Exhibit 10.325

 

CONFIDENTIAL

 

REDACTED VERSION

 

[***] CERTAIN INFORMATION IN THIS EXHIBIT HAS BEEN OMITTED AND FILED SEPARATELY
WITH THE COMMISSION.  CONFIDENTIAL TREATMENT HAS BEEN REQUESTED WITH RESPECT TO
THE OMITTED PORTIONS.

 

AGREEMENT

 

THIS AGREEMENT is made effective as of the 1st day of July, 2003 (the “Effective
Date”), between The American National Red Cross, a not-for-profit corporation
chartered by an act of Congress, 36 U.S.C. § 30010 et seq., having a principal
place of business at 2025 E Street, NW, Washington, DC 20006-5009 (“ARCHQ”), and
Chiron Corporation, a Delaware corporation (“Chiron”) having its offices at 4560
Horton Street, Emeryville, California 94608-2916 (the “Agreement”).

 

Background

 

WHEREAS, ARCHQ, operating through its Biomedical Services division (“ARC”)
provides, inter alia, blood services, including the collection of blood from
donors, and the screening, packaging and distribution of blood, blood components
and derivatives to those in need of such services;

 

WHEREAS, ARC currently screens for itself and for other blood banks in the
United States, human blood samples for viruses such as Human Immunodeficiency
Virus type-1 (“HIV-1”) and Hepatitis C Virus (“HCV”) by performing screening,
including without limitation amplified nucleic acid screening, in five (5) of
its national testing laboratories located in San Diego, Detroit, St. Louis,
Charlotte and Philadelphia and as further identified on Schedule 1.26 (each, an
“NTL”, and collectively, the “NTLs”);

 

WHEREAS, Chiron and ARCHQ are parties to that certain Sale and Servicing
Agreement effective as of August 1, 2002 (the “2002 Agreement”), pursuant to
which Chiron sells to ARC, and ARC purchases from Chiron, certain assays and
blood screening instruments to conduct nucleic acid amplification screening to
detect the presence of certain viruses in blood, including HIV-1 and HCV;

 

WHEREAS, Chiron, together with its collaboration partner, Gen-Probe Incorporated
(“Gen-Probe”), is developing an assay which can be used to conduct amplified
nucleic acid tests to detect the West Nile Virus in pooled and single donor
blood samples (the “WNV Assay”);

 

WHEREAS, substantial further development and testing of the WNV Assay is
necessary before Chiron and Gen-Probe may seek to obtain FDA approval for the
commercial distribution and use of such WNV Assay;

 

WHEREAS, the costs and efforts required for such further development and testing
far exceed those that Chiron and Gen-Probe will undertake without assistance and
collaboration from other entities, and the absence or delay of such assistance
and collaboration of those entities would significantly delay the further
development and testing, and, thus, the commercial availability of the WNV Assay
in the Territory;

 

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WHEREAS, the rapid development and availability of the WNV Assay for the testing
of blood donations is of critical importance to ARC’s mission and obligation to
ensure the safety of the blood products it manufactures, and to the protection
of the public health;

 

WHEREAS, ARC desires to collaborate with and support Chiron and Gen-Probe in the
further development and testing of the WNV Assay necessary for obtaining FDA
approval or licensing for commercial distribution of the WNV Assay, subject to
the terms and conditions stated below:

 

NOW, THEREFORE, in consideration of the foregoing premises and of the mutual
covenants of the Parties hereinafter contained, the Parties hereto hereby agree
as follows:

 

ARTICLE 1 - DEFINITIONS

 

Capitalized terms used and not otherwise defined in this Agreement shall have
the following meanings:

 

1.1                                 “2002 Agreement” shall mean that certain
Sale and Servicing Agreement effective as of August 1, 2002, between ARCHQ and
Chiron pursuant to which Chiron sells to ARC, and ARC purchases from Chiron,
certain assays and blood screening instruments to conduct nucleic acid
amplification screening to detect the presence of certain viruses in blood,
including HIV-1 and HCV.

 

1.2                                 “Affiliate” shall mean, with respect to any
specified Person, any other Person which directly or indirectly controls, is
controlled by, or is under common control with, the specified Person.  For
purposes of this definition, the term “control” shall mean (i) ownership
interests representing more than fifty percent (50.0%) of the equity or more
than fifty percent (50.0 %) of the ordinary voting power or more than fifty
percent (50.0%) of the general partnership interests are, at the time such
determination is being made, held, directly or indirectly, by such Person, or
(ii) whether used as a noun or verb, refers to the possession, direct or
indirect, of the power to direct, or cause the direction of, the management or
policies of any Person, whether through the ownership of voting securities, by
contract or otherwise.

 

1.3                                 “Agreement” shall have the meaning set forth
in the introductory paragraph of this agreement.

 

1.4                                 “Amended Order Request” shall have the
meaning set forth in Section 2.5(b).

 

1.5                                 “ARC Fiscal Year” shall mean each July 1 to
June 30.

 

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1.6                                 “ARC Indemnitees” shall have the meaning set
forth in Section 7.5.

 

1.7                                 “Blood Screening Field” shall mean the
nucleic acid probe-based screening of (i) human blood, recovered and voluntary
source plasma, platelets or other blood products intended for transfusion or
other administration to humans, including autologous donors and (ii) recovered
and voluntary source plasma for further manufacture, but specifically excluding
paid source plasma intended for further manufacture.

 

1.8                                 “Blood Screening Systems” shall mean the
instrument(s) and the related software for DNA/RNA amplified assay processing
purchased by ARC from Chiron under the 2002 Agreement, including the Software
acquired by ARC under this Agreement.

 

1.9                                 “Chiron Indemnitees” shall have the meaning
set forth in Section 7.6.

 

1.10                           “Confidential Information” means any and all
technical, business and other information and materials disclosed by or on
behalf of one Party to the other Party pursuant to this Agreement or during
discussions leading to the execution of this Agreement, except to the extent
that the receiving Party can provide evidence that such information:

 

(a)                                  is known to the receiving Party prior to
its disclosure by the disclosing Party; or

 

(b)                                 is obtained by the receiving Party from a
source other than the disclosing Party which source (i) did not require the
receiving Party to hold such information in confidence; or (ii) did not limit or
restrict the receiving Party’s use thereof, or

 

(c)                                  has become public knowledge otherwise than
through the fault of the receiving Party; or

 

(d)                                 has been developed by the receiving Party
independently of the information received from the disclosing Party as shown by
the receiving Party’s written records; or

 

(e)                                  is required to be disclosed by the
receiving Party by law or for the purpose of complying with governmental
regulations and/or the obligations of the receiving Party to a licensing or
regulatory authority in connection with this Agreement, provided the receiving
Party provides the disclosing Party with prompt notice of such disclosure so
that the disclosing Party has the opportunity to seek a protective order or
other appropriate remedy.

 

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1.11                           “Damages” means any liability for bodily injury,
death or property damage (whether arising out of fault, strict liability or
otherwise) in the form of an obligation, loss, fine, judgment for damages,
arbitration award, settlement amount, penalty or claim, and all reasonable costs
and expenses related thereto (including reasonable costs of investigation, fees
and expenses payable to outside counsel, independent accountants and similar
professional advisors or consultants, but not including any corporate allocation
for use, of similar in-house services or facilities).

 

1.12                           “Data” shall have the meaning set forth in
Section 6.7.

 

1.13                           “Documentation” shall mean text material,
including the Package Insert and Software manuals, that describes the design,
functions, operation, or use of the WNV Assays and related Software, that is
delivered by Chiron to ARC.  Documentation for the Software shall be the same
that is provided to licensees of such Software generally.

 

1.14                           “Effective Date” means the date set forth in the
introductory paragraph on the first page of this Agreement.

 

1.15                           “Enhancement” means an alteration or addition to
a Product [***], for which a separate fee will be imposed.

 

1.16                           “FDA” shall mean the United States Food and Drug
Administration, or any successor entity thereto.

 

1.17                           “Force Majeure Event” shall have the meaning set
forth in Section 9.1.

 

1.18                           “Gen-Probe” shall mean Gen-Probe Incorporated, a
Delaware corporation.

 

1.19                           “HCV” means the Hepatitis C virus.

 

1.20                           “HIV-1” means Human Immunodeficiency virus type
1.

 

1.21                           “Indemnifying Party” shall have the meaning set
forth in Section 7.8.

 

1.22                           “Indemnitee” shall have the meaning set forth in
Section 7.8.

 

1.23                           “IP Claim” shall have the meaning set forth in
Section 7.7(a).

 

1.24                           “IQA Procedures” shall have the meaning set forth
in Section 2.6.

 

1.25                           “Modified Order” shall have the meaning set forth
in Section 2.5(c).

 

1.26                           “Multi-Flavivirus Assay” means a nucleic acid
probe assay that is capable of detecting the presence of more than one member of
the

 

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Japanese encephalitis virus complex (which includes St. Louis Encephalitis,
Kunjin, Japanese encephalitis, Murray Valley encephalitis viruses, among others)
and/or the Dengue virus, for use in the Blood Screening Field, and which assay
shall have [***].

 

1.27                           “Normal Support Hours” shall have the meaning set
forth in Schedule 4.0, paragraph 2.4.

 

1.28                           “NTLs” means ARC’s national testing laboratories
identified on Schedule 1.26.

 

1.29                           “Outbreak Testing” means screening of samples
from up to [***] individual blood donations in each of the first and second
twelve Testing Months during the Term using a WNV Assay in Single Unit Testing
format, where such Single Unit Testing is determined by ARC to be necessary for
any reason, e.g., regional outbreaks of the West Nile Virus.

 

1.30                           “Package Insert” shall mean the draft package
insert to be submitted to the FDA for approval for the applicable WNV Assay and
attached to Schedule 2.0, as the same may be amended from time to time.

 

1.31                           “Panel” shall have the meaning set forth in
Section 12.4.

 

1.32                           “Party” or “Parties” means Chiron, ARC or Chiron
and ARC, respectively.

 

1.33                           “Person” shall mean an individual, corporation,
partnership, limited liability company, trust, business trust, association,
joint stock company, joint venture, pool, syndicate, sole proprietorship,
unincorporated organization, governmental authority or any other form of entity
not specifically listed herein.

 

1.34                           “Pooled Testing” means the conduct of screening
of pools of samples from blood donations, including allogenic and autologous
donors, generally consisting of:

 

(a)                                  [***] and

 

(b)                                 [***]

 

1.35                           “Products” shall mean WNV Assay and related
Software.

 

1.36                           “Reagent Utilization Factor” means, with respect
to a specified time period, the [***].

 

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1.37                           “Regulations” shall mean all applicable and then
current laws, requirements, regulations, standards, Package Insert, and
directives, promulgated by the FDA or any other state or federal authorities.

 

1.38                           “Reportable Result” means a result obtained
through the use of a WNV Assay and Blood Screening System from which it is
determined to release for use or hold and not use (a) a blood donation intended
for transfusion or for further processing for other administration to humans or
(b) a product derived from such donation.

 

1.39                           “Requirement” shall have the meaning set forth in
Schedule 4.0, paragraph 3.3.

 

1.40                           “Rush Order” shall have the meaning set forth in
Section 2.5(d).

 

1.41                           “Services” shall have the meaning set forth in
Article 4.

 

1.42                           “Single Unit Testing” means screening of blood
donations consisting of (i) screening a sample from each individual blood
donation using a WNV Assay, including allogenic and autologous donors, (ii)
screening of individual samples relating to tissue and/or organ donation and
(iii) follow up repeat testing of positive results.

 

1.43                           “Software” means the following software programs,
including any subsequent Upgrades released during the Term of this Agreement
that ARC elects to acquire pursuant to this Agreement, but specifically
excluding NAT Tracker:

 

Procleix® WNV Assay Software, Version 2.0.1.0

 

1.44                           “Specifications” shall mean with respect to each
Product, the specifications, tests, procedures, process description, storage and
handling requirements and other information relating to such Product and packing
thereof prepared by Chiron, its Affiliates, Gen-Probe or other Third Party
manufacturers provided to ARC by Chiron under separate cover, including without
limitation such information contained within the Documentation, which may be
amended from time to time by Chiron after as much advance written notice to ARC
of such amendment as is reasonably practicable is given; provided, however that
the foregoing information shall be consistent with the IND and/or other
information required by the Regulations of each of Chiron and Gen-Probe, or any
of their respective Affiliates, in connection with their performance under this
Agreement.

 

1.45                           “Standing Order” shall have the meaning set forth
in Section 2.5(b).

 

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1.46                           “Technologists” means the employees of ARC
trained at a facility of ARC by either a Trainer or Chiron technical
representative.

 

1.47                           “Term” shall have the meaning set forth in
Section 8.1.

 

1.48                           “Territory” means the United States of America,
including Puerto Rico, Guam and all other protectorates of the United States.

 

1.49                           “Testing Month” means a calendar month during
which ARC makes use of the Products to generate Reportable Results for [***] of
the blood donations screened by ARC during such month for HCV and HIV-1 under
the 2002 Agreement.

 

1.50                           “Third Party” shall mean any Person other than
ARC, and Chiron.

 

1.51                           “Trainer” shall mean an employee of ARC trained
by Chiron to perform troubleshooting, training of Technologists and such other
services to ARC as set forth in the “Train the Trainer” program referenced in
paragraph 2.2 of Schedule 4.0.

 

1.52                           “Upgrades” means (i) changes to a Product that
are made available to correct design faults, discrepancies or defects (so called
“bugs”), (ii) alterations to a Product [***], for which a separate charge will
not be imposed and (iii) changes to a Product that are mandated by the FDA.

 

1.53                           “West Nile Virus” means a mosquito-borne
flavivirus, classified as a member of the Japanese encephalitis virus complex. 
The virus primarily infects birds, but has been found in several other animal
species, including horses, dogs, alligators and humans.  Humans are a ‘dead-end’
host for the virus, hence the majority of infected humans (~80 %) are
asymptomatic.  Another ~20% of infected individuals develop a mild fibrile
disease, sometimes accompanied by rash.  A final ~1% of all humans infections
result in severe and fatal encephalitis.  The virus has been shown to be
transmissible by blood transfusion or by transplant with infected organs.

 

1.54                           “WNV Assays” shall mean the nucleic acid probe
assays under development by Chiron and Gen-Probe that are provided by Chiron
under this Agreement, which shall be used by ARC in the Territory to screen for
the West Nile Virus in the Blood Screening Field pursuant to this Agreement, and
which assays shall have [***], as defined in the Specimen Collection, Storage
and Handling section of the Package Insert.

 

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ARTICLE 2 - PROVISION OF WNV ASSAYS

 

2.1                                 Supply, Handling and Storage Obligation. 
During the Term of this Agreement Chiron agrees to supply to ARC the WNV Assays
specified on Schedule 2.0 to permit each NTL to conduct screening of blood
donations in the Territory.  ARC agrees to store and handle all WNV Assays in
accordance with the applicable Package Insert and other Specifications.  Any WNV
Assays lost or damaged due to failure to comply with the applicable Package
Insert and such Specifications will be replaced at ARC’s expense.

 

2.2                                 Purchase Obligation.  During the Term of
this Agreement, ARC agrees to acquire from Chiron ARC’s requirements of WNV
Assays in the Territory.  However, nothing in this Agreement will restrict the
right of ARC to evaluate new technologies and products commercially available
from Third Parties or to perform, in its discretion, any confirmatory and
supplementary nucleic acid screening with Third Party products.

 

2.3                                 Packing and Delivery of WNV Assays.  Chiron
shall ensure that all WNV Assays will be suitably packed and transported to
ensure safe transport to ARC in accordance with applicable Specifications and
delivered to ARC’s designated NTL, and each delivery will be accompanied by a
packing slip indicating the quantity delivered, the Product lot number(s) and
the expiration date(s).  WNV Assays will be delivered during normal business
hours and accompanied by storage instructions and arrive at the temperatures
specified in the applicable Specifications or Package Insert.  The WNV Assays
will be delivered in kit form, with appropriate distribution between screening
tests, discriminatory tests and related calibrators.

 

2.4                                 Shipping.  Except as set forth in this
Section 2.4, all shipping, handling and risk of loss charges for the Products
will be borne entirely by Chiron on shipments to the NTLs pursuant to a Standing
Order or a back order and will be shipped, fully insured, to the designated
NTL.  All shipping, handling and risk of loss charges for shipping requests
other than to an NTL as requested by ARC, and all incremental shipping, handling
and risk of loss charges for Modified Orders or Rush Orders, will be borne by
ARC.

 

2.5                                 Forecasts and Orders.

 

(a)                                  ARC will provide Chiron with a written
twelve month forecast by NTL of its requirements of WNV Assays (each a “Product
Requirements Forecast”) for each ARC Fiscal Year during the Term of this
Agreement on or prior to the May 1st immediately prior to the commencement of
such ARC Fiscal Year.  Such Product Requirements Forecasts shall include the
requested delivery dates for WNV Assays for each NTL.  ARC may modify its
Product Requirements Forecasts for any ARC Fiscal Year upon thirty (30) days
advance written notice, provided that if ARC elects to suspend

 

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use of WNV Assays for any period of greater than thirty (30) days, ARC shall
provide not less than ninety (90) days notice.

 

(b)                                 Each month within the then current Product
Requirements Forecast shall constitute a standing order (“Standing Order”) and
may be amended either on a temporary (i.e., with respect to one or two (2)
months) basis by ARC (an “Amended Order Request”).  ARC will provide Chiron as
much advance written notice as reasonably practicable if ARC desires to amend
its Standing Order with an Amended Order Request.

 

(c)                                  If the variance between any Amended Order
Request exceeds [***] of that originally projected in the Standing Order for the
same month(s) in the Product Requirements Forecast (measured on a number of WNV
Assays requested), Chiron will notify ARC within five (5) business days after
receipt of the amendment as to whether it accepts such Amended Order Request and
the delivery date(s) referenced therein.  If Chiron doesn’t respond to an
Amendment Order Request within the five (5) day period, acceptance of the
Amended Order Request shall be presumed by the Parties.  If an Amended Order
Request is accepted unmodified, Chiron agrees to deliver such amounts of WNV
Assays on the delivery date(s) stated therein.  If an Amended Order Request is
not accepted, the Parties will use all commercially reasonable efforts to agree
on modifications to the Amended Order Request (a “Modified Order”), subject to
Gen-Probe’s ability to accommodate Chiron’s requests for changes in forecasted
amounts.  Chiron’s failure, if any, to deliver any volume of WNV Assays in
excess of the Standing Order amount would not constitute a breach by Chiron
under this Agreement, provided that Chiron uses commercially reasonable efforts
to deliver such increased volume in accordance with an accepted Amended Order
Request or Modified Order and notifies ARC in writing as promptly as practicable
of the extent Chiron expects to deliver such increased volume.

