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EXHIBIT 10.317

 
   
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.

Association Agreement Regarding the Sale and Servicing
of Blood Screening Products

This Association Agreement Regarding the Sale and Servicing of Blood Screening
Products (this "Association Agreement") is made effective as of May 1, 2002,
between America's Blood Centers ("ABC"), a charitable and non-profit
corporation, having its principal office at 725 15th Street, N.W. Suite 700,
Washington, D.C. 20005, and Chiron Corporation, a Delaware corporation
("Chiron") having its offices at 4560 Horton Street, Emeryville, California
94608-2916.

Background

A.ABC is an association of non-profit community-based centers (each such blood
center, a "Member").

B.Chiron distributes, markets and sells certain Blood Screening Assays and Blood
Screening Systems for use to conduct nucleic acid amplification tests to detect
the presence of certain viruses in blood donation samples.

C.ABC wishes to make available such amplified nucleic acid tests of blood
donation samples by its Members using the Blood Screening Assays and Blood
Screening Systems.

D.Chiron and ABC desire to enter into an agreement on the following terms and
conditions by which (i) Members may purchase Blood Screening Assays from Chiron;
(ii) Members may obtain possession of and will use Blood Screening Systems that
Chiron or a Third Party lessor will make available to ABC through sale or lease;
and (iii) Members may obtain from Chiron installation, training, and instrument
service related to the use of Blood Screening Systems.

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 not defined herein shall have the meanings set forth in
Schedule A hereto.

ARTICLE 2—PURCHASE OF BLOOD SCREENING ASSAYS

Chiron agrees to sell, and Participating Members agree to buy, Blood Screening
Assays in accordance with the terms and conditions set forth in Schedule B
hereto.

ARTICLE 3—PROVISION OF BLOOD SCREENING SYSTEMS; SOFTWARE

Chiron agrees to sell, or a Third Party designated by it and identified in
Schedule C hereto (a "Third Party Lessor") will agree to lease, to Participating
Members during the term hereof, Blood Screening Systems in accordance with the
terms and conditions set forth in Schedule C hereto, and to license or
sublicense the Software necessary for operation of the Blood Screening Assays on
the

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Blood Screening Systems also in accordance with the terms and conditions set
forth in Schedule C hereto; provided that, if Blood Screening Systems are leased
to ABC by a Third Party Lessor, the effectiveness of the applicable Member
Supplement shall be subject to the Participating Member and the Third Party
Lessor executing and delivering a separate agreement that provides for Third
Party Lessor to lease Blood Screening Systems to the Participating Member
pursuant to such terms and conditions (the "Third Party Systems Agreement").

ARTICLE 4—SERVICES

Installation, training and servicing of Blood Screening Systems (collectively,
"Services"), shall be provided to each Participating Member by Chiron in
accordance with the terms and conditions set forth in Schedule D hereto.

ARTICLE 5—PRICES, PAYMENTS

5.1Prices. Each Participating Member agrees to pay to Chiron the prices set
forth in Schedule E hereto (as revised from time to time by mutual agreement of
Chiron, ABC and the Participating Members) for the Products purchased hereunder,
as determined by their respective testing volume, existing instrument base and
financing selection. If a Third Party Lessor is provided for in Schedule C
hereto, the prices to be paid by a Participating Member thereto will be as set
forth in the Third Party Systems Agreement, as the case may be.

5.2[**]

5.3Payments. All payments shall be made on a monthly basis by each Participating
Member as set forth in Schedule E. All payments due to Chiron hereunder shall be
paid in full by each Participating Member in U.S. Dollars within thirty
(30) days of the applicable due date. In the event of late payment, interest
shall be charged at the rate of [**] from the date such payment was due until
the date of actual payment, such interest to accrue daily and both before and
after judgment. Invoices for amounts due from a Participating Member to a Third
Party Lessor pursuant to the terms of Third Party Systems Agreement shall be
payable as provided therein.

