EXHIBIT 10.1
ENBREL SUPPLY AGREEMENT
THIS ENBREL SUPPLY AGREEMENT ("Agreement") is made effective as of April 12,
--------- 2002, by and between Immunex Corporation, a Washington corporation, having its principal place of business at 51 University Street, Seattle, Washington 98101 ("Immunex"), and Genentech, Inc., a Delaware corporation, having its principal ------- place of business at One DNA Way, South San Francisco, California 94080 ("Genentech"). ---------
BACKGROUND
----------
Immunex markets and sells a certain proprietary biological pharmaceutical product known as ENBREL(R) (etanercept). Immunex desires to obtain additional supply of commercial quantities of ENBREL bulk drug substance. Genentech has the experience and expertise necessary to perform the manufacturing and related services needed to supply ENBREL bulk drug substance, and Genentech owns a facility that, with some modifications, could be suitable for production of commercial quantities of ENBREL bulk drug substance.
Immunex desires to retain Genentech as a nonexclusive manufacturer of commercial quantities of ENBREL bulk drug substance and purchase commercial quantities of such product from Genentech, and Genentech desires to perform such services and sell commercial quantities of such product to Immunex, all on the terms and conditions set forth in this Agreement.
AGREEMENT
---------
NOW, THEREFORE, IN CONSIDERATION OF the mutual covenants set forth in this Agreement, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties hereby agree as follows:
ARTICLE 1. DEFINITIONS
----------------------
The following terms, whether used in the singular or plural, shall have the meanings assigned to them below for purposes of this Agreement.
1.1 "Acquisition Cost" means the actual invoiced price paid by Genentech to any
----------------
Third Party for acquiring any materials used in the manufacture of the
Product under this Agreement, including, but not limited to, shipping and
handling costs and customs duties incurred and paid by Genentech in
connection with the acquisition of such materials, and also including [*]
percent ([*]%) of the above amounts to cover such
* Portions of this exhibit have been omitted pursuant to a request for confidential treatment filed with the Securities and Exchange Commission. The omitted portions of this exhibit have been filed separately with the SEC.
Party's storage and overhead costs. This definition, including the [*]
percent ([*]%) markup, shall only apply in the circumstances set forth in
Section 6.2(a)(5) and Section 19.3(d)(1) hereof.
----------------- ------------------
1.2 "Affiliate" means, with respect to any Party, any other corporation or
---------
business entity that directly, or indirectly through one or more
intermediaries, controls, is controlled by or is under common control with
such Party. For purposes of this definition, the term "control" means
direct or indirect ownership of fifty percent (50%) or more of the
securities or other ownership interests representing the equity voting
stock or general partnership or membership interest of such entity or the
power to direct or cause the direction of the management or policies of
such entity, whether through the ownership of voting securities, by
contract, resolution or otherwise.
1.3 "Batch" or "Lot" means the quantity of Bulk Drug produced from a single
----- ---
Run, and refers to a Commercial Batch or Lot, a Development Batch or Lot,
and/or a Qualification Batch or Lot, as the context requires. A Run may
result in more than one subbatch or sublot due to splitting into tanks
downstream in the Manufacturing Process.
1.4 "Batch Records" shall have the meaning set forth in the Quality Agreement.
-------------
1.5 "BIP" means Boehringer Ingelheim Pharma KG.
---
1.6 "BIP Confidential Information" means Immunex Confidential Information that
----------------------------
has been identified in writing as confidential information of BIP, and is
referred to in Section 17.6 hereof.
------------
1.7 "Bulk Drug" means the bulk form of the Product which has been manufactured
---------
by Genentech pursuant to this Agreement, which has been purified to a
concentrated form from one or more Batches and can be stored in a liquid or
frozen form under appropriate conditions, and, except with respect to
Non-Conforming Bulk Drug, which has been manufactured in compliance with
cGMP and conforms to the Bulk Drug Specifications.
1.8 "Bulk Drug Commitment" refers to the first [*] months of each binding
--------------------
rolling Product Manufacturing Forecast (including all amendments thereto),
and means a commitment by Genentech to comply with and perform the number
of Runs set forth therein. The Bulk Drug Commitment is a rolling [*] month
commitment, and is described with more particularity in Section 4.2 hereof.
