Exhibit 10.16
DEVELOPMENT AND MANUFACTURING
SERVICE AGREEMENT
BETWEEN
LONZA BIOLOGICS ***
AND
TRUBION PHARMACEUTICALS, INC.
TABLE OF CONTENTS
PAGE
----
1. Definitions......................................................... 3
2. Customer Obligations, Warranties and Indemnities.................... 10
3. Provision of the Services........................................... 12
4. Quality; Project Management......................................... 15
5. Delivery, Transportation of Product and Customer Tests.............. 16
6. Price and Terms of Payment.......................................... 18
7. LB Warranties and Covenants and Indemnity........................... 19
8. Confidentiality and Non-Use......................................... 21
9. Termination; Ownership; License Rights.............................. 23
10. Force Majeure....................................................... 26
11. Governing Law, Jurisdiction and Enforceability; Dispute Resolution.. 27
12. Notices............................................................. 28
13. Miscellaneous....................................................... 28
14. Limitation of Liability; Exclusion of Certain Damages............... 30
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THIS AGREEMENT is made effective as of the 8th day of January 2004 (the
"Effective Date") BETWEEN
1. LONZA BIOLOGICS *** (herein after referred to as "LB"), and
2. TRUBION PHARMACEUTICALS, INC., (formerly known as GENECRAFT, INC.) of
24014th Avenue, Suite 1050, Xxxxxxx, XX 00000, XXX (herein after referred to as
the "Customer").
WHEREAS
A. The Customer has created or controls certain Cell Lines as defined
herein; and
B. LB has expertise in the evaluation and production of proteins for
therapeutic use using such Cell Lines; and
C. The Customer wishes to contract LB for Services as defined herein
relating to the Cell Line as described in the Agreement; and
D. LB is prepared to perform such Services for the Customer under the terms
and conditions set out herein.
NOW IT IS AGREED AS FOLLOWS:
1. DEFINITIONS. The following terms shall have the following meanings:
"Affiliate" means any company, partnership or
other entity which directly or
indirectly Controls, is Controlled
by or is under common Control with
the relevant party to this
Agreement. "Control" means the
ownership of more than fifty per
cent (50%) of the issued share
capital or the legal power to direct
or cause the direction of the
general management and policies of
the party in question.
"Agreement" means this agreement, including and
incorporating Schedule 1
(Definitions and Specifications),
Schedule 2 (Services), Schedule 3
(Price and Terms of Payment),
Schedule 4 (Quality Agreement), and
Schedule 5 (Commercial Terms for
Technology Transfer), all as the
same may be amended or varied from
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time to time by written agreement of
the parties.
"August 2003 Services Agreement" means that certain development and
manufacturing agreement dated 12
August 2003 between the parties for
the development and manufacture of
the Product, as amended or varied
from time to time by written
agreement of the parties.
"Batch" means the total quantity of
Manufactured Product obtained from
one fermentation and associated
purification run using the Process.
"Cell Line" means the cell line provided by
Customer to LB, the particulars of
which are set out in Schedule 1.
"cGMP" means the regulatory requirements
for current Good Manufacturing
Practices and General Biologics
Products Standards as promulgated by
the United States Food and Drug
Administration ("FDA") (or any
successor agency thereto) under the
United States Federal Food Drug and
Cosmetic Act and the Public Health
Service Act, at 21 CFR (Parts 210,
211, 600 and 610), and the Guide to
Good Manufacturing Practices for
Medicinal Products as promulgated
under European Directive 91/356/EEC,
all as the same may be amended from
time to time.
"cGMP Product" means Product which is required
under Schedule 2 to be manufactured
in accordance with cGMP.
"Certificate of Analysis" means, for each Batch, a document in
a format agreed to by the parties
and prepared by LB listing (a) the
date of manufacturing, unique Batch
number, tests performed,
Specifications, test dates, and test
results, (b) the quantity of
Manufactured Product in such Batch,
and certifying that such Batch was
manufactured in accordance with the
Specifications and cGMP, and (c) the
tests performed by LB or permitted
Testing Laboratories,
Specifications, and test
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results; all with respect to such
particular Batch and as required by
the Specifications, the accuracy of
which has been certified by LB.
"Critical Raw Materials" has the meaning given to it in
Clause 4.6 below.
"Customer" means Trubion Pharmaceuticals, Inc.,
and its successors in title and
lawful assigns.
"Customer Information" means (a) all Customer Know-How and
other tangible and intangible data,
information, and know-how, whether
in written, printed, graphic,
electronic, or oral form, supplied
by or on behalf of Customer to LB
hereunder or under the August 2003
Services Agreement; (b) all
Documentation and all tangible and
intangible data, information,
know-how, and Intellectual Property
included in the Documentation; (c)
all Deliverables and all tangible
and intangible data, information,
know-how, and Intellectual Property
included in the Deliverables; and
(d) all tangible and intangible
data, information, know-how, and
Intellectual Property included in
the Customer Process; "Customer
Information" does not include LB
Know-How, the LB Patent Rights, the
LB Process, the New General
Application Intellectual Property,
and LB's other Intellectual
Property, "Customer Information" is
a part of "Customer Technology."
"Customer Know-How" means all know-how, technical and
other information relating directly
or indirectly to the Cell Line, the
Customer Process (including for the
avoidance of doubt improvements or
modifications thereto from time to
time, other than and excluding the
LB Process and any New General
Application Intellectual Property),
Customer's business, technology,
finances or operations, trade
secrets, the Customer Materials,
and/or the Product, known by
Customer from time to time;
"Customer Know-How" does not include
LB Know-How, the LB Patent Rights
the LB Process, the New General
Application Intellectual Property,
LB's other
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Intellectual Property, and
information in the public domain;
"Customer Know-How" is a part of
"Customer Information."
"Customer Materials" means the materials (if any)
supplied by Customer to LB pursuant
to this Agreement.
"Customer Patent Rights" means all patents and patent
applications, together with any
extensions, reissues,
reexaminations, substitutions,
renewals, divisions, continuations,
and continuations-in-part thereof,
of any kind throughout the world
that are necessary or useful in
performance of the Services, which
from time to time Customer is the
owner of or entitled to use, other
than and excluding the LB Patent
Rights.
"Customer Process" means that portion of the Process
not composed of or included within
the LB Process, including without
limitation all processes,
procedures, protocols, know-how,
technology, information and
Intellectual Property developed by
LB and/or Customer specifically with
respect to manufacture of the
Product under or as a result of this
Agreement or the August 2003
Services Agreement; "Customer
Process" does not include LB
Know-How, the LB Patent Rights, the
LB Process, the New General
Application Intellectual Property,
or LB's other Intellectual Property.
"Customer Technology" means all data, information,
know-how, materials, and
Intellectual Property which from
time to time Customer is the owner
of or entitled to use, including
without limitation the Customer
Know-How, the Customer Patent
Rights, the Cell Line, the Customer
Materials, the Customer Information,
the Customer Process, the New
Customer Intellectual Property, and
the Product; "Customer Technology"
does not include LB Know-How, the LB
Patent Rights, the LB Process, the
New General Application Intellectual
Property, LB's other Intellectual
Property, and information in the
public domain.
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"Deliver", "Delivered" or "Delivery" has the meaning given to it in
Clause 5.1 below,
"Deliverables" means the data, information,
material, reports, Documentation,
Product, samples and other items
that LB is obligated to provide to
the Customer under the terms of the
Services, as set forth in Schedule
2.
"Documentation" means all data, information and
materials, whether in written,
printed, graphic, or electronic
form, resulting from the work
conducted and/or results achieved in
connection with the Services,
including without limitation
documents reasonably necessary for
Customer to complete any regulatory
filings for the Product;
"Documentation" does not include LB
Know-How, the LB Patent Rights, the
LB Process, the New General
Application Intellectual Property,
and LB's other Intellectual
Property; "Documentation" is a part
of "Customer Information."
"Intellectual Property" means proprietary methods,
discoveries, inventions, patents,
trade secrets, copyrights,
trademarks, service marks, trade
dress, compositions, products,
procedures, know-how, data, reports,
programs, processes, protocols,
written or electronic writings,
illustrations, images, and any other
form of proprietary rights, and, as
the context requires, includes,
among other things, the Customer
Know-How, the Customer Patent
Rights, the Customer Process, the
New Customer Intellectual Property,
the LB Know-How, the LB Patent
Rights, the LB Process and the New
General Application Intellectual
Property.
"LB Know-How" means all know-how, technical and
other information relating directly
or indirectly to the LB Patent
Rights, the LB Process (including
for the avoidance of doubt
improvements; or modifications
thereto from time to time, other
than and excluding the Customer
Process and any New Customer
Intellectual Property) LB's
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business, technology, finances or
operations, and trade secrets known
to LB from time to time; "LB
Know-How" does not include the
Customer Patent Rights, the Customer
Know-How, the New Customer
Intellectual Property, the Customer
Process, Customer's other
Intellectual Property, and
information in the public domain.
"LB Patent Rights" means all patents and patent
applications, together with any
extensions, reissues,
reexaminations, substitutions,
renewals, divisions, continuations,
and continuations-in-part thereof,
of any kind throughout the world
relating to the LB Process which
from time to time LB is the owner of
or is entitled to use; "LB Patent
Rights" does not include the
Customer Patent Rights and the New
Customer Intellectual Property and
Customer's other Intellectual
Property.
"LB Process" means the manufacturing process for
proteins that, as of the Effective
Date, is included within the LB
Patent Rights and LB Know-How, along
with any New General Application
Intellectual Property, as defined
herein in Clause 9.8.2.
"Legal Requirements" means any and all laws, rules,
regulations, ordinances, guidelines,
and standards of any international,
national, state, or local
governmental authority, applicable
to LB, the Services, the Product, or
any facility at which any of the
Services are performed, including
without limitation (a) cGMP, and (b)
all laws and regulations requiring
permits, licenses, filings and
certifications with respect to LB,
the Services, the Product, or any
facility at which any of the
Services are performed.
"Manufactured Product" means any and all tangible forms of
the Product which are manufactured
under this Agreement using the
Process, including without
limitation all in-process
intermediates, samples and
derivatives thereof.
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"New Customer Intellectual Property" has the meaning given to it in
Clause 9.8.3.
"New General Application
Intellectual Property" has the meaning given to it in
Clause 9.8.2.
"Price" means the price specified in
Schedule 3 for the Services.
"Process" means the process for the production
of the Product from the Cell Line
pursuant to this Agreement, which is
composed of the LB Process and the
Customer Process, and including any
improvements, changes or
modifications to such process from
time to time.
"Product" means the proprietary Small Modular
ImmunoPharmaceutical (SMIP) known as
TRU-015, including any derivatives
and improvements thereof; and, when
the context requires, the term
"Product" also means and refers any
and all tangible forms of the
Product which are manufactured under
this Agreement using the Process,
including without limitation all
in-process intermediates, samples,
derivatives, and improvements
thereof.
"Quality Agreement" means and refers to the quality
agreement between the parties, a
copy of which is attached hereto as
Schedule 4, as amended or varied
from time to time by written
agreement of the parties;
"Run" or "run" means a single fermentation start of
the manufacturing Process at LB's
facility.
"Services" means all or any part of the
services to be performed by LB under
this Agreement (including, without
limitation, cell culture evaluation,
purification evaluation, master,
working and extended cell bank
creation, sample and bulk
production, testing of finished
Product after fill-finish processing
of bulk Product at a third party
facility), as more particularly set
out in Schedule 2.