 

(d)                                 Shipments of WNV Assays based on Standing
Orders shall be made by Chiron automatically to each NTL every fourteen (14) or
twenty-eight (28) days at the election of each NTL.  Shipments of WNV Assays
pursuant to Standing Orders shall always take place within the first three (3)
days of a calendar week.  These shipment policies may be altered by agreement
between Chiron and any NTL.  From time to time, ARC may request that a portion
of a Standing Order for Products be shipped for the same day or next day
delivery (a “Rush Order”). Chiron shall use commercially reasonable efforts to
ship Rush Orders within twenty-four (24) hours after such request is made.

 

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2.6                                 IQA Procedures.  As of the Effective Date,
Chiron and ARC have reviewed and agreed to adapt and adopt the existing “IQA
Procedures” approved pursuant to the 2002 Agreement for quality assurance
testing of WNV Assays received by ARC and/or any of its NTLs under this
Agreement (“IQA Procedures”).  Chiron and ARC must agree to any modifications to
such IQA Procedures. The IQA Procedures include procedures for testing and
notice to Chiron and for implementing the return of WNV Assays for replacement. 
Chiron agrees to replace, at its sole cost and expense, WNV Assays which fail
the IQA Procedures.  If testing by Chiron or its supplier confirms the
non-conformity of the WNV Assays, Chiron will bear the shipping costs associated
with replacement.  If Chiron’s testing provides reasonably acceptable evidence
that the WNV Assays do conform to their Package Insert, the shipping costs
incurred by Chiron will be reimbursed by ARC.  The principal inspection and
testing and acceptance point by ARC for WNV Assays under this Agreement will
usually be the NTLs.  However, the inspection, testing and acceptance activities
may take place at any point, including Chiron’s facility, with prior notice to
Chiron.

 

2.7                                 Technical Support.  Chiron will provide ARC
with technical support to facilitate the operation by ARC of the WNV Assays on
the Blood Screening Systems in accordance with the terms set forth in
Schedule 4.0.

 

2.8                                 Nature of Screening.  ARC acknowledges that
it has determined, in its sole discretion, to use the WNV Assays supplied by
Chiron to conduct Pooled Testing.  If ARC desires to change from Pooled Testing
to Single Unit Testing or to any other pool size, ARC and Chiron shall enter
into an amendment to this Agreement reflecting any additional instrumentation or
any other amendments that may be applicable by reason of such change.

 

2.9                                 Performance Objectives.

 

(a)                                  Chiron hereby acknowledges that the
accuracy and operational efficiency of blood screening tests is of critical
importance to ARC.  Accordingly, Chiron and ARC have agreed to establish the
certain performance objectives for the Products set forth on Schedule 2.9 hereto
(the “Performance Objectives”).  Chiron and ARC acknowledge the Performance
Objectives set forth on Schedule 2.9 represent Chiron’s expectations regarding
the Products based on results obtained through the use of the Products during
their development.  Accordingly, Chiron does not represent or warrant that the
Products will be capable of achieving the Performance Objectives. 
Notwithstanding the foregoing, Chiron, together with ARC, will monitor the
actual performance of the Products on a quarterly basis throughout the Term
beginning September 1, 2003 as against the Performance Objectives set forth on
Schedule 2.9 (each period, a “Performance Measurement Period”).  [***]

 

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(b)                                 If the FDA requires any greater analytical
sensitivity level than that set forth in the Performance Objectives on
Schedule 2.9, Gen-Probe and Chiron shall take all reasonable steps to attain the
required sensitivity.  If the only reasonable means by which to attain the
required sensitivity is reduced pool size, ARC and Chiron will negotiate in good
faith to achieve reasonable and equitable distribution of the attendant
incremental cost while striving to mitigate costs to either party.

 

ARTICLE 3 -BLOOD SCREENING SYSTEMS; SOFTWARE

 

3.1                                 Blood Screening Systems.

 

(a)                                  General.  The ARC shall use the WNV Assay
only on the Blood Screening Systems purchased and maintained pursuant to the
2002 Agreement.  Chiron bears no responsibility with respect to any use of the
WNV Assays on instrument systems other than the Blood Screening Systems.

 

(b)                                 Upgrades.  All Blood Screening Systems shall
be revised as needed to incorporate Upgrades necessary to perform the WNV Assay
at no additional cost to ARC.  Chiron shall coordinate the installation of
Upgrades with ARC to minimize the impact on ARC’s operations.  If requested by
Chiron, ARC shall return prior versions of Blood Screening Systems to Chiron
within a reasonable period of time following completion of the Upgrade
installation.

 

(c)                                  Warranties.  Use by ARC of the WNV Assay on
the Blood Screening Systems in accordance with this Agreement shall not void the
warranties set forth in Section 3.1(e) of the 2002 Agreement.

 

3.2                                 Software and Documentation.

 

(a)                                  Software.  Chiron agrees to provide to ARC,
at no additional charge, all Software and Documentation necessary to run the WNV
Assays on the Blood Screening Systems as contemplated by this Agreement;
provided, further that Chiron shall make available to ARC, at no additional
cost, all of the same to the extent that any Software has been provided by a
licensor other than Chiron.

 

(b)                                 Title.  Chiron, or the applicable licensor
of the Software to be provided hereunder, shall own and retain title to the
Software, including all intellectual property rights embodied therein.  Any copy
which ARC makes of the Software, in whole or in part, is and shall

 

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remain the property of Chiron or the applicable licensor. If ownership of the
Software or any work product does not result as provided in this Agreement or by
operation of law, then the Parties each assign and shall cause their respective
employees, agents, and contractors to assign, without further consideration, the
ownership thereof, including all associated intellectual property rights, as
necessary to give effect to the ownership terms specified in this Agreement. 
Each Party agrees to perform, at the reasonable request of the other Party, such
further acts as may be necessary or desirable to transfer ownership of, and to
perfect and defend, the Software in order to give effect to such ownership
terms.

 

(c)                                  Upgrades.  All Software shall be revised as
needed to incorporate Upgrades at no additional cost to ARC.  Chiron shall
coordinate the installation of Upgrades with ARC to minimize the impact on ARC’s
operations.  If requested by Chiron, ARC shall return prior versions of Software
to Chiron within a reasonable period of time following completion of the Upgrade
installation.

 

(d)                                 License.  Chiron hereby grants, and ARC
hereby accepts, subject to the terms and conditions of this Agreement, a
nonexclusive, nontransferable and nonassignable (except as permitted under this
Agreement) object code license (or sublicense, as applicable) to use the
Software at the NTLs solely for ARC’s own use in connection with the operation
of the WNV Assays on the Blood Screening Systems during the Term of this
Agreement, and to copy the Software solely for the purposes expressly authorized
under this Section 3.2.  In addition, Chiron hereby grants to ARC the right to
use the Documentation in connection with its use of the Software hereunder. 
Documentation may not be copied.  Additional copies of the Documentation may be
obtained from Chiron, subject to payment of Chiron’s reasonable copying charges
then in effect.  No right to use, copy, display, or print the Software or
Documentation, in whole or in part, is granted, except as expressly provided in
this Agreement.

 

(e)                                  Confidentiality.  ARC acknowledges that the
Software is the proprietary intellectual property of Chiron or the applicable
manufacturer/licensor, and ARC shall take reasonable precautions to protect the
Software and to prevent the disclosure thereof to Third Parties.

 

(f)                                    Restrictions on Use.  The grant of rights
stated in this Section 3.2 is subject to the terms and conditions of this
Agreement as well as the following restrictions:

 

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(i)                                     Use of the Software may be subsequently
transferred to other NTLs, provided (A) the total number of NTLs at which the
Software is used does not exceed the number of NTLs specified in this Agreement
and (B) ARC provides Chiron with written notice thirty (30) days before such
transfer.

 

(ii)                                  In the event that disaster or other
circumstances affecting ARC prevents ARC from using the Software at the NTLs
identified in this Agreement, the effected NTLs shall have the right to use the
Software at a disaster recovery facility without prior notice to Chiron, but
shall promptly notify Chiron as soon as circumstances permit.

 

(iii)                               ARC shall not use (or cause to be used) the
Software for rental, in the operation of a service bureau or for any similar
purpose, nor shall ARC allow access to the Software through terminals located
outside ARC’s business premises by persons who are not ARC’s employees or
authorized agents, contractors or representatives.

 

(iv)                              ARC shall not distribute the Software, in
whole or in any part, to any Third Party or parties, nor permit its
sublicensing, leasing, or other transfer, except as permitted under Section 13.3
of this Agreement.

 

(v)                                 ARC shall not, either directly, or through a
Third Party, reverse engineer, disassemble or decompile the Software, or make
any attempt in any fashion except as specifically provided in this Agreement to
obtain the source code to any Software.

 

(vi)                              Any use of the Software not in accordance with
this Agreement, or any modification or alteration of the Software not expressly
authorized in writing by Chiron, shall be deemed a breach of this Agreement.

 

(vii)                           Upon expiration or termination of this
Agreement, ARC shall (A) cease all use of the Software and the Documentation;
(B) return to Chiron the Software and the Documentation and any copies thereof
(unless required to retain such material for regulatory purposes); and (C) erase
from memory all copies of the Software (unless required to retain such material
for regulatory purposes).  ARC shall certify in writing to Chiron that it has
not retained the Software and Documentation or any copies thereof (unless
required to retain such material for regulatory purposes).

 

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(g)                                 Electronic Records; Electronic Signatures. 
Chiron shall utilize commercially reasonable efforts to develop and install
Upgrades necessary to ensure the Software is capable of being utilized in
compliance with 21 CFR Part 11.  ARC shall have the right to perform an audit of
the Software to ensure such compliance.

 

(h)                                 Warranties; Limitation of Liability.

 

(i)                                     Performance.  Chiron warrants that the
Software, under normal use and service, will perform all of the material
functions described in the Documentation of such Software.  Chiron warrants that
the Documentation shall be free from material defects in materials and
workmanship.  If any such defect or deviation appears during the applicable
periods, the Software or Documentation may be returned to Chiron for replacement
by Chiron without charge;

 

(ii)                                  Anti-Virus.  Chiron warrants that to the
best of its knowledge after employing reasonable technical means to detect
computer viruses, the Software at the time of delivery will not contain any
virus or computer software code, routines or devices designed to disable,
damage, impair, or erase the Software or other software or data.  For failure to
comply with this warranty, Chiron shall, at Chiron’s expense, immediately
replace all copies of the affected Software in the possession of ARC; and

 

(iii)                               Chiron warrants that as of the Effective
Date of this Agreement it has full rights and authority to license the Software
to ARC, or the authority to do so without infringing the rights of any Third
Party.  Chiron shall not incorporate any other software having any limitation on
its use or transfer into any Software provided to ARC without giving prior
written notice to ARC and receiving written approval from ARC.

 

ARTICLE 4 - SERVICES

 

Installation, training, telephone support, and other servicing of any of the
Products (collectively, “Services”), shall be provided to ARC by Chiron in
accordance with the terms and conditions set forth in Schedule 4.0 attached
hereto.

 

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ARTICLE 5 - COMPENSATION, PAYMENTS

 

5.1                                 Support.  ARC agrees to assist with the
costs related to the development and supply of the WNV Assay and other costs
incurred by Chiron and Gen-Probe under this Agreement by paying to Chiron the
amounts set forth in Schedule 5.0 attached hereto for the Products and Services.

 

5.2                                 Payments.  All payments shall be made as set
forth in Schedule 5.0.  All payments due to Chiron hereunder shall be paid in
full by ARC in U.S. Dollars within thirty (30) calendar days of the applicable
invoice date.  In the event of late payment, interest shall be charged at the
rate of [***], as reported in the Wall Street Journal on the date such payment
was due, until the date of actual payment, such interest to accrue daily and
both before and after judgment.

 

Chiron’s invoices must be submitted to The American National Red Cross, Shared
Services Center, Post Office Box 410500, Charlotte, North Carolina 28241-0500. 
Chiron shall invoice incremental freight charges relating to Modified Orders and
Rush Orders separately.

 

Each invoice must contain:

 

•                  Chiron’s name and address;

•                  Agreement and purchase order number;

•                  any applicable task or shipping instruction number;

•                  a description of the goods or services and the dates
delivered or performed;

•                  any applicable unit prices and extensions;

•                  shipping and payment terms; and

•                  any additional information required by this Agreement.

 

5.3                                 Books & Records; Audit.  ARC shall keep
reasonably detailed and accurate records and books of account to enable a
determination of the amounts payable by ARC to Chiron for Reportable Results as
provided hereunder.  Upon thirty (30) days written notice by Chiron, not more
frequently than once per calendar year, Chiron, at its cost (except as otherwise
provided below in this Section 5.3) may have such records and books of account
relating solely to Reportable Results examined at an ARC location during
reasonable business hours by an independent certified public accountant selected
by Chiron for the purpose of verifying the amounts due hereunder and engaged on
payment terms reasonably acceptable to ARC.  A copy of any final written report
provided by the independent accountant to Chiron shall be given concurrently to
ARC.  [***]  In all cases, such examination by Chiron shall not be permitted
unless [***] to which the books and records pertain.  Where such examination
results in a finding that ARC underpaid Chiron [***], ARC

 

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shall reimburse Chiron for its reasonable costs and expenses in conducting such
examination.  ARC and Chiron shall promptly rectify underpayments and
overpayments by repaying such amounts, together with interest thereon accruing
from and, at the rate of [***] as reported in the Wall Street Journal on, the
date such under- or overpayments [***] in the aggregate for such Fiscal Year,
until the date of actual payment.

 

5.4                                 Taxes.  Chiron hereby acknowledges that ARC
is a not-for-profit, charitable corporation, exempt from the payment of sales
and use taxes and ARC shall have no tax liability on Products unless
specifically legislated by a particular state.  Chiron is responsible for
requesting and obtaining all tax exemption numbers as required.  [***] 
Notwithstanding the above, if any federal, state, provincial, county or
municipal sales or use tax, excise or similar charge, or other tax assessment
(other than that assessed against income), is assessed or charged on the sale of
the WNV Assays and Blood Screening Systems sold to ARC by Chiron pursuant to
this Agreement, it shall be paid by ARC.

 

ARTICLE 6 - CERTAIN AGREEMENTS

 

6.1                                 WNV Assay IND.  Gen-Probe has prepared and
submitted an Investigational New Drug Application in accordance with the
Regulations to the FDA (“IND”) to permit the ARC to conduct nucleic acid
amplification screening to detect the presence of the West Nile Virus using the
Products (BB-IND 10920).  Gen-Probe, or Chiron on Gen-Probe’s behalf, shall
notify ARC in advance and provide ARC with a copy of any amendment to
Gen-Probe’s IND.

 

6.2                                 Protocol IND.  ARC has prepared and
submitted an IND to the FDA for the clinical protocol and preclinical studies to
be undertaken in connection with the screening of blood, plasma, other blood
components and tissue and organ samples using the Products, which application
shall cover the donor, product, and recipient management (BB-IND 11036).

 

6.3                                 ARC Use of WNV Assays Per IND.  ARC shall
not use the Products in a manner not specifically described in the ARC’s or
Gen-Probe’s IND protocol at any time.  ARC shall notify Chiron in advance and
provide Chiron with a copy of any amendment to ARC’s IND.

 

6.4                                 Provision of Facilities by ARC.  ARC agrees
to make available, at its sole expense and discretion, adequate facilities
(including any necessary facility improvements) and personnel necessary to
conduct the clinical trials described in ARC’s IND and otherwise for use of the
Products in accordance with all applicable Regulations and Documentation.

 

6.5                                 Regulatory Compliance.

 

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(a)                                  ARC shall be solely responsible for
compliance with all reporting and other regulatory requirements imposed on it by
the Regulations, including, but not limited to, 21 C.F.R. Part 812.  Upon
reasonable request of Chiron, ARC shall provide Chiron with copies of reports to
the FDA relating to the use of the Products, so long as such information
requested does not violate any Regulations or confidentiality obligations of ARC
to Third Parties.

 

(b)                                 Chiron shall be solely responsible for
compliance with all reporting and other regulatory requirements imposed on it by
the Regulations, including, but not limited to, 21 C.F.R. Part 812.  Upon
reasonable request of ARC, Chiron shall provide ARC with copies of reports to
the FDA relating to the use of the Products, so long as such information
requested does not violate any Regulations or confidentiality obligations of
Chiron to Third Parties.

 

(c)                                  Gen-Probe shall be solely responsible for,
or Chiron on Gen-Probe’s behalf shall be solely responsible for, Gen-Probe’s
compliance with all reporting and other regulatory requirements imposed on it by
the Regulations, including, but not limited to, 21 C.F.R. Part 812.  Upon
reasonable request of the ARC, Gen-Probe, or Chiron on Gen-Probe’s behalf, shall
provide ARC with copies of reports to the FDA relating to the use of the
Products, so long as such information requested does not violate any Regulations
or confidentiality obligations of Chiron or Gen-Probe to Third Parties.

 

(d)                                 Any Party hereunder agrees to make available
to the requesting Party (with authority to provide to its Affiliates or any
governmental regulatory agency) such records as may be reasonably required in
accordance with a reasonably based legal opinion for the requesting Party to
satisfy its regulatory requirements in the United States.

 

(e)                                  Each Party agrees to provide access to
their facilities and documents pertaining to this Agreement, without any prior
or written notice, to the FDA should it require access in accordance with any
FDA policy, communication, or regulation. To the extent that the FDA requires
access and is investigating Products related to this Agreement, the Party being
investigated shall give notice to the other Party.

 

(f)                                    Each Party, and Chiron on behalf of
Gen-Probe, agrees to perform, on reasonable request of the other Party, such
further acts as may be reasonably necessary or desirable for the requesting
Party to stay compliant with the Regulations; provided that the non-

 

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requesting Party may disagree or deny such request if such Party deems such
request to require more than commercially reasonable efforts to satisfy the
request.

 

6.6                                 FDA Approval.  Each Party, and Chiron on
behalf of Gen-Probe, agrees to exercise due diligence and commercially
reasonable efforts to obtain the requisite approval from the FDA to commercially
distribute the Products during the Term.  Notwithstanding the above, if the FDA
alters its recommendation for the screening of human blood, covered and
voluntary source plasma, platelets or other blood products intended for
transfusion or other administration to humans for the presence of the West Nile
Virus to recommend screening using a Multi-Flavivirus Assay, then the obligation
of the parties to seek FDA approval to commercially distribute the Products
shall be suspended and ARC and Chiron shall meet and confer regarding the
development of a Multi-Flavivirus Assay, including without limitation, the
discriminatory assays relating thereto.

 

6.7                                 Data.   ARC shall provide to Chiron and, at
Chiron’s request and direction, to Gen-Probe, in an agreed format data generated
in connection with the use of the Products as required for proper submission of
the Gen-Probe IND and otherwise as is sufficient to monitor the performance of
the Products for quality assurance and to perform their respective regulatory
obligations in the Territory (collectively the “Data”).  Each Party shall have
the right to disclose, and as to Chiron, to have Gen-Probe disclose, such data
to the FDA in support of the IND without prior written consent of the other
Party.  The Data shall be deemed confidential information of ARC.