5.4Books & Records; Audit. Each Participating Member shall keep reasonably
detailed and accurate records and books of account, including without limitation
retaining all Data on donations tested, to enable a determination of the amounts
payable to Chiron 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 5.4) may have the records and books of
account of a Participating Member examined during reasonable business hours by
an independent certified public accountant selected by Chiron for the purpose of
verifying the amounts due hereunder. A copy of any final written report provided
by the independent accountant to Chiron shall be given concurrently to the
Participating Member. Such examination shall not be permitted unless [**] to
which the books and records pertain. Where such examination results in a finding
that a Participating Member underpaid Chiron [**], the Participating Member
shall reimburse Chiron for its reasonable costs and expenses in conducting such
examination. The Participating Member and Chiron shall promptly rectify any
overpayments or underpayments by repaying such amounts together with interest
thereon at the rate set forth in Section 5.3 of this Association Agreement. The
parties shall endeavor to resolve any dispute between a Participating Member and
Chiron as to amounts owing hereunder arising out of an audit pursuant to this
Section 5.4 pursuant to Article 11 of this Association Agreement.

5.5Taxes. Each Participating Member is a non-profit, charitable corporation,
exempt from the payment of sales and use taxes and 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

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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 Blood
Screening Assays and Blood Screening Systems sold by Chiron pursuant to this
Agreement, it shall be paid by the applicable Participating Member.

ARTICLE 6—CERTAIN AGREEMENTS

6.1Facilities. Each Participating Member agrees to grant Chiron reasonable
access during normal business hours to inspect the facilities used for the
conduct of nucleic acid amplification testing of blood donation samples.
Participating Members shall perform such testing in accordance with all
applicable laws and regulations and the instructions received from Chiron.

6.2Regulatory Approvals. Chiron will use commercially reasonable efforts, at
Chiron's sole expense, to obtain and maintain any applicable regulatory approval
for use of the Blood Screening Assays for testing of blood donations in the
Territory. Chiron will be solely responsible for compliance with all regulatory
requirements imposed on it in connection with the maintenance of such approvals,
including all regulatory reporting requirements. ABC and the Participating
Members will cooperate with Chiron to support its efforts pursuant to this
Section 6.2. For clarity of understanding, Chiron has no obligation or
responsibility with respect to regulatory approval or compliance relating to
blood donor, blood product or blood recipient management.

6.3Regulatory Compliance.

(a)The Participating Members shall be solely responsible for compliance with all
reporting and other regulatory requirements imposed on them. Upon reasonable
request of Chiron or any Participating Member, any Participating Member or
Chiron shall provide to the requesting party copies of regulatory reports
relating to the use of the Blood Screening Assays or the Blood Screening
Systems.

(b)Chiron shall be solely responsible for compliance with all reporting and
other regulatory requirements imposed on it.

(c)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 for the requesting party to satisfy
its regulatory requirements.

(d)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.

6.4Data. Each Participating Member shall provide to Chiron data generated in
connection with the use of the Blood Screening Assays or Blood Screening Systems
sufficient to monitor the performance of the Products for quality assurance, to
determine amounts due from the Participating Members hereunder, and to perform
their respective regulatory obligations in the Territory (collectively the
"Data"). The Data shall be deemed confidential information of the providing
Participating Members, and shall be subject to Section 6.5, except that the
limitations of Section 6.5 shall not apply to the uses of Data specifically
authorized under Section 6.4(b) of this Association Agreement.

(a)Chiron and to its Affiliates shall have the right to use the Data in
connection with other regulatory applications, submissions and notifications, in
any country, with respect to Blood Screening Assays, Blood Screening Systems or
related products. ABC and the Participating Members agree to cooperate in
providing to Chiron such information as either may reasonably believe
appropriate or necessary and in applying for any such government approvals. At
ABC's or any Participating Member's request, Chiron agrees to seek from such
governmental

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regulatory agencies confidential treatment of the Data, to the extent such
confidential treatment is available.

(b)Chiron agrees that the Data will be available for publication by ABC and/or
the Participating Members only. Any such publication shall appropriately
acknowledge the contributions of Chiron, ABC and the applicable Participating
Members.

(c)The parties acknowledge and agree that nothing in this Agreement or otherwise
will require ABC or any Participating Members 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 ABC and the applicable Participating Member in
writing immediately on becoming aware of such a requirement so that ABC and the
applicable Participating Member have an opportunity to seek a protective order
or other remedy; and (ii) ABC and the applicable Participating Members shall
provide the required identifying information to the extent it has such
information, subject to the terms of such protective order or other remedy.