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"Specialized Raw Materials" has the meaning given to it in
Clause 3.10 below.
"Specifications" means the quality, functional and
analytical specifications for
Product, the particulars of which
are set out in Schedule 1.
"Terms of Payment" means the terms of payment specified
in Schedule 3.
"Testing Laboratories" means any third party who has been
instructed by LB and authorized by
Customer to carry out tests on the
Cell Line or the Product.
References to the singular number include the plural and vice versa, references
to Clauses and Schedules are references to clauses and schedules to this
Agreement.
2. CUSTOMER OBLIGATIONS, WARRANTIES AND INDEMNITIES
2.1 Customer shall pay the Price set out in Schedule 3 for provision
of the Services together with any additional costs and expenses mutually agreed
upon in writing by the parties that fall due under this Agreement in accordance
with the Terms of Payment.
2.2 As agreed by the parties, the Customer shall supply to LB certain
Customer Know-How, together with full details of any hazards known to Customer
relating to the Cell Line and/or the Customer Materials, and their storage and
use. On review of this Customer Know-How by LB, the Cell Line and/or the
Customer Materials shall be provided to LB at LB's request, all as set forth
with more particularity in and in accordance with Schedule 2 (Services) hereto.
All right, title, and interest in and to the Cell Line, the Customer Materials,
the Customer Know-How and any other Customer Technology supplied to LB in
connection with this Agreement or the August 2003 Services Agreement shall, as
between the parties, remain vested in the Customer. Risk of loss to the Cell
Line, Customer Materials and any tangible Customer Information supplied to LB
under this Agreement shall transfer to LB upon delivery to LB premises.
2.3 Subject to the terms and conditions of this Agreement, the
Customer hereby grants LB the non-exclusive, non-transferable (other than to
LB's Affiliates), right to use the Cell Line, the Customer Materials, the
Customer Know-How, and the New Customer Intellectual Property during the term of
this Agreement solely for the purpose of providing Services under this
Agreement.
2.4 The Customer warrants and covenants to LB that:
2.4.1 Customer has the right to enter into this Agreement;
2.4.2 ***;
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2.4.3 ***;
2.4.4 ***;
2.4.5 ***; and
2.4.6 ***.
2.5 Subject to Clauses 2.8 and 14 below, and subject to and except to
the extent of any indemnification from LB pursuant to Clause 7 below, the
Customer undertakes to indemnify and to maintain LB promptly indemnified against
all losses, damages, liabilities, settlements, penalties, fines, costs and
expenses of any nature (including court costs and reasonable legal fees on a
full indemnity basis), that***.
2.6 Subject to Clauses 2.8 and 14 below, and subject to and except to
the extent of any indemnification from LB pursuant to Clause 7 below, the
Customer shall further indemnify and maintain LB promptly indemnified against
all losses, damages, liabilities, settlements, penalties, fines, costs and
expenses of any nature (including court costs and reasonable legal fees on a
full indemnity basis), that LB may incur arising out of or resulting from:
2.6.1 ***; and
2.6.2 ***.
2.7 A party that intends to claim indemnification under this Agreement
(the "Indemnitee") shall promptly notify the indemnifying party (the
"Indemnitor") in writing of any third party claim, suit or proceeding included
within the scope of the indemnification) described in Clauses 2 or 7 hereunder
(each a "Claim") with respect to which the Indemnitee intends to claim such
indemnification, and shall tender the defense of such Claim to the Indemnitor,
and the Indemnitor shall have sole control of the defense and/or settlement of
such Claim. An Indemnitee hereunder shall have the right to retain its own
counsel, subject to the following conditions: (a) the Indemnitee's counsel's
role shall be limited to monitoring the Claim and performing a watching brief of
the Claim and the Indemnitee's counsel shall have no right to actively
participate in the defense and/or settlement of such Claim; and (b) the
Indemnitor shall have the right to veto the Indemnitee's selection of counsel,
acting reasonably and having provided substantive justification for such veto.
So long as the foregoing conditions are met, the Indemnitor shall bear the
reasonable costs and expenses of one attorney acting as the Indemnitee's counsel
in accordance with this Clause 2.7, subject to the following additional
conditions: (x) the attorney's hourly rate must be reasonable and cannot exceed
the prevailing rate, based on the venue of the claim, suit or proceeding; and
(y) the Indemnitor shall have the right to review and approve the Indemnitee's
counsel's invoices. The indemnification obligations under this Agreement shall
not apply to amounts paid in settlement of any Claim if such settlement is
effected without the consent of the Indemnitor, such consent not to be
unreasonably withheld. At the Indemnitor's request and expense, each Indemnitee
shall, and shall cause its employees to, provide full information and reasonable
assistance to Indemnitor and its legal representatives with respect to the
related Claim(s).
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2.8 Notwithstanding anything herein seemingly to the contrary,
Customer shall have no indemnity obligations under this Clause 2 for any losses,
damages, liabilities, settlements, penalties, fines, costs and expenses to the
extent such losses, damages, liabilities, settlements, penalties, fines, costs
and expenses arise out of or result from:
2.8.1 ***; or
2.8.2 ***, or
2.8.3 ***; or
2.8.4 ***.
2.9 The provisions of this Clause 2, and the obligations of the
Customer and LB, respectively, under this Clause 2, shall survive the expiration
or termination for whatever reason of the Agreement.
2.10 CLAUSE 2.4 IS IN LIEU OF ALL OTHER CONDITIONS, WARRANTIES AND
STATEMENTS IN RESPECT OF THE CELL LINE, CUSTOMER MATERIALS, CUSTOMER
INFORMATION, CUSTOMER KNOW-HOW, CUSTOMER PATENT RIGHTS, CUSTOMER PROCESS, NEW
CUSTOMER INTELLECTUAL PROPERTY, AND CUSTOMER TECHNOLOGY, WHETHER EXPRESSED OR
IMPLIED BY STATUTE, CUSTOM OF THE TRADE OR OTHERWISE (INCLUDING WITHOUT
LIMITATION ANY SUCH CONDITION, WARRANTY OR STATEMENT RELATING TO THE DESCRIPTION
OR QUALITY OF THE CELL LINE, CUSTOMER MATERIALS, CUSTOMER INFORMATION, CUSTOMER
KNOW-HOW, CUSTOMER PATENT RIGHTS, CUSTOMER PROCESS, NEW CUSTOMER INTELLECTUAL
PROPERTY, AND CUSTOMER TECHNOLOGY, THEIR FITNESS OR SUITABILITY FOR A PARTICULAR
PURPOSE OR USE UNDER ANY CONDITIONS WHETHER OR NOT KNOWN TO CUSTOMER) AND ANY
SUCH CONDITION, WARRANTY OR STATEMENT IS HEREBY EXCLUDED.
3. PROVISION OF THE SERVICES
3.1 LB shall diligently carry out the Services as provided in Schedule
2, and shall use all reasonable efforts consistent with levels of effort that LB
uses with its most important customers, to achieve the objectives and estimated
timescales set out in that Schedule and deliver the Product, samples of the
Product, and other Deliverables to Customer as provided in Schedule 2; provided,
however, that the timescales and Product quantities set forth in Schedule 2 are
estimates only. LB shall communicate with Customer regularly regarding LB's
performance of the Services and shall inform Customer promptly if LB determines
that LB will not or may not be able to meet the objectives or timescales, or
deliver the Product quantities, Product samples, or other Deliverables set forth
in Schedule 2.
3.2 LB shall perform Runs and manufacture the Product in accordance
with this Agreement, and, except as expressly set forth to the contrary in
Schedule 2 or as otherwise agreed to
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by the parties from time to time, in compliance with the Legal Requirements,
including without limitation the requirements of cGMP, LB warrants and covenants
that, except as expressly set forth to the contrary in Schedule 2 and in Clause
3.3 below, the Product resulting from the Runs shall conform to the
Specifications. The Product resulting from the Runs shall be provided to
Customer at no additional cost to Customer over and above the Price, and
Customer may make whatever further use of such Product as Customer shall
determine in its sole discretion, provided, however, that, in accordance with
Schedule 2, the Product manufactured in Stage 5 shall not be used in humans.
3.3 The parties agree that the *** Batches of Product manufactured
under Stage 8 of Schedule 2 attached hereto shall comply fully with cGMP and
with the parameters and target Specifications agreed to jointly by LB and the
Customer, with an emphasis on the safety of the Product for use in human
clinical testing and with pass/fail testing for analytical methods relating to
safety. In addition, notwithstanding anything in Schedule 3 seemingly to the
contrary, with respect to the Batches of Product manufactured under Stage 8,
Customer shall ***.
3.3.1 ***
If a failure to perform the Services or produce the Product for Delivery
arises due to a breach of this Agreement by LB, or LB's negligent act or
omission or willful misconduct, Customer shall be entitled to all of its rights
and remedies.
3.4 LB shall comply with cGMP and the International Committee for
Harmonisation ("ICH") regulatory requirements, from time to time and to the
extent that the foregoing are applicable to the Services. In the event of a
conflict between the ICH regulatory requirements and the cGMP regulatory
requirements, the cGMP regulatory requirements shall prevail, except as may
otherwise be agreed by the parties in writing.
3.5 LB hereby undertakes not to use the Cell Line, the Customer
Materials, the Customer Information, the Customer Technology, the Customer
Know-How or the Customer Patent Rights, or any part of any of the foregoing, for
any purpose other than to perform the Services and supply Product under this
Agreement. The obligations of LB under this Clause 3.6 shall survive the
expiration or termination for whatever reason of the Agreement.
3.6 LB shall:
3.6.1 at all times use best efforts to keep the Cell Line, the
Customer Materials and the Product secure and safe from loss and damage;
3.6.2 not part with possession of the Cell Line or the Customer
Materials or the Product, except as permitted under Clause 3.8 below for the
purpose of tests at the Testing Laboratories.
3.7 LB shall procure that all Testing Laboratories are subject to
obligations of confidence and non-use substantially in the form of and at least
as strict as those obligations of confidence and non-use imposed on LB under
this Agreement. Each Testing Laboratory shall be
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subject to the prior written approval of Customer, which approval shall not be
unreasonably withheld. Notwithstanding anything herein seemingly to the
contrary, Customer shall have the right, at Customer's option and with no
penalty, to enter into an agreement directly with one or more of the Testing
Laboratories, and transfer the associated testing services from LB under this
Agreement to the Testing Laboratory. LB shall ensure that Customer has the right
to perform, directly or through Customer's representatives, inspections and
audits of all Testing Laboratories, and Customer may condition Customer's
approval of any Testing Laboratory to Customer's performance of and satisfaction
with the results of such an inspection and audit. Customer shall perform and
shall cause its representatives to perform any such inspections and audits in
compliance with Clause 4 of this Agreement. Notwithstanding Customer's approval
of any Testing Laboratory, LB shall not disclose the contents of this Agreement
(including without limitation the Schedules hereto) or any of Customer's
Confidential Information to such approved Testing Laboratory except to the
extent necessary for such Testing Laboratory to conduct the related tests, and
LB shall not transfer possession of any of the Cell Line, Customer Materials or
Product to such approved Testing Laboratory except to the extent necessary for
such Testing Laboratory to conduct the related tests. Neither LB nor Customer
shall be liable in connection with this Agreement for any of the acts or
omissions of the Testing Laboratories. LB waives, releases and agrees not to
assert against Customer any claims for any losses, damages, liabilities,
settlements, penalties, fines, costs and expenses of any nature that LB may
incur which directly or indirectly arise out of or result from any negligent
acts or omissions or willful misconduct of the Testing Laboratories; ***. LB
shall, at Customer's expense, cooperate fully with Customer in the investigation
and prosecution of any claim, lawsuit or other proceeding by Customer against a
Testing Laboratory in connection with this Agreement for losses, damages,
liabilities, settlements, penalties, fines, costs and expenses of any nature
that Customer may incur which directly or indirectly arise out of or result from
any negligent acts or omissions or willful misconduct of the Testing
Laboratories, Nothing in this Clause shall release or shall be deemed to release
either party from any liability which arise out of or result from that party's
own negligent acts or omissions or willful misconduct. This Clause 3.8 shall
survive the expiration or termination for whatever reason of the Agreement.
