certain material
(indicated by an asterisk) has been omitted from this document
pursuant to a request for confidential treatment. the omitted
material has been filed separately with the securities and exchange
commission.
DATA TRANSFER, CLINICAL
TRIAL
AND MARKET SUPPLY
AGREEMENT
THIS DATA
TRANSFER, CLINICAL TRIAL AND MARKET SUPPLY AGREEMENT (the
“Agreement”), is made effective as of the 3rd day of
November, 2005 (the “Effective Date”) by and between
InterMune, Inc. (“InterMune”), a California
corporation, having an address at 3280 Bayshore Boulevard,
Brisbane, California 94005, USA, and Boehringer Ingelheim Austria
GmbH (“BI Austria”), an Austrian corporation, having
its registered office at Dr. Boehringer-Gasse 5 — 11,
A-1121 Vienna, Republic of Austria. InterMune and BI Austria may be
referred to herein each individually as a “Party” and
jointly as the “Parties.”
W HEREAS , InterMune holds an
exclusive license from Amgen Inc., a company organized under the
laws of Delaware (“Amgen”), to use and commercialize
interferon alfacon-1 (“INTERFERON ALFACON-1”, as
further described herein) products in the USA and certain other
territories. INTERFERON ALFACON-1 is approved by the FDA for the
indication chronic hepatitis C virus (HCV) infection, and is sold
in the USA under the trade-mark INFERGEN â
, and InterMune intends to seek
approval for additional dosing registrations and/or additional
indications; and
WHEREAS ,
Amgen is currently InterMune’s exclusive manufacturer of
INTERFERON ALFACON-1 and in December 2004, Amgen and InterMune
have amended their licensing agreement to allow InterMune to
transfer the manufacturing of INTERFERON ALFACON-1 to a new
supplier; and
W HEREAS , BI Austria and its
affiliate Boehringer Ingelheim Pharma GmbH & Co. KG own
facilities specialized for cGMP manufacture of biopharmaceuticals
and employ personnel who have experience in the production, quality
control as well as in the registration of biopharmaceuticals;
and
WHEREAS,
InterMune wishes BI Austria, and BI Austria agrees, to provide the
SERVICES (as defined in this Agreement) for the transfer of the
manufacturing process of INTERFERON ALFACON-1 from Amgen to BI
Austria; and
W HEREAS, InterMune wishes BI
Austria, and BI Austria agrees, to manufacture and supply InterMune
with finished INTERFERON ALFACON-1 product for its conduct of
clinical trials and supply of market needs in accordance with the
terms and conditions of this Agreement upon the completion of the
manufacturing transfer from Amgen to BI Austria; and
W HEREAS, InterMune and BI
Austria have entered into a Side Letter Agreement Re Infergen
Manufacturing Transfer dated May 9, 2005 in anticipation of
this Agreement, which Side Letter Agreement shall be incorporated
by reference herein.
N OW, THEREFORE, in
consideration of the foregoing recitals which are hereby
incorporated by reference herein and for good and valuable
consideration, the receipt and sufficiency of which hereby
acknowledged and agreed upon, the Parties hereto agree as
follows:
1.
The following
capitalized definitions will apply throughout this
Agreement:
1.1
AFFILIATE means
(i) any corporation or business entity fifty percent (50 %) or
more of the voting stock of which is and continues to be owned
directly or indirectly by any party hereto; (ii) any corporation or
business entity which directly or indirectly owns fifty percent (50
%) or more of the voting stock of any party hereto; or
(iii) any corporation or business entity under the direct or
indirect control of such corporation or business entity as
described in (i) or (ii).
1.2 AMGEN
PRODUCT means the
formulation of INTERFERON ALFACON-1 manufactured in the US by Amgen
for sale under the trademark INFERGEN ® and approved by the FDA for the treatment of
chronic hepatitis C virus (HCV) infection.
1.3 AMGEN
TECHNOLOGY means all
INFORMATION relating to the manufacture, use or sale of INTERFERON
ALFACON-1 that is licensed to InterMune pursuant to that certain
License and Commercialization Agreement dated June 15, 2001,
as amended, by and between InterMune and Amgen, including without
limitation the Manufacturing Process as defined in the SIDE LETTER
AGREEMENT, and all patents and patent applications covering such
INFORMATION.
1.4
APPROVAL means a
regulatory approval required from a HEALTH AUTHORITY in order to
manufacture DRUG SUBSTANCE or DRUG PRODUCT for use in clinical
trials or market supply as applicable, in the applicable
jurisdiction.
1.5 BI
AUSTRIA’S IMPROVEMENTS shall mean any improvements to the Manufacturing
Process as defined in the SIDE LETTER AGREEMENT or to INTERMUNE
TECHNOLOGY conceived, created or discovered (or reduced to
practice) solely by BI Austria under this Agreement or during the
period of time from February 1, 2005 to the Effective Date,
either individually or in conjunction with one or more third
parties or BI Austria AFFILIATES, including all patent and patent
applications covering any of the foregoing.
1.6 BI
AUSTRIA’S TECHNOLOGY means all INFORMATION in the field of
manufacturing and testing of biopharmaceuticals, including all
patents and patent applications covering any of the foregoing, that
are owned or CONTROLLED by BI Austria or BI Pharma at any time
prior to the Effective Date of this Agreement or during the term of
this Agreement and that are related to or useful in BI
Austria’s carrying out its obligations under this Agreement,
but specifically excluding INTERMUNE’S TECHNOLOGY, AMGEN
TECHNOLOGY and BI AUSTRIA’S IMPROVEMENTS.
