Exhibit 10.1
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
CENTOCOR/CBSI DEVELOPMENT AND
MANUFACTURING AGREEMENT
This Development and Manufacturing Agreement (the "Agreement") is
effective as of the 14th day of January, 1999 (the "Effective Date") by and
between Centocor, Inc. on its own behalf and on behalf of its subsidiaries and
Affiliates, whether now existing or hereafter formed ("Centocor"), 000 Xxxxx
Xxxxxx Xxxxxxx, Xxxxxxx, Xxxxxxxxxxxx 00000, and Covance Biotechnology Services
Inc. ("CBSI"), 6051 Xxxxxx Xxxxx Xxxx Drive, P.O. Box 13865, Research Xxxxxxxx
Xxxx, Xxxxx Xxxxxxxx 00000-0000.
W I T N E S S E T H
WHEREAS, CBSI provides a full range of bioprocessing services to the
biopharmaceutical industry, including process development, fermentation, cell
culture, separation/purification, bioanalytical chemistry, quality control,
quality assurance, and regulatory affairs;
WHEREAS, Centocor has acquired the rights to, among other things,
manufacture and distribute the pharmaceutical product known as Retavase(TM) in
the United States of America and Canada;
WHEREAS, Centocor desires to engage CBSI to perform contract
manufacture and development services on behalf of Centocor in connection with
the manufacture of the bulk form of the pharmaceutical product known as
Retavase(TM), and CBSI desires to perform such services and to manufacture the
Drug Substance, all on the terms and subject to the conditions set forth in this
Agreement and Exhibits hereto, which Exhibits are expressly incorporated by
reference herein.
NOW THEREFORE, in consideration of the above statements and other good
and valuable consideration, the sufficiency and receipt of which are hereby
acknowledged, the parties hereto agree as follows:
1. Definitions.
-----------
Terms defined elsewhere in this Agreement shall have the meanings set forth
therein for all purposes of this Agreement, unless otherwise specified to the
contrary. The following terms shall have the following meanings:
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
1.1 "Active Ingredient" means recombinant reteplase (rPA).
1.2 "Affiliate" means any corporation or other business entity controlled
by, controlling, or under common control with a Party. For this
purpose, "control" of any Party, corporation, or other business entity
shall mean direct or indirect beneficial ownership of at least fifty
percent (50%) of the voting interests, or at least a fifty percent
(50%) interest in the income of, such Party, corporation, or other
business entity, or such other relationship as, in fact, constitutes
actual control of such Party, corporation, or other business entity.
1.3 "Agreement" means this document as signed by the Parties including the
referred Exhibits, Attachments, and any amendments and additions to
this Agreement.
1.4 "Assumptions" has the meaning set forth in Section 2.5(c)(i).
1.5 "Authorized Representative" means a person or persons representing the
quality assurance and/or operations group of a Party to this
Agreement, who is authorized to discuss and agree upon matters
concerning the quality and Manufacture of the Drug Substance, its raw
materials and excipients and whose name and signature are listed in
the Quality Requirements for the Drug Substance attached hereto as
Exhibit "B", and incorporated herein by reference.
1.6 "Batch" means a defined quantity of Drug Substance processed and
produced in one process or series of processes so that it is
homogeneous, which is approximately XXXXXX of active Drug
Substance.
1.7 "Batch Record" means a record made concurrently with the performance
of each step of the manufacturing process for the Drug Substance such
that successive steps in the manufacture may be traced, which is
written by CBSI and approved by Centocor.
1.8 "Boehringer Mannheim" or "BM" means Boehringer Mannheim GmbH,
Mannheim, Germany, a wholly owned subsidiary of Roche Holding, Ltd.
1.9 "Calendar Quarter" means the period of three consecutive calendar
months ending March 31, June 30, September 30, or December 31.
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Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
1.10 "Calendar Year" means the period beginning January 1 and ending
December 31.
1.11 "CBSI Group" has the meaning set forth in Section 18.2.
1.12 "CBSI Inventions" has the meaning set forth in Section 23.1.
1.13 "Centocor Group" has the meaning set forth in Section 18.1.
1.14 "cGMP" means current Good Manufacturing Practice, including without
limitation, that described in 00 XXX 000 (XXX), as amended or updated
from time to time, as well as Canadian cGMP, as amended or updated
from time to time.
1.15 "Claim" has the meaning set forth in Section 18.1.
1.16 "CMC" means chemistry manufacturing controls.
1.17 "Confidential Information" has the meaning set forth in Section 21.1.
1.18 "Consent Order" has the meaning set forth in Section 2.3.
1.19 "Cross-Validation" means the comparison of the appropriate Drug
Substance tests performed at two or more sites to demonstrate that
such test results are equivalent.
1.20 "Development Phase" or "Pre-commercial" means the Manufacture of the
Drug Substance for test purposes and for purposes of Validation and
approval of the process and Facility by the FDA and HPB, prior to
commercial production of Drug Substance.
1.21 "Drug Product" means the final dosage form pharmaceutical medicine,
containing Active Ingredient, which Centocor markets in the United
States and Canada, under the trade name of Retavase(TM).
1.22 "Drug Substance" means the bulk form drug substance from which Drug
Product is made, processed and Manufactured in accordance with the
Specifications, which, after formulation, filling, lyophilizing,
labeling and packaging, Centocor sells to its customers in the United
States and Canada.
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Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
1.23 "DSP" means down stream processing.
1.24 "Effective Date" means the date set forth in the preamble.
1.25 "Equipment" has the meaning set forth in Section 3.2.
1.26 "Errors and Omissions Insurance" means the errors and omissions
insurance policies purchased by CBSI and described on Exhibit "F"
attached hereto and incorporated herein by reference.
1.27 "Executive Liaisons" shall mean XXXXXX A Party may appoint a new
executive liaison with the consent of the other Party.
1.28 "FDA" means the United States Food and Drug Administration, or any
successor thereto.
1.29 "FTC" means the United States Federal Trade Commission.
1.30 "Facility" or "RTP Facility" means the CBSI manufacturing facility
located, at 6051 Xxxxxx Xxxxx Xxxx Drive, P.O. Box 13865, Research
Xxxxxxxx Xxxx, Xxxxx Xxxxxxxx 00000-0000.
1.31 XXXXXX
1.32 "HPB" means the Canadian Health Protective Branch, or any successor
thereto.
1.33 "IB" means inclusion bodies.
1.35 "Initial Term" has the meaning as set forth in Section 24.1.
1.36 "Item Specifications" means quality acceptance parameters mutually
agreed to by the Parties for components, raw Materials and CBSI
produced Materials.
1.37 "Loss" has the meaning set forth in Section 18.1.
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Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
1.38 "Manufacture" means all services provided by CBSI hereunder including,
without limitation, the development, production, formulation,
warehousing, delivery and/or quality testing and quality assurance of
the Drug Substance, as set forth in the Scope of Work, this Agreement,
the Quality Requirements or as otherwise agreed to in writing by the
Parties.
1.39 "Manufacturing Process" has the meaning set forth in Section 22.1.
1.40 "Manufacturer's Working Cell Bank" means the manufacturing working
cell bank for Drug Substance, which is developed from the Master Cell
Bank and owned by Centocor.
1.41 "Master Cell Bank" means the Master Cell Bank expressing Active
Ingredient, owned by Centocor.
1.42 "Material(s)" means the Manufacturer's Working Cell Bank, and raw
materials, as all of the foregoing are utilized in Manufacture of Drug
Substance.
1.43 "Modification" has the meaning set forth in Section 2.5(c)(i).
1.44 "Party/Parties" means either CBSI or Centocor, or both, as the case
may be.
1.45 "Price List" means the Price List for commercial production Drug
Substance which is attached hereto as Exhibit "D", and incorporated
herein by reference.
1.46 "Program Assumptions" has the meaning set forth in Section 2.5(c)(i).
1.47 "Project Team" has the meaning set forth in Section 4.
1.48 "Protocol" means a step by step procedure to be followed indicating
all activities, analysis, interpretation and reporting to performed
with regard to Manufacture and Drug Substance.
1.49 "Purchase Order" means a written notification and authorization from
Centocor to CBSI to supply a quantity of Drug Substance.
1.50 "Purchase Price" means the price at which CBSI sells commercial
production Drug Substance to Centocor.
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Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
1.51 "Report" means a document recording the outcome of a particular study
or event containing summary, procedures and materials, results,
interpretation and conclusion sections.
1.52 "QA" means quality assurance.
1.53 "Qualification" means the procedure by which Quality Requirements,
manufacturing procedures and/or equipment is proven to be designed
properly and to perform according to each of their design criteria.
1.54 "Quality Requirements" means the quality requirements for the
Manufacture of Drug Substance, a copy of which is attached hereto as
Exhibit "B" and incorporated herein by reference, as may be amended
from time to time by Centocor.
1.55 "Regulatory Plan" has the meaning set forth in Section 13.5.
1.56 "Regulatory Requirements" means the applicable requirements of any and
all federal, state, local or other law, including without limitation,
the regulations, rules and permit or license requirements of the FDA
and HPB and any and all other applicable governmental and regulatory
authorities.
1.57 "Release" means a written statement from Centocor's authorized quality
assurance representative that a certain identified quantity of Drug
Substance or Material is ready for use in a further step in the
manufacturing process for the Drug Product.
1.58 "Scope of Work" shall mean the Scope of Work for the pre-commercial
and commercial production of Drug Substance attached hereto as Exhibit
"A" and incorporated herein by reference.
1.59 "SOPs" means the CBSI's standard operating procedures used to
Manufacture the Drug Substance, prepared by CBSI, as may be amended
from time to time.
1.60 "Special Damages" means incidental, indirect, consequential or special
damages.
1.61 "Specifications" means the requirements with respect to which tests,
analyses, test procedures, and test results for the Drug Substance,
its raw materials and excipients, as set forth in the Quality
Requirements, must conform.
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Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
1.62 "Supply Year" means the one year period beginning with the supply of
the first commercial lot of Drug Substance to Centocor by CBSI and
subsequent one year periods.
1.63 "Termination Fee" has the meaning set forth in Section 25.4.
1.64 "Total Development Price" has the meaning set forth in Section 2.5(a).
1.65 "Trustee" has the meaning set forth in Section 2.3.
1.66 "TTR" means technical transfer report.
1.67 "Validated Methodology" means analyte validation in accordance with
the Text on Validation of Analytical Procedures, ICH Harmonized
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Tripartite Guideline, 27 October 1994, as amended from time to time.
--------------------
1.68 "Validation" means establishing documented evidence which provides a
high degree of assurance that a specific process will consistently
produce a product meeting its pre-determined specification and quality
attributes as defined in FDA Guideline on General Principles of
----------------------------------
Process Validation, May, 1987.
------------------
1.69 "Waste" has the meaning set forth in Section 9.
1.70 "Working Volume" means sixty-five percent (65%) to seventy-five
percent (75%) of the total tank volume.
2. Development Phase Manufacture.
-----------------------------
2.1 Development Phase Scope of Work. CBSI agrees to use diligent efforts
-------------------------------
to perform the pre-commercial production of Drug Substance in the
Development Phase in accordance with the Scope of Work. CBSI agrees to
deliver the deliverables set forth in the Scope of Work for the
Development Phase in the manner and at the time stated in the Scope of
Work. In the event of a conflict between the Scope of Work and the
terms and conditions of this Agreement, the terms and conditions of
this Agreement shall govern. The Scope of Work may be amended only by
mutual written agreement of the Parties.