6.5Confidentiality. During the term of this Agreement and [**], absent the
consent of the other party, (i) ABC and the Participating Members agree to keep
in confidence and not to disclose to any Third Party other than their
Affiliates, agents or contractors who need to know in connection with ABC and
Participating Members 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 ABC or Participating Members 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 ABC and Participating Members. 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. Subject to this Section 6.5 and
except as required by a court order issued by a court having appropriate
jurisdiction, ABC and all Members agree not to disclose to any Third Party any
financial terms of this Agreement, or any terms of this Agreement relating to
the Blood Screening Assays and Blood Screening Systems provided hereunder,
without the prior written consent of Chiron. Chiron agrees to not disclose to
any Third Party any financial terms of this Agreement, or any terms of this
Agreement relating to the Blood Screening Assays and Blood Screening Systems,
except and only to the extent necessary to facilitate the enforcement of
applicable most favored nations provisions. Notwithstanding the above, Chiron
acknowledges that any disclosure by a Participating Member in violation of this
Section 6.5 shall not be deemed a breach of this Agreement by ABC.

6.6Intellectual Property; Inventions. The provision by Chiron to the
Participating Members of the Blood Screening Assays and Blood Screening Systems
hereunder includes the implied license or sublicense under Chiron and Gen-Probe
intellectual property to use the Blood Screening Assays and Blood Screening
Systems in the Territory as provided herein. Except for such implied license,
and except as specifically set forth herein, nothing in this Agreement conveys
to any party any rights or licenses under any intellectual property of any other
party. The parties do not anticipate that use of the Blood Screening Systems and
Blood Screening Assays as provided herein will result in new inventions by
Participating Members. However, in the event that any such new invention is made
solely by a Participating Member or persons obligated to assign inventions to a
Participating Member, arising from the use of the Blood Screening Systems and
Blood Screening Assays, the Participating Member will own such invention. If
such invention is an improvement to a Blood

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Screening Assay or a component within a Blood Screening System, the
Participating Member will provide written notice to Chiron of such invention,
and the parties will commence exclusive negotiations, [**], for Chiron to obtain
a worldwide license to such invention on commercially reasonable terms. If the
parties fail to reach agreement on licensing terms, the Participating Member
will be free to license the invention to any Third Party. If an invention is
made jointly by a Participating Member 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.

6.7Product Changes. In the event that any manufacturer of Blood Screening Assays
or Blood Screening Systems makes a change which is required by applicable law or
regulation, Chiron will provide ABC and the Participating Members with notice of
such change promptly on receiving such notice from the manufacturer, and, if
reasonably practicable, at least three months prior to implementation of such
change. If any manufacturer makes an improvement to any Blood Screening Assays
or Blood Screening Systems which is not mandated by applicable law or
regulation, and if Chiron elects to make such improvement available in the
Territory, Chiron will provide notice to ABC and the Participating Members of
the availability of such improvement. Each Participating Member may, in its
discretion, elect to implement such improvement, provided, however, that Chiron
reserves the right to discontinue the sale, support and servicing of Blood
Screening Assays or Blood Screening Systems that have been superceded by
improved versions thereof, [**]. Each Participating Member shall be responsible,
at its expense, for validation of its own procedures and satisfaction of all
regulatory requirements applicable to the use of any improvements to the Blood
Screening Assays or Blood Screening Systems which such Participating Member
chooses to utilize. The parties acknowledge that the automated instrument system
for single unit testing currently under development is not to be deemed an
improvement for the purposes hereof. When commercially available, such automated
system will be subject to separate terms and conditions to be negotiated at such
time.

6.8Disaster Planning. Chiron shall work with ABC and the Participating Members
to develop a mutually agreeable disaster preparedness and/or loss control plan
to ensure continued supply of the Products in the event of a natural or man-made
disaster which seriously affects or compromises production capabilities at the
Product manufacturing or distribution facilities. In this connection, Chiron
shall disclose to ABC and the Participating Members its backup supply
capability, how it will keep the Participating Members supplied in the event of
a loss or other disaster, how it segregates its own exposures, and its full fire
and other loss protection measures for supply.

6.9Association Fee. Chiron agrees to pay ABC for management and service duties
performed during the term of the Association Agreement in [**]. This amount
shall be paid by Chiron to ABC quarterly within sixty (60) days of the close of
each quarter.