3.8 LB shall procure, maintain and store such amounts of raw materials
and components as required for the Runs, and shall perform testing and
evaluation of such materials and components as set forth in the Quality
Agreement attached hereto as Schedule 4 or agreed upon in writing by the
parties, and the cost and expense for such materials and components and the
testing and evaluation of such materials and components shall be deemed included
in the Prices shown on Schedule 3 hereto. LB shall be responsible for and
Customer may assist with oversight and coordination of the supply logistics for
the raw materials and components required for the Runs. LB shall not procure
Specialized Raw Materials (defined below) until authorized to do so by Customer.
3.9 The term "Specialized Raw Materials" as used in this Agreement
means the specialized raw materials and components which are used under this
Agreement to manufacture the Product. The parties shall in good faith agree in
writing which raw materials and components shall be deemed to be "Specialized
Raw Materials" for the purposes of this Clause 3.10. In the event the cost and
expense of any Specialized Raw Materials materially exceed LB's original pricing
assumptions for such Specialized Raw Materials under this Agreement, then
Customer shall pay to
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LB the difference between the assumed cost and expense for such Specialized Raw
Materials and the actual cost and expense (not including any LB xxxx-up or
administrative fees) for such Specialized Raw Materials.
4. QUALITY; PROJECT MANAGEMENT
4.1 Responsibility for quality assurance and quality control shall be
allocated between the parties in accordance with the Quality Agreement, a copy
of which is attached hereto as Schedule 4, and standard operating procedures as
may be agreed upon in writing by the parties from time to time.
4.2 Customer and its designated representatives shall have the right
to witness, inspect and audit the performance of LB's obligations, at the times
and for durations set forth in the Quality Agreement and as otherwise agreed by
the parties. Customer shall have access to the facilities, data and records of
LB which are related to this Agreement for the purpose of conducting such
inspections and audits, and LB shall use reasonable endeavours to ensure that
all Testing Laboratories provide similar access to the Testing Laboratories'
facilities, data and records which are related to this Agreement for such
purposes. In accordance with the Quality Agreement, Customer shall have the
right to review LB's non-proprietary standard operating procedures relating to
the services of LB under the Quality Agreement or this Agreement.
4.3 In accordance with the Quality Agreement, Customer will have the
sole right to correspond with and submit regulatory applications and other
filings to the FDA, EMEA and other regulatory authorities to obtain approvals to
import, export, conduct clinical trials with, or take any other action with
respect to the Product, alone or with other products (collectively,
"Approvals"), when and as Customer may deem useful or necessary. Accordingly,
except as otherwise required by Legal Requirements, LB will not correspond
directly with the FDA, EMEA or any other regulatory agency with respect to the
Product without, in each instance, first obtaining Customer's prior written
consent. Notwithstanding the foregoing, LB will assist Customer, as requested by
Customer and at Customer's expense, in preparing, submitting, and maintaining
applications for such Approvals.
4.4 As set forth with particularity in the Quality Agreement, LB will
permit the FDA, EMEA and other regulatory authorities to conduct inspections of
LB's facilities as the FDA, EMEA or other regulatory authorities may request,
and will cooperate with the FDA, EMEA or other regulatory authorities with
respect to the inspections and any related matters, in each case related to the
Product.
4.5 Notwithstanding anything in this Agreement seemingly to the
contrary, LB shall not undertake any modifications to the Process or testing
processes that could delay or otherwise impact the Approvals or other regulatory
submissions, including without limitation, regulatory product reviews,
Investigational New Drug applications (INDs), or any other compliance status
without in each case the prior written agreement of Customer.
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4.6 In accordance with the Quality Agreement, Customer shall have the
right (a) to review the specifications, grades and vendors of all raw materials
and components used under this Agreement to manufacture the Product, and (b) to
approve the specifications, grades and vendors of all Critical Raw Materials
(defined below), including excipients, and of all raw materials and components
of animal or human origin, all to the extent used under this Agreement to
manufacture the Product. Customer shall provide a written list to LB of those
certain raw materials and components which shall constitute and be deemed to be
"Critical Raw Materials" for purposes of this Agreement, and shall update the
list from time to time as appropriate. Each version of the written list of the
Critical Raw Materials shall be jointly agreed to by Customer and LB. Raw
materials of and components of animal or human origin shall be avoided when
possible.
4.7 By not later than March 31, 2004, the Parties will establish a
Joint Project Team (the "JPT"). The JPT shall be composed of representatives
appointed by each of LB and the Customer. Such representatives may include, but
not be limited to, the Project Manager, Technical Lead, Manufacturing Lead,
Quality Control Lead, Quality Assurance/Regulatory Lead, Raw Materials Lead,
Supply Chain Lead and Engineering Lead, or other individuals with expertise and
responsibilities in the same areas of manufacturing, process sciences, quality
control or regulatory affairs. The JPT will meet by teleconference at least once
each week, or more frequently, as agreed by the JPT. The JPT will operate by
unanimous decision, except as expressly set forth herein. If the JPT is unable
to resolve a dispute regarding any issue presented to it, such dispute shall be
resolved in accordance with Clause 11.4. The JPT is responsible for the daily
monitoring and guidance of the Services to successfully achieve the deliverables
of the project as outlined herein.
4.8 By not later than March 31, 2004, each Party shall appoint a
Project Manager to act as the primary contact for such Party in connection with
matters related to the performance of the Services. Each such Project Manager,
unless otherwise mutually agreed, shall serve as a member of the JPT.
4.9 As set forth in the Quality Agreement, Customer shall have the
right to designate one of its employees or consultants as Customer's person on
plant, to be present in LB's facility during normal business hours during the
term of this Agreement to observe the Runs and observe LB's performance of its
obligations under this Agreement at times and for durations to be agreed. While
at LB's facility, Customer's representative shall comply with all of LB's
applicable policies and procedures, and, at LB's option, shall be escorted by LB
personnel.
5. DELIVERY, TRANSPORTATION OF PRODUCT AND CUSTOMER TESTS
5.1 *** Unless otherwise agreed, LB shall package and label
Manufactured Product for Delivery in accordance with the Specifications and its
standard operating procedures and all applicable Legal Requirements. It shall be
the responsibility of the Customer to inform LB in writing in advance of any
special packaging and labeling requirements for Manufactured Product. All
additional costs and expenses of whatever nature incurred by LB in complying
with such special requirements shall be charged to the Customer in addition to
the Price, Transportation of Manufactured Product, whether or not under any
arrangements made by LB on behalf of Customer,
16
shall be made at the sole risk and expense of the Customer, provided that LB has
complied with any instructions provided by Customer with respect to
transportation and insurance as set forth in Clauses 5.2 and 5.3 below.
5.2 If requested in writing by the Customer, LB will (acting as agent
of the Customer for such purpose) arrange the transportation of Manufactured
Product from LB's premises to the third-party fill-finish contractor or other
destination indicated by the Customer, together with insurance coverage for
Manufactured Product in transit at its invoiced value. All additional reasonable
costs and expenses of whatever nature incurred by LB in arranging such
transportation and insurance shall be charged to the Customer in addition to the
Price provided that LB has obtained Customer's prior written consent to
incurring such additional costs and expenses.
5.3 If requested in writing by the Customer, LB will (acting as agent
for Customer) arrange for insurance of Product whilst held by LB after Delivery
(awaiting transportation). The costs and expenses of such insurance shall be at
Customer's expense and on reasonable terms equivalent to those under which LB
insures other comparable products prior to Delivery. All such additional
reasonable costs and expenses of whatever nature incurred by LB in arranging
such insurance shall be charged to the Customer in addition to the Price,
provided that LB has obtained Customer's prior written consent to incurring such
additional costs and expenses. Notwithstanding the foregoing, in the event LB
has been requested to arrange the transportation of Manufactured Product in
accordance with Clause 5.2 above, the costs and expenses of such insurance of
Manufactured Product whilst held by LB after Delivery (awaiting transportation)
shall be at LB's expense for up to fourteen (14) days and thereafter shall be at
Customer's expense, provided, however, that in the event the delay in
transportation is caused by LB, then the costs and expenses of such insurance
shall be at LB's expense until the Manufactured Product has been loaded onto the
appropriate collecting vehicle, except as may be otherwise agreed by the parties
in writing.
5.4 LB shall deliver to Customer the Certificate of Analysis not later
than the date of Delivery. Notwithstanding the foregoing, at Customer's request,
LB will Deliver Manufactured Product in quarantine prior to delivery of the
Certificate of Analysis. Such request shall be accompanied by Customer's written
acknowledgement that the Manufactured Product has been Delivered without the
transmittal to Customer of a Certificate of Analysis, that accordingly the
Manufactured Product cannot be administered to humans until transmittal of the
Certificate of Analysis, and that Customer nevertheless accepts full risk of
loss to and title and ownership of the Manufactured Product. The Delivery of
Product in quarantine shall be subject to such testing requirements as LB may
reasonably require, and the *** period referred to in Clause 5.7 shall run from
Customer's receipt of samples of such Manufactured Product together with the
related consolidated Batch record.
5.5 Where LB has made arrangements for the transportation of
Manufactured Product, the Customer shall diligently examine the Manufactured
Product as soon as practicable after receipt. Notice of all claims (time being
of the essence) arising out of:
17
5.5.1 visible damage to or total or partial loss of Manufactured
Product in transit shall be given in writing to LB within *** of receipt by
Customer at Customer's facility or of receipt by Customer's third party supplier
at such third party's facility; or
5.5.2 non-Delivery shall be given in writing to LB within ***
after the later of (a) the date of LB's despatch notice, and (b) Customer's
actual knowledge of non-Delivery.
5.6 The Customer shall make damaged Manufactured Product and
associated packaging materials available for inspection and shall comply with
the requirements of any insurance policy covering the Manufactured Product of
which LB has given Customer notice. LB shall offer the Customer all reasonable
assistance (at the cost and expense of the Customer) in pursuing any claims
arising out of the transportation of Manufactured Product.
5.7 LB shall deliver to Customer samples of all Batches manufactured
under this Agreement, as and when Batches are manufactured, together with the
related consolidated Batch record requested by Customer to enable Customer to
inspect and perform testing on such samples. Promptly following receipt of
Manufactured Product or any sample thereof, the Customer may inspect the
Manufactured Product or sample and carry out any of the tests outlined or
referred to in the Specifications set out in Schedule 1 and such additional
tests as may be prudent in Customer's reasonable discretion. Subject to Clause
3.2, if such tests show that the Manufactured Product fails to meet the
Specifications, the Customer shall give LB written notice thereof within ***
after Customer's receipt at Customer's facility of samples of such Batch
together with the related consolidated Batch record and shall return such
Manufactured Product (except for reference samples retained by Customer) at LB's
expense to LB's premises for further testing. In the absence of such written
notice, Manufactured Product shall be deemed to have been accepted by the
Customer as meeting the Specifications. Subject to Clause 3.2, if Customer has
reasonably demonstrated to LB that Manufactured Product returned to LB fails to
meet the Specifications, and LB has failed to prove that such failure is due (in
whole or in part) to acts or omissions of the Customer or any third party after
Delivery, LB shall at Customer's discretion refund that part of the Price that
relates to the production of such Manufactured Product or replace such
Manufactured Product at LB's own cost and expense. In the event Customer
requires LB to replace such Manufactured Product, LB shall use all reasonable
endeavours to do so as soon as possible with the minimum delay.