2.2 Objectives of Development Phase. The Parties agree that the objectives
-------------------------------
of the Development Phase are: (a) the transfer to Centocor for use by
CBSI of the technology currently used by Boehringer Mannheim in
Germany to manufacture Drug Substance; (b) the transfer from Centocor
to CBSI of the
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Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
manufacturing technology for production of Drug Substance; (c) to
prepare the Facility to Manufacture the Drug Substance in accordance
with the Specifications as developed by Boehringer Mannheim and in
accordance with cGMP and Regulatory Requirements; (d) to test
Manufacture to show: (i) the ability to Manufacture Drug Substance
comparable to that manufactured by Boehringer Mannheim; and (ii)
ability to Manufacture Drug Substance in accordance with
Specifications, cGMP, Regulatory Requirements and to Centocor's
satisfaction; (e) to obtain FDA and HPB approval for use of the
Facility to Manufacture Drug Substance for purposes of commercial sale
by Centocor in the United States and Canada; and (f) as otherwise
provided in the Scope of Work.
2.3 FTC Trustee. The Parties acknowledge that the transfer of technology
-----------
for Manufacture from Boehringer Mannheim to Centocor for use by CBSI
is done pursuant to, among other things, Agreement Containing the
Consent Order entered into by Roche Holding, Ltd. and the FTC, dated
February 11, 1998 (the "Consent Order") which Consent Order requires,
among other things, supervision of such transfer by a trustee
appointed by the FTC (the "Trustee"). CBSI agrees to cooperate fully
with the Trustee, to permit the Trustee access to the Facility upon
reasonable notice to inspect operations and documentation related to
the Manufacture of the Drug Substance; and to perform any reasonable
task requested by the Trustee and agreed to by Centocor in writing
with regard to the Manufacture of the Drug Substance during the
Development Phase. Such tasks requested by the Trustee not defined
within the Scope of Work will be separately invoiced and paid for by
Centocor at CBSI's standard rates for such tasks.
2.4 Samples. During each stage of the Development Phase, CBSI will supply
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Centocor with samples of in-process Materials and Drug Substance in
the amounts requested by Centocor in writing for the purpose of
testing against Specifications.
2.5 Price and Milestones for Development Phase Manufacture.
------------------------------------------------------
(a) Total Development Price. Centocor shall pay CBSI a Total Price
-----------------------
for services and expenses of XXXXXX for complete performance of
CBSI's obligations under this Agreement and the Scope of Work for
the Development Phase ("Total Development Price"). The Total
Development Price shall include, but is not limited to, fees for
services, Materials costs, travel costs, testing costs,
reasonable
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Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
miscellaneous costs, and all applicable taxes; provided however the
stability testing performed by CBSI shall be an additional charge.
(b) Payment Schedule. The Total Development Price shall be paid to
----------------
CBSI by Centocor in accordance with the payment schedule set
forth below. Centocor will make a payment to CBSI only when the
applicable deliverable is delivered in full by CBSI to Centocor's
reasonable satisfaction, including, without limitation, the
approval of Centocor's Executive Liaison. The Parties agree the
deliverables, delivery date and applicable payments are as
follows:
====================================================================================================================
Deliverables Delivery Date Payments
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(1) Execution of this Agreement by 12/31/98 XXXXXX as an advance toward payment
both CBSI and Centocor. of the deliverable stated in Section
2.5(b)(2).
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(2) Delivery to Centocor of 3/30/99 XXXXXX credited from Agreement
satisfactorily completed final Execution Payment set forth in
pre-construction Deliverable #1).
engineering design
of modifications
necessary to fit the Facility for
Manufacture of Drug Substance pursuant
to this Agreement. In addition, CBSI
has completed deliverables set forth
in the Precommercial Stages I and II
of the Scope of Work.
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(3) Completed transfer, implementation 11/30/99 XXXXXX
and Cross Validation of all in process
control and release assays as set
forth in the Precommercial Stage III
of the Scope of Work.
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Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
====================================================================================================================
Deliverables Delivery Date Payments
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(4) Satisfactory completion of 1/30/00 XXXXXX
installation of all significant
manufacturing equipment (including
piping) necessary for production of
Drug Substance.
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(5) Successful performance by CBSI of 4/01/00 XXXXXX
two full scale cGMP compliant
demonstration runs of Drug Substance
at the commercial supply scale
including full downstream processing
as set forth in Precommercial Stages
IV and V of the Scope of Work.
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(6) Completion and approval of 8/01/00 XXXXXX
Manufacturing documents for the
consistency lots.
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(7) Satisfactory completion of the 12/31/00 XXXXXX
Validation process (i.e., installation
and operation qualification) for the
Manufacture of Drug Substance for
Commercial Sale, including completion
of three (3) complete consistency lots as
set forth in Precommercial Stage VIII
of the Scope of Work.
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Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
====================================================================================================================
Deliverables Delivery Date Payments
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(8) Centocor submits applications to TBD XXXXXX
FDA and HPB for approval of CBSI
Facility for commercial production
of Drug Substance and all outstanding
audit observations (by Centocor and any
third party auditor) are reasonably
corrected by CBSI.
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(c) Change Orders.
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(i) The estimated Total Development Price for the
Development Phase specified in Section 2.5(a) of this
Agreement and the individual budget components and time
estimates specified in the Scope of Work are subject to
a number of general and program specific assumptions.
The program specific assumptions relate to the
Development Phase design and objectives, manpower
requirements, timing, capital expenditure requirements,
if any, and other matters relating to the completion of
the Development Phase as set forth in Section 2.2 of
the Scope of Work (the "Program Assumptions"). CBSI
also assumes that Centocor will perform its obligations
under this Agreement and Scope of Work in a timely
manner, that no event outside the control of CBSI will
occur and that there are no changes to any applicable
laws, rules or regulations which effect the Development
Phase (the foregoing assumptions together with the
Program Assumptions, collectively, the "Assumptions").
In the event that any of the Assumptions require
material modification or the Development Phase
objectives cannot be achieved based on the Assumptions
(each being a "Modification") then the Scope of Work
may be amended as provided in paragraph (ii) of this
Section 2.5(c).
(ii) In the event a Modification is identified by Centocor
or by CBSI, the identifying party shall notify the
other party as soon as is reasonably possible. CBSI
shall provide Centocor with a Change Order containing
an estimate of the required Modifications to the Total
Development Price in this Agreement and timeline
specified in the Scope of Work within twenty (20)
business days of receiving such notice. Centocor shall
use commercially reasonable efforts to respond in
writing to such
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Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
Change Order promptly. If Centocor does not approve
such Change Order and has not terminated the
Development Phase but wants the Development Phase to be
modified to take into account the Modification, then
Centocor and CBSI shall use commercially reasonable
efforts to agree on a Change Order that is mutually
acceptable. CBSI shall continue to work on the
Development Phase during any such negotiations, but
shall not commence work with respect to the Change
Order unless authorized in writing.
(d) Invoice. Upon completion of a deliverable to Centocor's
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reasonable satisfaction, CBSI will submit to Centocor an
invoice for payment of amounts due to CBSI for completion of
that deliverable. Payment shall be made by Centocor thirty
(30) days after the receipt of an invoice by Centocor. Late
payments are subject to an interest charge of one and
one-half percent (1 1/2%) per month. Any payments that are
greater than XXXXXX past due constitute a material
breach of this Agreement.
2.6 Re-Validation of Existing CBSI Systems and Equipment. CBSI agrees
----------------------------------------------------
to re-Validate its existing systems and equipment used in the
Manufacture of Drug Substance as mutually agreed by the Parties.
In the event that the Parties cannot agree, CBSI agrees to
re-Validate its existing systems and equipment as determined by
an independent third party auditor selected by Centocor. Such
re-Validation by CBSI shall occur prior to the first of either
(a) the Manufacture of the first commercial Batch of Drug
Substance; or (b) the inspection of the Facility by the FDA or
the HPB for approval of commercial manufacture of Drug Substance.
CBSI shall pay all costs associated with re-Validation pursuant
to this Section 2.6.
3. Materials and Equipment for the Development Phase and for Manufacture
---------------------------------------------------------------------
of Drug Substance for Commercial Sale.
-------------------------------------
3.1 Materials.
---------
(a) Drug Substance Materials. Centocor shall provide to CBSI at
------------------------
no cost to CBSI, the Manufacturer's Working Cell Bank and
the XXXXXX used to Manufacture the Drug Substance.
CBSI shall purchase and pay for all other Materials used to
Manufacture the Drug Substance. CBSI shall purchase
Materials from approved vendors and/or suppliers.
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Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
CBSI is responsible for testing all Materials and assuring
that Materials comply with Specifications.
(b) Facility Materials and Supplies. CBSI will also supply at
-------------------------------
its own expense all other materials that are normally
required for the operation and maintenance of the Facility
during the term of this Agreement.
3.2 Equipment. The parties agree that the equipment listed on XXXXXX
---------
(the "Equipment") XXXXXX, shall be mutually specified by the
Parties and installed, installation qualified, process qualified,
operation qualified and purchased by Centocor for use in the
Facility solely to perform the Manufacture of the Drug Substance
pursuant to this Agreement. XXXXXX may be amended from time to
time upon the mutual consent of the Parties. Centocor will pay
the amounts listed in XXXXXX to purchase the Equipment. Title to
the Equipment purchased by Centocor pursuant to this Paragraph
3.2 shall remain with Centocor. CBSI will at no additional cost
to Centocor maintain the Equipment in good working order;
provided that Centocor shall be responsible for the replacement
of the Equipment.
4. Project Team.
------------
Centocor and CBSI will each appoint representatives to a project team
("Project Team") in accordance with the Scope of Work. The purpose of the
Project Team is to facilitate the transfer and discussion of information
relating to activities required under this Agreement and the Scope of Work.
The Project Team will meet in the manner and at the times stated in the
Scope of Work.
5. Supply of Drug Substance for Commercial Sale.
--------------------------------------------
5.1 Products to be Supplied. Upon receipt of approval by the FDA for
-----------------------
Manufacture of the Drug Substance at the Facility for purposes of
commercial sale, and upon receipt by CBSI of written
authorization by Centocor to commence manufacture of the Drug
Substance at the Facility for purposes of commercial sale, CBSI
agrees to provide to Centocor and Centocor agrees to purchase
from CBSI Drug Substance in the amounts and in the manner set
forth in Section 6 of this Agreement.
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Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
5.2 Exclusivity. During the term of this Agreement, CBSI shall
-----------
Manufacture Drug Substance solely and exclusively for Centocor,
and/or provide and sell Drug Substance solely and exclusively to
Centocor. CBSI will not Manufacture for, nor sell nor provide
Drug Substance to any person or entity other than Centocor.
5.3 Manufacturing Standards. CBSI shall use commercially reasonable
-----------------------
efforts to perform the Manufacturing at all times at the Facility
strictly in accordance with this Agreement and in strict
conformity with (i) the Specifications, (ii) cGMP, (iii) all
Regulatory Requirements and (iv) the Quality Requirements. CBSI
will test all Drug Substance Manufactured according to Validated
Methodology and compare all Drug Substance with reference
standards to be supplied by Centocor. CBSI agrees to notify
Centocor immediately in writing of any test or other failures in
the Manufacture of the Drug Substance that indicate that such
Drug Substance fails to comply with the Specifications, Quality
Requirements, Regulatory Requirements or other requirements for
Drug Substance.
5.4 Samples. CBSI shall supply Centocor in the amounts and at the
-------
times requested by Centocor with samples of in-process Material
and/or Drug Substance.
5.5 Packing List. All shipments of Drug Substance must be accompanied
------------
by a packing list. The packing lists as well as all packages must
be clearly marked with the part numbers of CBSI and Centocor,
quantity, container numbers, Batch number, and expiration date.
The Drug Substance container label will contain the special
storage conditions and Centocor's Drug Product description, such
storage conditions and Centocor's Drug Product description to be
supplied by Centocor.