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

7.1Chiron Representations & Warranties. Chiron hereby represents and warrants
that: (a) it is duly organized, validly existing and in good standing under the
laws of the jurisdiction in which it was organized; (b) this Agreement, when
executed and delivered by it, will be the legal, valid and binding obligation of
Chiron, enforceable against Chiron in accordance with its terms; (c) the
execution, delivery and performance of this Agreement by Chiron do not and will
not (i) conflict with, or constitute a breach or default under, its charter
documents or any material agreement, contract, commitment, or instrument to
which Chiron is a party or (ii) require the consent, approval or authorization
of, or notice, declaration, filing or registration with, any Third Party or

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any governmental or regulatory authority; (d) Chiron has not previously granted
and will not grant any rights to any Third Party which are, nor contract with
any Third Party in any manner which is, inconsistent with the rights granted
herein.

7.2ABC Representations & Warranties. ABC hereby represents and warrants that:
(a) it is duly organized, validly existing and in good standing under the laws
of the jurisdiction in which it was organized; (b) this Agreement, when executed
and delivered by it, will be the legal, valid and binding obligation of ABC,
enforceable against ABC in accordance with its terms; (c) the execution,
delivery and performance of this Agreement by ABC do not and will not
(i) conflict with, or constitute a breach or default under, its charter
documents or any material agreement, contract, commitment, or instrument to
which ABC is a party or (ii) require the consent, approval or authorization of,
or notice, declaration, filing or registration with, any Third Party or any
governmental or regulatory authority; (d) ABC has not previously granted and
will not grant any rights to any Third Party which are, nor contract with any
Third Party in any manner which is, inconsistent with the rights granted herein.

7.3Participating Member Representations & Warranties. Each Participating Member,
by executing a Member Supplement, represents and warrants that: (a) it is duly
organized, validly existing and in good standing under the laws of the
jurisdiction in which it was organized; (b) the Member Supplement, when executed
and delivered by it, will be the legal, valid and binding obligation of it,
enforceable in accordance with its terms; (c) all Products shall be used in
accordance with the applicable manuals and instructions provided by Chiron and
with all applicable laws and regulations; (d) it has all authority and permits
required under applicable law and regulation to operate as a blood center and
use the Products; (e) it is not, and it will not use in providing Chiron with
any manner of service or work relating to this Agreement, a debarred person or
entity under the Generic Drug Enforcement Act, or otherwise prohibited from
providing such services or work, nor shall it use any investigator who has been
disqualified by the FDA.

7.4Disclaimer of Warranty. EXCEPT AS SET FORTH IN SECTION 7.1 OF THIS
ASSOCIATION AGREEMENT OR EXPRESSLY PROVIDED IN SCHEDULES B, C, AND D HEREOF,
CHIRON MAKES NO WARRANTIES OF ANY KIND, EXPRESS OR IMPLIED, WRITTEN OR ORAL,
INCLUDING WITHOUT LIMITATION ANY IMPLIED WARRANTIES OF MERCHANTABILITY OR
FITNESS FOR A PARTICULAR PURPOSE.

7.5Pass-Through of Warranty. Chiron agrees to pass through to each Participating
Member the benefit of the manufacturer's warranties with respect to the Blood
Screening Systems sold by Chiron after the effective date of the applicable
Member Supplement, to the extent it is legally permitted to do so.

7.6Participating Member Responsibility for Certain Damages. In no event shall
Chiron (or any Affiliate thereof) be responsible for any Damages suffered by ABC
or a Participating Member arising out of a Participating Member's own negligence
or willful acts or failure to act in connection with the storage, handling, or
use of the Products after transfer to the Participating Member of risk of loss
or damage thereto.

7.7Indemnity by Chiron. Chiron hereby indemnifies ABC and each Participating
Member, their respective officers, directors, agents, and employees (the "ABC
Indemnitees") and agrees to hold them harmless from and against all Direct
Damages and against all Third Party Damages arising out of bodily injury claims
of Third Parties, when such Damages arise from Chiron's breach of this Agreement
or from the negligence of Chiron, its officers, directors, agents, employees or
affiliates in the performance of Chiron's obligations under this Agreement,
except to the extent arising from negligence or willful misconduct of any of the
ABC Indemnitees.

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7.8Indemnity by ABC. ABC hereby indemnifies Chiron and its respective officers,
directors, agents and employees (the "Chiron Indemnitees") and agrees to hold
them harmless from and against all Direct Damages and against all Third Party
Damages arising out of bodily injury claims of Third Parties, when such Damages
arise from ABC's breach of this Agreement or from the negligence of ABC, its
officers, directors, agents or employees in the performance of its obligations
under this Agreement, except to the extent arising from negligence or willful
misconduct of any of the Chiron Indemnitees.

