturer shall be entitled to charge to Company [***]%) of the
Product Price for that Purchase Order.
3.5
Time for payments shall be of the essence. The Manufacturer reserves the right to charge
the lesser of either [***]% or the highest percentage allowed under
applicable law, per month on any overdue amount until the date of
payment in full save where part or whole payment is withheld by the
Company on a specific invoice as a result of a genuine dispute over
that invoice or part thereof.
3.6
Method of Payment; Currency. All payments due hereunder to Manufacturer shall
be paid to Manufacturer in [***] not later than [***] days
following the receipt of the applicable invoice, unless such
shipment of Product is rejected in accordance with the provisions
of Section 5.3. Company shall make payment by telegraphic
transfer to the account number 02140934 at HSBC., 17-19 Regent
Street, Wrexham, LL11 1RY, UK, Sort Code 40-47-26 or to such other
account of Manufacturer designated in writing to Company. All
currency amounts referenced in this Agreement are to
[***].
3.8
Effect of Certain Events. In the event of termination or expiration
of this Agreement, Manufacturer shall provide reasonable assistance
to Company to implement the transfer of manufacturing
responsibility for the Product to Company or its designee.
Such reasonable assistance shall include transfer of the
Manufacturing Process as described in Section 7.7 but always
with the exception of Manufacturer Inventions subject to Section
7.2. In the event of termination of this Agreement by Company
pursuant to Section 9.2(a) or (b) or 9.3(c), such reasonable
assistance will be provided at Manufacturer’s expense. In the
event of any other termination or expiration of this Agreement,
Company shall pay Manufacturer’s reasonable and documented
costs of providing such assistance. In the event of
termination or expiration of this Agreement, Manufacturer will
promptly return to Company all unused Pramlintide Acetate Drug
Substance provided to Manufacturer pursuant to Section 4.1 hereof
and Materials paid for by Company as directed by and at the expense
of Company.
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4.
Manufacturing.
4.1
Materials.
(a)
Except as stated in Section 4.1(b),
Manufacturer will obtain any Materials with the exception of
Pramlintide Acetate Drug Substance required for the manufacture of
the Product, in reasonable quantities consistent with
Company’s most recent forecast for the Product. All Materials
obtained by Manufacturer pursuant to this Section 4.1(a) shall meet
the specifications stated in the Quality Agreement and Manufacturer
shall order all Materials only from vendors approved in advance by
Company. Manufacturer shall ensure all Materials required to
manufacture the Batch are released for use, in accordance with
Manufacturer’s quality system and requirements stated in the
then current Quality Agreement, prior to the manufacturing of the
Batch. Company shall reimburse the Manufacturer all the costs of
all the Materials in stock or on order on behalf of the Company by
the Manufacturer, including QC testing costs and disposal costs, if
such Materials become redundant at any time if: (i) Company makes a
good faith determination not to continue with the commercialization
of Product, (ii) Company terminates this Agreement according to
Section 9.3(a), (iii) such materials expire due to insufficient
demand for Product, or (iv) such materials become obsolete due to a
change of specification advised by the Company;
provided , however , Manufacturer shall
use commercially reasonable efforts to either utilize such
materials in other areas of its business or to return the
materials, and Company shall not reimburse Manufacturer for any
such utilized or returned materials. The orders of Materials
will be placed keeping in view the future forecasts and delivery
lead times. Manufacturer will maintain a safety stock level of at
least [***] calendar [***], but no more than [***] calendar [***]
of approved Materials unless the minimum procurement quantity for
any Material provides sufficient stocks for greater than [***]
calendar [***]. For clarification purposes, safety stock
includes Materials needed to fulfill forecasts issued by Company
pursuant to Section 2.3. Manufacturer and Company will review
safety stock levels on a quarterly basis and will mutually agree to
make appropriate changes.
(b)
Company shall supply to
Manufacturer, free of charge, freight and duties prepaid and with
transportation insurance paid by Company, quantities of Pramlintide
Acetate and Pramlintide Acetate reference standard sufficient to
enable Manufacturer to manufacture and perform agreed analytical
testing of the quantities of the Product ordered by Company.