1.7 BI
PHARMA means BI
Austria’s AFFILIATE Boehringer Ingelheim Pharma GmbH &
Co. KG.
1.8
BLA means a Biologics
License Application, as defined by the regulations promulgated
under the FD&C ACT, and any equivalent application with
respective HEALTH AUTHORITIES.
2.
1.9
cGMP means the current
Good Manufacturing Practices of all applicable HEALTH AUTHORITIES,
including without limitation, the FDA, and including without
limitation all applicable rules, regulations, guides and guidance,
such as (a) the U.S. Federal Food, Drug and Cosmetics Act as
amended (21 USC 301 et seq .), (b) relevant U.S.
regulations found in Title 21 of the U.S. Code of Federal
Regulations (including but not limited to Parts 11, 210, 211, 600
and 611), (c) EEC Directive 91/356/EEC of 13 June 1991,
and (d) the EC Guide to Good Manufacturing Practice for
Medicinal Durg Products, including respective guidance documents
and any comparable laws, rules or regulations of any agreed upon
foreign jurisdiction, as each may be amended from time to time.
cGMP also includes adherence to any applicable DRUG PRODUCT license
requirements, to the current requirements of the United States
Pharmacopoeia/National Formulary, the current requirements of the
European Pharmacopoeia and the relevant current International
Conference on Harmonization (ICH) guidance documents,
including without limitation the ICH Guidance Q7A Good
Manufacturing Practice Guide for Active Pharmaceutical
Ingredients.
1.10
CMC means the chemistry,
manufacturing, and controls content of a submission to a HEALTH
AUTHORITY.
1.11
COA means the Certificate
of Analysis prepared for the DRUG PRODUCT, listing testing
parameters, specifications and test results (in a format and detail
as listed in Exhibit 2 ).
1.12
COC means a Certificate
of Compliance prepared for the DRUG PRODUCT confirming compliance
with cGMP regulations and signed by BI Austria’s authorized
Qualified Person and the Head of Quality Management (in a format
and such detail to be agreed upon by the Parties).
1.13
CONFIDENTIAL INFORMATION means any proprietary INFORMATION
(a) disclosed by one Party to the other Party (including
without limitation, such INFORMATION as was disclosed under the
Confidential Non-Disclosure Agreement dated February 17, 2005,
among InterMune, Amgen and BI Austria), or (b) developed by either
Party pursuant to this Agreement, except for INFORMATION which
(i) is already in the public domain at the time of its
disclosure to the receiving Party; (ii) becomes part of the
public domain through no wrongful action or omission of the
receiving Party after disclosure to the receiving Party;
(iii) is already known to the receiving Party at the time of
disclosure as evidenced by the receiving Party’s written
records; or (iv) is independently developed by the receiving
Party without the use or application of the disclosing
Party’s proprietary information.
1.14
CONTROLLED means, with
respect to any material, INFORMATION or intellectual property
right, possession of the ability by a Party to grant access, a
license, or a sublicense to such material, INFORMATION or
intellectual property right as provided for herein without
violating an agreement with a Third Party as of the time such Party
would be first required hereunder to grant the other Party such
access, license or sublicense.
1.15 DRUG
PRODUCT shall mean a
finished product manufactured by BI Austria and BI Pharma hereunder
and consisting of formulated INTERFERON ALFACON-1 filled into the
designated containers for clinical supply and for market supply, as
described in Exhibit 5 , or shall mean a finished
product manufactured by BI Austria and BI Pharma hereunder
and
3.
consisting of
formulation buffer filled into the designated containers for
clinical supply (placebo).
1.16 DRUG
SUBSTANCE means the
purified unformulated bulk form of INTERFERON ALFACON-1.
1.17 DRUG
SUBSTANCE SPECIFICATIONS mean the specifications for DRUG SUBSTANCE
listed in Exhibit 1.
1.18
EURO means the basic unit
of currency among participating European Union
countries.
1.19
FDA means the United
States Food and Drug Administration and any successor agency
thereto responsible for registration of medicines in the
US.
1.20
FD&C ACT means the
United States Food, Drug & Cosmetic Act as amended from time to
time and any supplements thereunder, and any equivalent regulation
of any HEALTH AUTHORITIES.
1.21 FINAL
RELEASE means the release
of DRUG SUBSTANCE or DRUG PRODUCT by InterMune for use in clinical
trials or for market supply, as applicable, in accordance with
InterMune’s respective SOPs. FINAL RELEASE signifies that the
material has been produced using approved processes, in compliance
with appropriate regulations, and meets the established
specifications, as determined by InterMune’s review of all
appropriate documentation.
1.22 HEALTH
AUTHORITIES mean all
regulatory authorities having jurisdiction over the manufacture,
use and/or sale of the DRUG PRODUCT in the TERRITORY, including but
not limited to the FDA.
1.23
INFORMATION means
(a) techniques, data, inventions, practices, methods,
knowledge, know-how, skill, experience, test data (including
pharmacological, toxicological and clinical test data), analytical
and quality control data, regulatory submissions, correspondence
and communications, marketing, pricing, distribution, cost, sales,
manufacturing, patent and legal data or descriptions, compositions
of matter, assays and biological materials, and (b) all
intellectual property rights in and to any of the
foregoing.
1.24
INTERFERON ALFACON-1 means the recombinant, bio-optimized,
non-naturally occurring type-1 interferon alpha that is the active
ingredient in INFERGEN Ò
. The relevant amino acid sequence
is set forth in Exhibit 3 .