7.9Indemnity by Participating Members. Each Participating Member, by executing a
Member Supplement, agrees to indemnify Chiron and its respective officers,
directors, agents and employees (the "Chiron Indemnitees") and agrees to hold
them harmless from and against all Direct Damages and against all Third Party
Damages arising out of bodily injury claims of Third Parties, when such Damages
arise from the Participating Member's breach of this Agreement or from the
negligence of the Participating Member, its officers, directors, agents or
employees in the performance of its obligations under this Agreement, except to
the extent arising from negligence or willful misconduct of any of the Chiron
Indemnitees.

7.10IP Infringement Indemnity. Chiron shall defend, at its expense, any legal
action brought against ABC or a Participating Member by a Third Party to the
extent that it is based on any claim that the use by a Participating Member of
any Products supplied by Chiron and sold pursuant to this Agreement constitute
an infringement of any patent or intellectual property rights claimed by such
Third Party in the Territory. Chiron will pay all Damages finally awarded
against ABC or a Participating Member in such action that are attributable to
such claim. Notwithstanding the foregoing, Chiron shall have no liability
hereunder to the extent that the infringement (or allegation of infringement)
arises from or is attributable to (i) the use of the Products in combination
with other products or materials not supplied 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. Chiron's obligation to indemnify shall be
subject to ABC or a Participating Member promptly notifying Chiron in writing of
such claim and providing reasonable cooperation to Chiron in the defense of such
claim or proceeding.

7.11Indemnification Procedures. Any party claiming indemnification under
Section 7.7, 7.8 or 7.9 of this Association Agreement (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 on 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.

7.12Exclusion of Consequential Damages. Excepting any obligation to indemnify
against Third Party Damages as provided in this Agreement, no party to this
Agreement shall be liable to any other party to this Agreement 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 Damages.

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7.13Insurance. Chiron and the Participating Members agree to insure their
potential liabilities resulting from this Agreement as follows:

(a)Participating Members shall obtain and maintain, at their sole cost, a policy
or policies of insurance with the coverages set forth in the applicable Member
Supplement.

(b)Chiron shall obtain and maintain at its sole cost, a policy or policies of
insurance with the following coverages, which shall be in full force and effect
for the term of this Agreement and thereafter through two years following the
termination of the Agreement: a) a Commercial General Liability policy including
Products and Completed Operations Liability in an amount of not less than [**]
combined single limit for each occurrence; and b) Workers' Compensation coverage
with statutory limits for each jurisdiction where the work required of such
party under this Agreement is performed and an employers' liability policy with
at least the following limits, [**] per accident, [**] per disease (policy
limit), and [**] disease (each employee).

(c)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. Each party must notify the other
within a reasonable time if there is a material change to any of the insurance
policies referred to in this Section 7.13. Such certificates shall provide for
thirty (30) days prior written notice to the certificate holder in the event of
non-renewal of the policies, cancellation or material change in the coverage
provided.

ARTICLE 8—TERM AND TERMINATION

8.1Term. This Association Agreement shall enter into force as of the Effective
Date and shall continue to the [**]. Six months before the expiration of this
Association Agreement, the parties shall meet to negotiate in good faith whether
or not this Association Agreement shall be extended and/or revised and/or
discontinued with effect from the termination date of such initial period. Each
Member Supplement will become effective and terminate on its own terms;
provided, however, that all Member Supplements shall terminate immediately upon
the termination or expiration of this Association Agreement. Any termination of
a Member Supplement shall have no impact on the continuing effectiveness of any
other Member Supplement or this Association Agreement.

8.2Termination. This Association Agreement may be terminated by written notice
to the other party at any time during the term of this Association Agreement,
which termination shall be effective when such termination notice is received in
accordance with Section 12.6 of this Association Agreement, as follows:

(a)by either ABC or Chiron if the other party fails to observe, perform or
otherwise breaches any of its material covenants, agreements or obligations
under this Association Agreement, provided such failure continues for a period
of thirty (30) days after receipt by the other party of an initial written
notice thereof specifying such failure and provided further Chiron shall not
have invoked its rights under Section 8.4 of this Association Agreement; or

(b)by either ABC or Chiron 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; or

(c)by mutual agreement of the parties at any time without penalty.

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8.3[**].