6. Forecasts and Orders of Drug Substance for Commercial Sale.
----------------------------------------------------------
6.1 Forecasts.
---------
(a) In order to assist CBSI in its production planning, Centocor
will provide CBSI on a Calendar Quarterly basis with a non-
binding twenty-four (24) calendar months rolling forecast of
anticipated requirements for the Drug Substance. Each forecast
will be updated each Calendar Quarter and will extend such
forecast for one additional Calendar Quarter. The forecast is for
planning purposes only. Subsequent forecasts may include changes
to the
14
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
anticipated requirements for the Drug Substance for the
Calendar Quarters addressed in a previously delivered
forecast. After the first forecast for commercial production
of Drug Substance is submitted by Centocor, in no event will
the anticipated requirements for Drug Substance forecasted
for any Calendar Year exceed the forecast for the previous
Calendar Year by more than twenty percent (20%) unless
otherwise mutually agreed upon by the Parties.
(b) Within five (5) business days after CBSI's receipt of
each forecast, CBSI will notify Centocor if it anticipates
that it will be unable to meet any portion of the forecasted
requirements. Within ten (10) business days of receipt of
such notification by Centocor, the Executive Liaisons shall
meet to discuss the forecast and resolve any production
scheduling issues.
6.2 Purchase Orders. Centocor shall send CBSI a written binding
---------------
Purchase Order for Drug Substance. Each Purchase Order shall
specify the quantity of Drug Substance that Centocor intends
to purchase for the applicable Calendar Quarter. Such
Purchase Order shall be received by CBSI at least ninety
(90) days prior to Centocor's required delivery date for the
Drug Substance that is the subject of the Purchase Order,
provided that CBSI will ship Drug Substance monthly or
quarterly as requested by Centocor in accordance with
Section 7.1. In no event will the quantity of Drug Substance
specified for purchase for a Calendar Quarter in a Purchase
Order be more than twenty percent (20%) above, or less than
twenty percent (20%) below, the amount of the Drug Substance
forecasted for that Calendar Quarter pursuant to Section 6.1
of this Agreement. CBSI shall use best efforts to meet fully
the requirements of each Purchase Order placed by Centocor.
6.3 Conflict Between this Agreement and Purchase Order. In the
--------------------------------------------------
event of a conflict between any Forecast or Purchase Order
and this Agreement, the terms and conditions of this
Agreement shall govern.
6.4 Minimum Annual Purchase Requirement. Centocor agrees to
-----------------------------------
purchase from CBSI a minimum of XXXXXX of commercial
production Drug Substance in addition to the Drug Substance
from the consistency lots in the first year of commercial
production of Drug Substance by CBSI, and a XXXXXX per year
for the nine (9) years thereafter of commercial production
of Drug Substance by CBSI. This minimum purchase requirement
shall be void and unenforceable in any year that CBSI is not
able, for any reason other than Centocor's failure to
perform
15
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
under this Agreement, including Force Majeure, to supply a
minimum of XXXXXX of commercial production Drug Substance;
provided that CBSI need only supply XXXXXX in the XXXXXX of
commercial production of Drug Substance.
7. Delivery, Storage and Acceptance or Rejection of Drug Substance for
-------------------------------------------------------------------
Commercial Sale.
---------------
7.1 Delivery Destination and Dates. CBSI shall ship the Drug
------------------------------
Substance to the destination specified by Centocor and on the
date specified by Centocor in the applicable Purchase Order.
Centocor may, at its sole option, request that Drug Substance be
shipped each month.
7.2 Required Delivery and Inventory. CBSI may only ship Drug
-------------------------------
Substance before or after the date specified by Centocor if CBSI
obtains Centocor's prior written consent. CBSI agrees to store at
the Facility at no additional cost to Centocor a minimum
inventory of three months supply of purified, commercial
production Drug Substance. CBSI will store Drug Substance and
Materials at the Facility under conditions specified in the SOPs.
7.3 Delivery to Carrier at CBSI's Facility. CBSI shall deliver the
--------------------------------------
Drug Substance at Centocor's expense in accordance with
Centocor's instructions, Ex Works, according to INCO terms 1990.
Delivery of Drug Substance by CBSI shall be deemed to have taken
place upon delivery to a Centocor designated and approved carrier
at the Facility.
7.4 Batch Acceptance or Rejection. Within five (5) business days
-----------------------------
after CBSI release of each Batch, CBSI shall, with respect to
each Batch, send copies of all appropriate Batch record
documentation, all certificates of analysis required in the
Specifications, and all other required documentation, including
without limitation, the documentation required under this
Agreement and under the Quality Requirements to Centocor.
Centocor shall have ten (10) business days from Centocor's
receipt of such records to accept or reject the Drug Substance.
Centocor may reject Drug Substance on a Batch-by-Batch basis in
the event such Batch of Drug Substance fails to comply with the
Specifications and other requirements set forth in this Agreement
and in the Quality Requirements, by giving written notice of
rejection to CBSI within ten (10) business days following receipt
by Centocor of the required documentation. Any rejected Batch
will be destroyed upon the request of Centocor and in
16
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
accordance with Centocor's written instructions. Acceptance of a
Batch by Centocor constitutes Release of a Batch by Centocor.
7.5 Replacement of Product. Any rejection of a Batch by Centocor
----------------------
submitted to CBSI pursuant to Section 7.4 shall be accompanied by
a report of analysis. In the event that Centocor rejects a Batch
in accordance with Section 7.4 and either CBSI agrees that such
rejection was justified or, pursuant to Section 7.6, a third
party determines that such rejection was justified, CBSI agrees
to Manufacture a replacement Batch complying with the
Specifications, the terms of this Agreement and the Quality
Requirements. CBSI shall promptly reimburse (or credit if so
approved by Centocor) Centocor for any amounts paid or payable by
Centocor with respect to the rejected Batch.
7.6 Dispute Resolution for Batch Rejection. If Centocor rejects any
--------------------------------------
Batch pursuant to Section 7.4 and if CBSI, after good faith
negotiations with Centocor, fails to agree that such rejection
was justified, the Parties shall mutually agree upon a third
party to review records and test data and other relevant
information developed by both Parties and determine whether the
rejection of the Batch is appropriate. If the Drug Substance is
found to comply with the Specifications, the other requirements
of this Agreement and the Quality Requirements, Centocor shall
pay the costs of such tests and third party and shall be required
to pay for such Batch. If the Drug Substance is not found to
comply with the Specifications, the other requirements of this
Agreement and the Quality Requirements, CBSI shall pay the costs
of such tests, third party and shall promptly reimburse Centocor
as provided in Section 7.5 and shall Manufacture a replacement
Batch as provided in Section 7.5.
8. Price and Payment for Drug Substance for Commercial Sale.
--------------------------------------------------------
8.1 Purchase Price.
--------------
(a) The Purchase Price to Centocor for commercial production Drug
Substance Manufactured by CBSI is set forth on XXXXXX hereto
which is incorporated herein by reference.
(b) In the event that an improvement or change to the
Manufacturing process for the Drug Substance is made, the
Purchase Price in effect at the time of the change or improvement
and thereafter for the term of this Agreement will be adjusted
proportionately, provided that any change or improvement during
the Development Phase will adjust the Purchase Price
17
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
proportionately in year one of commercial production of Drug
Substance and thereafter for the term of the Agreement.
8.2 CBSI Costs and Expenses Included in Purchase Price. The Purchase
--------------------------------------------------
Price includes, without limitation, all costs and expenses of
CBSI with regard to all labor, equipment, Materials and the
Facility used for Manufacture of the Drug Substance in accordance
with this Agreement, the Scope of Work, the SOPs, Batch records,
Quality Requirements, Specifications, and Regulatory Requirements
for the Drug Substance, except that Centocor will provide to CBSI
the Materials and the Equipment stated in Section 3 of this
Agreement.
8.3 Invoicing. CBSI shall invoice Centocor against the applicable
---------
Purchase Order for the supply of the Drug Substance after (a) the
CBSI Quality Assurance approval of a Batch of Drug Substance; (b)
receipt by Centocor of the completed documentation described in
Section 7.4; and (c) Release of the Batch by the Centocor Quality
Representative. All invoices shall be payable within thirty (30)
calendar days after receipt of invoice by Centocor. Late payments
are subject to an interest charge of one and one-half percent
(1 1/2%) per month. Any payments that are greater than XXXXXX
days past due constitute a material breach of this Agreement.
9. Waste Disposal. As used hereinafter, the term "Waste" shall mean all
--------------
rejects, improper goods or other waste arising from the Manufacture of
the Drug Substance, including but not limited to rejected, excess, or
unusable Materials, or Drug Substance. CBSI shall hire, direct, and
pay all costs for a waste contractor to remove all Waste from CBSI's
Facility.
10. Title and Risk of Loss.
----------------------
10.1 Ownership. Ownership of all Active Ingredient, Manufacturer's
---------
Working Cell Bank, and variants or derivatives thereof, XXXXXX
and Equipment purchased by Centocor remain with Centocor at all
times. Title to all Materials purchased by CBSI shall pass to
CBSI. Title to and risk of loss for Drug Substance shall pass to
Centocor upon delivery of the Drug Substance to a Centocor
designated and approved carrier at the Facility consistent with
Section 7.3 of this Agreement, except that Centocor shall be
entitled to reject Drug Substance in accordance with Paragraph
7.4 of this Agreement.
18
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
10.2 Risk of Loss. To the extent covered by insurance, CBSI shall
------------
assume all liability for, and defend and indemnify and hold
Centocor harmless from and against any loss or damage relating to
Equipment, Manufacturer's Working Cell Bank, XXXXXX or Drug
Substance arising from CBSI's negligence or willful misconduct
while CBSI has custody and control over the Equipment,
Manufacturer's Working Cell Bank, XXXXXX and/or Drug Substance.
11. Changes.
-------
11.1 Changes. CBSI will not implement any material changes or
-------
alterations to the Manufacturing process relating to the Drug
Substance without the prior written consent of the Centocor
Authorized Representatives listed in the Quality Requirements
attached hereto as amended from time to time. A material change
or manufacturing process alteration implemented by CBSI includes,
but is not limited to, any change or alteration that (a) impacts
the regulatory commitments made to regulatory authorities for the
Drug Product; (b) may require revalidation; (c) may affect the
quality, purity, identity, or strength of the Drug Product; (d)
would result in changing the Specifications, master Batch
records, or test methods with respect to the Drug Substance
and/or Drug Product; (e) results in change of Materials,
Manufacturing methods, sampling procedures, SOPs or Batch
worksheet relating to the Drug Substance; and (f) subcontracting
an operation currently performed by CBSI for Centocor. Centocor
will not change any Specifications regarding the manufacturing
process for the Drug Substance without prior written consent of
CBSI's Authorized Quality Representatives. Such consent by either
party for changes contemplated by this Paragraph shall not be
unreasonably withheld. Reasonable costs incurred by CBSI for such
changes shall be invoiced by CBSI and paid for by Centocor in
accordance with Section 8.3.
11.2 Impact of Permitted Changes. In the event the proposed changes
---------------------------
have an impact on delivery times, CBSI shall promptly inform
Centocor, and the Parties will meet to discuss and mutually agree
upon such proposed changes to delivery times.
12. Access and Audits by Centocor and Maintenance of Records.
--------------------------------------------------------
12.1 Access. CBSI shall permit one or more of Centocor's
------
representative(s), representatives of Boehringer Mannheim and
representatives of Roche access to the Facility at any time
(provided that, as to representatives at Boehringer
19
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
Mannheim and/or Roche, adequate notice is given to allow CBSI
time to protect the confidentiality of CBSI's other clients
information and technology) to observe and monitor the
Development Phase Manufacture of Drug Substance and the
Manufacture of Drug Substance for commercial sale. Such
representative(s) shall be nominated from time to time by
Centocor and shall comply with CBSI SOPs for the Facility.