1.25
INTERMUNE’S TECHNOLOGY means all INFORMATION that is CONTROLLED by
INTERMUNE at any time prior to the Effective Date of this Agreement
or
4.
during the term
of this Agreement that is related to or useful in BI
Austria’s manufacture of DRUG PRODUCT hereunder, and all
patents and patent applications covering any of the foregoing;
provided that “INTERMUNE’S TECHNOLOGY” shall not
include any BI AUSTRIA’S TECHNOLOGY, BI AUSTRIA’S
IMPROVEMENTS or the AMGEN TECHNOLOGY.
1.26
MCB means the original
Master Cell Bank derived from the [***]
1.27
MANUFACTURING PROCESS means the process for fermentation, purification
and filling of DRUG SUBSTANCE and DRUG PRODUCT, as described in
Exhibit 4 which process is a combination of the
Manufacturing Process as defined in the SIDE LETTER AGREEMENT with
the BI AUSTRIA’S IMPROVEMENTS to such Manufacturing Process.
For purposes of illustration, Exhibit 4 sets forth an
initial draft of a chart comparing the Manufacturing Process as
defined in the SIDE LETTER AGREEMENT and the MANUFACTURING PROCESS,
which draft is subject to modifications determined by the PROJECT
TEAM.
1.28
MATERIAL SUPPLY BREACH means a failure of BI Austria: (a) to
supply to InterMune at least [***] [***] of InterMune’s
binding forecasted requirements of DRUG PRODUCT (or actual orders,
if less) that are due for delivery by the designated delivery date
during the then-current calendar quarter and such failure occurs
for [***] consecutive calendar [***]; or (b) to repeatedly
([***] [***] [***] materially violate against cGMP, as described in
Sections 5.6 and 5.7.
1.29 OTHER
SERVICES means any
non-routine services and performances of work by BI Austria for
InterMune hereunder, which services and work (and the scope, costs
and timeline therefor) BI Austria and InterMune both agree to in
writing. OTHER SERVICES shall not include the SERVICES or the
manufacturing or supply of DRUG SUBSTANCE or DRUG PRODUCT for
InterMune’s clinical or commercial requirements.
1.30 PROJECT
MANAGER means the
responsible person designated by each Party to be responsible for
the communication of all information concerning this Agreement. As
of the Effective Date, the person designated as InterMune’s
PROJECT MANAGER and the person designated as BI Austria’s
PROJECT MANAGER are listed in Exhibit 6. Either Party
may change its own designated PROJECT MANAGER by providing written
notice thereof to the other Party.
1.31 DRUG
PRODUCT SPECIFICATIONS mean the specifications for the DRUG PRODUCT as
set forth in Exhibit 7 , or as otherwise agreed by the
Parties in writing.
1.32 PROJECT
TEAM means the team as
listed in Exhibit 6 and described in
Section 6.1.
*** 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.
1.33 QUALITY
AGREEMENT means that
quality agreement to be entered into by the Parties hereto in
accordance with Section 3.9 hereof, which agreement will
(i) define the obligations of BI Austria and InterMune with
respect to the manufacture, testing, storage and delivery of the
DRUG PRODUCT to InterMune, (ii) define the quality
requirements placed upon BI Austria with respect to the
manufacture, testing and delivery of DRUG PRODUCT and
(iii) form an integral part of this Agreement once such
quality agreement is entered into by the Parties. In the event of
any conflict between Sections 1.8-1.12 and Section 5 of
this Agreement and such Quality Agreement, the Quality Agreement
shall control except to the limited extent that a provision of such
Quality Agreement expressly and specifically states an intent of
those Sections of this Agreement to supercede.
1.34 QUALITY
REQUIREMENTS FOR MANUFACTURING TRANSFER mean InterMune’s quality requirements for
manufacturing transfer as set forth in Exhibit 8, as
may be amended from time to time by written agreement of the
Parties.
1.35
MANUFACTURER’S RELEASE means the release of the DRUG PRODUCT by BI
Austria to InterMune or its designee.
1.36
SERVICES mean the
services to be performed by BI Austria and BI Pharma in connection
with (a) conducting the necessary activities for the transfer of
the manufacturing process of INTERFERON ALFACON-1 from Amgen to BI
Austria, including, but not limited to, carrying out manufacturing
transfer and implementation runs and performing those technical
adaptations required to fit the manufacturing process to BI Austria
and BI Pharma facilities, (b) carry out conformance /
qualification runs for the cGMP manufacture of finished INTERFERON
ALFACON-1 product; (c) transfer of analytical methods for the
testing and release of buffers, intermediates, drug substance and
drug product to monitor production and release of material;
(d) perform method, cleaning and process validation;
(e) conduct stability testing for cell banks, inclusion
bodies, intermediate pools, drug substance, reference material,
buffers, etc.; (f) conduct an analytical comparison of the
AMGEN PRODUCT and the DRUG PRODUCT in order to show comparability
between the two; and (g) provide support in writing the amendment
to the CMC filing and prepare for FDA inspection in order for BI
Austria to be registered with the FDA as a cGMP-compliant
manufacturer for an INTERFERON ALFACON-1 product to be sold under
the INFERGEN ® trademark for the US market and other
territories controlled by InterMune, as further described in
Exhibit 9 and subject to Section 2.2 .
Exhibit 9 also includes the total cost for the SERVICES.
The timeline within which BI Austria and BI Pharma intend to
perform the SERVICES is described in Exhibit 10 which
may be modified from time to time as determined by the PROJECT TEAM
.
1.37 SIDE
LETTER AGREEMENT means
that certain Side Letter Agreement Re Infergen Manufacturing
Transfer dated May 9, 2005 entered into between InterMune and
BI Austria.