8.4[**].

ARTICLE 9—CONSEQUENCES OF THE TERMINATION OF THE AGREEMENT

9.1Payment Obligations Unaffected. The termination of this Association Agreement
for any reason whatsoever shall not affect any party's obligations to pay any
amount actually invoiced and due to Chiron prior to such termination. In the
event that termination occurs at a time prior to a Participating Member 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.

9.2Survival of Certain Provisions. In addition, notwithstanding anything herein
to the contrary, the following provisions of this Association Agreement shall
survive termination of this Association Agreement: Sections 6.5, 6.6 and 7.4
through 7.12, and Articles 9, 10, 11 and 12.

9.3Return of Confidential Information. Upon termination of this Agreement for
any reason whatsoever, unless required to retain such information for regulatory
purposes, 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 6.5 of this
Association Agreement.

9.4No Other Payment. No indemnity or compensation in any form whatsoever shall
be paid by either the 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 10—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 11—DISPUTES

11.1To 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.

11.2The 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. In the event that any problem or dispute is not
so resolved, either party may upon written notice to the other request that the
matter be referred to senior management officers within each respective
organization with express authority to resolve the problem or issue and who are
not immediately responsible for the matters contemplated by this Agreement. Such
senior management officers will meet or confer at least once in good faith to
negotiate a resolution.

11.3If the senior management officers are unable to resolve the problem or
dispute within thirty (30) days, either party may pursue the matter as set forth
in Sections 11.4 through 11.6 below. No party may institute a court proceeding
until the procedure has been completed unless, and to the extent that, doing so
is necessary to avoid irreparable harm.

11.4If any problem or dispute arising out of or related to this Agreement is not
resolved by the parties in the manner set forth in Sections 11.2 and 11.3 above,
at the request of either party, the matter will be submitted to mediation, or to
such other form of dispute resolution as the parties may then agree to. A
neutral person acceptable to both parties will conduct the mediation, and unless
other

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procedures are agreed to, it will be conducted in accordance with the Center for
Public Resources Model Procedure for Mediation of Business Disputes.

11.5Any controversy, claim or dispute arising out of or relating to this
Agreement, or the breach thereof, which is not resolved through the procedures
described in Sections 11.2 through 11.4 above shall be resolved by binding
arbitration. If arbitration is necessary pursuant to this paragraph, the parties
shall agree upon a single arbitrator. If the parties are unable to agree on an
arbitrator, then they will obtain nominations of three (3) potential arbitrators
who are retired federal or state judges and each party will have the right to
strike one candidate's name from the list.

11.6The 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 12—MISCELLANEOUS

12.1Force Majeure. Each party shall be excused from any delay in performance or
from failure to perform in accordance with the terms of this Agreement, to the
extent that such delay or failure to perform results from a Force Majeure Event.
The provisions of this paragraph shall apply only if such party shall have used
its reasonable efforts to avoid such Force Majeure Event. Such party shall give
notice to the other promptly in writing upon learning of the Force Majeure
Event. The affected party's time for performance shall be extended for the
period of the delay or inability to perform due to such Force Majeure Event and
notwithstanding any provision herein to the contrary, the affected party shall
not be liable for any Damages arising out of such Force Majeure Event.

12.2Exclusion of Convention of Vienna for the International Sale of Goods. The
parties hereby expressly exclude the application to this Agreement of the terms
of the Convention of Vienna for the International Sale of Goods.

12.3Equal Employment Opportunity. None of the parties 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. The parties agree to
abide by all federal, state and local employment and labor law notice posting
requirements.

12.4Assignment. This Agreement shall not be directly or indirectly assigned or
otherwise transferred by ABC or, as to a Member Supplement, by any Participating
Member, nor, except as expressly provided hereunder, may any right or
obligations of ABC or any Participating Member hereunder be assigned or
transferred (whether voluntarily, by operation of law or otherwise) without the
consent of Chiron. Chiron may assign and transfer to an Affiliate (provided
Chiron remains a guarantor of such Affiliate's obligations hereunder), or to a
Third Party possessing sufficient capitalization to satisfy its obligations
under the Agreement that is acquiring all or substantially all of the business
of Chiron, the rights and obligations of Chiron hereunder without further action
by ABC or any Participating Member. This Agreement shall inure to the benefit of
and be binding upon the parties hereto and their respective successors and
permitted assigns.