5.8 Subject to Clause 3.2, if there is any dispute concerning whether
Manufactured Product returned to LB fails to meet the Specifications or whether
such failure is due (in whole or in part) to acts or omissions of the Customer
or any third party after Delivery, such dispute shall be resolved in accordance
with the dispute resolution procedures described in Clause 11.4 below.
5.9 Subject to Clause 7, LB's liability hereunder in respect of
Manufactured Product that fails to meet the Specifications shall be limited to
refund or replacement, in accordance with and as set forth with more
particularity in Clause 5,7 above; provided, however, that the foregoing
limitation of liability shall not apply in the event such failure is caused by
the negligent act or omission or willful misconduct of LB.
18
6. PRICE AND TERMS OF PAYMENT
6.1 Unless otherwise indicated in writing by LB, all prices and
charges payable to Lonza are exclusive of Value Added Tax or of any other
applicable taxes, levies, imposts, duties and fees of whatever nature imposed by
or under the authority of any government or public authority, which shall be
paid by the Customer (other than taxes on LB's income). LB shall add all such
taxes as separate line items on invoices. All invoices are strictly net and
payment must be made within thirty (30) days of Customer's receipt of invoice.
Notwithstanding the foregoing, no amounts shall be invoiced until such amounts
are then due and payable in accordance with the Schedules to this Agreement,
including without limitation and as appropriate the completion of the related
Services and Customer's receipt and acceptance of the related Deliverables. The
invoices shall be in ***, and all payments made by Customer shall be made in
***.
6.2 In default of payment on due date:
6.2.1 interest shall accrue on any amount overdue at the per
annum interest rate *** above *** from time to time as published in the "Money
Rates" section of The Wall Street Journal, on the 1st business day of each
month, beginning with the month in which the payment became delinquent, with
interest to accrue on a day to day basis both before and after judgement, adjust
monthly on the 1st day of each month, beginning with the second month of
delinquency, and be calculated on the number of days such payment is delinquent;
and
6.2.2 For so long as such payment delinquency remains uncured, LB
shall, at its sole discretion, and without prejudice to any other of its accrued
rights, be entitled to suspend the provision of the Services or, if Customer has
not remedied such payment delinquency within *** of the receipt by Customer of
notice of nonpayment and demand for remedy, to treat the Agreement as
repudiated.
7. LB WARRANTIES AND COVENANTS AND INDEMNITY
7.1 LB warrants and covenants that:
7.1.1 the Services shall be performed in accordance with this
Agreement, including without limitation Clauses 3.1 and 3.2 above;
7.1.2 LB has the right and necessary corporate authorisations to
enter into this Agreement;
7.1.3 LB has the necessary rights to licence or permit Customer
to use the LB Process, LB Know-How, LB Patent Rights, and New General
Application Intellectual Property in accordance with the terms of this
Agreement, including without limitation in accordance with and pursuant to
Clause 9 below;
7.1.4 any of the LB Process, LB Know-How, LB Patent Rights, and
New General Application Intellectual Property referred to in Clause 7.1.3 above
that are not owned by LB
19
are licensed to LB under a licence which grants LB the necessary rights to
licence or permit Customer to use the LB Process, LB Know-How, LB Patent Rights,
and New General Application Intellectual Property in accordance with the terms
of this Agreement, including without limitation in accordance with and pursuant
to Clause 9 below;
7.1.5 LB will not cause or permit any liens or encumbrances of
any kind arising through LB to attach to Product, and unencumbered title to
Manufactured Product will be conveyed to Customer upon Delivery;
7.1.6 the LB Know How, LB Patent Rights, LB Process and the New
General Application Intellectual Property are owned by LB or LB is otherwise
entitled to use them for the purposes of providing Services under this Agreement
and LB shall not do or cause anything to be done which would adversely affect
their ownership or entitlement to use the same for those purposes;
7.1.7 to the best of LB's knowledge and belief, the use of the LB
Process, LB Know-How, LB Patent Rights, and New General Application Intellectual
Property in accordance with the terms of this Agreement (including without
limitation the use by Customer in accordance with and pursuant to the provisions
of Clause 9 below) do not and will not infringe any intellectual property rights
or industrial property rights of any third party (including without limitation
any LB Affiliate) and do not involve the wrongful use of any trade secret or
confidential information, nor is there any claim to the contrary outstanding;
7.1.8 LB will notify Customer in writing immediately if it
receives or is notified of a claim that the use by LB of the LB Process, LB
Know-How, LB Patent Rights and/or New General Application Intellectual Property
for Services or the use by Customer in accordance with the terms of this
Agreement infringes any third party's intellectual property rights or industrial
property rights or involves the wrongful use of any trade secret or confidential
information; and
7.1.9 at the date of this Agreement LB is not a party to any
agreement that prohibits or prevents it from performing the Services or
otherwise fulfilling its obligations under this Agreement and covenants that it
will not enter into any such agreement.
7.2 CLAUSES 3, 4 AND 7.1 ARE IN LIEU OF ALL CONDITIONS, WARRANTIES AND
STATEMENTS IN RESPECT OF THE SERVICES AND/OR THE PRODUCT WHETHER EXPRESSED OR
IMPLIED BY STATUTE, CUSTOM OF THE TRADE OR OTHERWISE (INCLUDING BUT WITHOUT
LIMITATION ANY SUCH CONDITION, WARRANTY OR STATEMENT RELATING TO THE DESCRIPTION
OR QUALITY OF THE PRODUCT, ITS FITNESS OR SUITABILITY FOR A PARTICULAR PURPOSE
OR USE UNDER ANY CONDITIONS WHETHER OR NOT KNOWN TO LB) AND ANY SUCH CONDITION,
WARRANTY OR STATEMENT IS HEREBY EXCLUDED.
7.3 Subject to and except to the extent of any indemnification from
Customer pursuant to Clauses 2.5 and 2.6 above, LB undertakes to indemnify and
to maintain Customer
20
promptly indemnified against all losses, damages, liabilities, settlements,
penalties, fines, costs and expenses of any nature (including court costs and
reasonable legal fees on a full indemnity basis), that Customer may incur to the
extent such liabilities arise directly out of or result from any claim, lawsuit
or other action by a third party arising out of or resulting from (a) any breach
of any of the warranties given by LB in Clause 7.1 above; or (b) any negligent
act or omission or willful misconduct of LB.
7.4 Notwithstanding anything herein seemingly to the contrary, LB
shall have no indemnity obligations under this Clause 7 for any losses, damages,
liabilities, settlements, penalties, fines, costs or expenses to the extent such
losses, damages, liabilities, settlements, penalties, fines, costs and expenses
arise out of or result from: ***
7.5 Nothing contained in this Agreement shall purport to exclude or
restrict any liability for death or personal injury resulting directly from
negligence by LB in carrying out the Services or any liability for breach of the
implied undertakings of LB as to title.
7.6 This Clause 7 and the obligations of LB under this Clause 7 shall
survive the expiration or termination for whatever reason of the Agreement.
8. CONFIDENTIALITY AND NON-USE
8.1 The Customer acknowledges that LB Know-How, LB Process, LB Patent
Rights and General Application Intellectual Property and any of LB's other
Intellectual Properly disclosed to, supplied to or held by Customer pursuant to
this Agreement, and LB acknowledges that Customer Know-How, Customer Patent
Rights, Customer Technology, Customer Information, Customer Process, New
Customer Intellectual Property, Customer Materials and the Cell Line and any of
Customer's other Intellectual Property disclosed to, supplied to or held by LB
pursuant to this Agreement (all of the foregoing collectively referred to as
"Confidential Information") is, subject to Clause 8.5, supplied and shall be
held in circumstances imparting an obligation of confidence and each agrees to
keep the other party's Confidential Information secret and confidential and to
respect the other's proprietary rights therein and not at any time for any
reason whatsoever to disclose or permit such Confidential Information to be
disclosed to any third party save as expressly provided herein or to be used for
any purpose not expressly authorized under this Agreement For the avoidance of
doubt, the parties agree that all portions of documents and records describing
and to the extent relating to the Product and the Customer Process shall be kept
confidential by Lonza in accordance with the terms of this Clause 8.
8.2 The Customer and LB shall each procure that all their respective
employees, consultants, contractors and persons for whom it is responsible
having access to the other party's Confidential Information shall be subject to
the same obligations of confidence as the principals pursuant to Clauses 8.1 and
8.3 and, in addition, with respect to LB, to the same obligations of non-use
pursuant to Clauses 2.3, 3.6 and 8.1, and shall be bound, by written
confidentiality agreements in support of all such obligations.
21
8.3 LB and the Customer each undertake, except as set forth herein,
not to disclose or permit to be disclosed to any third party, or otherwise make
use of or permit to be made use of (a) any Confidential Information of the
other, or of any Affiliate of the other, or of any suppliers, agents,
distributors, licensees or other customers of the other which comes into the
receiving party's possession under this Agreement or (b) the commercial terms of
this Agreement, except to the extent that any of the foregoing is required to be
disclosed pursuant to subpoena, court order, judicial process or otherwise by
law, provided the receiving party provides prompt notice to the disclosing party
of such requirement in order to give the disclosing party an opportunity to
timely seek a protective order or other appropriate judicial relief. In the
event the disclosing party is unable to obtain a protective order or other
appropriate judicial relief, the receiving party shall disclose only that
portion of the disclosing party's Confidential Information which is legally
required to be disclosed, and ensure that all such Confidential Information of
the disclosing party shall be redacted to the fullest extent permitted by law
prior to such disclosure and that the disclosing party shall be given an
opportunity to review the Confidential Information prior to its disclosure.
Notwithstanding the foregoing, (i) LB may disclose Customer's Confidential
Information to LB's Affiliate, Lonza Biologics, Inc., for purposes consistent
with this Agreement; provided, however, that LB shall ensure that its Affiliate
is subject to obligations of confidentiality and non-use with respect to the
Confidential Information at least as strict as those set forth herein, and
provided further that LB shall remain liable for the acts or omissions of its
Affiliate with respect to such Confidential Information, and (ii) either party
may disclose the other party's Confidential Information to any contractors or
consultants approved in writing by the other party, such approval not to be
unreasonably withheld or delayed, for purposes consistent with this Agreement;
provided, however, that in each case the party disclosing the other party's
Confidential Information shall ensure that the third party receiving the
information is subject to contractual obligations of confidentiality and non-use
with respect to the Confidential Information at least as strict as those set
forth herein; and provided further that the party disclosing the other party's
Confidential Information shall remain liable for the acts or omissions of such
third party with respect to such Confidential Information.
8.4 The obligations of confidence referred to in this Clause 8 shall
not extend to any information which:
8.4.1 is or becomes generally available to the public otherwise
than by reason of a breach by the recipient party of the provisions of this
Clause 8;
8.4.2 is known to the recipient party and is at its free
disposal, without an obligation of confidence, prior to its receipt from the
disclosing party;
8.4.3 is subsequently disclosed to the recipient party without
being made subject to an obligation of confidence; or
8.4.4 is developed by any servant or agent of the recipient party
without access to or use or knowledge of the Confidential Information of the
disclosing party.