1.38
STEERING COMMITTEE means
the committee as listed in Exhibit 11 and as further
described in Section 6.2.
1.39
TERRITORY means
(i) the US, Canada, the possessions and territories of each
such country and (ii) Switzerland and those territories that
are members of the European Union and/or European Economic Area as
of the Effective Date hereof, all to the extent InterMune
has
6.
or may acquire
the right to manufacture, use or sell INTERFERON ALFACON-1 products
during the term of this Agreement.
1.40
US means the United
States of America.
2.
Data Transfer and Product
Comparison
2.1
InterMune’s Tasks and Responsibilities
InterMune shall
provide (or cause Amgen to provide) BI Austria with the relevant
documentation that is reasonably available to InterMune concerning
the AMGEN PRODUCT and its manufacture by Amgen, including
amendments and currently used batch records and testing procedures
and all material correspondence with the HEALTH AUTHORITIES in the
US as listed in Exhibit 12 . The Parties acknowledge
that BI Austria is already in receipt of most of the relevant
documentation.
InterMune shall
provide (or cause Amgen to provide) BI Austria with original [***]
vials from Amgen and samples of DRUG SUBSTANCE manufactured by
Amgen, as well as of the final labeled product INFERGEN
â
, in such reasonable amounts and at
such times as agreed by the PROJECT TEAM. InterMune shall also
supply BI Austria, as reasonably requested and in reasonable
amounts, with reference material, antibodies and reagents for
analytical testing, and all other material reasonably available to
InterMune and reasonably requested by BI Austria that may be
suitable as a basis for comparison between the AMGEN PRODUCT and
the DRUG PRODUCT.
InterMune shall
also provide (or cause Amgen to provide) to BI Austria, as
reasonably requested, all technical data and equipment
specifications reasonably available to InterMune that are used in
the manufacture of the AMGEN PRODUCT in the US.
InterMune shall
(or cause Amgen to) timely send all documentation and materials,
and otherwise timely provide all information and other assistance,
reasonably requested by BI Austria for use under this Agreement.
InterMune shall provide such reasonable technical support at its
own expense, which support shall include access to
InterMune’s expert personnel upon reasonable notice and at
such reasonable times as the Parties may agree.
2.1.5 Contact
with HEALTH AUTHORITIES
2.1.5.1 InterMune, as the license holder for the AMGEN
PRODUCT in the US, shall have the overall responsibility regarding
all contacts with the HEALTH AUTHORITIES and shall be solely
responsible for filing all regulatory documents required by any
HEALTH
7.
AUTHORITIES,
such as any amendments to the BLA for the AMGEN PRODUCT. BI Austria
shall support InterMune in all matters regarding the manufacturing
and quality control of DRUG PRODUCT as reasonably requested by
InterMune, but InterMune shall be the leading Party, responsible
for co-ordination of all regulatory matters.
2.1.5.2 InterMune will notify BI Austria in advance of any
meeting with any HEALTH AUTHORITIES with regard to manufacture,
supply and quality control of the DRUG PRODUCT manufactured by BI
Austria or BI Pharma under this Agreement. Where reasonably
possible, InterMune will notify BI Austria at least five
(5) business days in advance of such meeting; provided,
however that the Parties understand and agree that InterMune will
not always be able to notify BI Austria of a meeting with HEALTH
AUTHORITIES within the aforementioned five (5) business day
period because the HEALTH AUTHORITIES may not always schedule such
meeting far enough in advance so as to allow InterMune to notify BI
Austria within such five (5) business day period. Nonetheless,
InterMune will promptly notify BI Austria as soon as any such
meeting with the HEALTH AUTHORITIES is scheduled. BI Austria shall
have the right to participate in such meetings with such HEALTH
AUTHORITIES during the portion of such meetings relating to BI
Austria’s or BI Pharma’s manufacture, supply and
quality control of the DRUG PRODUCT.
2.1.5.3 BI Austria will be responsible for drawing up the
annual report required by the HEALTH AUTHORITIES reasonably in
advance of the due date, and will be responsible of matters
regarding the manufacture of DRUG PRODUCT. InterMune shall submit
such report to the HEALTH AUTHORITIES and shall provide BI Austria
with a copy of the finally submitted report.
2.1.6 Shipment
of Material by InterMune
All material, e.g.
samples, sent by InterMune to BI Austria shall be made by shipment
from InterMune’s or Amgen’s facility to BI
Austria’s facility in Vienna or BI Pharma’s facility in
Biberach, as appropriate. Shipping costs including insurance will
be borne by InterMune, and risk of loss in transit shall lie with
InterMune.
2.2 BI
Austria’s Tasks and Responsibilities
2.2.1 Scope of
Services. Subject to this Section 2.2, BI Austria’s
tasks and responsibilities with respect to the performance of the
SERVICES are as set forth in Exhibit 9 and the timeline
for the performance of such SERVICES are as set forth in
Exhibit 10. To the extent any task or responsibility of
BI Austria is subcontracted to BI Pharma by BI Austria as permitted
under this Agreement, BI Austria shall be responsible for BI
Pharma’s performance thereof.
2.2.2
Comparison of Documentation and Materials
2.2.2.1 As a part of the SERVICES, BI Austria shall evaluate
and compare all documentation and other materials relating to the
manufacture and testing of the AMGEN PRODUCT with all relevant
documentation and other materials relating to the manufacture and
testing of the DRUG PRODUCT that is necessary to demonstrate
comparability between such Amgen documentation, as listed in
Exhibit 12, and such BI Austria documentation.
8.
2.2.2.2 As a part of the SERVICES, BI Austria shall also
carry out an analytical comparison of the DRUG PRODUCT and DRUG
SUBSTANCE with the AMGEN PRODUCT based on a mutually agreed
protocol .