12.2 Audit Right. Centocor's personnel shall have the right, at
-----------
Centocor's expense, to inspect and have access to the facilities
used in the Manufacturing, receiving, sampling, analyzing,
storing, handling, packaging, shipping and disposing of the raw
Materials, the Drug Substance, Waste and all records related to
this Agreement, and the subject matter hereof, during regular
business hours and upon reasonable advance written notice to CBSI
for the purpose of conducting quality audits, conducting
operation audits regarding Manufacture and otherwise auditing
compliance with this Agreement. CBSI shall cooperate with
Centocor in conducting such audits and shall allow Centocor
representatives to copy records set forth in Section 12.3 for
liability, regulatory and quality control purposes. CBSI also
agrees to permit external audits to be performed by qualified
experts chosen by Centocor and approved by CBSI, such approval by
CBSI to not be unreasonably withheld, provided that any such
experts must sign a confidentiality agreement with CBSI
containing substantially similar terms to the terms set forth in
Section 21 of this Agreement. In addition, Centocor may conduct
cGMP audits, at its expense. The date and the agenda of the cGMP
audits shall be mutually agreed upon at least five (5) business
days prior to the date of such audit. All information obtained by
Centocor and its third party representatives pursuant to this
Section shall be subject to the confidentiality provisions of
Section 21. Centocor will inform CBSI of any adverse findings
discovered during the audits. CBSI will provide Centocor with its
intended corrective actions, including time schedule, within
fifteen (15) business days of receiving such information. If any
disagreement with respect to the level of corrective action
occurs, Centocor and CBSI will agree upon and share the cost of a
third party quality or regulatory compliance expert who will make
the final decision on the issue in dispute.
12.3 Maintenance of Records. CBSI shall maintain for XXXXXX
----------------------
after termination of this Agreement all quality assurance
manufacturing records, samples relating to each Batch sufficient
to substantiate and verify its duties and obligations hereunder,
Batch production records and other records related in any way to
the Manufacture of the Drug Substance and as may be necessary to
comply with Regulatory Requirements, including without
limitation, records
20
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
of orders received, Drug Substance manufactured, work in process,
Drug Substance analysis and quality control tests, disposal of
Waste, and other similar records. Before destruction of any such
records, CBSI shall provide Centocor with at least sixty (60)
days prior written notice of the intended destruction and, if
requested by Centocor, will provide Centocor with copies of any
such records or originals as requested by Centocor.
Notwithstanding the foregoing, at any time after XXXXXX years
from the date of Manufacture of each Batch (or such longer period
as may be required by applicable laws or regulations), CBSI may
dispose of or deliver to Centocor any records relating to such
Batch in accordance with Centocor's instructions. If Centocor
fails to give said instructions, CBSI shall so notify Centocor;
and if said instructions are still not forthcoming within sixty
(60) days of said notification, then CBSI may destroy such
property in accordance with SOPs.
13. Regulatory Matters.
------------------
13.1 Inspections. CBSI will notify Centocor immediately (within 24
-----------
hours) of any regulatory inspections that involve Drug Substance
supplied or to be supplied to Centocor. CBSI will notify Centocor
of any issues that affect regulatory approval, filings, Drug
Substance supplied or continued supply of the Drug Product. If
Centocor deems appropriate, Centocor has the option of attending
the inspection to address Drug Substance and Drug Product related
issues.
13.2 CBSI's Filings. Centocor is authorized to review and approve all
--------------
regulatory filings or communications between CBSI and any
regulatory agency that affect Centocor's Drug Product or
registration.
13.3 Regulatory Submissions. Centocor shall be responsible for all
----------------------
routine submissions (e.g. annual reports, stability updates) as
well as all submissions regarding changes to the licensed
manufacturing process for Drug Substance to the FDA and/or the
HPB or any successors thereto. Centocor shall be responsible for
filing and obtaining approval for all submissions to the FDA and
HPB pertaining to the Manufacture and testing of Drug Substance
by CBSI and Centocor shall own all such submissions. CBSI shall
provide to Centocor, in a timely manner, all assistance
reasonably requested to prepare a regulatory submission
including, but not limited to, the regulatory support services
stated in the Scope of Work. Regulatory services not covered in
the Scope of Work will be separately invoiced and be paid for by
Centocor at CBSI's reasonable standard rates for such services.
CBSI agrees to comply with all commitments
21
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
made in regulatory submissions regarding CBSI's manufacturing
responsibilities as described herein.
13.4 Regulatory Responsibilities. Centocor shall be responsible for
---------------------------
the compliance of the Drug Product, including the Specifications
for Drug Product, with the FDA, the HPB and all required
regulatory standards. CBSI shall be responsible for compliance
with cGMPs and all applicable Regulatory Requirements in the
Manufacture of Drug Substance except that Centocor is responsible
for the Release of Drug Substance. Each Party will provide
reasonable assistance to the other, at no charge, if necessary to
respond to FDA and/or HPB and other regulatory agency audits,
inspections, inquiries or requests concerning the Drug Substance
or the Manufacture of the Drug Substance.
13.5 Regulatory Plan. Centocor agrees to prepare a written plan
---------------
setting forth the obligations of each Centocor and CBSI with
regard to compliance with Regulatory Requirements for the
Manufacture of Drug Substance (the "Regulatory Plan"). CBSI shall
review, and the Parties shall mutually agree on the Regulatory
Plan prior to implementation. The Regulatory Plan shall be
completed within six months after the Effective Date, and shall
be attached to this Agreement as XXXXXX and incorporated
herein by reference.
13.6 Notices Regarding Safety of Products. Each Party shall provide
------------------------------------
the other Party with prompt notice of any information either of
them receive regarding the safety of the Drug Product, including
any confirmed or unconfirmed information on adverse, serious or
unexpected events associated with the use of the Drug Product.
For serious, unexpected events, notice must be given by telephone
within three (3) calendar days after receipt of the information,
and followed by written notice not less than two (2) calendar
days thereafter. All responsibility and cost for filing any
reports with the FDA concerning such reactions (including Drug
Experience Reports) caused by the Drug Substance Manufactured for
Centocor shall be borne by Centocor. Furthermore, Centocor will
be responsible at its cost for handling all Drug Product
complaints. CBSI will provide reasonable assistance in responding
to any complaints including reviews of retained samples and Batch
records as well as testing the Drug Product engendering a
complaint against the appropriate retained samples, if required,
and Centocor will reimburse CBSI for reasonable out of pocket
expenses incurred therewith. The costs of such testing shall be
borne by Centocor; however, if it is determined that the Drug
Product complaint was directly or indirectly caused by CBSI's
Manufacture and if the Drug Product complaint is related to the
Drug Substance's failure to
22
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
conform to any of its Specifications or other requirements under
this Agreement and/or the Quality Requirements, CBSI shall
reimburse Centocor for the costs of such testing.
14. CBSI Representations and Warranties. CBSI represents and warrants to
-----------------------------------
Centocor, in addition to the other representations and warranties set
forth in this Agreement, that:
14.1 Corporate Organization, Good Standing and Qualification to do
-------------------------------------------------------------
Business. CBSI is a corporation duly and validly existing under
--------
the laws of the State of Delaware. CBSI is in good standing under
the laws of its jurisdiction of incorporation and is duly
qualified to do business and is in good standing in the State of
North Carolina.
14.2 Power and Authority and Agreement Validity. CBSI has the
------------------------------------------
corporate power and authority to execute and deliver this
Agreement and to perform its obligations hereunder. The
execution, delivery and performance by CBSI of this Agreement has
been duly and validly authorized, and no additional authorization
or consent is required in connection with the execution, delivery
and performance by CBSI of this Agreement.
14.3 Due Execution. This Agreement has been duly executed and
-------------
delivered by CBSI and constitutes the valid and legally binding
obligation of CBSI, enforceable in accordance with its terms,
except as such enforcement may be limited by applicable
bankruptcy, insolvency, reorganization, moratorium, and other
similar laws affecting the enforcement of creditors' rights
generally from time to time in effect and general principles of
equity.
14.4 No Conflict. To the best of CBSI's knowledge, the execution and
-----------
delivery of this Agreement do not, and the consummation by CBSI
of the transactions contemplated hereby and the performance by
CBSI of its obligations hereunder will not, violate the
provisions of, or constitute a default or give rise to rights of
any entity under, (i) CBSI's Articles of Incorporation or Bylaws
or (ii) any law applicable to CBSI or (iii) any judgment, decree
or order of any court or governmental or regulatory agency
applicable to CBSI, its subsidiaries, its Affiliates or their
respective assets or (iv) any agreement, contract or commitment
to which CBSI or any of its subsidiaries or Affiliates is a party
or by which they or their respective assets are bound.
23
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
14.5 Litigation. To CBSI's knowledge, there is no pending or
----------
threatened lawsuit or proceeding of any governmental or
regulatory authority against or concerning CBSI in connection
with the type of services to be provided by CBSI hereunder which,
if adversely determined, would (i) prohibit the execution,
delivery or performance of this Agreement or (ii) have a material
adverse effect on CBSI or on CBSI's ability to consummate the
transactions contemplated hereby or to perform its obligations
under this Agreement.
14.6 Condition of Assets. All property of CBSI and its subsidiaries
-------------------
and Affiliates, whether real or personal, that is used in the
production or Manufacture of the Drug Substance is in good
condition, reasonable wear and tear excepted, and is sufficient
for its intended use pursuant to this Agreement.
14.7 Compliance with Specifications and Quality Agreement. All Drug
----------------------------------------------------
Substance, Manufactured and supplied hereunder, shall comply with
the requirements of the Specifications and of the Quality
Requirements and the requirements of this Agreement.
14.8 THE FOREGOING WARRANTIES ARE IN LIEU OF ALL OTHER WARRANTIES,
EXPRESS OR IMPLIED, WITH REGARD TO THE SERVICES PROVIDED UNDER
THIS AGREEMENT AND THE MANUFACTURE OF THE DRUG SUBSTANCE,
INCLUDING, WITHOUT LIMITATION, THE IMPLIED WARRANTIES OF
MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE AND CBSI
HEREBY EXPRESSLY DISCLAIMS ALL SUCH OTHER WARRANTIES OR ANY
WARRANTY THAT THE DRUG SUBSTANCE PRODUCED HEREUNDER WILL SATISFY
THE REQUIREMENTS OF ANY REGULATORY AGENCY AT THE TIME OF A
REGULATORY SUBMISSION REGARDING SUCH DRUG TO SUCH AGENCIES
REGARDLESS OF WHETHER CBSI IS FAMILIAR WITH THE PURPOSES FOR
WHICH CENTOCOR INTENDS TO USE THE DRUG SUBSTANCE.
15. CBSI Covenants. CBSI covenants and agrees that throughout the term of
--------------
this Agreement:
15.1 Maintenance of Licenses, Permits, etc. CBSI will maintain in
-------------------------------------
effect during the term of this Agreement any and all federal,
state and/or local licenses, regulatory approvals, registrations
and permits which may be required to be maintained by CBSI in
order to Manufacture the Drug Substance hereunder.
24
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
15.2 Compliance with Law. In its performance of this Agreement, CBSI
-------------------
will comply with all applicable federal, state and local laws,
regulations and executive orders and amendments thereto and all
Regulatory Requirements.
15.3 Performance Standards. CBSI will Manufacture the Drug Substance
---------------------
in strict compliance with all of the Specifications, the Quality
Requirements, the terms of this Agreement and in strict
compliance with all requirements of the Product's FDA and HPB
approvals.
15.4 Storage and Handling. CBSI will store and handle all Materials
--------------------
and the Drug Substance in compliance with the storage and
handling conditions set forth in the Specifications and Quality
Requirements.
15.5 Certain Actions. CBSI will not take any action or omit to take
---------------
any action that could reasonably be expected to interfere with,
or impair or jeopardize, its ability to supply the Drug
Substance, in accordance with this Agreement, including without
limitation, the Specifications, the Quality Requirements and
Regulatory Requirements.