 

(a)                                  Each Party acknowledges the other party’s
interest in disclosing or publishing, in oral or written form, certain
information related to ARC’s use of the Products to obtain recognition within
the scientific community, to advance the state of scientific knowledge and for
marketing purposes.  Each Party also recognizes the other Party’s interest in
preserving the confidentiality of certain information.  Therefore, neither party
will publish any information relating to use of the Products, including Data
each Party generates during clinical trials, without the express written consent
of the other Party, which consent shall not be unreasonably withheld.  A Party
wishing to publish shall provide a copy of the draft publication and provide the
other Party not less than thirty (30) to review and comment prior to
publication.  Any such publication shall appropriately acknowledge the
contributions of the other Party.  At the request of either Party, the Parties
shall reasonably consider joint publications.

 

(b)                                 Chiron, and on behalf of its Affiliates or
Gen-Probe, shall have the right to request use of Data in connection with other
regulatory applications, submissions and notifications, in any country, with

 

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respect to the Products, Blood Screening Systems or related products.

 

(c)                                  The Parties acknowledge and agree that
nothing in this Agreement or otherwise will require ARC to disclose to Chiron
patient-specific, or donor or recipient identifying information (including
information that could identify a group of donors, recipients or their
geographical location), unless and to the extent that such information is
required by any applicable law, regulation or court order.  In such event, (i)
Chiron must provide notice to ARC in writing immediately on becoming aware of
such a requirement so that ARC has an opportunity to seek a protective order or
other remedy; and (ii) ARC shall provide the required identifying information to
the extent it has such information, subject to the terms of such protective
order or other remedy.

 

6.8                                 Confidentiality.   During the Term of this
Agreement and [***], absent the consent of the other Party, (i) ARC agrees to
keep in confidence and not to disclose to any Third Party other than its
Affiliates, agents or contractors who need to know in connection with ARC
activities under this Agreement, or use for any purpose, except pursuant to, and
in order to carry out, the terms and objectives of this Agreement, any
Confidential Information of Chiron, including Confidential Information of
Gen-Probe which is disclosed to ARC by or through Chiron; and (ii) Chiron agrees
to keep in confidence and not to disclose to any Third Party other than
Gen-Probe and their respective Affiliates, agents or contractors who need to
know in connection with Chiron activities under this Agreement, or use for any
purpose, except pursuant to, and in order to carry out, the terms and objectives
of this Agreement, any Confidential Information of ARC.   Disclosures of
Confidential Information to Third Parties authorized hereunder shall be
permitted only if the Third Party is bound by confidentiality obligations not
less restrictive than those set forth herein.

 

(a)                                  Subject to this Section 6.8 and except as
required by a court order issued by a court having appropriate jurisdiction, the
Parties agree not to disclose to any Third Party any financial terms of this
Agreement, or any terms of this Agreement relating to the WNV Assays and Blood
Screening Systems provided hereunder, without the prior written consent of the
non-disclosing Party; provided, however, that the Parties may disclose the
existence and general nature of this Agreement to Third Parties.

 

(b)                                 The Parties acknowledge that a violation of
this Section 6.8 may cause irreparable harm to the non-disclosing Party for
which no adequate remedy at law exists and the Parties therefore agree that, in
addition to any other remedies available, the non-disclosing Party

 

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shall be entitled to seek injunctive relief to enforce the terms of this
Section 6.8.

 

6.9                                 Intellectual Property; Inventions.  The
provision by Chiron to ARC of the Products hereunder includes the implied
license or sublicense under Chiron and Gen-Probe intellectual property to use
the Products in the Territory as provided herein.  Except for such implied
license to the Products, and except as specifically set forth herein, nothing in
this Agreement conveys to either Party any rights or licenses to any
intellectual property of the other Party.  The Parties do not anticipate that
use of the Products as provided herein will result in new inventions by ARC.  
However, in the event that any such new invention is made, solely by ARC or
persons obligated to assign inventions to ARC, arising from the use of the
Products, ARC will own such invention and ARC grants to Chiron the option to
obtain a non-exclusive worldwide license to such invention (with a right to
sublicense for manufacturing purposes only), on commercially reasonable terms to
be negotiated by the Parties in good faith.  If an invention is made jointly by
ARC or persons obligated to assign inventions to it, and Chiron or persons
obligated to assign inventions to it, such invention will be owned jointly by
the Parties.  All inventions made solely by Chiron or persons obligated to
assign inventions to it will be owned by Chiron.

 

6.10                           Inventory Levels.  Chiron shall, at no cost to
ARC, assist each NTL monthly in managing its inventory, as well as actual
Product usage versus the Product Requirement Forecasts.

 

6.11                           Technical and Operational Reviews.  From time to
time, Chiron shall conduct technical and operational reviews with ARC of the
Products and other Services provided by Chiron, as well as Agreement
performance, at each Party’s respective expense.  The Parties shall mutually
agree upon the scheduling and locations of such reviews.

 

6.12                           Clinical Monitor Fees.  In consideration of ARC’s
allocation of resources, facilities and Data pursuant to this Agreement, Chiron
shall pay ARC [***] for such amount from ARC, to offset those costs incurred by
ARC from the engagement of Medical Marketing Consultants in connection with
monitoring of Products pursuant to the existing IND applications (BB-IND 10920
and BB-IND 11036 for each of Gen-Probe and ARC, respectively).

 

ARTICLE 7 - REPRESENTATIONS & WARRANTIES; WARRANTY DISCLAIMER; INDEMNIFICATION;
LIMITATION OF LIABILITY; INSURANCE

 

7.1                                 Chiron Representations & Warranties. Chiron
hereby represents, warrants and covenants to ARC that:

 

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(a)                                  All Products and Services provided pursuant
to this Agreement shall conform to the Regulations, including, but not limited
to, 21 C.F.R. Part 812.

 

(b)                                 [***]

 

(c)                                  (i) Chiron is duly organized, validly
existing and in good standing under the laws of the jurisdiction in which it was
organized, (ii) this Agreement, when executed and delivered by Chiron, will be
the legal, valid and binding obligation of Chiron, enforceable against Chiron in
accordance with its terms, (iii) the execution, delivery and performance of this
Agreement by Chiron does not and will not (1) conflict with, or constitute a
breach or default under, Chiron’s organizational documents or any material
agreement, contract, commitment, or instrument to which Chiron is a party or (2)
require the consent, approval or authorization of, or notice, declaration,
filing or registration with, any Third Party or any governmental or regulatory
authority, and (iv) Chiron has not previously granted and will not grant any
rights to any Third Party which are, nor has contracted or will contract with
any Third Party in any manner which is, inconsistent with the rights granted
herein.

 

(d)                                 There are no FDA proceedings or other
regulatory actions pending, threatened (orally or in writing) or probable of
assertion against Chiron or any employee, agent or subcontractor thereof for
violations of any requirements of the United States Food, Drug and Cosmetic Act,
the Public Health Service Act and/or accompanying regulations, or any other
Regulations, which would prohibit or limit the provision of the Products as set
forth in this Agreement.

 

(e)                                  Chiron has commercial insurance necessary
to conform with the terms and conditions of this Agreement and all Chiron
commercial insurance shall be and remain in full force and effect during the
Term of this Agreement.  In no event shall any ARC Indemnitee’s recovery for
Damages assumed by Chiron be limited to the amount of the insurance limits
requested.

 

7.2                                 ARC Representations & Warranties. ARC hereby
represents, warrants and covenants that:

 

(a)                                  ARC shall not make any warranty or
representation, either express or implied, with respect to any Product, which
differs from any warranty or representation made by Chiron or the applicable
manufacturer in the applicable Documentation for the Product.

 

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(b)                                 ARC shall store, handle and use the Products
in its control in conformity with the Package Insert and shall comply with all
Regulations applicable to the use of such Products.

 

(c)                                  (i) ARC is a not for profit corporation
chartered by an act of Congress, 36 U.S.C. § 30010 et seq., and has the full and
unrestricted corporate power and authority to execute and deliver this Agreement
and to carry out the transactions contemplated hereby, (ii) this Agreement, when
executed and delivered by ARC, will be the legal, valid and binding obligation
of ARC, enforceable against ARC in accordance with its terms, and (iii) the
execution, delivery and performance of this Agreement by ARC does not and will
not (1) conflict with, or constitute a breach or default under, ARC’s
organizational documents or any material agreement, contract, commitment, or
instrument to which ARC is a party or (2) require the consent, approval or
authorization of, or notice, declaration, filing or registration with, any Third
Party or any governmental or regulatory authority that is material to ARC’s
ability to carryout the transactions contemplated hereby.

 

(d)                                 ARC has commercial insurance necessary to
conform with the terms and conditions of this Agreement and all ARC commercial
insurance shall be and remain in full force and effect during the Term of this
Agreement.  In no event shall any Chiron Indemnitee’s recovery for Damages
assumed by ARC be limited to the amount of the insurance limits requested.

 

7.3                                 Limitation of Warranty.  Chiron is not the
manufacturer of the WNV Assays provided to ARC under this Agreement.  Further,
the WNV Assays are not licensed by the FDA or any other regulatory body for use
in the screening and release of blood, plasma or other blood components and are
development stage products, provided to ARC pursuant to an IND submitted to the
FDA.  EXCEPT AS EXPRESSLY PROVIDED ELSEWHERE IN THIS AGREEMENT, CHIRON MAKES NO
WARRANTIES OF ANY KIND AS TO THE PRODUCTS PROVIDED HEREUNDER, EXPRESS OR
IMPLIED, WRITTEN OR ORAL, INCLUDING WITHOUT LIMITATION ANY IMPLIED WARRANTIES OF
MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE.

 

7.4                                 Pass-Through Warranty.  With no further act
required by ARC, Chiron agrees to pass through to ARC the benefit of Gen-Probe’s
manufacturer warranties with respect to each of the Products, and Chiron with
respect to any other Third Party manufacturer’s shall also pass through to ARC
the benefit of any manufacturer’s warranties with respect to each of the
Products, to the extent it is legally permitted to so by the applicable Third
Party manufacturers.

 

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7.5                                 Indemnity by Chiron.  Chiron agrees to
protect, defend, indemnify and hold harmless ARC, the NTLs and all ARC units,
including without limitation, all ARC chapters and other operating units, and
their respective officers, directors, governors, employees, Affiliates, assigns,
successors, and agents (collectively, the “ARC Indemnitees”) and agrees to hold
them harmless from and against all Damages arising from the negligence or
willful misconduct of any of the Chiron Indemnitees or Gen-Probe in the
performance of Chiron’s or Gen-Probe’s obligations under this Agreement,
including without limitation:

 

(a)                                  any breach or violation by Chiron,
Gen-Probe or any Chiron Indemnitee of any of the applicable Regulations related
to Chiron’s or Gen-Probe’s performance under this Agreement;

 

(b)                                 Chiron’s provision of any Services pursuant
to this Agreement;

 

(c)                                  [***]; or

 

(d)                                 loss or damage to any of Chiron’s or any
Chiron Indemnitee’s property, real or personal, while performing Chiron’s or
Gen-Probe’s respective obligations pursuant to this Agreement;

 

provided, that in all of the above cases Chiron’s indemnification
responsibilities to ARC Indemnitees shall be reduced to the extent that any of
such Damages claimed by any ARC Indemnitee results from the willful misconduct,
negligence or omission of ARC or any ARC Indemnitee or ARC’s breach of its
representations, warranties, covenants or other agreements and obligations
provided in this Agreement.

 

7.6                                 Indemnity by ARC.  ARC agrees to protect,
defend, indemnify and hold harmless Chiron and its Affiliates, and their
respective officers, directors, employees, assigns, successors, contractors,
subcontractors, suppliers and agents (collectively, the “Chiron Indemnitees”)
and agrees to hold them harmless from and against all Damages arising from the
negligence or willful misconduct of any of the ARC Indemnitees in the
performance of ARC’s obligations under this Agreement, including without
limitation:

 

(a)                                  any breach or violation by ARC or any ARC
Indemnitee of any of the applicable Regulations related to ARC’s performance
under this Agreement;

 

(b)                                 any use of the Products by ARC or any ARC
Indemnitee other than in accordance with the Package Insert and/or Documentation
for such Products; or

 

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(c)                                  loss or damage to any of ARC’s or any ARC
Indemnitee’s property, real or personal, while performing their respective
obligations pursuant to this Agreement;

 

provided, that in all of the above cases ARC’s indemnification responsibilities
will be reduced to the extent that any of such Damages claimed by any Chiron
Indemnitee results from the willful misconduct, negligence or omission of Chiron
or any Chiron Indemnitee or Chiron’s breach of its representations, warranties,
covenants or other agreements and obligations provided in this Agreement.

 

7.7                                 IP Infringement Indemnity.

 

(a)                                  In addition to Chiron’s indemnification
obligations set forth herein, Chiron, at its own expense, will defend and
indemnify ARC from any Damages from any suit or claim which may be brought
against any ARC Indemnitee for the infringement, misappropriation or other
violation of any Third Party’s patent(s), trademark(s), copyright(s), trade
secret(s), moral right(s), semi-conductor chip protection, proprietary
information, confidential information or other proprietary right (“IP Claim”)
resulting from ARC’s use of any of the Products, and in such suit Chiron will
satisfy any final judgment or award for any such infringement, misappropriation
or other violation.

 

(b)                                 Notwithstanding the foregoing, Chiron shall
have no liability hereunder to the extent that the IP Claim arises from or is
attributable to (i) the use of the Products in combination with other products
or materials not provided by Chiron hereunder; (ii) part (or all) of the
Products being used for a purpose other than that indicated by this Agreement;
or (iii) use of the Products other than in accordance with the Documentation
provided by Chiron to ARC.  Chiron’s obligation to indemnify shall be subject to
ARC promptly notifying Chiron in writing of such claim and providing reasonable
cooperation to Chiron in the defense of such claim or proceeding.

 

(c)                                  If, in Chiron’s opinion, a Product
furnished hereunder is likely to or does become the subject of any IP Claim,
then without diminishing Chiron’s obligation to satisfy any final judgment or
award, Chiron may, at its option, substitute for that Product a modified version
thereof that is satisfactory to ARC or, at Chiron’s option and expense, obtain
the right for ARC and the NTLs to continue using the Product.  If the use of
such Product by ARC or the NTLs shall be prevented by permanent injunction, or
Chiron is unable to procure the right for ARC and the NTLs to continue using
such Product at a reasonable cost, ARC may terminate this Agreement as to the
affected Product and upon such termination, Chiron shall

 

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accept the return of the remaining unused affected WNV Assays and refund the
amount paid Chiron for such unused WNV Assays and/or accept the return of the
affected Blood Screening Systems.  Chiron shall also reimburse ARC for any
shipping charges paid by ARC to return the Products to Chiron and bear all risk
of loss during shipment.

 

7.8                                 Indemnification Procedures.  Any ARC
Indemnitee or Chiron Indemnitee claiming indemnification (the “Indemnitee”)
shall notify the Party from which indemnification is claimed (the “Indemnifying
Party”) in writing promptly upon becoming aware of any claim to which such
indemnification may apply.  Failure to provide such notice shall constitute a
waiver of the Indemnifying Party’s indemnity obligations hereunder if, and only
to the extent that, the Indemnifying Party is materially damaged thereby.  The
Indemnifying Party shall have the right to assume and control the defense of the
claim at its own expense.  If the right to assume and have sole control of the
defense is exercised, the Indemnitee shall have the right to participate in, but
not to control, such defense at its own expense.  If the Indemnifying Party does
not assume the defense of the claim, the Indemnitee may defend the claim at the
Indemnifying Party’s expense.  The Indemnitee will not settle or compromise the
claim without the prior written consent of the Indemnifying Party, and the
Indemnifying Party will not settle or compromise the claim in any manner which
would have an adverse effect of the Indemnitee without the consent of
Indemnitee, which consent, in each case, will not be unreasonably withheld.  The
Indemnitee shall reasonably cooperate with the Indemnifying Party and will make
available to the Indemnifying Party all pertinent information under the control
of the Indemnitee.

 

7.9                                 Exclusion of Consequential Damages;
Limitation of Liability.  Unless recovery for such damages is otherwise
expressly provided for in this Agreement, neither Party shall be liable with
respect to the subject matter of this Agreement under breach of contract,
negligence, strict liability or any other cause of action for any consequential,
incidental or indirect loss or damage (whether arising directly or indirectly
from a breach of this Agreement), including loss of profit or for any cost of
procurement of substitute goods, technology or services, except to the extent of
liability to Third Parties for bodily injury or death as to which each of the
Parties are obligated to indemnify each other under Sections 7.5 and 7.6,
respectively.  Notwithstanding any provision herein to the contrary, in no event
shall Chiron be liable to ARC with respect to the subject matter of this
Agreement under breach of contract, negligence, strict liability or any other
cause of action in an aggregate that exceeds the total amount paid by ARC to
Chiron hereunder, except to the extent of liability to Third Parties for bodily
injury or death as to which Chiron is obligated to indemnify ARC under
Section 7.5.

 

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7.10                           Insurance.  Chiron and ARC agree to maintain
insurance as follows:

 

(a)                                  Insurance Required of Chiron.  Chiron shall
maintain at its sole cost and expense the following insurance coverages in full
force and effect for the Term of this Agreement [***]:

 

(i)                                     A Commercial General Liability policy
with each ARC Indemnitee named as an additional insured as their interests may
appear as respects this Agreement, and the amount of the policy will be at least
[***] combined single limit for each occurrence and in the aggregate for each
policy term;

 

(ii)                                  A Products Liability policy applicable to
the design, manufacture, production and recall of any Product supplied to ARC
under this Agreement with at least [***] for each occurrence and in the
aggregate and naming each ARC Indemnitee as an additional insured as their
interests may appear with respect to this Agreement;

 

(iii)                               A Commercial Auto Liability policy including
owned and non-owned and hired vehicles with at least [***] in coverage with each
ARC Indemnitee named as an additional insured as their interests may appear as
respects this Agreement;

 

(iv)                              Workers’ Compensation coverage with statutory
limits for each jurisdiction where the work required under this Agreement is
performed;

 

(v)                                 An employers’ liability policy with at least
the following limits: [***] per accident, [***] per disease, and [***] disease
(each employee); and

 

(vi)                              “All Risk” property insurance policy at full
replacement cost on all facilities, property and equipment used in manufacturing
the Products.  Chiron shall also maintain an “All Risk” transit insurance policy
at full replacement cost insuring all Products while being shipped to or from
ARC.