As a part of the
SERVICES and subject to Section 2.2.4, BI Austria shall carry
out the necessary number of production runs of DRUG PRODUCT in
order to obtain APPROVAL in the US as a cGMP manufacturer of DRUG
SUBSTANCE (known as “conformance batches” or
“conformance lots”), and to have BI Pharma obtain
APPROVAL in the US as a cGMP manufacturer of DRUG PRODUCT. DRUG
SUBSTANCE and DRUG PRODUCT derived from these runs shall be used
for evidencing comparability between the AMGEN PRODUCT and the DRUG
PRODUCT. The Parties anticipate that at least three (3) such
production runs will be necessary for such purposes. For such
production runs, BI Austria shall provide to InterMune access to or
copies of those QUALITY REQUIREMENTS FOR MANUFACTURING TRANSFERS
listed in Exhibit 8 .
If any HEALTH
AUTHORITIES request further analytical testing and/or production
runs in addition to those described in Exhibit 9 , BI
Austria shall perform such testing and/or production runs as
requested by InterMune and the Parties will negotiate in good faith
the cost and responsibility for such non-foreseeable additional
activities.
2.2.5
Additional Documentation
If any HEALTH
AUTHORITIES request that InterMune or BI Austria provide, in
connection with BI Austria’s and/or BI Pharma’s receipt
of approval as a manufacturer of DRUG PRODUCT hereunder, further
documentation regarding the manufacture of DRUG PRODUCT in addition
to the documentation as foreseen under the SERVICES set forth in
Exhibit 9 (e.g. certain reports), BI Austria will
provide such additional documentation to InterMune for provision to
such HEALTH AUTHORITIES as soon as reasonably possible and the
Parties will negotiate in good faith the cost and responsibility
for the provision of such additional documentation. Such additional
documentation may be either (a) product and/or process-related or
(b) facility-related (e.g. infrastructure, utilities,
personnel, training etc.).
2.2.6.1 As a part of the SERVICES, BI Austria shall provide
all site-relevant documentation (both from itself and from BI
Pharma) and all data relevant for compiling the CMC section
necessary for InterMune’s drafting of the BLA supplement
required by the FDA due to the change of manufacturer for the AMGEN
PRODUCT. BI Austria agrees to use commercially reasonable efforts
and fully co-operate with InterMune in obtaining and
9.
maintaining all
US governmental approvals and registrations relevant to the CMC
section of the registration dossier (and their foreign equivalents)
as requested by InterMune.
2.2.6.2 The Parties shall consult with each other concerning
the scope and content of all regulatory filings, and shall jointly
define the requirements for the necessary DRUG PRODUCT registration
with the HEALTH AUTHORITIES so that BI Austria shall be able to
fulfill its obligations under this Agreement with respect to the
CMC portion of such DRUG PRODUCT registration. Any regulatory
filings which contain any BI Austria data shall be subject to BI
Austria’s review and written approval prior to submission to
the HEALTH AUTHORITIES (which approval shall not be unreasonably
withheld or delayed).
2.2.7 Format
and Content of Documents
BI Austria’s
Quality Management System demands a special format for certain
documents (i.e. batch records, testing procedures, technical
reports) which is binding. For those documents where a binding
format is not obligatory the Parties shall agree in writing on a
master format. With respect to the dates contained in these
documents, and in particular in all reports and when dates occur in
connection with signatures, the European writing style shall apply.
The order shall be as follows: dd / mm / yy
(day/month/year).
2.2.8 Standard
of Performance
BI Austria shall
diligently perform the SERVICES, and shall ensure that BI Pharma
diligently performs the SERVICES, in a manner consistent with good
scientific / regulatory / business practices. InterMune
acknowledges that the SERVICES are of biological nature and
therefore neither success nor commercial exploitability can be
guaranteed by BI Austria.
3.
Manufacture and
Supply
3.1.1
[***] for use and commercialization in the TERRITORY, DRUG
SUBSTANCE or DRUG PRODUCT for use in the treatment or prevention of
any human disease or condition. BI Austria shall not supply DRUG
SUBSTANCE or DRUG PRODUCT for use in the treatment of any human
disease or condition to any third party for use and/or sale in the
TERRITORY without InterMune’s prior written consent. [***]
all of InterMune’s clinical trial supply, and from the time
BI Austria and BI Pharma are approved by the HEALTH AUTHORITIES
also [***] for the term of this Agreement, subject to
Section 3.7.
3.1.2 All
DRUG SUBSTANCE manufactured by BI Austria hereunder, and all DRUG
PRODUCT manufactured and supplied to InterMune by BI Austria
hereunder, shall be manufactured and supplied in accordance with
the DRUG SUBSTANCE SPECIFICATIONS and DRUG PRODUCT SPECIFICATIONS,
the cGMP requirements and all applicable laws, regulations and
ordinances of the jurisdiction in which such manufacture
occurs.
*** 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.
10.
3.1.3 BI
Austria shall manufacture DRUG SUBSTANCE according to the DRUG
SUBSTANCE SPECIFICATIONS. BI Austria shall manufacture DRUG PRODUCT
according to DRUG PRODUCT SPECIFICATIONS for clinical supply. Upon
receipt of FDA APPROVAL of BI Austria’s facility as well as
BI Pharma’s facility, BI Austria shall also manufacture DRUG
PRODUCT for market supply. DRUG SUBSTANCE for clinical and market
supply shall be manufactured at BI Austria and transferred to BI
Pharma for filling of vials and/or syringes . Manufacturing
and filling of vials and/or syringes as well as the storing of DRUG
PRODUCT shall be in accordance with the DRUG PRODUCT
SPECIFICATIONS, the cGMP requirements and all applicable laws,
regulations and ordinances of the jurisdiction in which such
manufacturing and/or filling occurs. Notwithstanding the fact that
BI Austria takes BI Pharma as a toll manufacturer for filling of
DRUG PRODUCT, BI Austria takes responsibility for the manufacture
and supply of DRUG PRODUCT to InterMune in accordance with the
terms and conditions of this Agreement.