8.5 The parties acknowledge that:
22
8.5.1 without prejudice to any other rights and remedies that the
parties may have, the parties agree that the Confidential Information is
valuable and that damages may not be an adequate remedy for any breach of the
provisions of Clauses 2.3, 3.6, 8.1, 8.2, 8.3 and 8.4. The parties agree that
the relevant party will be entitled without proof of special damage to the
remedies of an injunction and other equitable relief for any actual or
threatened breach by the other party;
8.5.2 Customer acknowledges that, save as expressly provided in
this Agreement (including without limitation Clauses 9.8.4 and 9.8.7 below), the
Customer shall not at any time have any right, title, license or interest in or
to LB Know-How, the LB Patent Rights, the LB Process, the New General
Application Intellectual Property or any of LB's other Intellectual Property,
and
8.5.3 LB acknowledges that, save as expressly provided in this
Agreement, LB shall not at any time have any right, title, license or interest
in or to the Customer Information, the Customer Materials, the Cell Line,
Customer Know-How, Customer Patent Rights, the Customer Technology, the New
Customer Intellectual Property, the Customer Process or any of Customer's other
Intellectual Property.
8.6 This Clause 8 and the obligations of LB and the Customer under
this Clause 8 shall survive the expiration or termination for whatever reason of
the Agreement.
9. TERMINATION; OWNERSHIP; LICENSE RIGHTS
9.1 This Agreement shall begin on the Effective Date and, unless
earlier terminated as set forth in this Clause 9, shall terminate and expire
when the last obligation to be performed under this Agreement has been
performed. If it becomes apparent to either LB or the Customer at any stage in
the provision of the Services that it will not be possible to complete the
Services for scientific or technical reasons, and such party gives written
notice thereof to the other party, *** period shall be allowed for good faith
discussion and attempts to resolve such problems. If such problems are not
resolved within such period, LB and the Customer shall each have the right to
terminate the Agreement forthwith by notice in writing. In the event of such
termination, the Customer shall pay to LB a termination sum calculated by
reference ***.
9.2 Customer may in its sole discretion terminate the Services at any
time for any reason or for no reason whatsoever by giving not less than ***
notice in writing to LB. In the event of termination pursuant to this Clause 9.2
and subject to Clauses 9.4 and 9.5, the Customer shall pay LB a termination sum
calculated in accordance with the principles of Clause 9.1 above plus;
9.2.1 in the event notice to terminate Services pursuant to this
Clause 9.2 is issued to LB ***or less before LB's then estimated start date for
any stage of those Services which include cGMP fermentation activities, Customer
shall pay LB a sum ***, which payment shall fall due to LB on or before the date
of termination of such Services; or
9.2.2 in the event notice to terminate Services pursuant to this
Clause 9.2 is issued to LB more than *** but not more than *** before LB's then
estimated start date for any
23
stage of those Services which include cGMP fermentation activities, Customer
shall pay LB a sum equal to ***, which payment shall fall due to LB on or before
the date of termination of such Services; or
9.2.3 in the event notice to terminate Services pursuant to this
Clause 9.2 is issued to LB more than *** before LB's then estimated start date
for any stage of Services which include cGMP fermentation activities, no payment
shall be due for the stage or stages in question.
9.3 The obligation to make payment under Clause 9.2 shall be reduced
(retrospectively, and hence LB shall make an appropriate refund to Customer) to
the extent that LB mitigates its loss in this regard (and LB shall promptly
notify the Customer of any such mitigation). LB shall make all reasonable
efforts so to mitigate such losses. This provision shall not entitle the
Customer to be refunded an amount greater than that paid by Customer to LB
pursuant to this Clause 9 ***.
9.4 For the avoidance of doubt, activities relating to cGMP
fermentation shall be deemed to commence with the date of removal of the vial of
cells for the performance of the fermentation from frozen storage.
9.5 In addition to the termination rights set forth above, the parties
may each terminate the Agreement forthwith by notice in writing to the other
party upon the occurrence of any of the following events:
9.5.1 if one party commits a material breach of the Agreement
(which shall include without limitation a breach of the warranties set out in
Clauses 2 and 7 respectively), and such breach is not capable of remedy, then
the non-breaching party may terminate the Agreement forthwith by notice in
writing to the breaching party, and, if such breach is capable of remedy but is
not remedied within *** of the receipt by the breaching party of notice
identifying the breach and requiring its remedy, then the non-breaching party
may terminate the Agreement forthwith by notice in writing to the breaching
party; or
9.5.2 if one party ceases for any reason to carry on business or
compounds with or convenes a meeting of its creditors or has a receiver or
manager appointed in respect of all or any part of its assets or is the subject
of an application for an administration order or of any proposal for a voluntary
arrangement or enters into liquidation (whether compulsorily or voluntarily) or
undergoes any analogous act or proceedings under foreign law, then the other
party may terminate the Agreement forthwith by notice in writing to the
breaching party.
9.6 Upon the termination or expiration of the Agreement for whatever
reason:
9.6.1 LB shall cease all use of and shall promptly return to the
Customer all Customer Information and shall, as directed by Customer, dispose of
or return to the Customer the Customer Materials, the Cell Line, the Product,
the Deliverables, the Documentation, any in-process Product or materials, and
any materials deriving from any of the foregoing. Notwithstanding the foregoing,
the parties agree that, in the event LB has terminated the Agreement pursuant to
24
Clause 9.5.1 above because of a material payment default by Trubion, men LB
shall have no obligation to deliver Manufactured Product (or Product to the
extent the term "Product" refers to the tangible forms of the Product
manufactured under this Agreement using the Process) to Trubion as required
under this Clause 9.6.1 unless and until the payment default has been cured;
9.6.2 LB shall not thereafter use or exploit the Customer
Know-How, Customer Patent Rights, the Customer Technology, the New Customer
Intellectual Property (including without limitation the Customer Process), the
Customer Information, the Cell Line, the Product, or the Customer Materials, or
any of Customer's other Intellectual Property;
9.6.3 the Customer shall promptly return to LB all LB Know-How it
has received from LB;
9.6.4 the Customer shall not thereafter use or exploit the LB
Patent Rights the LB Process or the LB Know-How or any of LB's other
Intellectual Property in any way whatsoever, except as permitted under and in
accordance with Clauses 9.8.4, 9.8.7, and 9.9 below and subject to the
provisions set forth in Clause 9.10 below;
9.6.5 LB shall refund within thirty (30) days of the effective
date of such termination all amounts paid to LB in excess of the amounts owed to
LB under this Agreement, including without limitation the amounts owed to LB if
any, pursuant to this Clause 9; and
9.6.6 LB and the Customer shall do all such acts and things and
shall sign and execute all such deeds and documents as the other may reasonably
require to evidence compliance with this Clause 9.6.
9.7 Expiration or termination of the Agreement for whatever reason
shall not affect the accrued rights of either LB or the Customer arising under
or out of this Agreement and all provisions which are expressed to survive the
Agreement shall remain in full force and effect. For the avoidance of doubt, the
provisions of Clauses 2, 3, 7, 8, 9, 11 and 14 will survive the expiration or
termination of this Agreement for any reason, and, except as otherwise expressly
provided in this Clause 9.7, all other rights and obligations of the parties
under this Agreement will terminate upon termination or expiration of this
Agreement.
9.8 Ownership; License Rights.
9.8.1 Except as expressly provided in Clause 2.3 above and Clause
9.8.7 below, neither party will, as a result of this Agreement, acquire any
right, title, or interest in any Intellectual Property that the other party
owned or controlled as of the Effective Date of this Agreement, or that the
other party obtains ownership or control of separate and apart from the
performance of this Agreement.
9.8.2 ***
9.8.3 ***
25
9.8.4 ***
9.8.5 LB shall use its reasonable efforts to procure that all
Testing Laboratories and other contractors arid agents of LB involved in the
performance of the Services, and their respective personnel, shall be subject to
the same agreements and obligations as LB pursuant to Clauses 9.8.3 and 9.8.4,
and shall be bound by written agreements in support of all such agreements and
obligations, including without limitation an assignment to Customer all of the
Testing Laboratories, contractors and agents' right, title and interest in any
New Customer Intellectual Property.
9.8.6 Upon the earlier of the completion of the Services or the
termination or expiration of this Agreement, LB shall deliver to Customer all
materials related to the New Customer Intellectual Property, regardless of the
method of storage or retrieval, in such form as such materials are then
currently in the possession of LB. Alternatively, at Customer's written request,
LB shall dispose of such related materials or retain them for a period of time
agreed upon by the parties; provided, however, that Customer shall pay the
reasonable costs associated with LB disposing of or retaining such materials.
9.8.7 ***
9.9 The parties intend that the Process shall be fully portable by
Trubion. ***.
9.10 Notwithstanding anything in Clause 9.8.4 or 9.8.7 seemingly to
the contrary, the parties agree as follows:
9.10.1 Upon the expiration or termination of this Agreement,
Customer shall have no right to exercise the license rights granted by LB to
Customer under Clauses 9.8.4 and 9.8.7 unless and until the Technology Transfer
fee has been paid in accordance with Clause 9.9 above.
9.10.2 During the term of this Agreement, Customer shall have no
right to exercise the license rights granted by LB to Customer under Clauses
9.8.4 and 9.8.7 to manufacture the Product at a Trubion facility or at a
third-party facility that is not owned or operated by Lonza or its Affiliates,
unless and until the Technology Transfer fee described in Clause 9.9 above has
been paid.
Furthermore, for the avoidance of doubt, the parties agree that the Technology
Transfer shall be performed in accordance with and subject to the provisions of
Clause 9.9, and the parties acknowledge that Clause 9.9, and the obligations of
the parties thereunder, shall survive the expiration or termination of this
Agreement.
9.11 The terms of this Clause 9 shall survive the expiration or
termination for whatever reason of this Agreement.
10. FORCE MAJEURE
26
10.1 If either party is prevented or delayed in the performance of any
of its obligations under the Agreement by Force Majeure and shall give written
notice thereof to the other party specifying the matters constituting Force
Majeure together with such evidence as the party giving notice reasonably can
give and specifying the period for which it is estimated that such prevention or
delay will continue, the party giving notice shall be excused from the
performance or the punctual performance of such obligations as the case may be
from the date of such notice for so long as such cause of prevention or delay
shall continue. Notwithstanding the foregoing, in the event that LB is prevented
from performance by Force Majeure by longer than ***, Customer shall be entitled
to terminate this Agreement upon written notice, but such termination shall not
be considered as termination under Clause 9.5.1 hereof.
10.2 The expression "Force Majeure" shall be deemed to include any
cause affecting the performance by a party of the Agreement to the extent that
it arises from or attributable to acts, events, acts of God, omissions or
accidents beyond the reasonable control of the party giving notice of the Force
Majeure event.
11. GOVERNING LAW, JURISDICTION AND ENFORCEABILITY; DISPUTE RESOLUTION
11.1 The construction, validity and performance of the Agreement shall
be governed by the laws of ***. This Agreement shall not be governed by the
United Nations Convention on Contracts for the International Sale of Goods, the
application of which is disclaimed.
11.2 No failure or delay on the part of either LB or the Customer to
exercise or enforce any rights conferred on it by the Agreement shall be
construed or operate as a waiver thereof nor shall any single or partial
exercise of any right, power or privilege or further exercise thereof operate so
as to bar the exercise or enforcement thereof at any time or times thereafter.