 

(b)                                 Insurance Required of ARC.  ARC shall
maintain at its sole cost and expense the following insurance coverages in full
force and effect for the Term of this Agreement [***]:

 

(i)                                     A Commercial General Liability policy
with each Chiron Indemnitee named as an additional insured as their interests
may appear as respects this Agreement, and the amount of

 

26

--------------------------------------------------------------------------------

 

the policy will be at least [***] combined single limit for each occurrence and
in the aggregate for each policy term;

 

(ii)                                  A Professional Liability (Errors and
Omissions) policy in an amount not less than [***] each claim and in the
aggregate;

 

(iii)                               A Commercial Auto Liability policy including
owned and non-owned and hired vehicles with at least [***] in coverage with each
Chiron Indemnitee named as an additional insured as their interests may appear
as respects this Agreement;

 

(iv)                              Workers’ Compensation coverage with statutory
limits for each jurisdiction where the work required under this Agreement is
performed;

 

(v)                                 An employers’ liability policy with at least
the following limits: [***] per accident, [***] per disease, and [***] disease
(each employee);

 

(vi)                              “All Risk” property insurance policy at full
replacement cost on all facilities, property and equipment used in connection
with the Products, other than such facilities, property and equipment for which
this Agreement requires the provision of insurance by Chiron.

 

(c)                                  All liability policies will be written as
primary coverage and not contributing with, or in excess of, any coverage which
the other Party shall carry with respect to the obligations of each Party.  All
workers’ compensation policies shall contain a waiver of subrogation for the
benefit of the other Party, except as to [***].  All insurance required under
this Agreement that is provided through commercial carriers shall be placed with
insurers which, at the time the insurance is placed, [***].  This insurance
shall be and remain in full force and effect during the Term of this Agreement. 
Each Party shall provide the other with certificates of insurance evidencing the
coverage required herein upon execution of this Agreement, and renewal
certificates on request from the other Party.  Such certificates shall provide
for thirty (30) days prior written notice to the certificate holder in the event
of the non-renewal or cancellation of the policies.  Each Party shall provide
the other with prompt written notice of (i) any material change to the coverage,
limits, terms, or conditions of any insurance below those required herein, (ii)
the exercise of the batching provision under its catastrophic insurance
coverage, whether related to any potential liabilities under this Agreement or
otherwise, or (iii) any other potential impairment of the coverage provided
under any of the

 

27

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insurance policies set forth in Section 7.10(a) or (b) above.  All information
contained within such notice shall be deemed Confidential Information of the
notifying Party.  Following delivery of such notice, the Parties will meet and
confer regarding the impact of the occurrence described in such notification on
the Parties. Each of the Parties acknowledge that during the period which the
Parties are meeting and conferring with one another, as provided in the
immediately preceding sentence, the notified Party shall refrain from submitting
a notice of termination under Section 8.2(a) on the basis of the information
provided to it pursuant to this Section 7.10(c), until at least thirty (30) days
have passed from the date the Section 7.10(c) notice was first received.

 

ARTICLE 8 - TERM AND TERMINATION

 

8.1                                 Term.  This Agreement shall be effective as
of the Effective Date and shall continue  [***] (the “Term”), unless terminated
earlier by mutual agreement of the Parties without penalty, or otherwise in
accordance with this Agreement.  The obligations under this Agreement shall
terminate and expire without any further action by the Parties upon the
expiration of the Term unless, no less than six (6) months before the expiration
of this Agreement, the Parties mutually agree in writing to extend this
Agreement.

 

8.2                                 Termination for Cause.  This Agreement may
be terminated for cause by written notice to the other Party at any time during
the Term of this Agreement, which termination shall be effective when such
termination notice is received in accordance with Article 13, as follows:

 

(a)                                  by either Party if the other Party fails to
observe, perform or otherwise materially breaches any of its covenants,
representations, warranties, or agreements or materially defaults in the
performance of its obligations under this Agreement, provided such breach or
failure continues without cure for a period of thirty (30) days after receipt by
the other Party of an initial written notice thereof specifying such breach or
failure;

 

(b)                                 by either Party if the other Party files a
petition in bankruptcy, becomes bankrupt or insolvent or subject to the
reorganization of its business for the benefit of creditors under any law or
regulation relating to bankruptcy, or a receiver is appointed for all or
substantially all of its property or assets, or upon the making by such other
Party of a composition with its creditors, or upon the taking by such other
Party of any act for the winding up of its business, or upon any governmental
authority exercising any power or authority resulting in the expropriation or
confiscation of all or substantially all of its business and assets.  If Chiron
enters into

 

28

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proceedings relating to bankruptcy, whether voluntary or involuntary, Chiron
will furnish, by certified mail, written notification of the bankruptcy to the
person identified in Section 13.5.  The notification must be furnished within
[***] of the initiation of the bankruptcy proceedings.  The notification must
include the date on which the petition was filed, and a list of ARC purchase
orders for which final payment has not yet been made.  This obligation remains
in effect until final payment under this Agreement;

 

(c)                                  by either Party if a Force Majeure Event
prevents a Party from performing its obligations under this Agreement for a
period exceeding [***], measured from the day notice is received of the
existence of such Force Majeure Event; or

 

(d)                                 by either Party if any of the Regulations
are amended in a way that precludes a Party from lawfully performing its
obligations under this Agreement, effective upon the effective date of such
amended Regulation; provided, however, that [***] prior written notice must be
given by the Party intending to terminate under this subsection and such Party
shall make a good faith effort to implement commercially reasonable strategies
for compliance with any amended Regulations.

 

(e)                                  by either Party if (i) the notifying
Party’s institutional review board (“IRB”) withdraws approval of an IND before
the expiration of the Term or (ii) the FDA revokes any approval of any of the
Products or a Party’s IND;

 

(f)                                    [***]; or

 

(g)                                 [***].

 

ARTICLE 9 - FORCE MAJEURE

 

9.1                                 Force Majeure.  Neither Party shall be
liable for any failure or delay in performing any of its obligations under this
Agreement to the extent that such failure or delay is due to any cause beyond
the affected Party’s reasonable control, including without limitation war,
terrorism, riot, insurrection or other civil commotion, any strike, lockout or
other labor dispute, any governmental or court order, decree or regulation, any
fire, flood, epidemic, earthquake, unusually severe weather condition or other
act of God, or any freight embargo or public utility failure (a “Force Majeure
Event”).

 

(a)                                  The affected Party shall give prompt notice
to the other Party of, and shall exercise due diligence to eliminate or remedy
all such

 

29

--------------------------------------------------------------------------------

 

causes, and shall give the other Party prompt notice when such causes have been
eliminated or remedied. Notwithstanding the foregoing, (i) a Party affected by a
Force Majeure Event shall use commercially reasonable efforts (taking into
consideration the adverse effect and duration of the Force Majeure Event) to
mitigate and ameliorate the adverse effects thereof, and (ii) the obligations of
such Party shall not be suspended pursuant to this Section 9.1 to the extent
that performance of such obligations was due before the occurrence of the Force
Majeure Event.  Further, the affected Party shall have the burden of proving the
existence, duration and adverse effect of such Force Majeure Event.

 

(b)                                 If Chiron is the Party affected by the Force
Majeure Event and such Force Majeure Event has prevented Chiron from performing
its obligations under this Agreement for in excess of [***], [***].

 

ARTICLE 10 - CONSEQUENCES OF THE TERMINATION OF THIS AGREEMENT

 

10.1                           Outstanding Payment Obligations Unaffected.  The
termination of this Agreement for any reason whatsoever shall not affect any
Party’s obligations to perform those obligations due and already accrued prior
to such termination.  In the event that termination occurs at a time prior to
ARC having made full payment that is due and owing for any Products, the Parties
agree that Chiron shall have all applicable ownership rights to such Products
until such payment has been made in full to Chiron.

 

10.2                           Reimbursement upon Termination.  If this
Agreement is terminated other than by mutual agreement of the Parties or for
cause by ARC pursuant to Section 8.2, then ARC shall be obligated to reimburse
Chiron for certain un-recovered costs and expenses related to the development of
the Products in an amount to be calculated in accordance with Schedule 5.0,
paragraph 2.

 

10.3                           Transition.  If the Term of this Agreement
expires, upon such expiration and for a period of no more than [***] thereafter,
Chiron shall continue to make available to ARC for purchase, at prices not to
exceed [***] of the then current prices for such quantity of Products under this
Agreement, such quantity of Products and Services as ARC deems necessary for its
use in the Blood Screening Field to facilitate an orderly transition to the
replacement service provider.

 

In the event of a termination of this Agreement by ARC for any reason, Chiron
shall cooperate with ARC in the transfer of Chiron’s obligations hereunder to a
replacement service provider.  After receiving notice of such termination and
except as otherwise directed by ARC, Chiron shall

 

30

--------------------------------------------------------------------------------

 

continue to make available to ARC for purchase, at prices not to exceed [***] of
the then current prices for such quantity of Products under this Agreement, such
quantity of Products and Services as ARC deems necessary for its use in the
Blood Screening Field to facilitate an orderly transition to the replacement
service provider during the time period required for such transition, not to
exceed [***].

 

During any such transition following expiration or termination by ARC, ARC’s
purchase obligations with respect to the quantity of such Products and/or
Services shall be reduced to the extent ARC deems necessary to transition to the
replacement service provider.

 

10.4                           Survival of Certain Provisions.  In addition,
notwithstanding anything herein to the contrary, the following provisions of
this Agreement shall survive termination of this Agreement: Sections
3.2(f)(vii), 5.3, 6.5(d), 6.7, 6.8, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, and 7.10
and Articles 10, 11, 12 and 13.

 

10.5                           Return of Confidential Information.  Upon
termination of this Agreement for any reason whatsoever, the Parties shall
immediately return to the other all confidential information in documentary or
printed form and any copies or extracts thereof and shall thereafter cease to
use such information but without prejudice to the then surviving confidentiality
obligations provided for in Section 6.8 hereof.

 

10.6                           No Other Payment.  No indemnity or compensation
in any form whatsoever shall be paid by either Party to the other in connection
with a termination in accordance with the terms hereof (subject to any liability
that may exist in respect of any material breach prior to such termination).

 

ARTICLE 11 - APPLICABLE LAW

 

This Agreement shall be governed by and construed in accordance with the laws of
the State of California, without giving effect to any conflict of law rules and
regulations.

 

ARTICLE 12 - DISPUTES

 

12.1                           To the extent that there are disputes with
respect to performance under this Agreement, such disputes (other than
non-payment) are not cause for Chiron to stop performance under this Agreement,
but will be resolved in due course to the extent possible in accordance with
this Article.

 

12.2                           The Parties to this Agreement will attempt to
resolve any problem or dispute arising out of, or related to, this Agreement
through good faith consultation in the ordinary course of business.

 

31

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12.3                           If the Parties are unable to resolve the problem
or dispute within thirty (30) days, either Party may initiate and submit a
matter through the dispute resolution procedure set forth in Section 12.4
below.  No Party may institute litigation until the dispute resolution procedure
has been completed unless, and to the extent that, doing so is necessary to
avoid irreparable harm.

 

12.4                           Dispute Resolution Procedure.  If any problem or
dispute arising out of or related to this Agreement is not resolved by the
Parties in the above described manner, the Parties hereby agree to resolve such
dispute by arbitration conducted in accordance with the Commercial Arbitration
Rules of the American Arbitration Association.  The place of arbitration shall
be Arlington, Virginia.  The arbitration panel shall consist of three
arbitrators, one arbitrator appointed by each of the Parties, and the third
arbitrator appointed by the two appointed arbitrators (the “Panel”).  The Panel
may, at its discretion, provide for discovery by the Parties not to exceed a
period of sixty (60) days from the date of filing of the notice of arbitration. 
The Panel shall render its decision within ninety (90) days from the date of
filing the notice of arbitration and may, at its discretion, award costs and
expenses but shall not have the right to award punitive damages.  The decision
of the Panel shall be final and binding on the Parties, and shall be enforceable
in any court of competent jurisdiction.

 

12.5                           The prevailing Party shall be entitled to recover
all costs and expenses, including reasonable attorney’s fees, incurred because
of any legal action arising in relation to this Agreement.

 

ARTICLE 13- MISCELLANEOUS

 

13.1                           National Testing Laboratories.  The full names
and addresses of the NTLs participating in this Agreement are set forth in
Schedule 1.36, which may be modified from time to time as determined by ARC. 
Any change to the number or location of NTLs shall be provided in writing by ARC
to Chiron at least ninety (90) days in advance of such change, wherever
possible.

 

13.2                           Equal Employment Opportunity.  Neither ARC nor
Chiron will discriminate, in terms and conditions of employment, against
employees or applicants because of age, race, color, religion, sex, national
origin, qualified disability or any other basis protected by applicable state or
local law.  ARC and Chiron agree to abide by all federal, state and local
employment and labor law notice posting requirements.

 

13.3                           Assignment.  This Agreement shall not be directly
or indirectly assigned or otherwise transferred by the Parties, nor, except as
expressly provided hereunder, may any right or obligations of either of the
Parties hereunder

 

32

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be assigned or transferred (whether voluntarily, by operation of law or
otherwise) without the prior written consent of the other Party. Either Party
may assign and transfer to an Affiliate, or any Third Party acquiring all or
substantially all of the business assets or liabilities necessary to transact
business, as contemplated hereunder, provided that (i) the assigning Party
provides written notice of such assignment at least forty-five (45) days prior
to its intended effectiveness and (ii) the assignee provides to the
non-assigning Party adequate assurances of its intent to perform under this
Agreement. This Agreement shall inure to the benefit of and be binding upon the
Parties hereto and their respective successors and permitted assigns.

 

13.4                           Subcontracting.  Chiron’s obligations under this
contract may not be subcontracted without the prior written consent of ARC.  Any
attempt to subcontract without such consent will be null and void and of no
effect.

 

Chiron must require that all subcontractors approved by ARC be bound by the
terms of this Agreement and to assume toward Chiron all obligations and
responsibilities which Chiron assumes toward ARC.  Chiron must make available to
each approved subcontractor, prior to the execution of any subcontract
agreement, a copy of this Agreement to which the subcontractor will be bound. 
For purposes of any subcontracts entered into pursuant to this Section 13.4, the
term “Chiron” as used in this Agreement, will include any and all ARC-approved
subcontractors.

 

Each subcontract agreement must preserve and protect the rights of ARC with
respect to the goods or services provided by Chiron.  The subcontractor must
enter into similar agreements with all sub-subcontractors.  ARC retains the
unrestricted right to review all subcontract agreements, or other documents
pertaining to the retention of any subcontractor at any tier, for performance
under this Agreement, prior to the execution of such subcontract or other
agreement.  Upon ARC approval, each subcontract agreement shall be assigned by
Chiron to ARC; provided, however that assignment shall only be effective in the
event Chiron terminates a subcontracting agreement with a subcontractor and ARC
accepts such assignment by notifying the subcontractor in writing.  Chiron must
expressly provide for such assignment in all of its subcontract agreements.

 

Chiron must require each ARC-approved subcontractor, if any, to procure and
maintain insurance of the types and amounts required of Chiron in favor of ARC. 
In addition, the subcontractors must assume indemnification responsibilities
identical to those provisions agreed to by Chiron and contained in this
Agreement, in favor of ARC.

 

33

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Chiron agrees to include in all subcontracts entered into under this Agreement a
provision to the effect that ARC and its authorized representatives will, until
[***] after final payment under the subcontract, or for any shorter period
specified by law for particular records, have access to and the right to examine
any books, documents, papers, or other records of the subcontractor relating to
the subcontract.

 

Nothing in this Agreement will be deemed to entitle subcontractors, materialmen,
or lower-tier subcontractors rights as Third Party beneficiaries of this
Agreement between ARC and Chiron.  Notwithstanding any statement to the
contrary, Chiron will at all times be responsible for all acts and/or omissions
of its subcontractors.

 

13.5                           Notices.  Any Notice or request required or
permitted to be given in connection with this Agreement shall be deemed to have
been sufficiently given if sent by (i) pre-paid registered or certified mail,
return receipt requested, or (ii) hand-delivered by a nationally recognized
courier, to the address set forth below or to such other address as may have
been notified in writing.

 

If to Chiron:

 

Chiron Corporation

 

 

Attention:  President, Blood Testing

 

 

4560 Horton Street

 

 

Emeryville, California  94608

 

 

Phone: [***]

 

 

 

With a copy to:

 

General Counsel

 

 

 

If to ARC:

 

American National Red Cross

 

 

Attention: Vice President, NTRL

 

 

13504 South Point Boulevard

 

 

Charlotte, North Carolina 28273

 

 

Phone: [***]

 

 

 

With a copy to:

 

The American National Red Cross

(which shall not

 

Attention: Office of the General Counsel

constitute notice)

 

2025 E Street, NW

 

 

Washington, DC 20006-5009

 

 

Phone:  [***]

 

A notice, consent, approval or other communication takes effect from the time it
is received unless a later time is specified in it, and receipt shall be deemed
to occur as follows:

 

(a)                                  If it is sent by mail, seven (7) calendar
days after posting; and

 

34

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(b)                                 If it is sent by courier, on the date and at
the time shown on the courier’s standard written confirmation of receipt.

 

13.6                           Entire Agreement.  This Agreement constitutes the
entire agreement between the Parties in respect of the subject matter hereof. 
This Agreement cancels and supersedes any and all pre-existing agreements,
either oral or in writing between the Parties.  There are not and shall not be
any oral statements, representations, warranties, undertakings or agreements
between the Parties other than as provided by this Agreement and any mutually
accepted written amendments or letter agreements attached hereto.  This
Agreement may not be amended, altered or modified except by a written document
executed by all of the Parties hereto.

 

13.7                           Order of Precedence; Conflict Between Terms and
Conditions.  In the event of a conflict between the terms of this Agreement and
any other document related hereto, the terms of this Agreement shall govern. 
Unless otherwise explicitly stated in this Agreement, in the event of any
conflict between the terms of this Agreement and the terms of any of the
Schedules or Exhibits hereto, or the terms and conditions of this Agreement and
any terms and conditions that may be set forth in any order, invoice, verbal
agreement or otherwise, the terms and conditions of this Agreement shall control
and govern any interpretative efforts.

 

13.8                           Interpretation.  This Agreement shall be
construed as if both Parties drafted it jointly, and shall not be construed
against either Party as principal drafter.

 

13.9                           No Waiver.  The failure on the part of either
Party hereto to exercise or enforce any right conferred upon it by this
Agreement shall not be a waiver of any such right nor shall any single or
partial exercise of any right or power hereunder or further exercise thereof
operate so as to bar the later exercise or enforcement thereof.

 

13.10                     Nature of Relationship; Independent Contractor. 
Nothing herein contained shall be deemed to be or construed as constituting
either Party the agent or partner of the other Party.  The relationship between
ARC and Chiron shall be that of an independent contractor.  No Party shall have
the right, title or authority to enter into any contract, agreement or
commitment on behalf of the other or to bind the other Party in any manner
whatsoever.

 

13.11                     Compliance with Applicable Law.  In performing this
Agreement, the Parties shall comply with all applicable laws and Regulations. 
Nothing in this Agreement shall be construed so as to require the violation of
law, and wherever there is any conflict between any provision of this Agreement
and any rule of mandatory law, the latter shall prevail, but in

 

35

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such event, the affected provision of this Agreement shall be ineffective only
to the extent necessary to comply with the applicable law, the remainder of this
Agreement shall remain in full force and effect, and the Parties hereto
undertake to replace the invalid and/or unenforceable provision by a valid
and/or enforceable provision, the nature and scope of which will come as close
as possible to the contractual provision to be replaced, taking into account the
economic intentions and business purposes of the Parties.