12.5Subcontracting. Chiron's obligations under this contract may not be
subcontracted without the prior written consent of the effected Participating
Members. Any attempt to subcontract without such consent will be null and void
and of no effect. Chiron must require that all subcontractors approved by the
affected Participating Members be bound by the terms of this Agreement and to
assume toward Chiron all obligations and responsibilities which Chiron assumes
toward the affected Participating Members. Chiron must make available to each
approved subcontractor, prior to the execution of any subcontract agreement, a
copy of this Agreement to which the

10

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subcontractor will be bound. For purposes of any subcontracts entered into
pursuant to this Section 12.5, the term "Chiron" as used in this Agreement, will
include any and all subcontractors.

12.6Notices. 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 pre-paid registered or certified mail, by courier or by facsimile at
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, CA 94608
Telephone: (510) 923-2416
Fax: (510) 655-8556
cc: General Counsel
 
 
If to ABC:
 
America's Blood Centers
Attention: Jim MacPherson, Chief Executive Officer
725 15th Street, N.W., Suite 700
Washington, DC 20005
Telephone: (202) 393-5725
Fax: (202) 393-1282

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;

(b)if it is sent by courier, on the date and at the time shown on the courier's
standard written confirmation of receipt;

(c)if it is sent by facsimile, on the date and at the time shown on a successful
transmission report by the machine from which the facsimile was sent.

12.7Entire 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, including without limitation the Agreement, dated as of
April 15, 2000 by and among Chiron, ABC and Gen-Probe, as amended. 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 hereto.

12.8No 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.

12.9Nature of Relationship. 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 Chiron and each Participating Member 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. In no event shall ABC have any
responsibility for the financial obligations of any Participating Member, nor
shall any Participating Member have any responsibility for the financial
obligations of any other Participating Member.

11

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12.10 Conflict Between Terms and Conditions. In the event of any conflict
between the terms and conditions of this Association Agreement and any terms and
conditions that may be set forth in a Member Supplement or on any invoice or
purchase order or other similar document, the terms and conditions of this
Association Agreement govern.
12.11
Compliance with Applicable Law. In performing this Agreement, the parties shall
comply with all applicable laws. 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 such event, the affected provision of this Agreement shall be
ineffective only to the extent necessary to comply with the applicable law, 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.
12.12
Counterparts. This Association Agreement and any Member Supplement 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.
12.13
Severability. In the event that any provision of this Agreement is found to be
invalid or in conflict with any applicable law or regulation, the affected
provision of this Agreement shall be limited or eliminated only to the extent
necessary to comply with such law or regulation, and the remainder of this
Agreement shall remain in full force and effect, provided that the remainder of
this Agreement is consistent with the economic intentions of the parties as
evidenced by this Agreement as a whole.

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.

CHIRON CORPORATION   AMERICA'S BLOOD CENTERS
By:
 
/s/  WILLIAM G. GREEN      

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By:
 
/s/  JIM MACPHERSON      

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

Name:
 
William G. Green
 
Name:
 
Jim MacPherson
Title:
 
President of Blood Testing
 
Title:
 
CEO

12

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CONFIDENTIAL   REDACTED VERSION

SCHEDULE A

Definitions

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

1.1"Affiliate" shall mean (i) any corporation or business entity of which
securities or other ownership interests representing fifty percent (50%) or more
of the equity or fifty percent (50%) or more of the ordinary voting power or
fifty percent (50%) or more of the general partnership interests are, at the
time such determination is being made, owned, Controlled (as hereinafter
defined) or held, directly or indirectly, by such corporation or business
entity, or (ii) any other corporation or business entity which, at the time such
determination is being made, is Controlling, Controlled by or under common
Control with, such corporation or business entity. For purposes of this
definition, "Control", 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 corporation or business entity, whether through
the ownership of voting securities, by contract or otherwise.

1.2"Agreement" shall mean collectively this Association Agreement, including the
Schedules hereto, and all Member Supplements, including the Exhibits thereto.

1.3"Blood Screening Assays" shall mean the TMA Assays purchased by Chiron from
Gen-Probe from time to time and available for sale hereunder, as more
specifically described in one or more schedules, labeled B-1, B-2, etc.

1.4"Blood Screening Field" shall mean the testing of human blood, plasma,
platelets or other blood products intended for transfusion or further processing
for other administration to humans, including autologous donors, as limited by
the Intended Use for each Blood Screening Assay, as set forth in the applicable
Package Insert, as amended from time to time.