11.3 The illegality or invalidity of any provision (or any part
thereof) of this Agreement shall not affect the legality, validity or
enforceability of the remainder of its provisions or the other parts of such
provision as the ease may be.
11.4 If any dispute arises relating to the performance of either party
under this Agreement that the parties are unable to resolve in the ordinary
course of business (a "Dispute"), the parties will use good-faith efforts to
resolve the matter in accordance with this Clause 11.4 prior to instituting any
legal proceeding in connection therewith; provided, however, that nothing herein
will require either party to forego or delay the institution of any proceeding
to seek equitable or injunctive relief to stop or prevent any breach of this
Agreement if it reasonably believes that it would be irreparably harmed by any
delay in seeking such relief. If a dispute occurs, either party may, by written
notice to the other party, have such dispute referred to their respective
officers designated below (or their respective designees) for attempted
resolution by good faith negotiations within *** after such notice is received.
The original designated officers are:
For LB: ***
For Customer: Xx. Xxxxx X. Xxxxxxxx, MD, President and CEO.
27
In the event the designated officers (or their respective designees) are
not able to resolve such dispute within such ***, or such other period of time
as the parties may mutually agree in writing, the parties shall have the right
to pursue any and all remedies at law and in equity. Notwithstanding the
foregoing, Disputes regarding nonconforming bulk Product under Section 5.9 above
will be referred first to the officers designated above and then, in the event
that such officers are unable to resolve the Dispute, to an independent expert
(acting as an expert and not as an arbitrator) to be appointed by agreement
between LB and the Customer or, in the absence of agreement, by the President
for the time being of the Association of the British Pharmaceutical Industry.
The costs of such independent expert shall be borne equally between LB and the
Customer. The decision of such independent expert shall be in writing and, save
for manifest error on the face of the decision, shall be binding on both LB and
the Customer.
12. NOTICES
12.1 Any notice or other communication to be given under this
Agreement shall be delivered personally or sent by facsimile transmission and
acknowledged by the intended recipient, or if facsimile transmission is not
available, by first class pre-paid post addressed as follows:
If to Lonza Biologics to: Lonza Biologics ***
***
***
***
***
***
For the attention of: ***
If to the Customer to: Trubion Pharmaceuticals, Inc.
00000xx Xxx., Xxxxx 0000
Xxxxxxx, XX 00000
XXX
Facsimile: x0-000-000-0000
For the attention of: Xxxxxxx X. Xxxxxx, Ph.D.
Senior Vice President, R & D
or to such other destination as either party hereto may hereafter notify to the
other in accordance with the provisions of this Clause 12.
12.2 All such notices or other communications shall be deemed to have
been served as follows:
12.2.1 if delivered personally, at the time of such delivery;
28
12.2.2 if sent by facsimile, upon receipt of the transmission
confirmation slip showing completion of the transmission;
12.2.3 if sent by first class pre-paid post, upon receipt by the
addressee.
13. MISCELLANEOUS
13.1 Neither party shall be entitled to assign, transfer, charge or in
any way make over the benefit and/or the burden of this Agreement without the
prior written consent of the other which consent shall not be unreasonably
withheld or delayed, save that either party shall be entitled without the prior
written consent of the other to assign, transfer, charge, sub-contract, deal
with or in any other manner make over the benefit and/or burden of this
Agreement to an Affiliate or to any company with which the assigning party may
merge or to any company to which it may transfer its assets and undertakings.
13.2 The text of any press release or other communication to be
published by or in the media concerning the subject matter of the Agreement
shall require the prior written approval of LB and the Customer, LB shall not
make use of Customer's name in any advertisement or promotional material or
customer list without in each case the prior written consent of Customer.
Consent to be given under this Clause 13.2 shall not be unreasonably withheld or
delayed. Notwithstanding anything in this Agreement seemingly to the contrary,
LB hereby consents to Customer's disclosure of LB's name to Customer's current
and potential employees, directors, shareholders, investors, partners, and
subcontractors.
13.3 The Agreement embodies the entire understanding of LB and the
Customer and there are no promises, terms, conditions or obligations, oral or
written, expressed on implied, other than those contained in the Agreement, The
terms of the Agreement shall supersede all previous agreements (if any) which
may exist or have existed between LB and the Customer relating to the Services.
13.4 The parties to this Agreement do not intend that any term hereof
should be enforceable by virtue of the Contracts (Rights of Third Parties) Xxx
0000 by any person who is not a party to this Agreement.
13.5 No variation of or addition to this Agreement or any part thereof
shall be effective unless in writing and signed on behalf of both parties,
Notwithstanding the above the parties hereby confirm that amendments to the
Specifications shall be effective if reduced to writing and signed by the
quality and/or regulatory representative of both parties, which quality and/or
regulatory representative shall be nominated from time to time by each party. In
the event of any conflict between the main body of this Agreement and any
Schedule, the terms of the main body of this Agreement shall control.
13.6 Each of the parties to this Agreement is an independent
contractor and nothing herein contained shall be deemed to constitute the
relationship of partners, joint venturers, nor of
29
principal and agent between the parties. Neither party shall hold itself out to
third parties as purporting to act on behalf of, or serving as the agent of, the
other party.
13.7 This Agreement and any amendment hereto may be executed in any
number of counterparts, each of which shall be deemed an original and all of
which shall constitute the same instrument This Agreement may be executed by
facsimile or original, and a facsimile signature shall be deemed to be and shall
be as effective as an original signature.
14. LIMITATION OF LIABILITY; EXCLUSION OF CERTAIN DAMAGES
14.1 LB's aggregate liability for direct damages arising out of or in
connection with this Agreement or the transactions contemplated hereby shall not
exceed ***, except that the foregoing limitation shall not apply in the case of
(a) breach of Clause 8 (Confidentiality and Non-Use) by LB, (b) personal injury
or death, or (c) grossly negligent or intentionally wrongful acts or omissions
of LB. The foregoing limitation shall also not apply to claims arising under, or
LB's breach of, Clause 7.1 within Clause 7 (LB Warranties and Covenants and
Indemnity); provided, however, that LB's aggregate liability for direct damages
arising out of or in connection with claims arising under, or LB's breach of,
Clause 7.1 within Clause 7 (LB Warranties and Covenants and Indemnity), shall
not exceed ***.
14.2 NEITHER PARTY SHALL BE LIABLE TO THE OTHER FOR ANY INCIDENTAL,
PUNITIVE, INDIRECT, OR CONSEQUENTIAL DAMAGES OF ANY KIND, INCLUDING LOST
PROFITS, LOST DATA, LOST REVENUES, AND LOSS OF BUSINESS OPPORTUNITY, WHETHER OR
NOT THE OTHER PARTY WAS AWARE OR SHOULD HAVE BEEN AWARE OF THE POSSIBILITY OF
THESE DAMAGES, EXCEPT THAT THE FOREGOING LIMITATION SHALL NOT APPLY IN THE CASE
OF (a) BREACH OF CLAUSE 8 (CONFIDENTIALITY AND NON-USE) BY EITHER PARTY, (b)
PERSONAL INJURY OR DEATH, OR (c) GROSSLY NEGLIGENT OR INTENTIONALLY WRONGFUL
ACTS OR OMISSIONS. The terms of this Clause 14 shall survive the expiration
or termination for whatever reason of this Agreement.
[The remainder of this page intentionally left blank]
30
AS WITNESS the hands of the duly authorised representatives of the parties
hereto the day and year first above written.
Signed for and on behalf of ***
LONZA BIOLOGICS *** ----------------------------------------
Senior Vice President
***
----------------------------------------
TITLE
Signed for and on behalf of /s/ Xxxxx X. Xxxxxxxx
TRUBION PHARMACEUTICALS, INC. ----------------------------------------
President & CEO
TITLE
31
SCHEDULE 1
DEFINITIONS AND SPECIFICATIONS
DEFINITIONS
For the purpose of this document:
"Cell Line" shall mean the *** cell line created by the Customer expressing
Product.
"Product" shall mean the Small Modular ImmunoPharmaceutical (SMIP) produced by
the Cell Line known as TRU-015.
SPECIFICATIONS
1.1 EXAMPLE OF TYPICAL INITIAL SPECIFICATION FOR BULK PURIFIED PRODUCT
(These examples are only examples of typical specifications, and shall not
be considered to be the specifications related to the Product)
TEST METHOD SPECIFICATION
--------------- ------ -------------
CHARACTERISTICS
1.1.1 *** *** ***
1.1.2 *** *** ***
1.1.3 *** *** ***
1.1.4 *** *** ***
1.1.5 *** *** ***
1.1.6 *** *** ***
1.1.7 *** *** ***
1.1.8 *** *** ***
1.1.9 *** *** ***
1.1.10 *** *** ***
1.1.11 *** *** ***.
1.1.12 *** -*** ***-
1.2 EXAMPLE OF TYPICAL SPECIFICATION FOR BULK FERMENTER HARVEST
(These examples are only examples of typical specifications, and shall not
be considered to be the specifications related to the Product)
1
TEST METHOD SPECIFICATIONS
---- ------ --------------
1.2.1 *** *** ***
1.2.2 *** *** ***
1.2.3 *** *** ***
2
1.3 FINAL BULK PRODUCT DISPOSITION
1.3.1 Final Formulation Buffer: ***
1.3.2 Bottling of Bulk Product:
1.3.2.1 Containers ***
1.3.2.2 Denominations ***
***
1.3.3 Product Storage Conditions: ***
1.3.4 Shipment Temperature: ***
1.4 SPECIFICATION FOR CELL BANKS
STARTING MATERIAL DEFINITION
An *** of a cryopreserved *** will be created from the Cell Line provided
by the Customer and stored in individual ampoules in liquid nitrogen
refrigerators.
GENERAL *** SPECIFICATION
In order for the *** to be accepted into LB's cGMP facility, the following
testing is required and the appropriate specifications achieved.
TEST METHOD SPECIFICATIONS
---- ------ --------------
1.4.1 *** *** ***
***
*** *** ***
***
1.4.2 *** *** ***
1.4.3 *** *** ***
1.4.4 *** *** ***
1.4.5 *** *** ***
3
SCHEDULE 2
SERVICES
2. SERVICES
2.1 SUPPLY OF CUSTOMER MATERIALS AND CUSTOMER KNOW-HOW
Prior to commencement of the Services at LB or, if appropriate, prior to
the commencement of the relevant Stage of the Services, the Customer shall
supply LB with the following:
***
1
2.2 ACTIVITIES TO BE UNDERTAKEN BY LB
***
2
SCHEDULE 3
PRICE AND TERMS OF PAYMENT
1.0 PRICE
In consideration for LB carrying out the Services as detailed in Schedule
2, the Customer shall pay LB as follows:
***
3
SCHEDULE 3
PRICE AND TERMS OF PAYMENT
2.0 PAYMENT
Payment by the Customer of the Price for each Stage shall be made against
LB's Invoices that will be issued as follows:
2.1 FOR STAGE 1
*** upon commencement of Stage 1.
*** upon issue of the deliverables for Stage 1 to the Customer.
2.2 FOR STAGE 2
*** upon commencement of Stage 2.
*** upon issue of the deliverables for Stage 2 to the Customer.
2.3 FOR STAGE 3
*** upon commencement of Stage 3.
*** upon issue of the deliverables for Stage 3 to the Customer.
2.4 FOR STAGE 4
*** upon commencement of Stage 4.
*** upon issue of the deliverables for Stage 4 to the Customer.
2.5 FOR STAGE 5
*** upon commencement of Stage 5.
*** upon issue of the deliverables for Stage 5 to the Customer.
2.6 FOR STAGE 6
*** upon commencement of Stage 6.
*** upon issue of the deliverables for Stage 6 to the Customer.
2.7 FOR STAGE 7
*** upon commencement of Stage 7.
*** upon issue of the deliverables for Stage 7 to the Customer.
2.8 FOR STAGE 8
*** upon ampoule thaw of each batch manufactured under Stage 8.
*** upon issue of the certificate of analysis for each batch manufactured
under Stage 8.