-----------
1.9. "Bulk Drug Specifications" means specifications developed by Immunex for
------------------------
Bulk Drug as set forth in the Product sBLA, including, without limitation,
testing methods and acceptance criteria for each Batch generated, a summary
of which is attached to the Quality Agreement, as such specifications may
be amended from time to time in accordance with Section 6.2 hereof,
-----------
including, without limitation, such amendments as
* Portions of this exhibit have been omitted pursuant to a request for confidential treatment filed with the Securities and Exchange Commission. The omitted portions of this exhibit have been filed separately with the SEC.
Page 2
may be required to obtain approval from the FDA and other applicable
regulatory authorities in the United States.
1.10 "cGMP" means the regulatory requirements for current good manufacturing
----
practices promulgated by the FDA under the FD&C Act, 21 C.F.R.(S)(S)210,
211 and 600 et seq. and under the PHS Act, 21 C.F.R.(S)(S)600-610, as the
same may be amended from time to time.
1.11 "Cell Line" means a proprietary Immunex Chinese Hamster Ovary cell line
---------
that expresses the Product.
1.12 "Certificate of Analysis" means, for each Batch, a document prepared by
-----------------------
Immunex: (a) listing tests performed by Immunex, specifications, test
date(s), and test results, and certifying the accuracy of the foregoing;
(b) referring to the related Certificate of Compliance prepared by
Genentech, listing the manufacturing date, unique Batch number, and
quantity of Bulk Drug in such Batch, as certified by Genentech in such
Certificate of Compliance; and (c) referring to the related Certificate of
Testing prepared by Genentech, listing tests performed by Genentech,
specifications, test date(s), and test results, as certified by Genentech.
The Parties shall from time to time agree upon a format or formats for the
Certificate of Analysis to be used under this Agreement.
1.13 "Certificate of Compliance" means, for each Batch, a document prepared by
-------------------------
Genentech: (a) listing the manufacturing date, unique Batch number, and
quantity of Bulk Drug in such Batch, and (b) certifying that such Batch was
manufactured in accordance with the Bulk Drug Specifications and cGMP. The
Parties shall from time to time agree upon a format or formats for the
Certificate of Compliance to be used under this Agreement.
1.14 "Certificate of Testing" means, for each Batch, a document prepared by
----------------------
Genentech: (a) listing tests performed by Genentech, specifications, and
test results, and (b) certifying the accuracy of the foregoing. The Parties
shall from time to time agree upon a format or formats for the Certificate
of Testing to be used under this Agreement.
1.15 "Change of Control" means the merger, acquisition or consolidation of
-----------------
Immunex with or into Amgen Inc. or a subsidiary of Amgen Inc.
1.16 "Commercial Batch" or "Commercial Lot" means a Batch or Lot produced from a
------------------------------------
Commercial Run.
1.17 "Commercial Run" means a Run that is initiated following the commencement
--------------
of Commercial Production and is used to manufacture commercial Bulk Drug.
1.18 "Commercially Reasonable Efforts" means [*].
-------------------------------
* Portions of this exhibit have been omitted pursuant to a request for confidential treatment filed with the Securities and Exchange Commission. The omitted portions of this exhibit have been filed separately with the SEC.
Page 3
1.19 "Commercially Reasonable Best Efforts" means: for Immunex, [*]; and for
------------------------------------
Genentech, [*].
1.20 "Confidential Information" means Immunex Confidential Information and/or
------------------------
Genentech Confidential Information, as the context requires.
1.21 "Development Batch" means a Batch or Lot produced from a Development Run.
-----------------
1.22 "Development Run" means a Run used for process demonstration and
---------------
confirmation of some or all of the Manufacturing Process steps, and is
described in Section 3.7(a) hereof.
--------------
1.23 "Effective Date" means April 12, 2002, which is the date set forth in the
--------------
first paragraph of this Agreement and shall be the effective date of this
Agreement.
1.24 "EMEA" means the European Medicines Evaluation Agency, or any successor
----
agency.