 

13.12                     Publicity. Neither Party shall permit or generate any
publicity, advertising or promotion concerning this Agreement without the prior
written consent of the other Party.  Each Party recognizes that the name, logo
and marks of the other Party represent valuable assets of that Party and that
substantial recognition and goodwill are associated with such assets.  Each
Party hereby agrees that neither it nor any of its Affiliates shall use the
other Party’s name, logo or marks without the prior written authorization from
such other Party.

 

Each of the Parties acknowledges that a violation of this Section 13.12 would
cause irreparable harm to the other Party for which no adequate remedy at law
exists and each Party therefore agrees that, in addition to any other remedies
available, and notwithstanding any other provision of this Agreement, the
aggrieved Party shall be entitled to injunctive relief to enforce the terms of
this Section 13.12.  To the extent allowed by law, the prevailing Party shall be
entitled to recover all costs and expenses, including reasonable attorneys’
fees, incurred because of any legal action arising in relation to this
Section 13.12.

 

13.13                     Disclosure of Agreements and Terms.  Subject to mutual
agreement as to form and substance, each of the Parties may issue a press
release disclosing the existence of this Agreement.  Each Party may disclose any
of the terms of this Agreement to any Affiliate; provided that the recipient of
such disclosure is obligated to confidentiality terms no less restrictive than
those contained in Section 6.8.  Each Party may disclose any information
contained in or regarding this Agreement to the extent required in its
respective reasonable judgment by applicable law, regulation or order of any
court or governmental agency.  Further, each Party may determine in its
respective discretion to file this Agreement under the Securities and Exchange
Act of 1934, even if that filing may result in this Agreement becoming available
to the public generally.  The filing Party shall seek confidential treatment for
at least the essential financial terms hereof in connection with any such
filing, subject to applicable law and regulation, and shall notify the other
Party in advance of any such filing and consider such suggestions as the other
Party may make as to the terms herein as to which the filing party should seek
confidential treatment.

 

36

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13.14                     Counterparts.  This Agreement may be executed in two
or more counterparts, each of which shall be deemed to be an original and each
of which shall constitute one and the same Agreement.

 

[Remainder of page intentionally left blank]

 

[Signature pages follow.]

 

37

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IN WITNESS WHEREOF, the Parties hereto, through their authorized
representatives, have set their hands as of the date first above written,
whereby they evidence their intent to be legally bound to this Agreement.

 

CHIRON CORPORATION

THE AMERICAN NATIONAL RED CROSS

 

 

By:

/s/ Jack Goldstein

 

By:

/s/ Robert H. Kloak for

Name:

Jack Goldstein

Name:

Richard Platte

Title:

President, Chiron Blood Testing

Title:

Vice President, National Testing &

 

 

 

Reference Laboratories

 

 

 

 

 

 

By:

/s/ Philip Yenrick

 

 

Name:

Phil Yenrick  10-14-03

 

 

Title:

Director, National Contracting Office

 

38

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Schedule 1.26

 

NTLs

 

1.                                       Charlotte

13500 South Point Blvd.

Charlotte, NC  28273

 

2.                                       Detroit

100 Eliot Street

Detroit, MI  48201

 

3.                                       Philadelphia

700 Spring Garden Street

Philadelphia, PA  19123

 

4.                                       St. Louis

4050 Lindell Blvd.

St. Louis, MO  63108

 

5.                                       Southern CA

8885 Rehco Road

San Diego, CA  92121

 

39

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Schedule 2.0

 

WNV ASSAY

 

[Package Insert to be attached]

 

40

--------------------------------------------------------------------------------

 

Procleix® WNV Assay

 

For Investigational Use Only.

The performance characteristics of this product have not
been established.

5000 Test Kit

 

TABLE OF CONTENTS

 

 

 

INTENDED USE

 

1

 

SUMMARY AND EXPLANATION OF THE TEST

 

1

 

PRINCIPLES OF THE PROCEDURE

 

1

 

MATERIALS PROVIDED

 

2

 

MATERIALS REQUIRED, SOLD SEPARATELY

 

2

 

MATERIALS REQUIRED BUT NOT PROVIDED

 

2

 

REAGENTS

 

2

 

STORAGE INSTRUCTIONS

 

3

 

PRECAUTIONS

 

4

 

REAGENT PREPARATION

 

4

 

SPECIMEN COLLECTION, STORAGE, AND HANDLING

 

5

 

PROCEDURAL NOTES

 

5

 

INSTRUCTIONS FOR USE

 

7

 

Target Capture

 

7

 

Amplification

 

8

 

Hybridization Protection Assay (HPA)

 

8

 

QUALITY CONTROL PROCEDURES

 

9

 

Acceptance Criteria for the Procleix WNV Assay

 

9

 

Acceptance Criteria for the Calibration and Calculation of Cutoff

 

9

 

INTERPRETATION OF RESULTS

 

10

 

LIMITATIONS OF THE PROCEDURE

 

11

 

BIBLIOGRAPHY

 

11

 

 

 

INTENDED USE

 

The Procleix® WNV Assay* is a qualitative in vitro nucleic acid amplification
test for the detection of West Nile virus (WNV) RNA in human plasma from
volunteer donations of whole blood and blood components for transfusion, and
source plasma for further manufacturing, and from tissue and organ donations. 
The assay is intended for use in screening individual donor samples or pools of
human plasma comprised of equal aliquots of not more than 16 individual
donations.

 

SUMMARY AND EXPLANATION OF THE TEST

 

WNV is a mosquito-borne flavivirus that is associated with human disease ranging
from mild flu-like symptoms to severe neurological disease(1),(2).  Most WNV
infections are asymptomatic and approximately 20% lead to a mild illness known
as West Nile virus fever.  Less than 1% of infections are estimated to cause
serious neurological disease, with advanced age being the most significant risk
factor(3).  Prior to an outbreak in Queens New York in 1999, the presence of the
virus in North America had not been documented.  Since the original New York
outbreak, the virus, which is carried predominantly by the Culex, sp. of
mosquitoes, has continued to expand westward and is now thought to be
permanently established in North America(4).  A large number of avian species
serve as a reservoir host for the virus, whereas humans and animals, such as
horses and other mammals, are believed to be incidental hosts(5).

 

As of January 2003, the CDC reported nearly 4000 confirmed human WNV positive
cases and 259 human fatalities in the US.  The principal route of human WNV
infection is through the bite of an infected mosquito.  In 2002, new mechanisms
of person-to-person transmission were documented, including possible mother to
infant infection through breast milk, transplacental infection, and transmission
through organ donation and blood transfusion.  As of January 2003, fourteen
cases of transfusion associated transmission of WNV were confirmed(6),(7).

 

In most human infections, WNV multiplies to a relatively low level producing a
transient viremia that can be detected in whole blood and plasma.  Nucleic acid
testing (NAT) methods are capable of detecting infection prior to the presence
of antibodies during the viremic phase.  Immunoglobulin M (IgM) antibody can be
detected in serum or cerebrospinal fluid (CSF) collected within 8 days of
illness onset.  The IgM and the T memory cells can remain in the body for
years(3),(5).  Current methods for the diagnosis of WNV are IgM enzyme
immunoassay, Plaque Reduction Neutralization assays, and NAT methods.  Because
the serologically based assays detect host immune response after the primary
viremic phase, they may not be appropriate for blood screening.

 

Screening of whole blood donations with NAT has been in place in the United
States since early 1999 and licenses were granted for HIV-1 and HCV screening in
2002.  The Procleix WNV Assay, uses the same technology as the Procleix
HIV-1/HCV Assay to detect WNV RNA(8).

 

PRINCIPLES OF THE PROCEDURE

 

The Procleix® WNV Assay involves three main steps which take place in a single
tube:  sample preparation; WNV RNA target amplification by
Transcription-Mediated Amplification (TMA)(9); and detection of the
amplification products (amplicon) by the Hybridization Protection Assay
(HPA)(10).

 

During sample preparation, RNA is isolated from plasma specimens via the use of
target capture.  Plasma is treated with a detergent to solubilize the viral
envelope, denature proteins and release viral genomic RNA.  Oligonucleotides
(“capture oligonucleotides”) that are homologous to highly conserved regions of
WNV, are hybridized to the WNV RNA target, if present, in the test specimen. 
The hybridized target is then captured onto magnetic microparticles that are
separated from plasma in a magnetic field.  Wash steps are utilized to remove
extraneous plasma components from the reaction tube.  Magnetic separation and
wash steps are performed with the Chiron Procleix TCS.

 

Target amplification occurs via TMA, which is a transcription-based nucleic acid
amplification method that utilizes two enzymes, MMLV reverse transcriptase and
T7 RNA polymerase.  The reverse transcriptase is used to generate a DNA copy
(containing a promoter sequence for T7 RNA polymerase) of the target RNA
sequence.  T7 RNA polymerase produces multiple copies of RNA amplicon from the
DNA copy template.  The Procleix WNV Assay utilizes the TMA method to amplify
regions of WNV RNA.

 

Detection is achieved by HPA using single-stranded nucleic acid probes with
chemiluminescent labels that are complementary to the amplicon.  The labeled
nucleic acid probes hybridize specifically to the amplicon.  The Selection
Reagent differentiates between hybridized and unhybridized probes by
inactivating the label on unhybridized probes.  During the

 

--------------------------------------------------------------------------------

*Developed and manufactured by Gen-Probe Incorporated; distributed by Chiron
Corporation.

 

1

--------------------------------------------------------------------------------

 

detection step, the chemiluminescent signal produced by the hybridized probe is
measured in a luminometer and is reported as Relative Light Units (RLU).

 

Internal Control is added to each test specimen, external quality control (if
used), assay calibrator, and blank tube via the Target Capture Reagent that
contains the Internal Control.  The Internal Control in this reagent controls
for specimen processing, amplification and detection steps.  Internal Control
signal in each tube or assay reaction is discriminated from the WNV signal by
the differential kinetics of light emission from probes with different
labels(11).  Internal Control-specific amplicon is detected using a probe with
rapid emission of light (flasher signal).  Amplicon specific to WNV is detected
using probes with relatively slower kinetics of light emission (glower signal). 
The Dual Kinetic Assay (DKA) is a method used to differentiate between the
signals from flasher and glower labels(11).  When used for the detection of WNV,
the Procleix WNV Assay differentiates between Internal Control and WNV signals.

 

MATERIALS PROVIDED

 

 

Procleix® WNV Assay

 

5000 Test Kit P/N 301135

 

 

 

Internal Control Reagent

 

 

Target Capture Reagent

 

 

Amplification Reagent

 

 

Enzyme Reagent

 

 

Probe Reagent

 

 

Selection Reagent

 

 

Negative Calibrator

 

 

Positive Calibrator

 

 

Blank

 

 

 

MATERIALS REQUIRED, SOLD SEPARATELY

 

Procleix® Assay Fluids

 

P/N 301027

Wash Solution

 

 

Oil

 

 

Buffer for Deactivation Fluid

 

 

 

 

 

Procleix® Auto Detect Reagents

 

P/N 301121

Auto Detect 1

 

 

Auto Detect 2

 

 

 

 

 

Disposables

 

 

(Disposables are single use only, do not reuse. Use of other disposables is not
recommended.)

 

 

Ten-Tube Units (TTUs)

 

P/N TU0040

Ten Tip Cassettes

 

P/N 104578

Sealing Cards

 

P/N 102085

 

 

 

Procleix® WNV
Assay Calibrators and Blank

 

P/N 301151

 

 

 

Positive Calibrator

 

 

Negative Calibrator

 

 

Blank

 

 

 

 

 

Procleix® WNV
Proficiency Panels

 

P/N 301152

 

 

 

Positive Panel Members

 

 

Negative Panel Members

 

 

 

Chiron CPT (Correlated Pipetting Transfer) Pooling Software (Only required for
pooling)

 

The Chiron® CPT Pooling Software, used in combination with the TECAN GENESIS
RSP, performs sample scanning and pooling operations that combine aliquots from
individual samples into a single Master Pool Tube, which may be used for further
testing.

 

Equipment

 

Procleix® System (available from Chiron Corporation)

 

Dedicated fixed or adjustable repeat pipettor capable of delivering 400 µL of
Target Capture Reagent with a ± 5% accuracy and a precision of < 5% CV. (Only
required for manual sample pipetting method.)

 

Dedicated single channel pipettor capable of delivering 500 µl of specimen with
a ± 5% accuracy and a precision of < 5% CV.(only required for manual sample
pipetting method.)

 

MATERIALS REQUIRED BUT NOT PROVIDED

 

Eppendorf COMBITIPS repeat pipettor tips (12.5 mL, 5.0 mL, 1.25 mL) or
equivalent

 

Disposable 1000 µL filter tips in rack

 

Bleach

 

For use in final concentration of 5% sodium hypochlorite and 0.5% sodium
hypochlorite

 

Bleach alternative (optional)

 

Contact Chiron Technical Support for a list of bleach alternatives and
instructions for use.

 

Sterile, polypropylene conical tubes with sealing caps

 

Freestanding tubes are recommended in two different sizes (5 mL to 10 mL tube
and > 30 mL tube).  The tubes must be able to accommodate the diameter of an
Eppendorf Repeat pipettor tip

 

TECAN GENESIS disposable 1000 µL conductive filter tips

 

TECAN 100 mL reagent troughs

 

REAGENTS

 

Procleix® WNV Assay Kit:

 

P/N 301135 – 5000 Test Kit

 

CONTENTS

 

Number of vials/
Volume per vial

 

 

 

Reagent Name

 

5000
Test Kit

 

 

 

Internal Control Reagent

 

10 X 5 mL

A HEPES buffered solution containing detergent and an RNA transcript.

 

 

Store unopened reagent at –15° to –35°C.

 

 

 

 

 

Target Capture Reagent

 

10 X 280 mL

A HEPES buffered solution containing detergent, capture oligonucleotides and
magnetic microparticles.

 

 

Store at 2° to 8°C.  (Do not freeze)
Internal Control Reagent must be added to Target Capture Reagent before use in
the assay.

 

 

 

INO135 Rev. 1

 

2

--------------------------------------------------------------------------------

 

Amplification Reagent

 

15 X 32 mL

Primers, dNTPs, NTPs and co-factors in TRIS buffered solution containing PROCLIN
300 as preservative.
Store unopened reagent at –15° to –35°C.

 

 

 

 

 

Enzyme Reagent

 

10 X 18 mL

MMLV Reverse Transcriptase and T7 RNA Polymerase in HEPES/TRIS buffered solution
containing 0.05% sodium azide as preservative.
Store unopened reagent at –15° to –35°C.

 

 

 

 

 

Probe Reagent

 

10 X 75 mL

Chemiluminescent oligonucleotide probes in succinate buffered solution
containing detergent.
Store unopened reagent at –15° to –35°C.

 

 

 

 

 

Selection Reagent

 

10 X 180 mL

Borate buffered solution containing surfactant.
Store at 15° to 30°C.

 

 

 

 

 

Negative Calibrator

 

90 X 2 mL

A HEPES buffered solution containing detergent.
Store at –15° to –35°C.

 

 

 

 

 

Positive Calibrator

 

90 X 2 mL

A HEPES buffered solution containing detergent and a WNV RNA transcript.
Store at –15° to -35°C.

 

 

 

 

 

Blank

 

90 X 2 mL

A HEPES buffered solution containing detergent.
Store at –15° to –35°C.

 

 

 

STORAGE INSTRUCTIONS

 

A.                                   Room temperature is defined as 15° to 30°C.

 

B.                                     [GRAPHIC] The Probe Reagent is light
sensitive.  Protect this reagent from light during storage and preparation for
use.

 

C.                                     Target Capture Reagent (TCR) is stable
when stored unopened at 2° to 8°C.  If a precipitate forms in the Target Capture
Reagent during storage, see instructions under REAGENT PREPARATION.  DO NOT
VORTEX. DO NOT FREEZE Target Capture Reagent.

 

NOTE:  If after removing the TCR from storage at 2° to 8°C, the precipitate is
allowed to settle to the bottom of the container, the likelihood of the
formation of a gelatinous precipitate is increased substantially.

 

D.                                    Selection Reagent is stable when stored
unopened at room temperature.  Mix thoroughly prior to use.

 

E.                                      The following reagents are stable when
stored unopened at room temperature until the expiration date.

Wash Solution

Oil

Auto Detect 1

Auto Detect 2

Buffer for Deactivation Fluid

 

Do not use after the expiration date.

 

Note:  These are universal fluids and may be used with all Procleix assays.

 

F.                                      Once opened, Wash Solution, Oil,
Selection Reagent, Buffer for Deactivation Fluid, Auto Detect 1 and Auto Detect
2 are stable for 30 days when stored at room temperature.

 

G.                                     The following reagents are stable when
stored unopened at -15° to -35°C.

Internal Control Reagent

Amplification Reagent

Enzyme Reagent

Probe Reagent

Negative Calibrator

Positive Calibrator

Blank

 

H.                                    After thawing, the Amplification Reagent,
Enzyme Reagent, Probe Reagent, are stable when stored at 2° to 8°C for 30 days. 
Once completely thawed, these reagents may be kept at room temperature up to 8
hours per 24-hour period while in use, not to exceed 80 hours at room
temperature.  Do not refreeze Internal Control, Amplification, Enzyme, or Probe,
Reagents after the initial thaw.

 

I.                                         After thawing, the Negative
Calibrator, the Positive Calibrator, and the Blank may be kept at room
temperature up to 8 hours.  These are single use vials and must be discarded
after use.

 

J.                                        After addition of Internal Control
Reagent, the working Target Capture Reagent is stable when stored at 2° to 8°C
for 30 days and may be kept at room temperature up to 8 hours per 24-hour period
while in use, not to exceed 80 hours at room temperature.

 

K.                                    If precipitate forms in the Wash Solution,
Amplification Reagent, Probe Reagent, Negative Calibrator, Positive Calibrator
or Blank warm to 15° to 30°C and mix thoroughly prior to use.  See instructions
under REAGENT PREPARATION.

 

L.                                      If precipitate forms in the Selection
Reagent during storage, see instructions under REAGENT PREPARATION.

 

M.                                 Changes in the physical appearance of the
reagent supplied may indicate instability or deterioration of these materials. 
If changes in the physical appearance of the reagents are observed (e.g.,
obvious changes in reagent color or cloudiness apparent with microbial
contamination), they should not be used.

 

N.                                    The Blank is not master lot matched and
may be used with any master lot of reagents.

 

INO135 Rev. 1

 

3

--------------------------------------------------------------------------------

 

PRECAUTIONS

 

A.                                    For Investigational Use Only.  The
performance characteristics of this product have not been established.

 

B.                                     Specimens may be infectious.  Use
Universal Precautions when performing the assay(15).  Proper handling and
disposal methods should be established according to local, state and federal
regulations(12-14).  Only personnel qualified as proficient in the use of the
Procleix® WNV Assay, the use of the TECAN GENESIS RSP and/or manual sample/TCR
pipetting, and trained in handling infectious materials should perform this
procedure.