Pramlintide Acetate will be sampled according to the Quality
Agreement and held by Manufacturer under appropriate storage
conditions until such time as it is required for manufacture of
Product. Manufacturer and Company agree that in the case of Product
manufactured prior to satisfactory completion of the first [***]
commercial full scale batches (including the process validation
batches) of each of the presentations of Product, Manufacturer
shall make commercially reasonable efforts to maximize yields but
shall not be held liable for losses of Pramlintide Acetate
occurring as part of the Manufacturing Process. After satisfactory
completion of the first [***] commercial full scale batches of each
Product the parties shall meet to agree to a target yield for
future production (Target Yield). The Target Yield shall be defined
as at least [***]%)] of the average yield of the first [***]
batches of each presentations of Product. For clarity, “
satisfactory completion ” of a Batch will not include
a Batch with aberrant results. All shipments of Pramlintide
Acetate will be accompanied by a Certificate of Analysis indicating
the peptide content of such Pramlintide Acetate and such other
information as Company may specify and is to arrive approximately
thirty (30) days in advance of planned
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Product manufacture to allow for
testing. Within fifteen (15) business days of receipt of any
Pramlintide Acetate hereunder, Manufacturer will verify the
quantity and identity of such shipment of Pramlintide Acetate
according to test methods approved and provided by Company and
shall inspect the Pramlintide Acetate in accordance with
Manufacturer’s incoming material inspection procedures.
If Manufacturer detects any discrepancies in the Pramlintide
Acetate in quantity or in the identity based on the identity
testing performed, Manufacturer shall inform Company immediately
upon, but no later than five (5) Business Days after, having
detected such discrepancies. Manufacturer shall also inform
Company of any obvious damage to the Pramlintide Acetate or
container received within five (5) Business Days of
Manufacturer’s receipt thereof. Any rejected
Pramlintide Acetate shall be returned at Company’s expense
and direction. Company shall make all final determinations if
Materials are suitable for use in Product manufacturing.
4.2
Manufacture of Product. Manufacturer will manufacture and store
Product at the Facilities in accordance with the Quality Agreement,
the Specifications, applicable Regulatory Approvals, cGMPs and
other Applicable Laws, as then in effect. Manufacturer shall
not rework any Batch of the Product without Company’ prior
written consent, which consent shall not be unreasonably
withheld. Manufacturer shall allow an employee of Company
(and, with Manufacturer’s prior consent, other persons) to be
present during all manufacturing of the Product. The Manufacturer
shall perform quality control and quality assurance testing to
protocols and procedures agreed in writing between the parties
prior to shipment of Product to the Company. The Manufacturer shall
test a portion of each Batch manufactured for the Company prior to
delivering such Batch to the Company, and shall provide a
Certificate of Analysis (i) confirming that the Manufacturer
followed the agreed methods for the testing of such Product, (ii)
containing the quality control and quality assurance test results
for such Batch and (iii) confirming that such Batch has been
manufactured in accordance with the Batch Records and cGMP. The
Manufacturer shall notify the Company immediately of any test
failures noted in the manufacture of Product.
4.3
Change in Specifications or Manufacturing Process.
(a)
Each party shall notify the other in
advance of any proposed changes in Specifications, release testing,
stability testing, packaging, Materials, equipment, facilities,
processes or procedures used to manufacture Product under this
Agreement. No changes in Specifications, release testing,
stability testing, packaging or the Materials, equipment,
facilities, processes or procedures used to manufacture Product
under this Agreement, except changes required by any applicable
Regulatory Authority, will be made unless the parties have agreed
to such changes in writing prior to adoption of such changes. Any
such changes to the Product Specifications, release testing,
stability testing, packaging, Materials, equipment, facilities,
processes or procedures used to manufacture Product shall be
handled in accordance with the procedures established in the
Quality Agreement, with costs paid as provided in
Section 4.3(b), (c) or (d), as applicable.
(b)
In the event Company requests any
such changes be made, other than changes described in
Section 4.3(d), Manufacturer shall accommodate Company’s
requested changes to the extent technologically feasible. If
such changes would result in material change in the cost of
manufacture, then in that event the Product Price may be
suitably
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modified. If such changes require
the purchase of capital equipment, such costs and any related
installation and qualification costs will be to the account of the
Company and such capital equipment shall be owned by the
Company.
(c)
In the event Manufacturer requests
any such changes be made, other than changes described in
Section 4.3(d), and such changes would result in a material
increase in Manufacturer’s cost of manufacture, all costs
reasonably required in connection with such changes shall be paid
as mutually agreed by the parties.