1.25 "Enbrel License Agreement" means that certain License Agreement for
------------------------
Etanercept between Immunex and Genentech dated [*].
1.26 "Facility Modifications and Services Costs" means the actual invoiced price
-----------------------------------------
paid by Genentech to any Third Party for acquiring services, including,
without limitation, design and engineering services, and necessary
equipment, for modifications to the Genentech Facility needed to implement
the Manufacturing Process at the Genentech Facility, all to the extent
incurred in accordance with the Tech Transfer Agreement, and including,
without limitation, such amounts incurred in accordance with the Letter of
Intent (and also including, without limitation, such amounts incurred in
accordance with the Letter of Intent after expiration of the Letter of
Intent and prior to or on the Effective Date of this Agreement, as if the
Letter of Intent had been extended through and including the Effective Date
of this Agreement).
1.27 "Facility Validation" shall have the meaning ascribed to it in the Tech
-------------------
Transfer Agreement.
1.28 "FD&C Act" means the United States Federal Food, Drug and Cosmetic Act, as
--------
the same may be amended from time to time.
1.29 "FDA" means the United States Food and Drug Administration, or any
---
successor agency thereto.
1.30 "Field" shall mean the manufacture of Product utilizing the manufacturing
-----
process in actual use as of the Effective Date, as well as any
modifications to such manufacturing process that are implemented in
accordance with this Agreement into the manufacturing process actually used
by Genentech in manufacturing Product pursuant to this Agreement, as well
as any other modifications to such manufacturing process
* Portions of this exhibit have been omitted pursuant to a request for confidential treatment filed with the Securities and Exchange Commission. The omitted portions of this exhibit have been filed separately with the SEC.
Page 4
that are implemented by Immunex, its Affiliates, Product licensees or
contract manufacturers for Product either during or, with respect to [*].
1.31 "Finished Product" means Bulk Drug which has been formulated, compounded,
----------------
filled into containers, and labeled, and placed in final commercial
packaging.
1.32 "For Cause Audit" shall have the meaning set forth in the Quality
---------------
Agreement.
1.33 "Genentech Confidential Information" means all technical and other
----------------------------------
information, whether patented or unpatented, relating to the Genentech
Facility and/or Genentech processes, methods, operations, technologies,
forecasts and business information that are disclosed or supplied to, or
used on behalf of Immunex by Genentech pursuant to this Agreement, the Tech
Transfer Agreement and/or the Quality Agreement, or of which Immunex may
become aware of through the presence of their employees or agents at
Genentech offices or at the Genentech Facility, including, without
limitation, trade secrets, know-how, processes, concepts, experimental
methods and results and business and scientific plans and information and
facility layout and schematics.
1.34 "Genentech Facility" means Genentech's commercial manufacturing facility
------------------
located at One DNA Way in South San Francisco, California. In addition, in
the event Genentech, in its sole discretion, utilizes storage capacity in
its Vacaville, California facility to store Bulk Drug, then the term
"Genentech Facility" includes, when and as the context requires,
------------------
Genentech's facility located in Vacaville, California, but only to the
extent that, and with respect to those portions of, the Vacaville facility
that is used by Genentech to perform Genentech's obligations hereunder.
1.35 [*]
1.36 "Genentech Patents" shall have the same definition as set forth in the
-----------------
Enbrel License Agreement.
1.37 "Genentech [*] Patents" shall mean Patents containing claims covering [*],
---------------------
in each case which were [*].
1.38 "Immunex Confidential Information" means the Cell Line, Master Cell Bank,
--------------------------------
Working Cell Bank, Manufacturing Documentation, Manufacturing Process, and
Product, and all technical and other information, whether patented or
unpatented, relating thereto and/or to Immunex processes, methods,
operations, technologies, forecasts and business information that are
disclosed or supplied to Genentech by or on behalf of Immunex pursuant to
this Agreement, the Tech Transfer Agreement and/or the Quality Agreement,
or of which Genentech may become aware of through the presence of its
employees or agents at Immunex offices or facilities or at other facilities
that manufacture the Product, including, without limitation, trade secrets,
know-how, processes, concepts, experimental methods and results and
business and scientific plans and information and facility layout and
schematics. All portions of documents
* Portions of this exhibit have been omitted pursuant to a request for confidential treatment filed with the Securities and Exchange Commission. The omitted portions of this exhibit have been filed separately with the SEC.