 

C.                                     Use routine laboratory precautions.  Do
not pipette by mouth.  Do not eat, drink or smoke in designated work areas. 
Wear disposable gloves and laboratory coats when handling specimens and kit
reagents.  Wash hands thoroughly after handling specimens and kit reagents.

 

D.                                    To reduce the risk of invalid results,
carefully read the entire package insert for the Procleix WNV Assay and the
operator’s manuals for the Procleix System prior to performing an assay run.

 

E.                                      Material Safety Data Sheets are
available upon request.

 

F.                                      Avoid contact of Auto Detect Reagents 1
and 2 with skin, eyes and mucous membranes.  Wash with water if contact with
these reagents occurs.  If spills of these reagents occur, dilute with water
before wiping dry and follow appropriate site procedures.

 

G.                                     Dispose of all materials that have come
in contact with specimens and reagents according to local, state and federal
regulations(12-13).  Thoroughly clean and disinfect all work surfaces.

 

H.                                    Use only supplied or specified required
disposables.

 

I.                                         DO NOT interchange, mix, or combine
reagents from kits with different master lot numbers.

 

J.                                        Avoid microbial and ribonuclease
contamination of reagents.

 

K.                                    Store all assay reagents at specified
temperatures.  The performance of the assay may be affected by use of improperly
stored assay reagents.  See STORAGE INSTRUCTIONS and REAGENT PREPARATION.

 

L.                                      Do not combine any assay reagents or
fluids without specific instruction.

 

REAGENT PREPARATION

 

This step should be performed prior to beginning Target Capture in an area that
is free of template and amplicon.

 

Room temperature is defined as 15° to 30°C.

 

1.                                       Warm all reagents to room temperature
and mix thoroughly prior to use.  A dedicated waterbath at room temperature may
be used to aid this process.  Ensure that precipitates are dissolved.  Do not
use a reagent if precipitate or cloudiness is present.  See step 6 for Target
Capture Reagent preparation.

 

2.                                       DO NOT heat Probe Reagent, above 30°C.

 

3.                                       Thaw reagents upright.

 

4.                                       If necessary, thaw Amplification, Probe
and Enzyme Reagents at room temperature or at 2° to 8°C. Internal Control,
Amplification and Probe Reagents may be mixed by vortexing.  Enzyme Reagent
should be mixed thoroughly by gentle inversion taking care to avoid excessive
foaming.  Once completely thawed, these reagents may be kept at room temperature
up to 8 hours per 24-hour period while in use.  These reagents are stable for 30
days when stored at 2° to 8°C.  Record date of thaw (THAW DATE) for
Amplification, Probe and Enzyme Reagents in the space provided on the label.

 

5.                                       Precipitate will form in the Probe
Reagent when stored at 2° to 8°C.  Probe Reagent may be warmed in a water bath
to facilitate dissolution of precipitate, but temperature in the bath should not
exceed 30°C.  The Probe Reagent may take up to 4 hours with periodic mixing to
allow complete dissolution of precipitate if thawing is conducted on the lab
bench.  Ensure that precipitates in the Probe Reagent are dissolved.  Do not use
if precipitate or cloudiness is present.

 

6.                                       Selection Reagent is stored at room
temperature.  If Selection Reagent has been inadvertently stored at 2° to 8°C or
the temperature of the laboratory falls below 15°C, precipitate may form.  If
precipitate forms in the Selection Reagent during storage, heat at 60° ± 1° C
for no more than 45 minutes, shaking the bottle frequently (every 5 to 10
minutes).  Once all precipitate has gone back into solution, place the bottle in
a room temperature water bath and allow the bottle to equilibrate for at least 1
hour.  Do not use the Selection Reagent until it has equilibrated.  The
Selection Reagent must be at room temperature before use.  Do not use if
precipitate or cloudiness is present.

 

7.                                       Prepare working Target Capture Reagent:
thaw one vial of Internal Control Reagent at room temperature or 2° to 8°C.  Mix
the Internal Control Reagent thoroughly by inversion.  Remove Target Capture
Reagent (TCR)  from 2° to 8°C storage.  IMMEDIATELY upon removing from storage,
mix vigorously (at least 10 inversions).  DO NOT VORTEX.  After mixing, place
the TCR bottle at 22° to 30°C.  Approximately every 10 minutes shake the bottle
until all precipitate has disappeared.  TCR precipitate should normally dissolve
in about 30 minutes.  If a gel is observed after performing this procedure, a
new bottle must be used according to the handling recommendations above.  Return
the bottle with gel back to 2° to 8°C storage for subsequent use.  When the
Internal Control Reagent and TCR have reached room temperature, mix TCR
thoroughly by inversion.  Pour the entire vial of Internal Control Reagent into
the TCR bottle.  The total time for each of these reagents at room temperature
must not exceed 8 hours, in the first 24-hour period.  This is now the working
Target Capture Reagent.  Mix thoroughly.  Use the space indicated on the TCR
bottle to record the date Internal Control Reagent was added and lot number used
(IC LOT).  Record the date of manufacture of the working TCR in the space
provided on the label.

 

8.                                       Thaw calibrators and Blank at room
temperature.  These are single use vials and must be thawed prior to each run. 
Once thawed, use calibrators and blank within 8 hours.  Mix thoroughly by
inversion.

 

9.                                       Wash Solution is shipped at ambient
temperature and stored at room temperature.  Precipitates may form in the Wash
Solution during shipment or during storage when temperatures fall below 15°C. 
Wash Solution may be incubated in a warm water bath to facilitate dissolution of
precipitate.  Temperature in the bath should not exceed 30°C.  Ensure that
precipitates in

 

INO135 Rev. 1

 

4

--------------------------------------------------------------------------------

 

the Wash Solution are dissolved prior to use.  Do not use if precipitate or
cloudiness is present.

 

10.                                 Once opened, Wash Solution, Oil, Selection
Reagent, Buffer for Deactivation Fluid, Auto Detect 1 and Auto Detect 2 are
stable for 30 days when stored at room temperature.  Record the date the reagent
was first opened (OPEN DATE) in the space provided on the label.

 

11.                                 To prepare Deactivation Fluid, mix one part
Buffer for Deactivation Fluid with one part 5% sodium hypochlorite. 
Deactivation Fluid is stable for 30 days when stored at room temperature.

 

SPECIMEN COLLECTION, STORAGE AND HANDLING

 

NOTE:  Handle all specimens as if they are potentially infectious agents.

 

Take care to avoid cross-contamination during the sample handling steps.  For
example, discard used material without passing over open tubes.

 

A.                                   Plasma collected in K2EDTA, K3EDTA,
heparin, or in Becton Dickinson EDTA Plasma Preparation Tubes (PPT) may be
used.  Follow sample tube manufacturer’s instructions.  Specimen stability is
affected by elevated temperature.  Whole blood or plasma from pooled or
individual donor specimens may be stored for up to 72 hours from time of draw at
£ 25°C; temperatures not to exceed 30°C are acceptable for no more than 24
hours.  Specimens may be stored an additional five days at 2° to 8°C following
centrifugation.  Plasma separated from the cells may be stored for longer
periods of time at £ -20°C before testing.

 

Do not freeze whole blood.

 

[ex10-325image002.jpg]

 

--------------------------------------------------------------------------------

*The 2-30°C and 2-25°C periods indicated above may occur at any time.

 

B.                                     Additional specimens taken from blood or
plasma units collected in ACD or sodium citrate according to the collection
container manufacturer’s instructions may be used.  ACD or sodium citrate whole
blood or plasma may be stored as in A. above.

 

C.                                     Additional specimens may be taken from
whole blood or plasma units containing CPD, CP2D, or CPDA-1 anticoagulants
collected according to the collection container manufacturer’s instructions. 
Whole blood (not plasma units) collected in these anticoagulants may be stored
for up to 13 days at 2° to 8°C prior to centrifugation.  At any time within this
13-day period, the whole blood unit may have been stored for up to one day at
30°C and up to two days at 25°C.  Following centrifugation, the plasma may be
stored for an additional five days at 2° to 8°C before testing. Plasma separated
from the cells may be stored for longer periods of time at £ -20°C before
testing.

 

D.                                    No adverse effect on assay performance was
observed when plasma was subjected to three freeze-thaw cycles.

 

E.                                      Mix thawed plasma thoroughly and
centrifuge for 10 minutes at 1000 to 3000 X g before testing.  Centrifugation
times and speeds for thawed PPT tubes must be validated by the user.

 

F.                                      Other collection and storage conditions
should be validated by the user.  If specimens are to be shipped, they should be
packaged and labeled in compliance with applicable federal and international
regulations covering the transport of clinical specimens and etiologic
agents.(14)

 

G.                                     False positive results may occur if cross
contamination of specimens is not adequately controlled during specimen handling
and processing.

 

H.                                    Specimen Pooling

 

The Chiron CPT Pooling Software, used in combination with the TECAN GENESIS RSP,
performs sample scanning and pooling operations that combine aliquots from
individual samples into a single Master Pool Tube, which may be used for further
testing.

 

PROCEDURAL NOTES

 

A.                                   RUN SIZE

 

When the average run size is 55 tests or more, P/N 301135 should yield 5000
tests per kit.  Smaller run sizes will result in a lower yield.  Each run of up
to 100 tests must contain 3 replicates each of the Negative Calibrator, the
Positive Calibrator and the Blank.

 

B.                                     EQUIPMENT PREPARATION

 

1.                                       Three dedicated circulating water baths
must be used: one for target capture and pre-amplification (60° ± 1°C), one for
amplification (41.5° ± 1°C) and one for hybridization and selection (60° ±
1°C).  An additional water bath is required to be maintained at 23° ± 4°C for
the step preceding detection.

 

2.                                       Equilibrate circulating water baths to
60° ± 1°C for target capture and 41.5° ± 1°C for amplification incubations.

 

3.                                       Prepare the TECAN GENESIS RSP for use
according to instructions in the Operator’s Manual.

 

4.                                       Prepare the Chiron® Procleix® TCS for
use according to instructions in the Operator’s Manual.

 

5.                                       Wipe work surfaces and pipettors daily
with diluted bleach (0.5% sodium hypochlorite in water).  Allow bleach to
contact surfaces and pipettors for at least 15 minutes and then follow with a
water rinse.  A BLEACH ALTERNATIVE MAY BE USED IN PRE-AMPLIFICATION AREAS ONLY. 
DO NOT USE BLEACH ALTERNATIVES IN AMPLIFICATION AREAS OR IN AREAS SUSPECTED TO
BE CONTAMINATED WITH AMPLIFICATION PRODUCTS.  DO NOT USE DEACTIVATION FLUID ON
SURFACES.

 

6.                                       Equilibrate a circulating water bath to
60° ± 1°C for hybridization and selection incubations.  Prepare an additional
container of water at 23° ± 4°C for cool down prior to detection.

 

INO135 Rev. 1

 

5

--------------------------------------------------------------------------------

 

7.                                       Setup procedures for the Chiron
Procleix HC+ Luminometer are given in the Operator’s Manual.

 

C.                                     REAGENTS

 

1.                                       Add all reagents using an Eppendorf
repeat pipettor (or equivalent) capable of delivering specified volume with ± 5%
accuracy and a precision of < 5% CV.  Check pipettor functionality monthly and
calibrate regularly.

 

2.                                       To minimize waste of Amplification,
Oil, Enzyme, Probe, and Selection Reagents, aliquot each reagent for a given run
size.  Aliquoting must be performed after reagent preparation using sterile,
polypropylene conical tubes with sealing caps in an area that is template and
amplicon free.  The aliquoting area must be wiped down with diluted bleach (0.5%
sodium hypochlorite in water) before and after the aliquoting process.  A BLEACH
ALTERNATIVE MAY BE USED IN PRE-AMPLIFICATION AREAS ONLY.  DO NOT USE BLEACH
ALTERNATIVES IN AMPLIFICATION AREAS OR IN AREAS SUSPECTED TO BE CONTAMINATED
WITH AMPLIFICATION PRODUCTS.  The aliquoted reagents must be used the same day
the aliquoting was performed.  DO NOT store reagents in the aliquot conical
tubes.

 

3.                                       A color change will occur in the
reaction tube after the addition of Amplification Reagent, Enzyme Reagent, Probe
Reagent, and Selection Reagent.

 

D.                                    WORK FLOW

 

1.                                       To minimize the possibility of
laboratory areas from becoming contaminated with amplicon, the laboratory area
should be arranged with a uni-directional workflow.  Proceed from reagent
preparation to sample preparation to amplification and then to detection areas. 
Samples, equipment and reagents should not be returned to the area where a
previous step was performed.  Also, personnel may not move from the dedicated
HPA area back into previous work areas without proper anti-contamination
safeguards.

 

2.                                       Perform reagent preparation in a
template free area.

 

3.                                       Perform Target Capture and
Pre-Amplification steps in an amplicon-free area.

 

4.                                       Perform Hybridization Protection Assay
in an area separate from the reagent preparation and amplification areas.

 

Note:      Upon completion of pipetting specimens (individual samples or pools)
into TTUs, the TTUs are removed from the deck and loaded into a TTU rack.  If
the operator needs to pipette the same specimens (individual samples or pools)
for a different Procleix assay, the empty calibrator tubes and TCR trough must
be discarded but the specimens may be left on the deck.  The operator should
then change gloves after emptying the used empty calibrator tubes and TCR
trough.  Clean TTUs should then be loaded into the TTU carriers on the deck. 
Proceed with step A.3, under INSTRUCTIONS FOR USE.

 

E.                                      TEMPERATURE

 

1.                                       The Target Capture, Amplification,
Hybridization and Selection reactions are temperature dependent.  Therefore, it
is imperative that the water baths are maintained within the specified
temperature range.  Use a calibrated thermometer.

 

2.                                       Room temperature is defined as 15° to
30°C.

 

3.                                       Detection is sensitive to temperature. 
The laboratory temperature in the detection area must be 21° to 27°C.

 

F.                                      TIME

 

1.                                       The Target Capture, Amplification, and
Hybridization Protection Assay steps are all time dependent.  Adhere to specific
times outlined in INSTRUCTIONS FOR USE. Use a calibrated timer.

 

G.                                     VORTEXING

 

1.                                       Proper vortexing is important to the
successful performance of the Procleixâ WNV Assay.  Vortex equipment speed
settings may vary.  Start the vortexor at low speed and then adjust upward to
allow reaction mixture to reach and maintain a height within the upper half of
all tubes.  The reaction mixture should never touch the sealing cards.  It is
critical to have a homogeneous mixture after the additions of the Probe Reagent
and Selection Reagent.

 

H.                                    PIPETTING

 

1.                                       All the pipettes used in the Target
Capture, Amplification and HPA steps must be dedicated for these purposes only
to avoid cross contamination.

 

2.                                       Take care to deliver reagents,
excluding working TCR, to each tube without inserting pipette tip into the tube
or touching the rim of the tube to minimize the chance of carryover from one
tube to another.

 

I.                                         MANUAL SPECIMEN PIPETTING

 

1.                                       When using the manual sample/TCR
pipetting method, improper pipetting technique will affect the results of the
assay.  See PROCEDURAL NOTES, Section H. In order to avoid the loss of Positive
ID Tracking, verification of correct sample ID by a second individual is
recommended.

 

2.                                       Ensure that the TTU is oriented in the
rack with the pointed end on the left side and the rounded end on the right side
of the rack.  Pipette the first calibrator into the first tube next to the
pointed end of the TTU.  Samples are pipetted from left to right.

 

3.                                       Use a new pipette tip for each sample
and dispose of the tip in a biological waste container after use.  Take care to
avoid cross-contamination by pipetting the specimens and discarding the used
pipette tips without passing over open tubes or touching laboratory surfaces or
other pieces of equipment.

 

4.                                       To avoid the risk of contamination,
clean and decontaminate manual sample pipettors between assay runs.

 

5.                                       Ensure proper sample placement into the
correct TTU position as indicated on the manual work list record.

 

J.                                        DECONTAMINATION

 

1.                                       The extremely sensitive nature of the
test makes it imperative to take all possible precautions to avoid
contamination.  Laboratory bench surfaces, and pipettes must be decontaminated
daily with diluted bleach (0.5% sodium hypochlorite in water).  Allow bleach to
contact surfaces for at least 15 minutes and then follow with a water rinse. 
Chlorine solutions may pit equipment and metal.  Thoroughly rinse bleached
equipment to avoid pitting.

 

2.                                       A BLEACH ALTERNATIVE MAY BE USED IN
PRE-AMPLIFICATION AREAS ONLY.  DO NOT USE BLEACH ALTERNATIVES IN AMPLIFICATION
AREAS OR IN AREAS SUSPECTED TO BE

 

INO135 Rev. 1

 

6

--------------------------------------------------------------------------------

 

CONTAMINATED WITH AMPLIFICATION PRODUCTS.

 

3.                                       Reactions must be decontaminated with
Deactivation Fluid as described in the detection procedure.

 

K.                                    SEALING CARDS

 

1.                                       When applying sealing cards, cover the
TTUs with the sealing card and press gently to ensure complete contact with all
of the tubes.  Always use a new sealing card.  DO NOT re-use sealing cards.

 

2.                                       When removing sealing cards, carefully
lift and peel in one continuous motion to avoid aerosols and cross
contamination.  Immediately dispose of card in appropriate waste container.

 

INSTRUCTIONS FOR USE:

 

PROCLEIXâ WNV ASSAY ON INDIVIDUAL DONOR PLASMA SAMPLES OR ON POOLED PLASMA
SAMPLES

 

All specimens (individual donations or pooled samples) should be run in singlet
in the initial Procleixâ WNV Assay.

 

Procleixâ WNV Assay Calibrators are to be used with the corresponding master lot
of the Procleix WNV Assays.  The operator must check to ensure that the Procleix
WNV Assay Calibrators are used with the corresponding master lot of kit reagents
as indicated on the master lot sheet enclosed with each shipment of Procleix WNV
Assay Calibrators.

 

To run the Procleix WNV Assay for the detection of WNV RNA, follow the steps
below for Target Capture, Amplification and Hybridization Protection Assay.

 

Note: Continuous Process Flow:

 

All process steps described below are intended to be completed in a continuous
flow with a minimal, if any, delay between steps.

 

A.                                    TARGET CAPTURE

 

The Procleix WNV Assay has been verified using the TECAN GENESIS RSP.  The use
of manual pipetting requires additional operator training and demonstration of
proficiency.  Repeat pipettors used in this step must be dedicated for use only
in the TARGET CAPTURE steps.

 

IF USING THE TECAN GENESIS RSP PIPETTOR:

 

1.                                       Start the Chironâ Procleixâ Assay
Software.  Refer to the Procleix Assay Software Operator’s Manual for software
operating instructions.