2.9 FOR STAGE 9
*** upon commencement of Stage 9.
*** upon issue of the deliverables for Stage 9 to the Customer.
2.10 FOR STAGE 10
100% upon issue of each timepoint interim report and upon issue of the
final report.
2.11 FOR STAGE 11
*** upon commencement of Stage 11.
*** upon issue of the deliverables for Stage 11 to the Customer.
2.12 FOR STAGE 12
4
*** upon commencement of Stage 12.
*** upon issue of the deliverables for Stage 12 to the Customer.
2.13 FOR STAGE 13
*** upon commencement of Stage 13.
*** upon issue of the deliverables for Stage 13 to the Customer.
2.14 FOR STAGE 14
100% upon issue of each timepoint interim report and upon issue of the
final report.
5
SCHEDULE 4
QUALITY AGREEMENT
[The remainder of this page intentionally left blank]
6
QUALITY AGREEMENT
This quality agreement ("Quality Agreement") is dated effective as of 8th
January 2004, and it defines the roles and responsibilities for the quality
operations between LONZA BIOLOGICS ***, the registered office of which is at ***
(herein after referred to as "LB"), and TRUBION PHARMACEUTICALS, INC., (formerly
known as GENECRAFT, INC.) of 0000 0xx Xxxxxx, Xxxxx 0000, Xxxxxxx, XX 00000, XXX
(herein after referred to as the "Customer") with respect to manufacture of
Customer's proprietary Small Modular ImmunoPharmaceutical (SMIP) known as
TRU-015 ("TRU-015") under that certain development and manufacturing services
agreement between the parties of even date herewith (the "Services Agreement")
in preparation for regulatory filings and for human clinical use. When used in
this Quality Agreement, the term "Product" refers to TRU-015 and/or to the form
of TRU-015 manufactured under the Services Agreement, as the context requires.
This Quality Agreement takes the form of a detailed list of activities
associated with the manufacture, testing and release of Product. Responsibility
for each activity is assigned to either the Customer or LB, or is assigned to
both the Customer and LB, and additional details are provided in the Services
Agreement and in the SOP's referred to in this Quality Agreement.
This is the Quality Agreement that is referred to in the Services
Agreement. Capitalized terms used but not defined in this Quality Agreement
shall have the meaning given in the Services Agreement. This Quality Agreement
may be amended by written agreement of the parties. In the event of a conflict
between the Quality Agreement and the Services Agreement, the Services Agreement
shall control. This Quality Agreement may be executed in any number of
counterparts, each of which shall for all purposes be deemed an original and all
of which, taken together, shall constitute one and the same instrument. A
facsimile signature shall be deemed to be and shall be as effective as an
original signature.
The responsibilities and rights of the parties under this Quality Agreement
are set forth below:
A. OVERALL RESPONSIBILITIES
This Quality Agreement outlines the responsibilities of the Customer and LB
with respect to the quality assurance of Product manufactured and supplied by LB
for the Customer under the terms of the Agreement.
This Quality Agreement takes the form of a detailed list of activities
associated with the manufacture, testing and release of Product. Responsibility
for each activity is assigned to either the Customer or LB, or is assigned to
both the Customer and LB.
This detailed list describes generic quality activities that would be
performed by both parties for Product used in clinical trail supply. The
specific services to be provided by LB will be set out in
1
the Agreement (and any Amendments to the Agreement) on Price and other terms
acceptable to both parties.
LB is responsible for ensuring that the quality requirements for Product
are as specified in the approved Product specification and that Product is
manufactured, tested and stored in accordance with current Good Manufacturing
Practices (cGMP) and all applicable US and EU regulations and ICH guidelines.
The Customer is responsible for shipping and the final review, approval,
and release of product for use in the clinic. The Customer is responsible for
Product development, technical oversight, product specifications and regulatory
agency filings.
B. SPECIFIC RESPONSIBILITIES
RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
---- ----------------------------------------- -------------------------------------
1.0 Organisation and Personnel - Ensure adequate number of personnel - Right to audit
with appropriate training, skills,
knowledge and experience to
manufacture and test Product in and
Equipment utilities, equipment,
computerised systems and software
are properly designed, validated and
maintained in accordance with cGMP
- Ensure facilities, environment, - Right to audit
2.0 Facilities, Utilities and utilities, equipment, computerised
Equipment systems and software are properly
designed, validated and maintained
in accordance with cGMP
- Ensure Product is manufactured and - Right to audit
tested only at sites as agreed with
Customer
- Provide Customer with Drug Master - Include Drug Master File
File reference that will allow US reference into regulatory
FDA the ability to cross-reference submissions, as appropriate
other products that are manufactured
at LB's
----------
(1) Throughout the Quality Agreement, Customer's column includes the phrase
"right to audit" - the use of this phrase in certain instances but not in
others does not and shall not imply that Customer's audit rights pursuant
to Clause 15 below are limited to those boxes where "right to audit"
appears.
2
RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
---- ----------------------------------------- -------------------------------------
manufacturing and testing locations
- Provide Customer with documentation
that no penicillin is manufactured
or tested at site
3.0 Raw Materials for Process and - Source, test and release raw - Right to audit; right to review
Packaging of Product/Vendor materials and primary packaging of all raw material specifications,
Qualification Process appropriate quality for processing grades and vendors used in
of Product manufacture of Product
- Customer to provide LB with list
of critical raw materials used
in Customer process; update with
changes as necessary
- Propose and jointly agree - Right to approve vendor, grade
specifications, vendors and grade of and specifications of critical
critical raw materials used in raw materials used in Customer
Customer process in accordance with process, including excipients,
LB policy, with preference for and raw materials of animal or
non-animal and non-human derived raw human origin
materials
- Acknowledge and support Customer's
goal not to use any raw materials of
animal or human origin in the
development of Customer process
- Retain representative samples - Right to audit
4.0 Cell Banks - Prepare, characterise and store cell -
bank(s) if requested by Customer
- Jointly agree on testing
specifications and test methods to - Jointly agree on testing
enable release of cell banks for use specifications and test methods
in LB's multi-product manufacturing to enable Product manufactured
facility from cell banks to be used in
the clinic
- Perform stability testing of cell - Right to audit
bank(s) if requested by Customer and
share data with Customer
IF CELL BANK SUPPLIED BY CUSTOMER
- Review and approve characterisation - Supply cell bank
data. Store working stock or cell characterisation data for review
bank and approval. Transfer cell bank
(or portion
3
RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
---- ----------------------------------------- -------------------------------------
thereof) to LB
- Provide shipping validation data if - Right to audit
requested by Customer
IN ALL CASES
- Provide inventory levels
periodically upon request by
Customer
5.0 Production Specification - With the Customer determine and - With LB determine and approve
approve the following Product the following Product
specification(s) as required: specification(s) as required:
- Drug substance (including - Drug substance (including
testing performed on fermenter testing performed on
contents for adventitious fermenter contents for
agents) adventitious agents)
- Drug product - Drug product
- Bulk placebo - Bulk placebo
- Filled placebo - Filled placebo
6.0 Production and Process - Make available for review by - Right to review
Control Customer documents relating to
facility, equipment, Process and
test methods, and GMP systems
- Jointly review and approve Process - Jointly review and approve
descriptions Process descriptions
- Define and perform an in-process - Agree in-process testing
control and testing program strategy
- Using LB templates prepare master - Right to review and comment on
batch records for each processing master batch records
step and provide to Customer for
review and comment. Retain final
master batch record on site at LB
- Designate unique batch numbers for - Right to audit
raw materials, process materials and
Product
- Manufacture of Product in accordance - Right to audit
with Product Specifications, cGMP
standards, batch records, in-process - Relevant sections of Customer's
controls and in-process regulatory submissions to be
specifications made available to LB as
appropriate
- Ensure QA representatives on-site or - Right to audit
available at all times during
4
RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
---- ----------------------------------------- -------------------------------------
manufacture and testing of Product
- Permit Customer's person on plant to - Right to designate 1 of its
be present in LB's facility during employees or consultants as
normal business hours to observe the Customer's person on plant, to
Runs and observe LB's performance, be present in LB's facility
at times and for durations to be during normal business hours to
agreed. While at LB's facility, observe the Runs and observe
Customer's representative shall LB's performance, at times and
comply with all LB's applicable for durations to be agreed.
policies and procedures, and, at While at LB's facility,
LB's option, shall be escorted by LB Customer's representative shall
personnel comply with all of LB's
applicable policies and
procedures, and, at LB's option,
shall be escorted by LB
personnel
- Perform Product changeover testing - Review and comment on LB's
of Product-contacting equipment in policy for Product changeover
accordance with LB policy testing of Product-contacting
equipment
7.0 Product Storage, Labeling and - Store, label and package the Product - Right to audit
Packaging Prior to Shipment (including samples) as defined in
the Product Specification - Provide information on shipping
requirements
8.0 Shipment Requirements - Ship Product on behalf of Customer - Jointly agree with LB on process
to locations designated by Customer for shipping requirements
in accordance with jointly agreed
process for shipping requirements - Right to audit
- Acknowledge receipt of Product
- Provide shipping validation data for - Right to audit
Product if requested by Customer
9.0 Laboratory Controls (QC) - Perform Product release testing - Right to audit
against Product Specifications
- Jointly agree on SOP's describing - Jointly agreed on SOP's
Product-specific analytical testing describing Product-specific
methods analytical testing methods
- Provide LB with Product-specific
information as it relates to
sample storage, handling and
testing requirements
- Retesting, where required, will be - Review and comment on LB retest
performed in accordance with LB's procedure. Review OOS
5
RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
---- ----------------------------------------- -------------------------------------
retest procedure. Out of reports; comment on corrective
specification (OOS) Product release and preventative actions
testing results will be notified to
the Customer as soon as possible
within 3 business days of the OOS
being confirmed
- Send samples to Customer for - Perform Product potency testing
additional testing (including and provide data to LB; such
potency testing) in accordance with data will be provided for LB's
jointly approved SOP information only and not for
inclusion into LB's information
only and not for inclusion into
LB's Certificate of Analysis.