15.6 Notifications. CBSI will notify Centocor promptly within fifteen
-------------
(15) days in writing of any material civil, criminal or
administrative action brought against CBSI, its directors,
officers, employees or agents which could reasonably be expected
to have a material adverse effect on CBSI or on CBSI's ability to
consummate the transactions contemplated hereby or to perform its
obligations under this Agreement and promptly provide Centocor
with reasonably detailed information regarding CBSI's handling of
each such action.
15.7 Testing and Specifications. CBSI agrees to perform all tests
--------------------------
listed in the Specifications and/or the Quality Requirements in
the manner set forth in the Specifications and/or the Quality
Requirements. CBSI will promptly report to Centocor in writing
all test results that do not comply with the Specifications
and/or the Quality Requirements.
15.8 Insurance. Upon request from Centocor, CBSI shall furnish to
---------
Centocor an insurance carrier's certificate showing that CBSI has
Workmen's Compensation, Comprehensive General Liability and
Property Damage insurance coverage in amounts and coverages
reasonably acceptable to Centocor and/or as may be required by
this Agreement. The certificate shall set forth the amount of
coverage, policy number and date of expiration. CBSI shall
maintain in force during the term of this Agreement the insurance
stated in Section 19.1 of this Agreement.
25
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
15.9 Manufacturing Capacity. CBSI hereby covenants that as of the date
----------------------
of commencement of commercial production of Drug Substance, CBSI
shall have and shall maintain sufficient capacity available at
the Facility for Manufacture of XXXXXX of commercial production
Drug Substance for a period of ten years. This ten year period
will commence from the date commercial production of Drug
Substance has actually begun.
16. Centocor's Representations and Warranties. Centocor represents and
-----------------------------------------
warrants to CBSI, in addition to the other representations and
warranties set forth in this Agreement, as follows:
16.1 Corporate Organization. Centocor is a corporation duly organized
----------------------
and validly existing under the laws of the Commonwealth of
Pennsylvania.
16.2 Power and Authority and Agreement Validity. Centocor has the
------------------------------------------
corporate power and authority to execute and deliver this
Agreement and to perform its obligations hereunder. The
execution, delivery and performance by Centocor of this Agreement
has been duly and validly authorized, and no additional
authorization or consent is required in connection with the
execution, delivery and performance by Centocor of this
Agreement.
16.3 Due Execution. This Agreement has been duly executed and
-------------
delivered by Centocor and constitutes the valid and legally
binding obligation of Centocor, enforceable in accordance with
its terms, except as such enforcement may be limited by
applicable bankruptcy, insolvency, reorganization, moratorium,
and other rights generally affecting the enforcement of
creditors' rights generally from time to time in effect and
general principles of equity.
16.4 No Conflict. To the best of Centocor's knowledge, the execution
-----------
and delivery of this Agreement does not, and the consummation by
Centocor of the transactions contemplated hereby and the
performance by Centocor of its obligations hereunder will not,
violate the provisions of, constitute a default or give rise to
rights of any entity under, (i) Centocor's corporate documents,
or (ii) any law applicable to Centocor, or (iii) to Centocor's
knowledge, any judgment, degree or order of any court or
governmental or regulatory agency applicable to Centocor, or (iv)
to Centocor's knowledge, any agreement, contract or commitment to
which Centocor is a party or by which it is bound, (v) or to
Centocor's knowledge, the Consent Order.
26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
16.5 XXXXXX
27
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
17. Centocor Covenants. Centocor covenants and agrees that:
------------------
17.1 Maintenance of License and Permits, etc. Centocor will maintain
---------------------------------------
in effect during the term of this Agreement any and all federal,
state and/or local licenses, regulatory approvals, registrations
and permits which may be required to be maintained by Centocor in
order for CBSI to Manufacture the Drug Substance hereunder.
17.2 Compliance with Law. In its performance of this Agreement,
-------------------
Centocor will comply with all applicable federal, state and local
laws, regulations and executive orders and amendments thereto and
all Regulatory Requirements, and the Consent Order.
17.3 Certain Actions. Centocor will not take any action or omit to
---------------
take any action that could be reasonably be expected to interfere
with, or impair or jeopardize, CBSI's ability to Manufacture the
Drug Substance in accordance with this Agreement, including,
without limitation, the Specifications and the Quality
Requirements.
18. Indemnification.
---------------
18.1 CBSI shall indemnify Centocor and its Affiliates and their
respective officers, directors and employees (the "Centocor
Group") from any loss, damage, cost or expense (including
reasonable attorneys' fees)(a "Loss") arising from any
28
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
lawsuit, action, claim, demand, assessment or proceeding (a
"Claim") arising from or related to (i) personal injury or
property damage arising or occurring during the Manufacture of
the Batch as a result of CBSI's negligence, gross negligence or
intentional misconduct or inaction of CBSI in the performance of
its obligations under this Agreement, Scope of Work or Quality
Requirements; or (ii) CBSI's violation, non-conformance or
non-performance of any of the terms of this Agreement or CBSI's
breach of any representation or covenant made herein, provided
that if such Loss or Claim arises in whole or in part from
Centocor's negligence, gross negligence or intentional misconduct
or inaction, then the amount of the Loss that CBSI shall
indemnify Centocor for pursuant to this Section 18 shall be
reduced by an amount in proportion to the percentage of
Centocor's responsibilities for such Loss determined by a court
of competent jurisdiction in a final and non-appealable decision
or in a binding settlement between the parties.
18.2 Centocor shall indemnify CBSI and its Affiliates and their
respective officers, directors, employees and agents (the "CBSI
Group") from any Claim or Loss arising from or related to (i)
personal injury to any employee of the CBSI Group or the Centocor
Group directly or indirectly caused by Material or Equipment
provided by Centocor hereunder; (ii) CBSI's strict and complete
performance of its obligations under this Agreement or the Scope
related thereto; (iii) the Drug Substance, the Quality
Requirements or any aspect of the Scope of Work which violates
any applicable law, rule, regulation or ordinance, or the Consent
Order; (iv) the Drug Substance's harmful or otherwise unsafe
effect, including, without limitation, a Claim based upon
Centocor or any other person's use, consumption, sale,
distribution or marketing of Drug Substance; (v) the negligence,
gross negligence or intentional misconduct or inaction of
Centocor in the performance of its obligations under this
Agreement or Scope of Work, (vi) any alleged infringement of any
patent, trademark, copyright or any other intellectual property
right arising from CBSI's performance of this Agreement,
including, without limitation, the making, using, selling,
production or creation of the Drug Substance or use of the
Materials and the expression systems and process used to make,
create or produce the Drug Substance, or (vii) Centocor's
violation, non-conformance or non-performance of any of the terms
of this Agreement or Centocor's breach of any representation or
covenant made herein; provided that if such Loss or Claim arises
in whole or in part from CBSI's negligence, gross negligence or
intentional misconduct or inaction, then the amount of such Loss
that Centocor shall indemnify the CBSI Group for pursuant to this
Section 18 shall be reduced by an amount in proportion to the
percentage of CBSI's responsibilities for such Loss as determined
by a
29
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
court of competent jurisdiction in a final and non-appealable
decision or in a binding settlement between the parties.
18.3 Indemnification Procedure. The indemnified party shall give
-------------------------
prompt written notice to the indemnifying party of any suits,
claims or demands by third parties or the indemnified party which
may give rise to any loss for which indemnification may be
required under this Section 18; provided, however, that the
-------- -------
failure to give such notice shall not impair the obligation of
the indemnifying party to provide indemnification hereunder
except if and to the extent that such failure materially impairs
the ability of the indemnifying party to defend the applicable
suit, claim or demand. The indemnifying party shall be entitled
to assume the defense and control of any suit, claim or demand of
any third party at its own cost and expense; provided, however,
-------- -------
that the other party shall have the right to be represented by
its own counsel at its own cost in such matters. In the event
that the indemnifying party shall decline to assume control of
any such suit, claim or demand, the party entitled to
indemnification shall be entitled to assume such control, conduct
the defense of, and settle such suit, claim or action, all at the
sole cost and expense of the indemnifying party. Neither the
indemnifying party nor the indemnified party shall settle or
dispose of any such matter in any manner which would adversely
impact the rights or interests of the other party without the
prior written consent of the indemnified party, which shall not
be unreasonably withheld. Each party shall cooperate with the
other party and its counsel in the course of the defense of any
such suit, claim or demand, such cooperation to include using
reasonable efforts to provide or make available documents,
information and witnesses. XXXXXX Such indemnification shall not
be subject to the proportional reduction referred to in Section
18.2.
19. Insurance.
---------
19.1 CBSI Insurance. CBSI agrees (i) to obtain and maintain at its
--------------
cost and expense, while this Agreement is in effect, (a)
commercial general liability insurance, including commercially
reasonable coverage for the risks assumed by CBSI in Section 10.2
of this Agreement; (b) products liability insurance with coverage
limits of not less than XXXXXX per occurrence and
30
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX in the aggregate; (c) property damage insurance with
coverage limits of not less than XXXXXX per occurrence; and
(d) the Errors and Omissions Insurance; (ii) not to cancel the
insurance or reduce the coverage without giving at least thirty
(30) days prior written notice to Centocor. CBSI shall cause
Centocor to be a named additional insured party on each insurance
policy. In the event of cancellation or termination of the
coverage described herein, CBSI shall immediately obtain
substitute or replacement coverage.
19.2 Centocor Insurance. Centocor agrees to obtain and maintain at its
------------------
cost and expense, while this Agreement is in effect, commercial
general liability insurance and products liability insurance in
commercially reasonable amounts.
20. Recall. If Drug Product must be recalled by reason of failure to meet
------
any Regulatory Requirement, Centocor shall have the sole
responsibility to effect the recall. However, CBSI shall cooperate as
reasonably required in Centocor's efforts. Centocor shall reimburse
CBSI for any costs reasonably expended by CBSI to effect the recall,
unless the recall is required due to a failure of CBSI to conform in
all material respects to the Specifications or the Quality
Requirements. If the failure to meet applicable requirements resulting
in a recall is caused by the negligently or intentionally wrongful act
or omission of CBSI, CBSI shall reimburse Centocor for (a) any cost
reasonably expended by Centocor to effect the recall; (b) any amount
paid by Centocor for Materials used in recalled Drug Product; (c)
shipping fees and Manufacture fees paid to CBSI for recalled Drug
Product and for any Drug Product that cannot be shipped due to the
condition requiring the recall; provided however that any
reimbursement by CBSI shall not exceed amounts actually paid by
Centocor for the recall.
21. Confidentiality.
---------------
21.1 Definition of Confidential Information. During the term of this
--------------------------------------
Agreement, the Parties may provide to one another confidential
information, or may receive from Boehringer Mannheim, the Trustee
or Roche as the designees of Centocor, documents or other
materials which may be unpublished, including without limitation,
unpatented technical and other information which is not in the
public domain, information comprising or relating to concepts,
discoveries, data, formulae, the Active Ingredient, the Master
Cell Bank, the Manufacturer's Working Cell Bank, inventions,
procedures for experiments and tests and results of
experimentation and testing, results of research, development
processes, manufacturing processes, specifications and
31
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
techniques, economic information, business or research
strategies, trade secrets, the cell line of the Drug Product,
patents, unpublished patent applications and material embodiments
thereof. As used herein, "Confidential Information" means any of
such information or documents described above or any other
information or documents furnished for the purposes of
Manufacturing the Drug Substance which is furnished to or comes
to the attention of either Party and shall include without
limitation, the terms of this Agreement, information provided by
Roche or Boehringer Mannheim or their representatives regarding
the Drug Substance or Drug Product or the manufacturing process
for the Drug Substance or Drug Product, information that consists
of, or relates to, an unpublished patent application, know-how,
technical specifications, the Specifications, development
processes, manufacturing processes, operating manuals, services
information concerning current, future or proposed products and
services, Drug Product and service descriptions, financial or
Drug Substance or Drug Product forecasts or plans, security
procedures or passwords, computer programs, customer or client or
prospective customer or client lists and printouts, records, and
any or all other information, data or material relating to the
business trade secrets and technology of either Party.