3.1.4
Notwithstanding the exclusive arrangement set forth in
Section 3.1.1 above, the Parties acknowledge and agree that
there will be an overlapping period of time during which Amgen will
be winding down and completing its manufacturing and supply
obligations under the License and Commercialization Agreement dated
June 15, 2001, as amended, by and between Amgen and InterMune
and during which BI Austria will be completing its SERVICES and
beginning its manufacturing and supply obligations under this
Agreement. Consequently, BI Austria agrees that during such
overlapping transition time period, Amgen may continue to supply to
InterMune any remaining inventory of AMGEN PRODUCT or DRUG
SUBSTANCE manufactured by Amgen for InterMune until Amgen completes
its winding down of its manufacturing and supply activities for
InterMune.
3.1.5 With
respect to conformance batches produced as part of the production
runs described under Section 2.2.3, the Parties acknowledge
and agree that such conformance batches may be suitable for use to
produce DRUG PRODUCT for commercial supply. Accordingly, the
Parties agree that they will work together in good faith to have BI
Austria to use as much of the DRUG SUBSTANCE resulting from such
conformance batches as possible to produce DRUG PRODUCT for supply
to InterMune under this Agreement. If all the DRUG SUBSTANCE from
the conformance batches must be destroyed, the Parties agree that
the maximum obligation of InterMune to BI Austria for the
destruction of such DRUG SUBSTANCE is [***]. In the event that less
than all of the DRUG SUBSTANCE resulting from the conformance
batches must be destroyed, then the payment obligation by InterMune
shall be reduced on a pro rata basis based on the percentage that
is destroyed. For example, if 1/3 of DRUG SUBSTANCE is destroyed,
then the payment obligation by InterMune will be [***].
3.1.6
Notwithstanding the exclusive arrangement set forth in
Section 3.1.1 above, the Parties acknowledge and agree that
InterMune may conduct research feasibility studies for and develop
additional configurations for the DRUG SUBSTANCE other than vials
or pre-filled syringes currently included in the definition of DRUG
PRODUCT. In such event, InterMune shall have the right to purchase
from BI Austria and BI Austria shall sell to InterMune DRUG
SUBSTANCE. If InterMune desires to purchase DRUG SUBSTANCE before
APPROVAL of BI Austria in the US as a cGMP manufacturer of DRUG
SUBSTANCE, then the price at which BI AUSTRIA will sell such DRUG
SUBSTANCE to InterMune will be negotiated by the Parties
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11.
in good faith.
If InterMune desires to purchase DRUG SUBSTANCE after APPROVAL of
BI Austria in the US as a cGMP manufacturer of DRUG SUBSTANCE, then
the price at which BI Austria will sell such DRUG SUBSTANCE to
InterMune will be provided by BI Austria to InterMune as set forth
in Exhibit 14. Should InterMune desire to fill and
finish the DRUG SUBSTANCE in such newly developed configurations
for clinical and/or commercial supply, InterMune shall provide
written notice to BI Austria and shall first negotiate exclusively
in good faith with BI Austria to have BI Austria fill and finish in
such configurations; provided, however, that in the event the
Parties are unable to reach agreement therefor within ninety
(90) days after the aforementioned notice is provided by
InterMune to BI Austria, InterMune shall have the right to fill and
finish the DRUG SUBSTANCE in such newly developed configurations on
its own or through a third party for clinical and/or commercial
use.
3.1.7 The
Parties further acknowledge and agree that BI Austria will be
required to subcontract to a third party the radioactive bioassay
testing for the DRUG PRODUCT. The Parties will cooperate with one
another and work together in good faith to decide upon the
appropriate third party to conduct such bioassay testing. BI
Austria shall assume the responsibility and cost for such bioassay
testing within the framework of the MANUFACTURER’S
RELEASE.
3.2.1 No
later than [***] prior to [***] of DRUG PRODUCT requested by
InterMune for clinical and/or market supply, InterMune shall send
to BI Austria a forecast for [***] (which forecast may commence on
the first day of any calendar quarter). After such first forecast
is given, InterMune will update the forecast on a [***] basis at
the latest on the first day of each ensuing [***] [***] during the
term of this Agreement. The forecast provided by InterMune shall
become binding no later than [***] prior to the first delivery date
of DRUG PRODUCT as follows: The first [***] of such forecast shall
be firm (red zone). For [***] (blue zone) InterMune can reduce its
forecast by [***] but only once in each one (1) of these
quarters, and may increase its forecast by [***] once in each one
(1) of these quarters. [***] will constitute a non-binding
forecast (green zone). InterMune agrees to order the DRUG PRODUCT
in filling lot quantities or multiples thereof. [***] Prior to
InterMune submitting the first forecast required hereunder, the
Parties will mutually agree upon the final lot size for each of the
vials and syringes, which lot size will be within the applicable
range set forth above.
Following BI
Austria’s and BI Pharma’s FDA approval to manufacture
DRUG PRODUCT for market supply, InterMune shall order the requested
amounts of DRUG PRODUCT. There shall be no annual minimum purchase
obligations imposed upon InterMune for the DRUG PRODUCT unless and
until results from InterMune’s daily INFERGEN
® Phase III clinical trial (IRHC-0001)
(“DIRECT TRIAL”) becomes available and such results are
[***]
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12.