Page 5
and records describing or to the extent relating to the Manufacturing
Process at the Genentech Facility, including, without limitation, process
trend and variability data related to the Product, shall be deemed to be
Immunex Confidential Information.
1.39 "Letter of Intent" means that certain letter of intent and authorization to
----------------
proceed between the Parties dated February 4, 2002, as amended on March 22,
2002, regarding the intent of the Parties to negotiate in good faith and
execute this Agreement, and which letter is superceded in accordance with
its terms by this Agreement.
1.40 "Manufacturing Documentation" means all documents and records describing or
---------------------------
otherwise related to the Manufacturing Process or any part of the
Manufacturing Process provided to Genentech by or on behalf of Immunex
under this Agreement, the Tech Transfer Agreement or the Quality Agreement,
including, without limitation, documents and records consisting of or
containing piping and instrumentation diagrams, software logic and
descriptions, batch records, standard operating procedures, including,
without limitation, standard operating procedures for in-process quality
control testing, facility layout schematics, equipment and instrumentation
specifications and process trend and variability data.
1.41 "Manufacturing Process" means the [*] production process for the
---------------------
manufacture of Bulk Drug pursuant to this Agreement, as summarily described
in the Quality Agreement and as described in the Tech Transfer Agreement,
as such process may be changed from time to time in accordance with this
Agreement. [*]
1.42 "Master Cell Bank" means Immunex's reference deposit or collection of vials
----------------
of the Cell Line, from which the Working Cell Bank is derived.
1.43 "Milestone I" means [*], and is referred to in Section 5.2(a) hereof.
----------- --------------
1.44 "Milestone II" means [*] referred to in Section 5.2(b) hereof.
------------ --------------
1.45 "Milestone III" means [*] or, if earlier, [*], and is referred to in
-------------
Section 5.2(c) hereof.
--------------
1.46 "Milestone IV" means [*], and is referred to in Section 5.2(d) hereof.
------------ --------------
1.47 "Net Sales" shall have the same definition as set forth in the Enbrel
---------
License Agreement.
1.48 "Non-Conforming Bulk Drug" means Bulk Drug that fails to conform to any of
------------------------
the warranties set forth in Section 6.1(a) hereof.
--------------
1.49 "Non-Portable Equipment" means the Equipment (as defined in Section 14.2
---------------------- ------------
hereof), excluding any Portable Equipment. Components of the Non-Portable
Equipment, such as valves, pumps and agitators, shall also be deemed
Non-Portable Equipment. Non-Portable Equipment includes the related
documentation regarding the design,
* Portions of this exhibit have been omitted pursuant to a request for confidential treatment filed with the Securities and Exchange Commission. The omitted portions of this exhibit have been filed separately with the SEC.
Page 6
validation, operation, calibration and maintenance of such equipment.
1.50 "PHS Act" means the Public Health Service Act, Biological Products, as
-------
amended, as the same may be amended from time to time.
1.51 "Party" or "Parties" means Genentech and/or Immunex, as the context
----- -------
requires.
1.52 "Patents" shall mean, with respect to an invention, any patent or patent
-------
application, and any patent issuing therefrom, together with any
extensions, reissues, reexaminations, substitutions, renewals, divisions,
continuations and continuations-in-part thereof, and any patent or patent
application claiming priority to any application in common with any such
patent containing a disclosure substantially similar to any such patent,
all to the extent the foregoing contain claims covering such invention.
1.53 "Portable Equipment" means the portable equipment described with
------------------
particularity in the Tech Transfer Agreement and referred to in Section 5.1
-----------
hereof, including, without limitation, the related documentation regarding
the design, validation, operation, calibration, and maintenance of such
equipment. The Portable Equipment is a part of the Equipment, as defined in
Section 14.2 hereof. Components of the Portable Equipment, such as valves,
------------
pumps and agitators, shall also be deemed Portable Equipment.