(d)
In the event changes are requested
by a Regulatory Authority or required to bring either of the
Facilities into compliance with Applicable Laws, or additional
changes, activities, or manufacturing is required to bring the
Manufacturing Process into compliance with Applicable Laws,
Specifications or other Product Requirements, Manufacturer shall
accommodate such changes to the extent technologically feasible,
and all costs reasonably required in connection with such changes,
activities, or manufacturing shall be borne by the
Manufacturer. In such an event the Product Price may be
suitably revised to accommodate such changes.
4.4
Regulatory Matters.
(a)
Manufacturer shall provide to
Company such documentation, data and other information relating to
the Facilities, Product, or Manufacturer’s Manufacturing
Processes and procedures for Product as Company may request for
submission to Regulatory Authorities.
(b)
Company shall be responsible for all
filings necessary for Regulatory Approvals. The parties agree
that Company shall be the sole and exclusive owner of all right,
title and interest in and to all Drug Approval Applications and
Regulatory Approvals related to the Product in the United States
and any OUS Country. Manufacturer shall assist Company in the
preparation of all documents necessary to effectuate
Company’s rights in all Drug Approval Applications and
Regulatory Approvals related to the Product and agrees to transfer,
effect, confirm, perfect, record, preserve, protect and enforce all
rights, title and interests transferred hereunder, at the
reasonable request and expense of Company. Manufacturer will use
commercially reasonable efforts to assist Company in obtaining such
Regulatory Approvals. For the avoidance of doubt, Company has sole
responsibility for the content of all Drug Approval
Applications. This Agreement automatically terminates if
Amylin terminates development of the Product following final
rejection of the Product by the FDA.
4.5
Compliance with Quality Agreement and Applicable
Laws. The parties
shall comply with the terms and conditions of the Quality
Agreement. Manufacturer shall comply with all Applicable Laws with
respect to activities under this Agreement.
Manufacturer represents and warrants to Company that it has and
will maintain during the Term all establishment licenses and
permits, including without limitation health, safety and
environmental permits, necessary for the conduct of
Manufacturer’s activities under this Agreement.
4.6
Manufacturer Facilities. Manufacturer warrants and represents that
it has, and will maintain, all licenses, permits and approvals
necessary to fulfill its obligations
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under this Agreement.
Manufacturer covenants to design and operate the facilities it uses
to manufacture, package, test, or store Product to successfully
pass inspections conducted by regulatory authorities. Manufacturer
agrees to maintain appropriate security measures at its facilities
no less stringent than measures that are customary in the
pharmaceutical industry.
4.7
QA Audits. Upon written
notice of no less than [***] Business Days for routine audits to
Manufacturer, Company shall have the right to have representatives
visit the Facilities during normal business hours to review
Manufacturer’s manufacturing operations, assess its
compliance with cGMPs and quality assurance standards, and discuss
any related issues with Manufacturer’s manufacturing and
management personnel. Manufacturer shall maintain the
Facilities in accordance with cGMPs. Manufacturer’s
failure to correct any cGMP deficiency regarding any aspect of
Manufacturer’s manufacture within a reasonable time period
after notice of such deficiency shall be a material breach of this
Agreement. Upon reasonable notice, the Manufacturer will allow
employees of the Company access to the Facility, documentation, and
personnel to audit and for observation of the production process
and quality control testing of the Product, disposal of waste and
adherence to cGMP requirements and this Agreement. During such
inspections, employees of the Company (number of persons should be
restricted to not more than [***]) shall have the right to audit
any aspect of the Manufacturers manufacture of Product, and such
audit may include, without limitation, verification of
Manufacturers maintenance of drug establishment registrations with
the FDA and other applicable Regulatory Authorities, and review of
conditions and documentation of any aspect of manufacture of
Product.
4.8
Regulatory Inspections. Manufacturer agrees to permit the FDA and other
Regulatory Authorities to inspect any aspect of
Manufacturer’s manufacture and testing of the Product
including, without limitations, any pre-approval inspection
(“PAI”). Manufacturer shall cooperate with Company, and
with any Regulatory Authority, as necessary to facilitate prompt
approvals by such Regulatory Authority of the Manufacturing Process
or testing process for the Product, including preparation and
submission of necessary data relating to the manufacturing or
testing processes, including without limitation any PAI or
subsequent inspection. Manufacturer shall notify Company if either
or both of the Facilities are the subject of an inspection by any
Regulatory Authority or any compliance inspection relating to, or
that could reasonably be expected to, affect the manufacture
or