 

2.                                       Place TTU Carriers on the TECAN GENESIS
RSP deck according to the deck layout indicated on the screen.  Load sufficient
Ten Tube Units (TTUs) for the run into TTU Carriers.

 

3.                                       Mix working Target Capture Reagent
thoroughly to resuspend microparticles.  This is important before putting into
the TECAN GENESIS RSP reagent trough.  Put sufficient working Target Capture
Reagent into the reagent trough and place on the TECAN GENESIS RSP deck as
indicated on the deck layout screen.  If pipetting can not be completed within 2
hours, remix prior to use.

 

4.                                       Place calibrators, blank, and samples
into TECAN 16-Tube Strip Racks.  Place TECAN 16-Tube Strip Racks on the TECAN
GENESIS RSP deck according to the deck layout indicated on the screen.

 

Note: Samples may already be in strip racks, on the Tecan deck, from pipetting a
prior Procleix assay.

 

5.                                       Reference the Procleixâ Assay Software
Operator’s Manual for instructions on pipetting.  The TECAN GENESIS RSP will
read bar codes of all carriers, TTUs, calibrators, blanks, and samples.  The
TECAN GENESIS RSP will pipette 400 mL of working TCR into each reaction tube and
then pipette 500 mL each of calibrators, blank, and test samples into assigned
reaction tubes.  An electronic work list will be created.

 

6.                                       When all samples have been pipetted,
transfer the TTUs to a TTU rack.  Cover the TTUs with sealing cards.  See
PROCEDURAL NOTES.

 

7.                                       Vortex the rack of TTUs a minimum of 20
seconds and until magnetic microparticles are resuspended.  See PROCEDURAL
NOTES.

 

8.                                       Rack may remain at room temperature up
to 75 minutes prior to proceeding to the 60°C ± 1°C incubation.

 

9.                                       Incubate the tubes in a water bath at
60° ± 1°C for 20 minutes ± 1 minute.

 

10.                                 Remove the rack of TTUs and transfer to
target capture area.

 

11.                                 Incubate the rack of TTUs on the lab bench
at room temperature for 14 minutes to 20 minutes.

 

12.                                 Transfer the rack of TTUs to the Chironâ
Procleixâ TCS separation bay for 9 to 20 minutes.

 

13.                                 Carefully remove and dispose of the sealing
cards.  See PROCEDURAL NOTES.

 

14.                                 Aspirate the solution from each tube
according to the Procleixâ TCS Operator’s Manual.

 

15.                                 Add 1 mL of Wash Solution to each tube. 
Cover the TTUs with sealing cards.  See PROCEDURAL NOTES.  Remove the rack of
TTUs from the Chiron Procleix TCS separation bay and vortex to resuspend the
microparticle pellets.  See PROCEDURAL NOTES.

 

16.                                 Place the rack of TTUs on the Chiron
Procleix TCS separation bay for  4 to 10 minutes.

 

17.                                 Carefully remove and dispose of the sealing
cards.  See PROCEDURAL NOTES.

 

18.                                 Aspirate the solution from each tube
according to the Procleix TCS Operator’s Manual.

 

19.                                 Add 1 mL of Wash Solution to each tube. 
Cover the TTUs with sealing cards.  Remove the rack of TTUs from the Target
Capture System separation bay and vortex to resuspend the
microparticle pellets.  See PROCEDURAL NOTES.

 

20.                                 Place the rack of TTUs on the Chiron
Procleix TCS separation bay for 4 to 10 minutes.

 

21.                                 Carefully remove and dispose of the sealing
cards.  See PROCEDURAL NOTES.

 

22.                                 Completely aspirate the solution from each
tube according to the Procleix TCS Operator’s Manual.  Cover the TTUs with a
sealing card.

 

23.                                 Remove the rack of TTUs from the Chiron
Procleix TCS separation bay and proceed directly to Amplification.

 

IF USING THE MANUAL SAMPLE PIPETTING METHOD:

 

The assay results within the run report will be marked “M” indicating that the
specimens were manually pipetted.

 

1.                                       For sample tracking, an electronic
worklist must be created using the Procleix Worklist Editor software.  Refer to
the Worklist Editor Operator’s Manual for instructions.  Verification of correct
sample ID on the

 

INO135 Rev. 1

 

7

--------------------------------------------------------------------------------

 

 

worklist with the specimen tubes and with the detailed assay run report by a
second individual is recommended.

 

2.                                       Load sufficient Ten Tube Units (TTUs)
for the run into a TTU rack.

 

3.                                       Thoroughly mix working TCR immediately
before use to resuspend microparticles.

 

4.                                       Refer to the worklist and carefully
pipette 400 mL of working TCR to each reaction tube that will contain a
specimen.  To dispense, insert the tip approximately one quarter of the way into
the tube at an angle and pipette working TCR down the side of the tube.  Always
pipette the working TCR first, followed by the specimen.

 

5.                                       Pipette specimens.

a.                                       Refer to the worklist to identify the
TTU number with the corresponding calibrator and test specimen identification
numbers.

b.                                      Aspirate 500 mL of each calibrator,
external quality control (if used), blank, or test sample from its collection
tube using a single channel pipettor with corresponding filtered disposable
tip.  Insert only the end of the pipette tip into the specimen.  Do not disturb
the sediment, if any.

c.                                       To dispense, insert the pipette tip
halfway into the tube taking care not to touch the sides of the upper half of
the tube with the pipette tip.  At an angle, pipette the specimen down the side
of the bottom half of the tube.  Hold down the plunger of the pipettor while
removing it from the tube.  Take care to avoid touching the rim or the side of
the tube with the pipette tip when removing it from the tube.

 

6.                                       Replace pipette tip with a new tip and
repeat Step 5 until all specimens have been pipetted.

 

7.                                       Visually inspect tubes to ensure proper
specimen volume and working TCR volume have been dispensed.

 

8.                                       Cover the TTUs with sealing cards.  See
PROCEDURAL NOTES. Proceed to Step 7 of section titled “If Using the TECAN
GENESIS RSP 150/8 Pipettor”, above.

 

B.                                    AMPLIFICATION

 

The repeat pipettors used in this step must be dedicated for use only in
AMPLIFICATION steps.  DO NOT USE BLEACH ALTERNATIVES IN THIS AREA.

 

1.                                       Carefully remove and dispose of the
sealing cards.  See PROCEDURAL NOTES.

 

2.                                       Deliver 75 mL of Amplification Reagent
to the bottom of each tube using the dedicated repeat pipettor.  Take care to
deliver the reagent to the bottom of each tube without inserting the pipette tip
into the tube or touching the rim of the tube.

 

3.                                       Add 200 mL of Oil to each reaction tube
using the dedicated repeat pipettor.  Angle the pipette tip toward the sides of
the tubes, not straight to the bottom, to avoid splashback.

 

4.                                       Cover the TTUs with sealing cards.  See
PROCEDURAL NOTES.

 

5.                                       Vortex the rack of TTUs a minimum of 20
seconds and until all microparticles are resuspended.  Ensure that magnetic
particles are no longer adhering to the walls of the tube, and are evenly
dispersed in the aqueous phase.

 

6.                                       Incubate the TTUs in a water bath at
60° ± 1°C for 10 minutes ± 1 minute, then at 41.5° ± 1°C for 9 to 20 minutes.

 

7.                                       Leaving the rack of TTUs at 41.5° ±
1°C, carefully remove and dispose of the sealing cards.  See PROCEDURAL NOTES.  
Proceed immediately to enzyme addition.  Add 25 mL of the Enzyme Reagent into
each tube using the dedicated repeat pipettor.  Take care to deliver the reagent
to the bottom of each tube without inserting the pipette tip into the tube or
touching the rim of the tube.  Place new sealing cards over the TTUs.  See
PROCEDURAL NOTES.  Remove the rack of TTUs from the water bath and shake to
mix.  DO NOT VORTEX.  Minimize the time the tubes are out of the water bath.

 

8.                                       Incubate the rack of TTUs in the water
bath at 41.5° ± 1°C for 60 minutes ± 5 minutes.

 

9.                                       Remove the rack of TTUs from the water
bath and transfer it to the Hybridization Protection Assay area.  Rack may
remain at room temperature for up to 30 minutes prior to the addition of Probe
Reagent.

 

C.                                    HYBRIDIZATION PROTECTION ASSAY (HPA)

 

The repeat pipettor used in this step must be dedicated for use only in
HYBRIDIZATION PROTECTION ASSAY.

 

A separate, dedicated location for the Hybridization Protection Assay (HPA) step
is recommended to minimize amplicon contamination in the assay.  This dedicated
area should be on a separate bench in a separate area from the reagent and
sample preparation and amplification areas.  DO NOT USE BLEACH ALTERNATIVES IN
THIS AREA.

 

1.                                       Hybridization

a.                                       Carefully remove and dispose of the
sealing cards.  See PROCEDURAL NOTES.

b.                                      Add 100 mL of Probe Reagent into each
tube using the dedicated repeat pipettor.  Take care to deliver the reagent to
the bottom of each tube without inserting the pipette tip into the tube or
touching the rim of the tube.  Angle the pipette tip toward the sides of the
tubes, not straight to the bottom, to avoid splashback.

c.                                       Cover the TTUs with sealing cards.  See
PROCEDURAL NOTES.

d.                                      Vortex the rack of TTUs a minimum of 20
seconds and until a homogeneous solution is achieved.  To avoid possible
contamination, do not allow reaction mixture to come in contact with the sealing
card.  See PROCEDURAL NOTES.

e.                                       Incubate the rack of TTUs in a
dedicated water bath at 60° ± 1°C for 15 minutes ± 1 minute.

 

2.                                       Selection

a.                                       Remove the rack of TTUs from the 60° ±
1°C water bath.  Carefully remove and dispose of the sealing cards.  See
PROCEDURAL NOTES.

b.                                      Add 250 mL of Selection Reagent to each
tube using a repeat pipettor.  Take care to deliver the reagent to the bottom of
each tube without inserting the pipette tip into the tube or touching the rim of
the tube.  Angle the pipette tip toward the sides of the tubes, not straight to
the bottom, to avoid splashback.

c.                                       Cover the TTUs with sealing cards.  See
PROCEDURAL NOTES.  Vortex the rack of TTUs a minimum of 20 seconds and until a
homogeneous solution is achieved.  To avoid possible contamination, do not allow
reaction mixture to come in contact with the sealing card.  See PROCEDURAL
NOTES.

 

INO135 Rev. 1

 

8

--------------------------------------------------------------------------------

 

d.                                      Return the rack of TTUs to the 60° ± 1°C
water bath for 10 minutes ± 1 minute.

e.                                       Remove the rack of TTUs from the 60° ±
1°C water bath.

f.                                         Cool the rack of TTUs in a 23° + 4°C
container of water for a minimum of 10 minutes while preparing for Detection
(step 3a).

g.                                      Remove the rack of TTUs from the 23° ±
4°C container of water onto absorbent material.

 

3.                                       Detection

a.                                       Prepare the Chiron Procleix HC+
Luminometer for operation as indicated in the Operator’s Manual.  Ensure that
there are sufficient volumes of Auto Detect 1 and Auto Detect 2 to complete the
tests.

b.                                      Select the “WNV” assay protocol from the
Chiron Procleix WNV System Software menu.

c.                                       Carefully remove and dispose of the
sealing cards.  See PROCEDURAL NOTES.

d.                                      Before transferring TTUs to the
luminometer, wipe the outside of the tubes using an absorbent tissue dampened
with deionized water.  This will ensure that no residue is present on the
outside of the tubes and will help reduce static electricity that may affect
luminometer readings.

e.                                       Transfer TTUs to the luminometer
according to the software instructions.  Note: Tube reading should be completed
within 75 minutes after completing the selection reaction (step 2e in Selection
procedure).

f.                                         When the analysis is complete, remove
the TTUs from the luminometer.

g.                                      After removing the TTUs from the
luminometer, add at least 1mL Deactivation Fluid to each tube.  Allow to sit at
room temperature for at least 30 minutes before disposing the contents of the
tubes.  This will help to prevent contamination of the laboratory environment
with amplicon.

h.                                      TTU racks should be decontaminated by
complete immersion in diluted bleach (0.5% sodium hypochlorite in water) for a
minimum of 15 minutes.  The bleach should then be rinsed off with water and the
rack may be allowed to air dry or may be wiped dry.

 

QUALITY CONTROL PROCEDURES:

 

PROCLEIXâ WNV ASSAY ON INDIVIDUAL DONOR PLASMA SAMPLES OR ON POOLED PLASMA
SAMPLES

 

I.                                         ACCEPTANCE CRITERIA FOR THE PROCLEIXâ
WNV ASSAY

 

Run Validity Criteria

 

A.                                   A run is valid if the minimum number of
calibrators is valid and calibrators meet acceptance criteria (see II below).

 

1.                                       In a Procleixâ WNV Assay run, at least
4 of the 6 calibrator replicates must be valid.  At least 2 of the 3 negative
calibrator replicates and 2 of the 3 positive calibrator replicates must be
valid.

 

2.                                       The Procleix System Software will
automatically invalidate a run if less than the minimum number of calibrators is
valid. All specimens in an invalid run due to calibrators must to be retested.

 

3.                                       Cutoff values will be automatically
calculated for Internal Control (flasher) and Analyte (glower) in a valid run
(see II.A. below).

 

4.                                       For Positive Calibrators or samples
which are Reactive for Analyte (glower signal), an Internal Control signal below
the cutoff is not used to invalidate the result.

 

5.                                       The Blank is not used to determine run
validity.  No results are reported for the Blank.

 

B.                                     Procleixâ  WNV Assay. The Procleix WNV
System Software will print an alert on the run report when more than 10% of the
calibrators and specimens in a run are invalid (see the Procleix HC+ Luminometer
Operator’s Manual for details).  Specimens that are invalid due to insufficient
sample or TCR are not included in the calculation of the 10% invalid criterion.

 

C.                                     For runs that exceed the 10% invalid
rate, review of package insert procedures should be performed to monitor for
operator errors.  In addition, the run report should be reviewed using the
criteria described below.

 

1.                                       If the invalid specimens are all from
the same TTU, those specimens contributing to the 10% invalid rate may have been
inadequately washed, or erroneous reagent addition may have occurred.  All
nonreactive and invalid specimens in the affected TTU should be repeated.

 

2.                                       If the invalid specimens are randomly
located throughout the run, there were calibrator failures, and no specific
procedural error can be identified, the nonreactive and invalid specimens must
be repeated.

 

Note: Reactive specimens in a manually invalidated run due to the 10% invalid
alert criteria, must become the test of record.  The specimens should be
resolved according to the resolution algorithm for reactive specimens, as
explained in the INTERPRETATION OF RESULTS section, step 4.

 

D.                                    An assay run or an individual sample may
also be invalidated by an operator if specific technical/operator/instrument
difficulties were observed and documented.  If individual samples are
invalidated by an operator, then the percent invalid rate must be manually
recalculated.  The individual invalid specimens must be repeated.

 

II.                                     ACCEPTANCE CRITERIA FOR THE CALIBRATION
AND CALCULATION OF CUTOFF

 

Procleixâ WNV Assay

Negative Calibrator Acceptance Criteria

 

Each individual Negative Calibrator (NC) must have an Internal Control (IC)
value greater than or equal to 75,000 RLU and less than or equal to 400,000
RLU.  Each individual Negative Calibrator must also have an Analyte value less
than or equal to 40,000 RLU and greater than or equal to 0 RLU.  If one of the
Negative Calibrator values is invalid due to an IC value or an Analyte value
outside of these limits, the Negative Calibrator mean (NCx) will be recalculated
based upon the two acceptable values.  The run is invalid and must be repeated
if two or more of the three Negative Calibrator values have IC values or Analyte
values that are outside of these limits.

 

INO135 Rev. 1

 

9

--------------------------------------------------------------------------------

 

Determination of the mean of the Negative Calibrator values (NCx) for Internal
Control [NCx (Internal Control)].

 

Example:

Negative Calibrator

 

Internal Control
Relative Light Units

1

 

235,000

2

 

200,000

3

 

210,000

Total Internal Control RLU =

 

645,000

 

NCx (Internal Control) =

Total Internal Control RLU

 = 215,000

 

3

 

 

Determination of the mean of the Negative Calibrator values (NCx) for Analyte
[NCx (Analyte)].

 

Example:

Negative Calibrator

 

Analyte
Relative Light Units

1

 

14,000

2

 

16,000

3

 

15,000

Total Analyte RLU =

 

45,000

 

NCx (Analyte) =

Total Analyte RLU

= 15,000

 

3

 

 

Positive Calibrator Acceptance Criteria

 

Individual Positive Calibrator (PC) Analyte values must be less than or equal to
2,700,000 RLU and greater than or equal to 400,000 RLU.  If one of the Positive
Calibrator values is outside these limits, the Positive Calibrator mean (PCx)
will be recalculated based upon the two acceptable Positive Calibrator values. 
The run is invalid and must be repeated if two or more of the three Positive
Calibrator Analyte values are outside of these limits.  IC values may not exceed
500,000 RLU.

 

Determination of the mean of the Positive Calibrator (PCx) values for Analyte
[PCx (Analyte)].

 

Example:

Positive Calibrator

 

Analyte
Relative Light Units

1

 

1,250,000

2

 

1,500,000

3

 

1,150,000

Total Analyte RLU =

 

3,900,000

 

PCx (Analyte) =

Total Analyte RLU

= 1,300,000

 

3

 

 

Calculation of the Internal Control Cutoff Value

 

Internal Control Cutoff Value = 0.5 X [NCx (Internal Control)]

 

Using values given in the Negative Calibrator example above:

 

Internal Control Cutoff Value = 0.5 X (215,000)

 

Internal Control Cutoff Value = 107,500 RLU

 

Calculation of the WNV Analyte Cutoff Value

 

Analyte Cutoff Value = NCx (Analyte) + [0.03 X WNV PCx (Analyte)]

 

Using values given in the Negative Calibrator and Positive Calibrator examples
above:

 

Analyte Cutoff Value = 15,000 + (0.03 X 1,300,000)

 

Analyte Cutoff Value = 54,000 RLU

 

Summary of Acceptance Criteria for Procleixâ WNV Assay

 

Acceptance Criteria:

 

Negative Calibrator

 

 

Analyte

 

> 0 and < 40,000 RLU

Internal Control

 

> 75,000 and < 400,000 RLU

 

 

 

Positive Calibrator

 

 

Analyte

 

> 400,000 and < 2,700,000 RLU

Internal Control

 

< 500,000 RLU

 

Summary of Cutoff Calculations for Procleixâ WNV Assay

 

Analyte Cutoff =

 

NC Analyte Mean RLU

 

 

+ 0.03 X (PC Analyte Mean RLU)

 

 

 

Internal Control Cutoff =

 

0.5 X (Negative Calibrator IC Mean RLU)

 

INTERPRETATION OF RESULTS

 

All calculations described above are performed by the Chironâ Procleixâ WNV
System Software.  Two cutoffs are determined for the WNV assay:  one for the
Analyte signal (glower signal) termed the Analyte Cutoff and one for the
Internal Control signal (flasher signal) termed the Internal Control Cutoff. 
The calculation of these cutoffs is shown above.  For each sample, an Analyte
signal RLU value and Internal Control signal RLU value is determined.  Analyte
signal RLU divided by the Analyte Cutoff is abbreviated as the Analyte
Signal/Cutoff (S/CO) on the report.