[***] As of the
date hereof, InterMune estimates that the results of the DIRECT
TRIAL will be available in the [***] Within a reasonable amount of
time, BI Austria and InterMune shall cooperate and work together in
good faith to commence and conclude negotiations on the annual
minimum and maximum purchase obligations for InterMune and the
annual minimum and maximum supply obligations of BI Austria such
that no later than two (2) years prior to the estimated time
for BI Austria’s and BI Pharma’s FDA approval to
manufacture DRUG PRODUCT for market supply, BI Austria and
InterMune shall have reached agreement on the annual minimum and
maximum purchase and supply obligations of the Parties, which
agreement shall be set forth in a separate addendum
hereto.
3.2.2 If
InterMune requires more DRUG PRODUCT than is set forth in the
current firm forecast, BI Austria shall use commercially reasonable
efforts in good faith to supply InterMune with DRUG PRODUCT as
requested; provided that for the amounts of DRUG PRODUCT in
excess of such forecast which BI Austria is unable to supply,
despite such commercially reasonable efforts, InterMune may use a
secondary source manufacturer in accordance with the procedures set
forth in Section 3.7.
3.2.3 If
InterMune reduces the forecast for [***] by an amount in excess of
[***] (net of any increases in actual orders for these [***] [***],
then InterMune shall be [***] which was [***] of [***] [***] at the
[***] [***] of the unit price of the DRUG PRODUCT then in
effect.
3.2.4 For
planning purposes only, no later than January 31, 2006
InterMune will provide to BI Austria a non-binding estimate of
InterMune’s requirements for the DRUG PRODUCT for the [***]
following the estimated commercial market launch of each such
presentation of the DRUG PRODUCT, which non-binding estimate shall
be attached hereto as Exhibit 13.
3.3.1 All
purchases of DRUG PRODUCT hereunder shall be made pursuant to
written purchase orders provided to BI Austria by InterMune. To the
extent that the terms of a purchase order of InterMune or of BI
Austria’s or BI Pharma’s “General Conditions of
Sale” are inconsistent with the terms of this Agreement, this
Agreement shall prevail.
3.3.2 BI
Austria shall guarantee that at the date of MANUFACTURER’S
RELEASE all DRUG PRODUCT supplied to InterMune shall have a minimum
residual shelf life of not less than [***] off the shelf life of
the DRUG PRODUCT in existence at the date of the manufacturing of
such DRUG PRODUCT. The Parties acknowledge and agree that the shelf
life at the time of the manufacturing of the DRUG PRODUCT is
dependent on the information on the current expiry of the DRUG
PRODUCT.
3.3.3 BI
Austria shall ship all DRUG PRODUCT as set forth in
Section 3.4 by the date and in the quantities specified in the
applicable purchase order. BI Austria shall be obligated to accept
any purchase order within the range of permitted variation in the
forecasted quantities as
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13.
set forth in
Section 3.2.1. and 3.2.2. Any other purchase order shall be
binding on BI Austria only if it is accepted by BI Austria, which
acceptance shall not be unreasonably withheld. If BI Austria does
not accept such a purchase order, then InterMune may use a
secondary source manufacturer for such purchase order in accordance
with the procedures set forth in Section 3.7.
3.3.4
InterMune shall be obligated to buy and BI Austria shall be
obligated to sell only the quantities of DRUG PRODUCT which are
subject to a purchase order accepted by BI Austria. Any purchase
order (or portion thereof) for which InterMune has not received a
written rejection from BI Austria within [***] of BI
Austria’s receipt of such purchase order shall be deemed
accepted by BI Austria. Without limiting the generality of the
foregoing, with respect to DRUG PRODUCTS ordered by InterMune for
its clinical supply requirements, the number of vials or syringes
supplied by BI Austria shall not exceed the number of vials or
syringes subject to the applicable purchase order submitted by
InterMune; provided, however, that if the number of vials or
syringes BI Austria is able to supply falls below the number of
vials or syringes ordered by InterMune in such purchase order and
such lesser number is within a reasonable range of the number
ordered by InterMune, BI Austria shall notify InterMune in writing
and inquire as to whether such lesser number of vials or syringes
is acceptable and if not, whether BI Austria should produce an
additional batch of DRUG SUBSTANCE to produce enough vials or
syringes to satisfy InterMune’s purchase order. If InterMune
notifies BI Austria that such lesser number of vials or syringes is
acceptable to InterMune, then the applicable purchase order shall
be deemed to be amended to provide for such lesser number of vials
or syringes and BI Austria shall be deemed to have accepted such
purchase order in accordance with Section 3.3. On the other
hand, if InterMune notifies BI Austria that BI Austria should
manufacture an additional batch of DRUG SUBSTANCE to produce the
number of vials or syringes ordered by InterMune in its purchase
order submitted to BI Austria, then (i) the Parties will
mutually agree upon a reasonable delivery date for such vials or
syringes derived from such additional batch of DRUG SUBSTANCE,
(ii) BI Austria shall be obligated to produce the additional
batch of DRUG SUBSTANCE, (iii) InterMune shall be obligated to
purchase any excess vials or syringes of DRUG PRODUCT produced by
BI Austria from such additional batch of DRUG SUBSTANCE, (iv) the
purchase order submitted to BI Austria by InterMune shall be deemed
amended to account for any excess vials or syringes resulting from
the additional batch of DRUG SUBSTANCE and to account for the
agreed upon delivery date for the vials or syringes derived from
such additional batch of DRUG SUBSTANCE and (v) such purchase
order shall be deemed accepted by BI Austria in accordance with
Section 3.3.