21.2 Confidentiality and Non-Use. Both Parties shall maintain in
---------------------------
strict confidence all such Confidential Information and both
Parties shall take all steps necessary to ensure that such
Confidential Information does not enter the public domain or come
into the possession of unauthorized persons, provided however,
----------------
that if and to the extent that disclosure is required by
applicable law, or to obtain regulatory approvals, such Party
seeking to disclose the Confidential Information may disclose
such Confidential Information after giving the other Party prior
written notice of the intended disclosure. CBSI shall not use
such Confidential Information for any purpose other than for the
Manufacture and provision of Drug Substance hereunder and shall
not use the Confidential Information in any way, directly or
indirectly, detrimental to Centocor. Both Parties will ensure
that only those of its officers and employees who are directly
concerned with carrying out this Agreement have access to such
Confidential Information and are informed of the secret and
confidential nature of it. Each Party will maintain a secure
system for the storage and handling of Confidential Information.
21.3 Exclusions. Confidential Information shall not include
----------
information that: (i) is shown by contemporaneous documentation
of the recipient to have been in its possession prior to receipt
from the providing Party or its designee and was not acquired,
directly or indirectly, from any person in violation of a
32
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
restriction on disclosure in favor of the providing Party; (ii)
is or becomes, through no fault of the recipient, publicly known;
(iii) is furnished to the recipient by a third party without
breach of a duty to the disclosing Party and without any
obligation of confidentiality; or (iv) is made public by the
party otherwise having the right to keep the Confidential
Information confidential.
21.4 Required Notifications. Each Party shall notify the other
----------------------
immediately if a subpoena or other legal process or demand
related to the Confidential Information is served upon or
received by such Party or any of its employees, contractors,
subcontractors or agents, and such Party shall cooperate at the
other Party's expense in any lawful effort to contest such
subpoena or other legal process or demand.
21.5 Injunctive Relief. Each Party acknowledges and agrees that any
-----------------
breach or threatened breach of this Section 21 may result in
immediate and irreparable harm and that in such event there may
be no adequate remedy at law. Either Party shall therefore be
entitled to seek immediate injunctive relief, specific
performance, and other equitable relief for such breach or
threatened breach, and such resort to any such equitable relief
shall not be deemed to waive or to limit in any respect any right
or remedy which either Party may have with respect to such breach
or threatened breach.
21.6 Return of Confidential Information. Upon any expiration or
----------------------------------
termination of this Agreement, subject to Section 12.3 of this
Agreement, each Party shall, at the request or without the
request of the other Party, either return or destroy (as
evidenced by a written certificate of destruction) all
Confidential Information previously furnished by the other Party;
provided however, that each Party shall be entitled to retain one
----------------
(1) copy of such Confidential Information for archival purposes.
21.7 Use of Name. Neither Party shall, without the prior consent of
-----------
the other party, use in advertising, publicity or otherwise, the
name, trademark, logo, symbol or other image of the other Party.
21.8 Survival. All obligations of confidentiality and non-use imposed
--------
under this Section 21 shall survive the expiration or termination
of this Agreement for any reason for a period of ten (10) years.
33
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
22. License Solely for Purpose of Manufacture.
-----------------------------------------
22.1 License Grant. Centocor hereby grants to CBSI a non-exclusive,
-------------
royalty-free license, without right to sublicense, to use the
manufacturing technology, trade secrets and know-how used to
manufacture the Drug Substance ("Manufacturing Process") solely
and exclusively for the purpose of performing the Manufacture of
the Drug Substance, in accordance with terms and conditions of
this Agreement, such license to terminate immediately upon the
termination of this Agreement by either Party.
22.2 No Implied License. Subject to Section 22.1, nothing in this
------------------
Agreement does, is intended to, or shall be construed to create,
confer, give effect to or otherwise imply in CBSI or anyone
claiming through CBSI any license, right, or property interest,
in or to Centocor patents or patent rights, Centocor trademarks
or trade names, or any other Centocor trade secrets, know how or
property.
23. Establishment of Proprietary Position.
-------------------------------------
23.1 Ownership. CBSI will promptly inform Centocor of any ideas,
---------
improvements and inventions arising out of the performance of
Manufacture of Drug Substance under this Agreement solely by CBSI
personnel or by CBSI personnel jointly with employees from
Centocor. Inventions, including inventions relating to
manufacturing methods and processes, made solely by CBSI
personnel and any patent applications and patents thereon shall
be owned by CBSI ("CBSI Inventions"). XXXXXX
23.2 CBSI Patent Responsibilities. CBSI shall be responsible for
----------------------------
filing and prosecuting United States and foreign patent
applications on CBSI Inventions. While CBSI shall be responsible
for making decisions regarding the scope and content of any such
applications and prosecution thereof, Centocor shall have an
opportunity to review and provide input thereto. The expenses in
connection with filing and prosecution of any such patent
applications, United States and/or foreign, and the maintenance
of issued patents thereon shall be borne by CBSI.
34
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
23.3 Centocor Patent Responsibilities. Centocor shall be entitled to
--------------------------------
file and prosecute United States and/or foreign patent
applications on jointly owned inventions. CBSI and Centocor shall
be jointly responsible for making decisions regarding the scope
and content of applications and prosecution thereof on any such
jointly owned inventions. CBSI will assist in assembling
inventorship information and data for filing patent applications
on jointly owned inventions. Decisions on when, where and whether
to file on jointly owned inventions will be made by Centocor
after consulting with CBSI. The expenses in connection with
filing and prosecution of any jointly owned patent applications,
United States and/or foreign, and the maintenance of issued
patents thereon shall be borne by Centocor.
23.4 CBSI Election Not to File Patent. In the event that CBSI elects
--------------------------------
not to file a patent application on any CBSI Invention or decides
to discontinue prosecution or maintenance of any such application
or maintenance of any patent issued thereon, Centocor may at its
own expense file, prosecute and/or maintain any such patent
application or patent as the case may be. If Centocor assumes
responsibility of jointly owned patent applications or patents
under this subparagraph, Centocor, upon written request from
CBSI, shall grant to CBSI a royalty-free license thereunder.
23.5 Centocor Election Not to File Patent. In the event that Centocor
------------------------------------
elects not to file a patent application on any invention referred
to in Paragraph 23.3 or decides to discontinue prosecution or
maintenance of any such application or maintenance of any patent
issued thereon, CBSI may at its own expense file, prosecute
and/or maintain any such patent application or patent as the case
may be. If CBSI assumes responsibility of jointly owned patent
applications or patents under this subparagraph, CBSI, upon
written request from Centocor, shall grant to Centocor a
royalty-free license thereunder.
23.6 License to Centocor.
-------------------
(a) In consideration of Centocor's promises and covenants and
other consideration hereunder, CBSI hereby grants to
Centocor:
(i) an exclusive, worldwide royalty-free license to make
or have made, use or sell Drug Substance and/or Drug
Product using CBSI Inventions or joint inventions of
Centocor and CBSI;
(ii) an exclusive, worldwide royalty-free license under any
patent rights to CBSI Inventions or joint inventions
of CBSI to make,
35
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
have made, use and sell Drug Substance and or Drug
Product; and
(iii) the licenses granted by CBSI to Centocor under
Paragraphs 23.6(i) and 23.6(ii) shall include the
right to grant sublicenses of no greater than the
license granted to Centocor hereunder.
24. Term.
----
24.1 Initial Term. This Agreement shall begin on the Effective Date
------------
and shall expire ten years after the date CBSI begins commercial
production of Drug Substance (the "Initial Term"), unless earlier
terminated pursuant to Section 26.
24.2 Extensions. Centocor will have the right, exercisable by written
----------
notice to CBSI given no later than twelve (12) months before the
expiration of the Initial Term, to request that the term of this
Agreement be extended for an additional three or four years, at
Centocor's sole option.
25. Termination and Default.
-----------------------
25.1 Termination by Centocor. In addition to the termination of this
-----------------------
Agreement upon expiration of its Initial Term or any extension
thereof, Centocor may at any time terminate this Agreement as
follows: (a) after initiation of Manufacture of commercial
production Drug Substance by CBSI by providing XXXXXX written
notice to CBSI; or (b) during the Development Phase, without
incurring any further liability with respect to the Agreement, by
providing written notice to CBSI that for reasons other than a
material wrongful act or omission of Centocor, in Centocor's
reasonable opinion (i) the process used by Boehringer Mannheim to
manufacture Retavase(TM) Drug Substance does not transfer to the
Facility; (ii) CBSI fails to deliver the deliverable set forth in
Section 2.5(b)(5) of this Agreement, (iii) CBSI is unable to
deliver any deliverable as set forth in Section 2.5(b) as the
result of force majeure; or (iv) a Modification as defined in
Section 2.5(c)(i) is unacceptable to Centocor after good faith
negotiations by the Parties.
25.2 Termination by CBSI. CBSI may terminate this Agreement after
-------------------
initiation of Manufacture of commercial production Drug Substance
by CBSI by giving Centocor XXXXXX prior written notice to
Centocor. CBSI may
36
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
not terminate this Agreement for any reason during the
Development Phase. Notwithstanding the foregoing, CBSI may
terminate this Agreement at any time upon XXXXXX written notice
in the event Centocor is in default of a material obligation
under this Agreement which Centocor fails to cure within thirty
(30) days after a face to face meeting of the Executive Liaisons
pursuant to Section 29.2(a). Such face to face meeting shall
occur within fifteen (15) days of receipt by Centocor of written
notice of termination for material breach by CBSI.
25.3 Right to Termination is Additional Right. The right to terminate
----------------------------------------
this Agreement shall be in addition to and not in substitution or
limitation of any other rights available under this Agreement or
under applicable law.
25.4 Termination Prior to Commencement of Commercial Production. In
----------------------------------------------------------
the event that Centocor terminates this Agreement prior to the
completion of the Development Phase for a reason other than (a)
reasons provided in Section 25.1(b) herein, or (b) any other
failure of CBSI to perform its material obligations under this
Agreement for the Development Phase, Centocor will pay CBSI a
termination fee of XXXXXX ("Termination Fee") and Centocor will
pay the amounts due for completion of the Development Phase
deliverable in process at the time of termination. Payment of the
amounts due under this Section 25.4 and amounts due and owing to
CBSI under this Agreement as of the date of termination by
Centocor shall be made by Centocor XXXXXX after the date of the
written notice from Centocor to CBSI terminating this Agreement.
Payment of the amounts due under this Section 25.4 shall
constitute full and complete payment by Centocor to CBSI for any
services rendered or costs incurred by CBSI as the result of this
Agreement. Upon receipt of payment of amounts due under this
Section 25.4 by CBSI, neither party shall have any further
obligation to the other.
25.5 Termination After Commencement of Commercial Production. In the
-------------------------------------------------------
event that Centocor terminates this Agreement after commencement
of commercial production, CBSI will supply to Centocor sufficient
Drug Substance to meet the XXXXXX months Forecast, incorporating
the minimum annual purchase requirement of XXXXXX The parties
agree that in no event is Centocor required to purchase more than
ten years of commercial production of Drug Substance.