 

For a sample with Analyte signal less than the Analyte Cutoff (i.e., Analyte
S/CO < 1), the Internal Control (IC) signal must be greater than or equal to the
Internal Control Cutoff (IC Cutoff) for the result to be valid.  In this case
the Internal Control result will be reported as Valid and the sample is reported
as Nonreactive.  For a sample with the Analyte signal less than the Analyte
Cutoff (i.e., Analyte S/CO < 1) and the Internal Control signal less than the
Internal Control Cutoff, the Internal Control Result will be reported as Invalid
and the sample result is reported as Invalid.  For all samples, the Internal
Control signal may not exceed 500,000 RLU.  The sample will automatically be
reported as Invalid with the Chironâ Procleixâ WNV System Software.

 

Summary of Sample Validity:

 

Sample
Interpretation

 

Internal Control
Result

 

 

 

 

 

 

 

Nonreactive

 

Valid

 

Analyte S/CO < 1 and

 

 

 

 

IC > IC Cutoff and

 

 

 

 

IC < 500,000 RLU

 

 

 

 

 

Reactive

 

(Not used)

 

Analyte S/CO > 1and

 

 

 

 

IC < 500,000 RLU

 

INO135 Rev. 1

 

10

--------------------------------------------------------------------------------

 

1.                                       Any specimen with an invalid Procleixâ
WNV Assay result, must be retested in the same assay in singlet.

 

2.                                       If at any point in the testing
algorithm there is insufficient volume to complete the testing then an alternate
specimen from the index donation may be used as long as the storage criteria in
the package insert are met.

 

3.                                       Specimens with a valid internal control
and with an S/CO less than 1.00 in the Procleix WNV Assay are considered
Nonreactive for WNV RNA.

a.                                       IF THE NONREACTIVE SPECIMEN IS A POOL,
then each of the individual specimens comprising the pool is considered
Nonreactive and no further testing is required.

b.                                      IF THE NONREACTIVE SPECIMEN IS FROM AN
INDIVIDUAL DONATION, then the individual specimen is considered Nonreactive for
WNV and no further testing is required.

 

4.                                       Specimens with S/CO greater than or
equal to 1.00 are considered Reactive.

a.                                       IF THE REACTIVE SPECIMEN IS A POOL,
then each of the individual specimens comprising the pool is tested with the
Procleix WNV Assay.

(1)                                  If an individual specimen tests Nonreactive
with the Procleix WNV Assay, then the specimen is considered Nonreactive for WNV
and no further testing is required.

 

(2)                                  If an individual specimen tests Reactive
with the Procleix WNV Assay, then the individual specimen is considered Reactive
for WNV.  Further clarification of the Reactive specimens may be obtained by
testing another sample from the index donation with the Procleix WNV Assay, in
an Alternate NAT and/or by follow-up testing.

b.                                      IF THE REACTIVE SPECIMEN IS FROM AN
INDIVIDUAL DONATION, then the individual specimen is considered Reactive for
WNV.  Further clarification of the Reactive specimens may be obtained by testing
another sample from the index donation with the Procleix WNV Assay, an Alternate
NAT and/or by follow-up testing.

 

5.                                       Reactive specimens in a manually
invalidated run due to the 10% invalid alert criteria, as explained in the
ACCEPTANCE CRITERIA FOR THE PROCLEIX WNV ASSAY, section C, must become the test
of record.  Any reactive result (analyte signal/cutoff > 1) should be resolved
according to the resolution algorithm for reactive specimens, as explained in
the INTERPRETATION OF RESULTS section, step 4.

 

LIMITATIONS OF THE PROCEDURE

 

Assays must be performed, and results interpreted according to the procedures
provided.

 

Deviations from these procedures may produce unreliable results. Adverse
shipping, storage conditions of outdated calibrators and/or reagents may produce
erroneous results.

 

BIBLIOGRAPHY

 

1.                                       Campbell G. L., A. A. Marfin, R. S.
Lanciotti, and D. J. Gubler. 2002.  West Nile virus.  Lancet infect Dis.
2:519-529.

2.                                       Petersen L. R., and A. A. Marfin. 2002.
West Nile Virus: A primer for the clinician.  Ann Intern Med. 137:173-179.

3.                                       Centers for Disease Control. 
January 24, 2002.  West Nile virus (WNV) infection: information for clinicians. 
Clinical features.  Website posting.

4.                                       Centers for Disease Control. 
January 8, 2003.  West Nile virus: virus history and distribution. Website
posting.

5.                                       Centers for Disease Control. 
December 23, 2002.  West Nile virus: questions and answers.  Website posting.

6.                                       Centers for Disease Control. 
September 13, 2002.  Public health dispatch:  investigation of blood transfusion
recipients with West Nile virus infections.  MMWR.  51:823.

7.                                       Centers for Disease Control.  2002. 
CDC Public health dispatch; possible West Nile virus transmission to an infant
through breast-feeding.  MMWR. 51: 877-878.

8.                                       Giachetti, C., J. M. Linnen, D. P.
Kolk, J. Dockter, et al.  2002.  Highly sensitive multiplex assay for detection
of human immunodeficiency virus type 1 and hepatitis C virus RNA. J Clin
Microbiol. 40:2408-2419.

9.                                       Kacian, D. L. and T. J. Fultz. 1995. 
Nucleic acid sequence amplification methods.  U.S.  Patent 5,399,491.

10.                                 Arnold, L. J., P. W. Hammond, W. A. Wiese,
and N. C. Nelson.  1989.  Assay formats involving acridinium-ester-labeled DNA
probes.  Clin Chem 35:1588-1594.

11.                                 Nelson, N. C., A. Cheikh, E. Matsuda and M.
Becker.  1996.  Simultaneous detection of multiple nucleic acid targets in a
homogeneous format.  Biochem. 35:8429-8438.

12.                                 National Committee for Clinical Laboratory
Standards.  1986.  Clinical laboratory hazardous waste:  proposed guidelines. 
NCCLS Document GP5-P.  Villanova, PA.

13.                                 U. S. Environmental Protection Agency.  EPA
guide for infectious waste management.  Washington,  DC;  U.S. Environmental
Protection Agency, Publication No. EPA/530-SW-86-014. 1986.

14.                                 Title 42, Code of Federal Regulations, Part
72. 1992.

15.                                 29 CFR Part 1910.1030.  Occupational
exposure to bloodborne pathogens; Final Rule,  Federal Register/Vol. 56, No.
235/ December 6, 1991.

 

IN0135 Rev. 1

2003-02

 

Developed and manufactured by:

Gen-Probe Incorporated

10210 Genetic Center Drive

San Diego, CA 92121

(858) 410-8000

 

Distributed in U.S. by:

Chiron Corporation

4560 Horton Street

Emeryville, CA 94608-2916

Telephone (in U.S.): (800) CHIRON-8

(510) 655-8730

 

Distributed in rest of world by:

Chiron Ireland, Limited

United Drug House

Belgard Road, Tallaght

Dublin 24, Ireland

353 (0) 1 404 1599

 

INO135 Rev. 1

 

11

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Chiron Blood Testing Technical Support:

(North America)

Telephone: (800) 452-6877

FAX: (800) 462-3938

 

(Europe, Middle East, Latin America, Africa)

Hot Line: +800 CHIRON BT

or + 33 1 55 49 00 36

Telephone: +33 (1) 55 49 01 65

FAX: +33 (1) 55 49 01 69

 

(Asia/Pacific)

Telephone: +61 (0) 410 44 5810

FAX: +61 (0) 299 74 5411

 

Chiron, RIBA and Procleix are trademarks of Chiron Corporation; TECAN, GENESIS
(stylized), and RSP are trademarks of Tecan AG: eppendorf (stylized) and
COMBITIPS are trademarks of Eppendorf-Netheler-Hinz GmbH; PROCLIN (stylized) is
a trademark of Rohm and Haas Company.

 

This product and its intended use are covered by one or more of the following:
U.S. patent no. 5,185,439; 5,283,174; 5,399,491; 5,437,990; 5,480,784;
5,585,481; 5,612,200; 5,639,604; 5,656,207; 5,656,744; 5,658,737; 5,696,251;
5,756,011; 5,756,709; 5,827,656; 5,840,873; 5,888,779; 5,948,899; 5,955,261;
6,004,745; 6,031,091; 6,090,591;                6,110,678; 6,245,519; 6,280,952;
6,410,276; 6,414,152; RE37,891; and international counterparts.

 

Ó 2003 Gen-Probe Incorporated

 

INO135 Rev. 1

 

12

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Schedule 2.9

 

PERFORMANCE OBJECTIVES

 

Performance Objectives

 

Target

[***]

 

Assay shall detect the target virus in [***].

[***]

 

IUO -[***]

[***]

 

[***]

 

[***]

 

 

[***]

 

[***]

 

 

[***]

 

[***]

[***]

 

[***]

 

[***]

 

 

[***]

 

[***]

 

 

[***]

 

[***]

 

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Schedule 4.0

 

SERVICES

 

1.                                      Maintenance & Troubleshooting.

 

1.1                                 ARC shall store, handle and utilized the
Products in accordance with the Documentation, which may be amended from time to
time.

 

1.2                                 In the event that any NTL resolves a problem
with a Product, such problem shall be logged in writing, including a description
of the problem and the steps taken by ARC to resolve it.   ARC shall maintain a
log for the Products and make available all such logs to Chiron’s respective
employees, contractors, subcontractors, or agents whose responsibilities are to
provide Services to ARC (“Chiron Technical Support”) upon request.

 

1.3                                 If a NTL is unable to resolve a problem it
shall refer the problem to a Chiron Technical Support representative for
resolution in accordance with Paragraph 2 of this Schedule 4.0.

 

1.4                                 Except for routine maintenance and
troubleshooting activities of Technologists as provided in this Schedule 4.0, or
otherwise with the prior permission of Chiron, during the Term of this Agreement
only Chiron or Chiron’s agents shall install, service, alter or replace the
Products.

 

2.                                       Technical Support and Service.

 

2.1                                 Installation.  Chiron Technical Support
personnel will provide installation and set up of all Software on the Blood
Screening Systems, including verification of the operation of the Software in
conjunction with the Blood Screening Systems.  At such time as Chiron determines
that such setup and installation has been completed, the ARC shall acknowledge
the completion of such setup and installation and its acceptance of the Blood
Screening Systems in writing.

 

2.2                                 Training.  For purposes of this Agreement,
no additional Trainers will be separately trained for purposes of the Products
acquired under this Agreement and the parties hereby agree that the number of
Trainers set forth in Section 2.2 of Schedule 4.0 of the 2002 Agreement shall,
in addition to the training set forth in the 2002 Agreement, also be trained for
purposes of the Products acquired under this Agreement; provided, however, that
each of ARC and Chiron acknowledge and agree that the training as provided

 

42

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hereunder will be subject to each party’s scrutiny, and to the extent it is
determined that the training provided under the 2002 Agreement is inadequate for
purposes of the Products acquired under this Agreement, then one additional
Trainer will be trained by Chiron, at no additional cost to ARC, for each NTL. 
Consistent with Section 2.2 of Schedule 4.0 of the 2002 Agreement, the Parties
agree to meet and confer to develop a “Train the Trainer” program for
implementation by ARC.  Except as set forth above, ARC shall be responsible for
training of all Technologists.  Additional training may be requested by ARC from
Chiron for an additional charge.

 

2.3                                 Data & Materials.  ARC shall make available
to Chiron on a timely basis all data, information and other materials which are
reasonably necessary for Chiron to perform the Services.  Such data shall be
treated as confidential Data in accordance with Section 6.7 of the Agreement. 
Chiron shall have no liability for any failure to perform, or for the late
performance, of any Services to the extent such Services require data,
information or materials possessed, prepared or generated by the ARC, if the ARC
fails to provide the same in accordance with Chiron reasonable requests.

 

2.4                                 Support and Service.

 

(a)                                  Chiron Technical Support to ARC shall be
available 24 hours a day, 7 days a week including weekends and holidays via
telephone.  The ARC will refer problems to Chiron Technical Support through a
central toll-free telephone number ([***]).  A Chiron Technical Support
representative will be available at this number to receive problem referrals and
provide troubleshooting assistance from 7:30 a.m. to 5 p.m. PST, Monday through
Friday, holidays excepted (“Normal Support Hours”).  If a Chiron Technical
Support representative is not reached by the initial ARC call, a Chiron
Technical Support representative will return the call to acknowledge receipt of
the problem referral and engage in a determination of the Priority Status within
one (1) hour.  Messages left outside Normal Support Hours (including weekends
and holidays) will automatically page the on-call Technical Support personnel. 
A Chiron Technical Support representative will return all calls to acknowledge
receipt of problem referral and engage in a determination of the Priority Status
within one (1) hour.  Required message information left outside Normal Support
Hours should include a contact name, phone number and brief description of the
problem.  Telephone support will be initiated within the “Priority/Response”
timeframes set forth below.  If a problem

 

43

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cannot be resolved through telephone support within a reasonable amount of time,
taking into account its Priority status, the problem will be escalated to
Chiron’s Product Support Center, for analysis by Blood Screening System
specialists and if necessary, OEM support personnel.  If a problem cannot be
resolved following such escalation, Chiron Technical Support will be dispatched
to the NTL to provide service in accordance with the Priority/Response Time
Schedule set forth below.

 

Priority

 

Response*

Priority 1:       Products not operating and alternate or back-up equipment not
available; screening cannot be performed

 

•                  Immediate telephone support

•                  Decision to dispatch Support Technician within 4 hours

•                  Support Technician on site ASAP but no later than 10 hours
from initial problem referral

•                  Resolution ASAP, but no later than 24 hours (may be temporary
workaround)

 

 

 

Priority 2:       Products operational but screening process (processing time)
is affected

 

•                  Telephone support within 2 hours

•                  Support Technician on site within 24 hours, if needed

•                  Resolution within 48 hours

 

 

 

Priority 3: Products operational; no impact on screening process

 

•                  Telephone support next business day 

•                  Work commenced within 24 hours

•                  Resolution within 1 week

 

--------------------------------------------------------------------------------

*           All timeframes are approximate; actual response times may vary due
to flight availability, weather-related delays, nature of the problem, etc.

 

(b)                                 Chiron will maintain full records of all
problem referrals and subsequent actions pursuant to Regulations.

 

(c)                                  Chiron will provide a list of all field
service technical personnel by name, including contact information and a
description of all certifications.  Such list shall be updated and confirmed
annually for all additions and deletions.

 

3.                                       Warranty; Limitation of Liability.

 

3.1                                 Chiron warrants that the Services provided
by Chiron, its agents, employees or contractors pursuant to this Agreement will
be rendered in a competent workmanlike manner and in accordance with industry
standards.

 

3.2                                 The Services shall cover latent and hidden
defects in design, material or workmanship of the Products, and shall include

 

44

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coverage of all Upgrades, but shall exclude (i) replacement of operating
supplies, necessaries, consumables or expendable parts; (ii) repairs required
due to improper storage, accident, neglect, misuse, electrical stress, air
conditioning, humidity control, transportation, and force majeure events, use of
non-approved accessories, consumables or supplies, or causes other than intended
normal use; (iii) service for Products that have been tampered with,
disassembled, altered, changed or modified, maintained by anyone other than
Trainers or Technologists or repaired (or attempts have been so made) by anyone
other than Chiron Technical Support personnel or BMIT-certified Technologists
under the direction of Chiron Technical Support; (iv) and (v) service for any
other equipment not manufactured or supplied by Chiron.

 

3.3                                 If any applicable law implies a condition or
warranty which cannot be excluded or modified in this Agreement (a
“Requirement”), then such Requirement is deemed to be included in this
Agreement.

 

45

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Schedule 5.0

 

COMPENSATION

 

1.                                       The ARC agrees to pay to Chiron the
agreed compensation in monthly increments, such increments to be equal to the
number of Reportable Results achieved by the ARC each month, multiplied by the
applicable Per Reportable Result amount from the chart set forth below:

 

POOLED TESTING &
OUTBREAK TESTING

 

SINGLE UNIT TESTING

Per Reportable Result

[***]

 

[***]

 

On or prior to the 5th business day of each month during the Term, ARC shall
provide Chiron with a report showing the Reportable Results obtained through
Pooled Testing, Single Unit Testing and Outbreak Testing and Reagent Utilization
Factor for the prior month for each NTL.  On or prior to the 15th calendar day
of each month, Chiron shall prepare and deliver an invoice to ARC for each NTL
based on such report.  If ARC’s report is not timely received by Chiron, Chiron
will prepare an invoice that reflects the then current Standing Order for the
applicable month multiplied by the applicable Per Reportable Result amount.  The
Parties shall “true-up” payments made to the actual Reportable Results achieved
on a quarterly basis, rectifying any under- or over-payment on the next
subsequent invoice, without application of interest.  ARC shall make payment on
invoices in accordance with Section 5.2 of the Agreement.

 

Chiron and the ARC agree to monitor the Reagent Utilization Factor at each NTL
during the Term.  If the Reagent Utilization Factor for any NTL exceeds the
[***] (the “Target RUF”) [***], Chiron and the ARC shall use their best
endeavors to identify and correct the cause of the excess.

 

The Reagent Utilization Factor shall be calculated for the ARC promptly
following each successive ARC Fiscal Year aggregating all NTLs.  If the Reagent
Utilization Factor for the ARC for any ARC Fiscal Year scores above the
applicable Target RUF (or such other factor as determined in accordance with
subparagraph (c)), Chiron shall invoice the ARC on the next subsequent monthly
invoice, and the ARC agrees to pay, the additional fee set forth below.

 

46

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For each [***] increment by which the actual Reagent Utilization Factor during
each ARC Fiscal Year exceeds the Target RUF, the [***]; provided that no
additional fee shall be payable hereunder to the extent that the cause of the
Reagent Utilization Factor exceeding the Target RUF is attributable to (A) a
failure of the Products to achieve the Performance Objectives set forth in
Section 2.9 of the Agreement, or (B) the implementation of an Upgrade or
Enhancement required by Chiron.

 

2.                                       Termination Reimbursement.  The
Termination Reimbursement shall be calculated as follows:

 

[***],

 

multiplied by

 

[***],

 

multiplied by

 

[***].

 

3.                                       Additional Supplies.  The following
additional supplies are available from Chiron at the prices set forth below. 
The fees for such additional supplies may be increased [***] by Chiron in the
event of, and in the amount of, any price increases by the manufacturers of such
additional supplies.

 

External Run Controls ([***])

[***]

Ten-Tube Units (TTUs) ([***])

[***]

Ten-Tube Cassettes (TTCs) ([***])

[***]

Proficiency Panels ([***])

[***]

 

47

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