1.54 [*]
1.55 "Product" means the proprietary biological pharmaceutical product known as
-------
ENBREL(R)(etanercept), which is a [*].
1.56 "Purchase Price" means the purchase price to be paid by Immunex to
--------------
Genentech for Bulk Drug as determined in accordance with the terms of this
Agreement.
1.57 "Qualification Batch" or "Qualification Lot" means a Batch or Lot produced
------------------- -----------------
from a Qualification Run.
1.58 "Qualification Run" means a Run used to document the operability and
-----------------
reproducibility of the Manufacturing Process at the Genentech Facility, and
is described in Section 3.7(b) hereof.
--------------
1.59 "Quality Agreement" means the quality agreement between the Parties of even
-----------------
date herewith which refers to this Agreement.
1.60 "Roche" means Roche Holdings, Inc., a Delaware corporation, and its
-----
"Affiliates" (as hereinafter defined) other than Genentech and Genentech's
subsidiaries. With respect to Roche, "Affiliates" means any other
----------
corporation or business entity that directly, or indirectly through one or
more intermediaries, controls, is controlled by or is under common control
with Roche Holdings, Inc.; and, for purposes of this definition, the
* Portions of this exhibit have been omitted pursuant to a request for confidential treatment filed with the Securities and Exchange Commission. The omitted portions of this exhibit have been filed separately with the SEC.
Page 7
term "control" means direct or indirect ownership of fifty percent (50%) or
more of the securities or other ownership interests representing the equity
voting stock or general partnership or membership interest of such entity
or the power to direct or cause the direction of the management or policies
of such entity, whether through the ownership of voting securities, by
contract, resolution or otherwise.
1.61 "Run" means a single fermentation start or run of the Manufacturing Process
---
at the [*] liter fermentation scale at the Genentech Facility, and refers
to a Commercial Run, Development Run and/or Qualification Run, as the
context requires. A fermentation start for the Product shall be deemed to
be a Run if such fermentation start proceeds to the [*] at the [*] liter
scale or later in the Manufacturing Process.
1.62 "sBLA" means a biologics license application for the Product, any
----
equivalent successor filing thereto with the FDA, and any supplements or
amendments to any of the foregoing.
1.63 "Specialized Raw Materials" means the specialized raw materials described
-------------------------
with particularity in the Tech Transfer Agreement and referred to in
Section 3.6 hereof.
1.64 [*]
1.65 "Tech Transfer Agreement" means the technology transfer agreement and
-----------------------
process implementation plan between the Parties of even date herewith which
refers to this Agreement, and which describes the agreement of the Parties
regarding the transfer of technology and implementation of the
Manufacturing Process at the Genentech Facility, and the modifications to
the Genentech Facility needed to implement the Manufacturing Process at the
Genentech Facility, including a timeline, budget and statement of work
jointly developed by the Parties, as the same may be amended from time to
time by mutual written agreement of the Parties.
1.66 "Territory" means the entire world.
---------
1.67 "Third Party" means any party other than Immunex, Genentech and their
-----------
respective Affiliates.
1.68 "United States" or "U.S." means the United States of America, its
------------- ----
territories and possessions, and the Commonwealth of
Puerto Rico 1.69 [*]
1.70 "Working Cell Bank" means a vialed collection of serially subcultivated
-----------------
cells generated by Immunex that is derived from the Master Cell Bank. The
Working Cell Bank is used to establish seed cultures of the Cell Line to
initiate the Manufacturing Process.
* Portions of this exhibit have been omitted pursuant to a request for confidential treatment filed with the Securities and Exchange Commission. The omitted portions of this exhibit have been filed separately with the SEC.
Page 8
1.71 Each of the following definitions are found in the body of this Agreement,
or elsewhere, as indicated below:
Defined Term Section
------------ -------
"Acceptance Date" 4.3(e)
[*] 13.2(b)(2)(A)
"Allocable Overhead" 3.9
"Annual Maximum" 4.1
"Annual Minimum" 4.1
"Approved Suppliers" 3.6(a)
"Assigned Inventions" 14.1(d)
"Batch Record" Quality Agreement
"BIP ENBREL Supply Agreement" ...