37
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
25.6 Transition. In addition to any rights Centocor may have under
----------
this Agreement or under applicable law, in the event of the
expiration or termination of this Agreement for any reason, CBSI
agrees to return to Centocor within ninety (90) days of
termination of this Agreement all Manufacturer's Working Cell
Banks, Drug Substance, Equipment and XXXXXX in CBSI's possession,
provided that, in the event that Centocor, at its sole
discretion, elects not to have some or all of the Equipment
returned to it after expiration or termination of this Agreement,
CBSI may purchase such Equipment from Centocor at a commercially
reasonable price that is mutually agreeable to CBSI and Centocor.
Shipping, insurance and other costs of transportation shall be
borne by Centocor. CBSI agrees to work with Centocor for a period
of up to two (2) years to effect an orderly termination of this
Agreement, as may be reasonably requested by Centocor, including
without limitation, the return of Confidential Information.
25.7 Transition Costs. In the event that CBSI terminates this
----------------
agreement without cause, CBSI will pay all reasonable costs for
transitions incurred by Centocor and CBSI during the transition
period. In the event that CBSI terminates this Agreement with
cause, Centocor will pay all reasonable costs for transition
incurred by Centocor and CBSI during the transition period. In
the event that Centocor terminates this Agreement for cause, CBSI
will pay all reasonable costs incurred by Centocor and CBSI for
transition during the transition period. In the event that
Centocor terminates this Agreement without cause, Centocor will
pay all reasonable costs incurred by Centocor and CBSI for the
transition period. If the parties mutually agree to terminate
this Agreement, the reasonable costs for transition shall be
shared equally by Centocor and CBSI.
26. Independent Contractor Status. The relationship of Centocor and CBSI
-----------------------------
established by this Agreement is that of independent contractors, and
nothing contained in this Agreement shall be construed to: (i) give
either Party the power to direct or control the day to day activities
of the other; (ii) constitute the Parties as partners, joint-ventures,
co-owners or otherwise as participants in a joint or common
undertaking; or (iii) allow a Party to create or assume any obligation
on behalf of the other Party for any purpose whatsoever. Nothing in
this Agreement will give rise to the creation of any labor relation by
or between either Party and any employees of the other Party.
38
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
27. Assignability.
-------------
27.1 Centocor. Centocor may, without the prior consent of CBSI, assign
--------
this Agreement or any of its rights or obligations hereunder to
any parent, subsidiary or Affiliate of Centocor. Such assignee
may, without the prior written consent of CBSI, assign this
Agreement or any of the rights or obligations hereunder back to
Centocor or to any parent, subsidiary or Affiliate of Centocor.
27.2 CBSI. Neither this Agreement nor any of the rights or obligations
----
hereunder shall be assignable or otherwise transferable by CBSI
without the prior written consent of Centocor, such consent not
to be unreasonably withheld.
27.3 Permitted Assigns and Successors. This Agreement shall be binding
--------------------------------
upon, and inure to the benefit of, the permitted assigns and
successors of the Parties hereto.
28. Force Majeure.
-------------
28.1 Force Majeure Defined. Neither CBSI nor Centocor are liable to
---------------------
perform any of its obligations in so far as it proves to the
other Party:
(i) that the failure was due to an occurrence beyond the
control of the Party affected including but not limited to
acts of God, fire, explosion, weather, disease, war,
insurrection, riot, government action or power failure; and
(ii) that it could not reasonably be expected to have taken into
account the occurrence and the effects of the occurrence
upon its ability to perform at the time of the acceptance
of a Purchase Order; and
(iii) that it could not reasonably have avoided or overcome the
occurrence or at least its effects.
28.2 Force Majeure Limited. No Party shall have the right to avail
---------------------
itself of this article in the event the force majeure occurrences
arises from an act or from any negligence of that Party.
39
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
28.3 Excused from Performance. Either Party shall upon written notice
------------------------
to the other Party be excused from performance of its obligations
under the Agreement only for so long as force majeure may
continue.
28.4 Bear Own Cost. Each Party shall bear its own costs arising out of
-------------
or resulting from the occurrence of any force majeure event.
28.5 Adjustment of Forecast. As soon as the force majeure situation
----------------------
has ended, or as earlier as is feasible, the rolling forecast for
at least the next four (4) Calendar Quarters shall be adjusted in
good faith with the other Party.
28.6 XXXXXX
29. Miscellaneous Provisions.
------------------------
29.1 Limitation of Damages.
---------------------
(a) Development Phase. Centocor shall not be entitled to
-----------------
Special Damages arising in connection with a breach of,
negligent performance of and/or failure to perform of
CBSI's obligations under this Agreement, the Scope of
Work or any documents or attachments with regard thereto
to the extent such breach, negligence or failure to
perform directly relate to and occur during the
Development Phase.
XXXXXX
XXXXXX
40
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
29.2 Dispute Resolution.
------------------
(a) Senior Executive Meeting. In the event any dispute shall
------------------------
arise between Centocor and CBSI with respect to any of the
terms and conditions of this Agreement, then the Executive
Liaisons of Centocor and CBSI shall meet as promptly as
practicable after notice of such dispute to resolve in good
faith such dispute.
(b) Arbitration.
-----------
(i) If Centocor and CBSI are unable to resolve
satisfactorily the dispute, then such dispute shall be
settled by arbitration conducted in the English language in
accordance with the Commercial Arbitration Rules of the
American Arbitration Association (the "AAA"). The
arbitration shall be conducted by one arbitrator chosen by
mutual agreement of the Parties. If the Parties are unable
to agree on an arbitrator, they shall each pick one
arbitrator and the two arbitrators shall choose a third
arbitrator. The Parties will cooperate with each other in
causing the arbitration to be held in as efficient and
expeditious manner as practicable. Discovery in such
arbitration shall be conducted in accordance with the
Federal Rules of Civil Procedure and shall be completed
within one year after initiation of the arbitration. Any
arbitration proceeding instituted by a Party under this
Agreement shall be brought in Philadelphia, Pennsylvania.
(ii) Any award rendered by the arbitrator(s) shall be
final and binding upon the Parties hereto. Such award shall
be issued by the arbitrators no later than two years after
initiation of arbitration. Judgment upon the award may be
entered in any court of record of competent jurisdiction.
Each party shall pay its own expenses of
41
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
arbitration and the expenses of the arbitrator(s) shall be
equally shared unless the arbitrator(s) assesses as part of
his, her or their award all or any part of the arbitration
expenses of one Party (including reasonable attorney's fees)
against the other Party. Punitive damages shall not be
awarded to either party.
(iii) Centocor and CBSI irrevocably and
unconditionally consent to the jurisdiction of any such
proceeding and waives any objection that it may have to
personal jurisdiction or the laying of venue of any such
proceeding.
29.3 Notices. Any notice or other communication hereunder shall be in
-------
writing and shall be deemed given when so delivered in person, by
facsimile, by overnight courier (with receipt confirmed) or, if
given by mail, upon receipt, as follows (or to such other persons
and/or addresses as may be specified in writing to the other
Party hereto);
If to Centocor, to: Centocor, Inc.
000 Xxxxx Xxxxxx Xxxxxxx
Xxxxxxx, XX 00000
Attn: Corporate Secretary
Facsimile: 000-000-0000
With a copy to: Vice President, Worldwide Operations
If to CBSI, to: CBSI Covance Biotechnology Services Inc.
0000 Xxxxxx Xxxxx Xxxx Xxxxx
P.O. Box 13865
Research Xxxxxxxx Xxxx, XX 00000-0000
Attn: President
Facsimile: 000-000-0000
With a copy to: Senior Vice President, Commercial
Development
29.4 Entire Agreement and Modification. This Agreement together with
---------------------------------
the Exhibits hereto, constitutes the entire Agreement between the
Parties hereto and supersedes any previous agreements or
understandings whether oral or written. In the event of a
conflict between this Agreement and any of the Exhibits hereto,
the provisions of this Agreement shall be valid and binding on
each Party.
42
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
29.5 Invalid Clauses. If a judicial determination is made that any of
---------------
the provisions contained in this Agreement constitute an
unreasonable restriction against any Party or are otherwise
unenforceable, such provision or provisions shall be rendered
void or invalid only to the extent such judicial determination
finds such provision or provisions to be unreasonable or
otherwise unenforceable, and the remainder of this Agreement
shall remain operative and in full force and effect.
29.6 Headings. The headings, contained in this Agreement are inserted
--------
for convenience only and shall not be construed to limit or
otherwise modify its provisions.
29.7 Governing Law. This Agreement shall be governed by and
-------------
interpreted in accordance with the laws of the Commonwealth of
Pennsylvania, without regard to its choice of law principles.
29.8 Continuing Liability. Expiration or termination of this Agreement
--------------------
for any reason shall not release either Party from any liability,
obligation or agreement which has already accrued nor affect the
survival of any provision hereof which is expressly stated to
survive such termination. Termination of this Agreement for any
reason shall not constitute a waiver or release of, or otherwise
be deemed to prejudice or adversely affect any right, remedies or
claims, whether for damages or otherwise, which a Party may have
hereunder or which may arise out of or in connection with such
termination.
29.9 Survival. Notwithstanding any such termination, the obligations
--------
of the Parties in Sections 12.3, 13.6, 18, 20, 21, 23, 25.4,
25.5, 25.6, 25.7 and 29 of this Agreement and the Quality
Requirements shall survive termination of this Agreement.
29.10 Language. This Agreement is in the English language, which
--------
language shall be controlling in all respects, and all versions
hereof in any other language shall be for accommodation only and
shall not be binding upon the parties hereto. All communications
and notices to be made or given pursuant to this Agreement shall
be in the English language.
29.11 Publicity. Except as otherwise provided in Section 21, neither
---------
Party shall disclose this Agreement or any of the terms thereof
to any third party except a Party's independent auditors and
counsel, whether in writing or orally, without the prior written
consent of the other Party. Either Party may make disclosure if
but only to the extent such disclosure is, on advice of counsel,
required by
43
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
applicable law. The disclosing Party shall use all commercially
reasonable efforts to preserve the confidentiality of this
Agreement and the terms thereof notwithstanding any such required
disclosure, and will give the other Party written notice of such
required disclosure as reasonably far in advance thereof as is
practical. In the event either Party is required to file this
Agreement with the Securities and Exchange Commission or any
other regulatory agency, such Party shall apply for confidential
treatment of this Agreement to the fullest extent permitted by
law, shall provide the other Party a copy of the confidential
treatment request far enough in advance of its filing to give the
other Party a meaningful opportunity to comment thereon, and
shall incorporate in such confidential treatment request any
reasonable comments of the other Party. Notwithstanding the
foregoing, Centocor may disclose the terms of this Agreement to
the Trustee.
29.12 Remedies Not Exclusive. The rights and remedies contained in
----------------------
this Agreement are cumulative and are not intended to waive or
preclude any other claims, rights or remedies which may exist at
law (whether statutory or otherwise) or in equity with respect to
the matters covered hereby.
IN WITNESS WHEREOF, and intending to be bound hereby, Centocor and CBSI have
------------------
caused this Agreement to be executed.
CENTOCOR, INC. COVANCE BIOTECHNOLOGY
SERVICES, INC.
MPR /s/ Xxxxxx X. Xxxxxxx /s/ V. Xxxxx Xxxxxx, Ph.D.
------------------------- --------------------------
Xxxxxx X. Xxxxxxx V. Xxxxx Xxxxxx, Ph.D.
President and Chairman XXXXXX
Chief Operating Officer Covance Biotechnology Services, Inc.
Centocor, Inc.