3.4 Shipment
of DRUG PRODUCT and Material by BI Austria
3.4.1 The
DRUG PRODUCT and all material (e.g. samples) shall be shipped [***]
either BI Pharma’s facility in Biberach, Germany or BI
Austria’s facility in Vienna, Austria, as the case may be, to
InterMune or as directed by InterMune, in accordance with Incoterms
2000 as published by the International Chamber of Commerce.
InterMune’s designated carrier shall be used to ship DRUG
PRODUCT to the site designated by InterMune. The Parties
acknowledge and agree that the only deviation from the definition
of “EX WORKS” is that BI Austria shall be responsible
and bear the cost of stowage and loading the DRUG PRODUCT onto the
InterMune designated carrier such that the risk of loss and title
shall pass
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14.
from BI Austria
to InterMune only upon completion of the loading by BI Austria of
the DRUG PRODUCT onto the InterMune designated carrier. Risk of
loss in transit by InterMune’s designated contract carrier
shall lie with InterMune, except where such loss is caused by BI
Austria’s or BI Pharma’s negligence.
3.4.2 BI
Austria will provide or will have provided assistance to InterMune
regarding necessary procedures for exportation and/or importation
of DRUG PRODUCT. BI Austria shall also provide to InterMune every
two (2) months the shipping schedule for the DRUG
PRODUCT.
3.4.3 In
the event that DRUG PRODUCT, which has been ordered by InterMune
pursuant to a purchase order is not shipped to InterMune within
[***] calendar days of FINAL RELEASE for reasons solely and
directly assignable to InterMune (e.g., lack of shipping
instructions, etc.), the risk of the deterioration or perishing of
the DRUG PRODUCT resulting therefrom passes to InterMune. BI
Austria shall render invoice and InterMune shall pay for such DRUG
PRODUCT when the invoice becomes due. BI Austria shall be entitle
to claim reimbursement for commercially reasonable storage costs
incurred by BI Austria after expiry of the [***] calendar day time
limit. In the circumstances where InterMune has paid for the DRUG
PRODUCT but such DRUG PRODUCT is not available for shipment (e.g.,
analytical testing issues, regulatory filing issues), the Parties
will cooperate with one another in good faith and mutually agree
with one another on the appropriate allocation between the Parties
of risk of deterioration or perishing of the DRUG
PRODUCT.
3.5 Testing
and Rejection
3.5.1
Within [***] business days of its receipt of DRUG PRODUCT at such
destination as may be designated by InterMune, InterMune may
perform such tests and samplings as are appropriate to determine
whether such DRUG PRODUCT meets the applicable DRUG PRODUCT
SPECIFICATIONS. If InterMune refuses acceptance of DRUG PRODUCT,
then InterMune shall inform BI Austria in writing within [***]
further business days of any aspect in which such DRUG PRODUCT
fails to conform to the DRUG PRODUCT SPECIFICATIONS. If BI Austria
does not receive such a notice within [***] business days of
InterMune’s receipt of such DRUG PRODUCT, then InterMune
shall be deemed to have accepted the DRUG PRODUCT; provided that
InterMune shall have the right to revoke its acceptance of such
goods if it later discovers latent defects. A latent defect is a
deviation which constitutes a breach of one or more of BI
Austria’s warranties pursuant to Sec. 9.2.1 through 9.2.5 of
this Agreement, which was not reasonably discoverable at the time
of receipt and the cause of which is assignable solely to BI
Austria (or BI Pharma).
3.5.2 If
BI Austria receives a notice from InterMune pursuant to
Section 3.5.1 that InterMune does not accept any DRUG PRODUCT
supplied hereunder, then BI Austria shall immediately start
re-testing the DRUG PRODUCT using the retained samples in order to
evaluate process issues and other reasons for such
non-compliance.
3.5.3
Regardless of whether BI Austria agrees with InterMune’s
rejection of such DRUG PRODUCT, if requested in writing by
InterMune, BI Austria shall use reasonable efforts
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15.
to promptly
replace such allegedly defective DRUG PRODUCT, the costs of which
shall be borne as set forth in Section 3.5.4.
3.5.4 In
the event that BI Austria’s re-testing does not verify
InterMune’s reasons for rejecting such DRUG PRODUCT, the
Parties shall mutually agree on an independent laboratory that
shall determine by applying validated product-specific analytical
methods whether such DRUG PRODUCT meets the DRUG PRODUCT
SPECIFICATIONS. The conclusions of this independent laboratory
shall be binding upon both Parties. If such laboratory determines
that such DRUG PRODUCT does meet the DRUG PRODUCT SPECIFICATIONS,
then InterMune shall [***]. If such laboratory determines that such
DRUG PRODUCT does not meet the DRUG PRODUCT SPECIFICATIONS, then BI
Austria shall [***]
3.5.5
Neither Party may destroy any DRUG PRODUCT alleged not to meet the
DRUG PRODUCT SPECIFICATIONS until the independent laboratory
determines whether such DRUG PRODUCT meets the applicable DRUG
PRODUCT SPECIFICATIONS and provides written notification to the
Parties with respect to such determination, unless BI Austria
accepts InterMune’s basis for such rejection. Thereafter, BI
Austria shall have the obligation to destroy or have destroyed, at
its cost, all such rejected DRUG PRODUCT. Upon BI Austria’s
written request and at BI Austria’s cost, InterMune shall
either destroy or return to BI Austria any rej
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