Customer to create Certificate
of Analysis for potency testing
results. [Note from Trubion:
This text to clarify that
Trubion is performing the
potency testing and providing
the results to LB 'FOR
INFORMATION']
- Retain representative samples of - Right to audit
bulk Product from each batch in
accordance with LB SOP
- If requested by Customer, provide - Right to receive copies of raw
copies of raw data and testing data and testing records
records
- Take additional representative - Request additional samples to be
samples if requested and ship to shipped as required
Customer
- Prepare and characterise Product - Jointly approve Product
reference standard in accordance reference standard Protocol
with jointly agreed Protocol, if
requested by Customer - Right to audit
- Jointly approve Product reference - Jointly approved Product
standard report reference standard report
10.0 Use of Contract Testing - Qualify Contract Testing - Right to jointly audit
Laboratories Laboratories for Product release
testing in accordance with LB policy
- Notify Customer of Contract Testing - Consent or reject to the
Laboratories intended to be proposed use of Contract Testing
6
RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
---- ----------------------------------------- -------------------------------------
used for Product release testing Laboratories
- Facilitate audit by Customer if - Right to audit
requested from time to time
- If not prohibited by Contract - Right to request, receive and
Testing Laboratory, provide Customer use copies of LB's audits of
with copies of LB's audits of Contract Testing Laboratories
Contract Testing Laboratories when when possible, unless prohibited
possible, if requested by Contract Testing Laboratories
11.0 Product Release and Lot - Review batch record for compliance - Right to review completed and
Review with cGMP, manufacturing controls, reviewed Product batch records
and with the Product Specifications
- Provide Customer with a copy of the - Right to review
Process documentation including,
main operational steps from the
completed batch record. This will
include Product analysis, a summary
of batch related deviations and
environmental monitoring summaries,
as well as process data, as
requested
- If requested by Customer, send full - Right to request and receive
copies of actual deviations full copies of actual deviations
- Prepare manufacturer's Certificate - Prepare Certificate of Analysis
of Analysis, including related and Certificate of Compliance
Certificate of Compliance for release of product for use
in human clinical trials
- Release or reject Product - Release of reject Product for
use in human clinical trials
12.0 Deviations and Failed Run - Initiate investigations, evaluate - Right to audit
Investigations and Reports and define follow up actions and
final approval of deviations and
failure investigations
- Notify Customer of all significant - Review significant deviations;
deviations immediately and within at comment on corrective and
least 3 business days of the event preventative actions
being assigned as significant, and
send Customer the related
documentation. (A significant
deviation is defined in standard
7
RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
---- ----------------------------------------- -------------------------------------
operating procedure 3150)
- Notify Customer of failed runs - Review failure investigation
immediately and within at least 3 report and comment on corrective
business days of failure being and preventative actions
identified
- Immediately and within at least 3
business days of event being
identified, notify Customer of any
events which may impact batches
previously shipped or released
13.0 Change Control Procedures - Jointly agree on SOP for change - Jointly agree SOP for change
control procedures between the 2 control procedures between the 2
companies that describes the companies that describes the
intended use of each company's intended use of each company's
independent change control system independent change control
systems
CUSTOMER PROPOSED CHANGES
- Process Product-specific change - Propose Customer Product-
through change control and notify specific changes and provide
Customer of change approval. If rationale in writing
change rejected, discuss reasons for
rejection with Customer
- Approve proposed Product-specific
changes prior to implementation
LB PROPOSED CHANGES
- Proposed Product-specific changes - Process Product-specific change
and provide rationale for change to through change control and
process descriptions; test methods; notify LB of change approval. If
sampling plans; specifications for change rejected, discuss reasons
key raw materials (animal and / or for rejection with LB
human derived raw materials,
chromatography resins and final - Approve proposed
formulation excipients); Product Product-specific changed prior
specification(s) and stability to implementation
programme, in-process controls and
other key processing steps
- Inform Customer of changes to key - Right to audit
personnel as identified in Appendix
1
- Inform Customer of changes to major - Right to audit
items of equipment,
8
RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
----- ----------------------------------------- -------------------------------------
premises and utilities used for
manufacture of Product
ALL CHANGES
- With Customer define strategy for - With LB define strategy for
notifying change to Regulatory notifying change to Regulatory
Agency as appropriate (see Section Agency as appropriate (see
20.0, below, Regulatory Submissions) Section 20.0, below, Regulatory
Submissions)
- Inform Customer of Product batches
manufactured with the change until - Ensure Product is not
regulatory approval obtained, if distributed until Regulatory
required approval obtained, if required
- Cooperate with Customer in - Cooperate with LB in connection
connection with change controls; with change controls; respect
respect Customer's change controls, LB's change controls, and, as
and, as appropriate, use it to appropriate, use it to initiate
initiate LB's change controls Customer's change controls
14.0 Reprocessing / Rework - Processing to be performed in - Review and comment on LB's
accordance with LB SOP. With reprocessing / rework SOP; with
Customer agree on reprocessing / LB agree on reprocessing /
rework procedures, where possible rework procedures, where
prior to execution possible prior to execution
- Provided documented reason and - Right to audit
justification for reprocessing /
rework event - With LB agree the appropriate
testing required prior to
- With the Customer agree on the Product release
appropriate testing required prior
to Product release
15.0 Audit - Permit Customer representatives - Provide reasonable notice of
access as reasonably required to intention to audit
conduct a cGMP compliance audit,
including access to warehousing, - Right to 2 standard cGMP
manufacturing areas, laboratories, compliance audits per year, plus
and manufacturing records and right to additional "for cause"
documents, including SOPs (unless audits
they contain specific LB proprietary
information eg media formulations), - Right to audit each batch record
and personnel, for audit purposes.
Customer representatives to be - Hold an exit meeting to discuss
accompanied at all times by LB observations
personnel
- Provide an audit report within
30 days of completion of audit
9
RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
---- ----------------------------------------- -------------------------------------
- Two standard cGMP compliance audits
permitted per year, with an audit
not to exceed 3 working days and 2
groups of auditors.
Additionally the Customer may
request "for cause" audits to
address production of Product
quality issues
- One 2 day audit for each batch
record if requested by Customer
- Allow the Customer to observe
operations related to Product
manufacturing and testing providing
other Customer's confidentiality is
respected
- Provide a written response to all
audit findings that require
corrective action within 30 days of
receipt of the audit report.
Response to include expected
timelines
16.0 Product Complaints and Recall - Respond to requests for data to - Receive and investigate Product
assist Customer in their complaints and instigate Product
investigation. Agree a time scale recall as appropriate
for response
17.0 Batch Records - Retain records associated with - Right to audit
manufacture and testing records of
Product including records associated
with the inspection and release of
raw materials and primary packaging
components of the Product for 5
years from the date of manufacture
of Product. Date of manufacture is
defined as the date Product is
dispensed in to the bulk product
container)
- Notify Customer of intent to destroy - Customer to approve destruction
records with option to send records or request receipt of records
to Customer
18.0 Process Validation / - With Customer define process - With LB define process
Stability Studies validation plans for Product validation plans for Product
including analytical validation and including analytical validation
and stability
10
RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
---- ----------------------------------------- -------------------------------------
stability studies studies
WHERE PROCESS VALIDATION IS PERFORMED BY
LB
- Provide Customer with Product - Approve Product specific
specific validation protocol(s) for validation protocol(s) including
approval prior to execution stability protocols
- Provide Customer with draft Product - Review and comment on Product
specific validation report(s) for specific validation report(s)
review and comment including stability reports
- Issue Customer with copy of final -
Product specific validation
report(s)
WHERE PROCESS VALIDATION IS PERFORMED
BY CUSTOMER
- Incorporate specifications in cGMP - Provide LB with process
documentation and regulatory validation reports
submissions
19.0 Regulatory Agency Inspection GMP INSPECTIONS
- Inform Customer of Regulatory Agency - For Regulatory Agency
inspections or regulatory action inspections or regulatory action
affecting manufacture, testing or affecting Product, provide
storage of Product assistance when requested by LB
- Notify Customer of inspection - Comment on proposed inspection
observations (including Deficiency responses to observations
Letters) affecting the Product, relevant to Product
process or systems relating to the
Product
20.0 Regulatory Submissions WHERE A DATA PACK IS PROVIDED BY LB TO
SUPPORT CUSTOMER'S CLINICAL TRIAL
APPLICATION
INITIAL APPLICATION, AMENDMENTS AND
RESPONSES TO QUESTIONS
- Provide Customer with data pack - Prepare and provide LB with copy
covering activities performed by LB of relevant sections of clinical
trial application for review and
- Review and comment on relevant comment prior to submission to
sections of clinical trial Regulatory Agency
application
- Provide LB with copy of relevant
sections as submitted to
11
RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
---- ----------------------------------------- -------------------------------------
Regulatory Agencies
TELECONFERENCES AND MEETINGS WITH THE
REGULATORY AGENCIES
- Attend teleconferences and meetings - Arrange for LB personnel to have
between the Customer and Regulatory option to attend teleconferences
Agencies arranged to specifically and meetings between Customer
discuss topics relating to LB's and Regulatory Agencies to
responsibilities specifically discuss topics
relating to LB's
responsibilities
12
QUALITY APPROVAL
LONZA BIOLOGICS ***
Name: *** Signature: ***
------------------------------- -----------------------------
Title: *** Date: ***
------------------------------ ----------------------------------
TRUBION PHARMACEUTICALS INC.
Name: Xxxxx X. Xxxxxxxx, MD Signature: /s/ Xxxxx Xxxxxxxx
-----------------------------
Title: President & CEO Date: 4/23/2004
13
APPENDIX 1 TO THE QUALITY AGREEMENT
CUSTOMER LONZA
-------- -----
SENIOR VICE PRESIDENT, HEAD OF LONZA CONTRACT MANUFACTURING:
RESEARCH AND DEVELOPMENT:
Xxxxxxx X Xxxxxx PhD ***
Senior Vice President
Research and Development
Trubion Pharmaceuticals Inc
0000 Xxxxxx Xxxxxx, Xxxxx 0000
Xxxxxxx, XX 00000
XXX
Tel:x0 000 000 0000
Fax: x0 000 000 0000
Email: xxxx0xx@xxxxxxx.xxx
HEAD OF QUALITY: HEAD OF QUALITY:
Xxxxx X Xxxxx
Senior Director, Regulatory Affairs ***
Trubion Pharmaceuticals Inc
0000 Xxxxxx Xxxxxx, Xxxxx 0000
Xxxxxxx, XX 00000
XXX
Tel:x0000 000 0000
Fax:x0 000 000 0000
Email: xxxxxx@xxxxxxx.xxx
HEAD OF MANUFACTURING: DIRECTOR OF MANUFACTURING, ***
Xxxx X Xxxxx
Vice President, Development ***
Trubion Pharmaceuticals Inc
0000 Xxxxxx Xxxxxx, Xxxxx 0000
Xxxxxxx, XX 00000
XXX
Tel: x0 000 000 0000
Fax: x0 000 000 0000
Email: xxxxxx@xxxxxxx.xxx
QUALITY CONTROL MANAGER: QUALITY CONTROL MANAGER:
Xxx Xxx PhD
Director, Product Development ***
Trubion Pharmaceuticals Inc
0000 Xxxxxx Xxxxxx, Xxxxx 0000
Xxxxxxx, XX 00000
XXX
Tel: x0 000 000 0000
Fax: x0 000 000 0000
Email: xxxx@xxxxxxx.xxx
14
SCHEDULE 5
SPECIAL TERMS
OUTLINE OF TERMS FOR THE TECHNOLOGY TRANSFER OF THE PROCESS FOR
MANUFACTURE OF PRODUCT TO CUSTOMER OR TO A THIRD PARTY
This Schedule 5 is the Schedule that is referred to in Clause 9.9 of the
Development and Manufacturing Services Agreement ("Development and Manufacturing
Services Agreement") between LONZA BIOLOGICS *** as "LB" and TRUBION
PHARMACEUTICALS, INC. as "Customer" related to the Technology Transfer of the
Process to Customer or a third party. This Schedule 5 sets forth some additional
commercial terms for any Technology Transfer. All capitalized terms used but not
defined in this Schedule 5 shall have the meanings given in the Development and
Manufacturing Services Agreement.
***
1