Date: 1/14/99 Date: 1/15/99
---------------- ------------------
44
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
Exhibit A: XXXXXX
---------
Exhibit B: Quality Requirements for the Manufacture and Supply of Retavase(TM)
--------- Drug Substance, including six (6) Attachments for the Drug
Substance:
Attachment 1: XXXXXX
Attachment 2: XXXXXX
Attachment 3: Authorized Representatives of the Parties
Attachment 4: XXXXXX
Attachment 5: XXXXXX
Attachment 6: XXXXXX
Exhibit C: XXXXXX
---------
Exhibit D: XXXXXX
---------
Exhibit E: XXXXXX
---------
Exhibit F: XXXXXX
---------
45
Confidential Treatment Requested
Exhibit A
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 2 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 3 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 4 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 5 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 6 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 7 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 8 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 9 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 10 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 11 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 12 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 13 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 14 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 15 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 16 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 17 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 18 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 19 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 20 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 21 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 22 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 23 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 24 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 25 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
PAGE 26 OF 26
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
Exhibit B
Quality Requirements for the Manufacture
and Supply of Retavase/TM/ Drug Substance
1. Definitions
Unless otherwise defined herein, all definitions used within these Quality
Requirements have the same meaning as defined in the Development and
Manufacturing Services Agreement between Centocor and CBSI dated as of December
31, 1998 (the "Agreement").
These Quality Requirements for the Manufacture and Supply of Drug Substance
XXXXXX are an integral and enforceable part of the Agreement. They specify the
quality requirements and responsibilities required for the successful and
acceptable Manufacture of the Drug Substance.
2. Manufacturing standards
2.1 Product definition.
Drug Substance will be Manufactured and tested in accordance with the
manufacturing Batch Records and test methods which will be generated by
CBSI and approved by Centocor.
2.2 Supply of Active Ingredient.
Centocor will provide CBSI with the Materials and Equipment stated in
Section 3 of the Agreement. CBSI will supply all other Materials for the
Manufacture of Drug Substance including, but not limited to, those items
designated in XXXXXX CBSI will only use Materials which have been released
by its QA department. CBSL will take samples of all materials and store
such samples for a minimum of two years after the date the sample was
taken, or for a longer period, as reasonably requested by Centocor.
2.3 Batch numbering.
CBSI will assign batch numbers for the Drug Substance upon completion of
and prior to delivery to Centocor in accordance with SOPs.
/s/ MPR JCS /s/ VBL
------------- ---------
JCS VBL
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
2.4 Processing responsibilities.
CBSI will Manufacture and inspect the Drug Substance in strict accordance
with cGMP, as set forth in 21 CER 211, as amended and updated from time to
time, as well as the HPB Guide to GMP, and all other appropriate Regulatory
Requirements.
2.5 Reprocessing.
CBSI shall not reprocess a Batch without the prior written consent of an
Authorized Representative of Centocor. Reprocess shall mean introducing an
intermediate or active pharmaceutical ingredient that does not conform to
established standards of specifications back into the process repeating a
step that it part of the Validated Manufacturing process. The Authorized
Representatives for Centocor and CBSI are listed in Attachment 3, which
------------
Attachment is incorporated herein by reference. Changes in the Authorized
Representatives may be made by each Party with prior written notice to the
other Party. CBSI shall not rework a Batch under any circumstances.
2.6 XXXXX
3. Testing
3.1 General Testing.
The Drug Substance will be tested by CBSI in accordance with the Validated
and cross Validated test methods which will be written by CBSI and approved
by Centocor Quality Product Development and Operation representatives in
accordance with the provisions in Attachment 2.
------------
3.2 Provision of Samples to Centocor.
In the event that Centocor requests samples of the Drug Substance and/or
supplies of in-process materials for testing and/or storage, they will be
shipped by CBSI to Centocor under the shipping conditions specified in the
SOP for shipping the Drug Substance.
3.3 Expiry dating.
CBSI will issue the expiration date for the Drug Substance based upon its
currently approved shelf life. The expiry date will be printed in the
format MMMYY for each batch of Product, e.g., Mar 99. The approved
abbreviations are:
2
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
JAN = January; FEB = February; MAR = March;
APR = April; MAY = May; JUN = June;
JUL = July; AUG = August; SEP = September;
OCT = October; NOV = November; DEC = December.
3.4 Packaging Specification
Labeling and packaging of Drug Substance will comply with the Batch Record,
SOPs and as provided in Section 5.5 of the Agreement.
4. Quality Responsibilities
4.1 Process deviations.
Any major unplanned deviations in Manufacture learned by CBSI after
occurrence at the CBSI facilities shall be reported to Centocor's
Authorized Quality Representative immediately. This includes non-conforming
test results. CBSI will provide Centocor's Authorized Quality
Representative a copy of all major deviations immediately via facsimile.
Centocor will make every reasonable effort to review a temporary change
request or quality deviation within five working days, either giving
approval or disapproval to proceed to CBSI or requesting additional
information. Centocor QA will review all deviations as part of the release
process. The resolutions of the deviations must be approved by Centocor's
Authorized Quality Representatives.
4.2 Changes to the Manufacturing Process
CBSI will not make any material changes relating to the Drug Substance
without obtaining the Centocor Quality and Operations Representatives'
prior written approval. A material change is defined as any change that a)
impacts the regulatory commitments for the Drug Product; b) may require
revalidation; c) may affect the quality, purity, identity or strength of
the Drug Product; d) would result in changing or modifying Centocor's or
CBSI's Specifications, test methods, SOPs or Batch worksheet relating to
the Drug Substance and/or (e) that is otherwise listed in Section 11 of the
Agreement. Centocor will have access to all documentation upon request.
4.3 Changes to Quality Requirements
These Quality Requirements or any part of them may be changed by the signed
and dated written agreement of the Parties, such Parties to include from
Centocor the Centocor Authorized Quality Representatives and the Authorized
Operations Representatives.
4.4 Quality Review
CBSI will provide Centocor's Authorized Quality Representative with a
written annual summary of the Manufacture of the Drug Substance in a format
acceptable to Centocor to assess compliance with Specifications at end of
shelf life.
3
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
4.5 Documentation
4.5.1 Transmission of documentation.
CBSI will send the appropriate Batch documentation and a certificate of
analysis for the Batch to the Centocor Authorized Quality Representative
for review within five business days after CBSI approval of the
Manufacture of the Batch. The documentation will include the data from
the sterility test, Quality Control testing, Batch Records and all
relevant deviations or investigations as applicable.
4.5.2 Statement of release.
Upon release of a Batch, the Centocor Authorized Quality Representative
will provide CBSI with a Release statement.
4.5.3 Retention of records.
Records relating to Manufacture shall be maintained by CBSI in accordance
with Section 12.3 of the Agreement.
4.5.4 Approval of CBSI documentation.
CBSI will provide its own SOPs, manufacturing and testing documentation
which will be approved by Centocor's Authorized Quality and Operation
Representatives before use by CBSI in the Manufacture. All CBSI SOPs
relating to the Manufacture of Drug Substance will be made available to
Centocor for inspection and copying upon request by Centocor.
4.6 Access by Centocor Representative
Upon Centocor's request, CBSI will permit Centocor to have one or more
representatives present in the Facility to observe Manufacture of Drug
Substance in accordance with Section 12 of the Agreement.
4.7 Performance of Quality Audits.
CBSI will also permit Centocor's Authorized Quality Representatives to
enter CBSI's Facility upon reasonable notice and at reasonable intervals
during regular business hours for the purpose of performing quality
audits of the facilities used in the Manufacture, storage, analysis and
shipping of the Drug Substance, in accordance with and as otherwise
provided in Section 12 of the Agreement.
5. Shipping and Transport of Product.
CBSI will pack Drug Substance according to Centocor's approved
Specifications and SOPs and label the shipping container with Drug
Substance name, lot number, container number, manufacturing date and
expiration date. CBSI will ship Drug Substance according to procedures
that are approved by Authorized Quality and Operation Representatives of
Centocor. Shipping must be arranged so that delivery occurs during normal
working hours on Monday, Tuesday, Wednesday or Thursday,
4
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
unless previously agreed to in writing by an authorized representative of
Centocor's Worldwide Operations Group. Shipping will be by road in a
dedicated refrigerated truck when the destination is within the United
States of America. To other destinations, shipping will be by air and in
approved packaging. XXXXXX
6. Regulatory Inspections
6.1 Notification of regulatory inspections.
CBSI will notify Centocor and Centocor will notify CBSI immediately of
any regulatory inspections that involve Drug Substance. Both Parties will
notify each other of any issues that affect regulatory approval, filings,
or continued supply of Drug Substance. If desired by Centocor, an
Authorized Quality Representative may attend any regulatory inspection
that applies to Drug Substance.
6.2 Review of regulatory findings.
CBSI agrees that Centocor may review and approve on all regulatory
filings or communications between CBSI and a regulatory agency that
directly affect Centocor's Drug Substance or Drug Product Registration.
6.3 Regulatory Agency access to Facility.
CBSI will allow access to its Facility to a regulatory agency in
accordance with Section 13 of the Agreement.
7. Term and Termination
These Quality Requirements shall begin on the Effective Date of the
Agreement and will remain in force throughout the duration of the
Agreement. If the Agreement is terminated for any reason, those articles
required by cGMP will remain in force for the time stipulated, unless
otherwise agreed in writing between the Authorized Quality
Representatives.
8. Communication
All communication affecting the Quality Requirements shall be between the
Authorized Quality Representatives, except as otherwise stated in the
Agreement.
5
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
9. Conflict Resolution
Any disputes or conflicts relating to these Quality Requirements will be
resolved by CBSI and Centocor Authorized Quality Representatives in a
timely and equitable manner and in compliance with all applicable
Regulatory Requirements and in accordance with cGMP. Such resolutions
shall be in writing and will be signed by a CBSI and Centocor Authorized
Representatives. If any issue remains unresolved for more than 30 days,
the senior corporate representatives from each Party will meet to resolve
the issue. If resolution remains unattainable for an additional 30 days,
then the issue will be resolved in accordance with Section 29.2 of the
Agreement.
6
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
7
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
Attachment 2
Method of Manufacture for Drug Substance
Drug Substance will be Manufactured according to Batch records written by CBSI
and approved by Centocor. Other Production documents required for Manufacture
include but are not limited to those set forth in XXXXXX
8
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
Attachment 3
Authorized Representatives of the Parties
The following represents the list of people allowed to approve changes to these
Quality Requirements ("Authorized Representatives"). Any change must be signed
by at least one Centocor Authorized Quality Representative and one Centocor
Authorized Operation Representative.
CENTOCOR
--------
Centocor Quality Representatives
--------------------------------
XXXXXX
XXXXXX
XXXXXX
Centocor Authorized Representatives
-----------------------------------
XXXXXX
XXXXXX
XXXXXX
Centocor Operations Representatives
-----------------------------------
XXXXXX
XXXXXX
XXXXXX
XXXXXX
XXXXXX
XXXXXX
9
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
CBSI
----
CBSI Quality Representatives
----------------------------
XXXXXX
XXXXXX
CBSI Authorized Representatives
-------------------------------
XXXXXX
XXXXXX
CBSI Operation Representatives
------------------------------
XXXXXX
XXXXXX
XXXXXX
XXXXXX
XXXXXX
XXXXXX
10
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
11
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
12
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
***CONFIDENTIAL ***
XXXXXX
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
***CONFIDENTIAL ***
XXXXXX
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
***CONFIDENTIAL***
XXXXXX
[signature]
---------------
Signature
***FOR INFORMATIONAL USE ONLY***
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
Attachment 6
Storage Conditions for Drug Substance
According to approved Centocor procedures.
13
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
/s/ MPR - JCS /s/ VBL
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JCS VBL
Confidential Treatment Requested
THE REGISTRANT HAS REQUESTED CONFIDENTIAL TREATMENT FOR CERTAIN PORTIONS OF THIS
AGREEMENT. THOSE PORTIONS HAVE BEEN OMITTED FROM THIS COPY OF THE AGREEMENT AT
THE PLACES INDICATED BY (XXXX); AND HAVE BEEN FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION
XXXXXX
/s/ MPR - JCS /s/ VBL
---- ----
JCS VBL
Confidential Treatment Requested