1.5"Blood Screening Systems" shall mean the instrument(s) and related Software
for DNA/RNA amplified assay processing that Chiron has available for sale or
lease hereunder, as more specifically described in Schedule C, as it may be
amended from time to time.

1.6"Confidential Information" means any and all technical, business and other
information and materials disclosed by or on behalf of such party to the other
party pursuant to this Agreement or during discussions leading to 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.

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1.7"Consequential Damages" means consequential damages as defined by California
law, including loss of profit or loss of business opportunity, and all Third
Party Damages.

1.8"Damages" means Direct Damages and Third Party Damages, collectively.

1.9"Direct Damages" means costs or expenses incurred by a party that are not
Consequential Damages, including without limitation, the incremental additional
costs of substitute products and costs or expenses of product recall.

1.10"Documentation" shall mean text material that describes the design,
functions, operation, or use of the Software and that is delivered by Chiron to
Participating Members. Documentation for the Software shall be the same that is
provided to licensees of such Software generally.

1.11"Effective Date" means the date set forth on the first page of this
Agreement.

1.12"FDA" shall mean the United States Food and Drug Administration, or the
successor thereto.

1.13"Force Majeure Event" shall mean a cause beyond the reasonable control of a
party, including without limitation, fires, floods, epidemics, quarantine
restrictions, strikes, war, earthquake, acts of God, labor difficulties, riot,
failure of public utilities, freight embargoes, unusually severe weather
conditions, delays in delivery of goods or services by suppliers or
subcontractors to such party, loss of goods in transit, and governmental or
court action.

1.14"Gen-Probe" shall mean Gen-Probe Incorporated, a Delaware corporation.

1.15"HCV" means the Hepatitis C virus.

1.16"HIV-1" means Human Immunodeficiency virus type 1.

1.17"Member" shall have the meaning set forth in the Recitals.

1.18"Member Supplement" shall mean the agreement executed after the Effective
Date of this Association Agreement by and among Chiron and a Member and
incorporating by reference the terms and conditions of this Association
Agreement.

1.19"Package Insert" shall mean the package insert approved by the FDA for the
applicable Blood Screening Assay, as the same may be amended from time to time.

1.20"Participating Member" shall mean a Member electing to utilize the Blood
Screening Assays and Blood Screening Systems that memorializes its election by
execution of a Member Supplement.

1.21"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.

1.22"Pooled Testing" means the conduct of testing on pools of samples from blood
donations as follows. For the purposes of this Agreement, Pooled Testing
consists of:

[**]

[**]

[**]

1.23"Primary Operators" means the employees of Participating Members trained by
Chiron at Chiron's facility.

1.24[**].

1.25"Products" shall mean Blood Screening Assays, Blood Screening Systems and
Software.

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1.26"Reagent Utilization Factor" means, with respect to a specified time period,
the quantity of Blood Screening Assay tests consumed by an applicable
Participating Member during such period divided by the number of Reportable
Results obtained by such Participating Member during such period.

1.27"Reportable Result" means a result obtained through the use of a Blood
Screening Assay and Blood Screening System in Pooled Testing or Single Unit
Testing 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.

1.28"Secondary Operator" means the employees of Participating Members trained at
the facility of a Participating Member by either a Primary Operator or Chiron.

1.29"Single Unit Testing" means testing of blood donations consisting of
(i) testing a sample from each individual blood donation using a Blood Screening
Assay, and (ii) follow up discriminatory testing of positive results for HIV-1
or HCV.

1.30"Software" means the following software programs:

CPT-16 Pooling Software, Version 2.0.0.2
Procleix™ Assay Software, Version 2.0.0.76
Procleix™ Assay Software LHP, Version 2.1
Procleix™ System Software, Version 3.0.3.4
Procleix™ Protocol, Version 2.1.0.0
Procleix™ Worklist Editor, Version 3.0.3.2

1.31"Specifications" shall mean, in respect of each Product, the specifications,
tests, procedures, process description, and other information relating to such
Product and packaging thereof prepared by Chiron or its Affiliates provided to
Participating Members by Chiron under separate cover, which may be amended from
time to time by Chiron in writing; provided, however, that the foregoing
information shall be consistent with the product registration in the Territory
from time to time. As to Blood Screening Assays, "Specifications" shall mean the
information set forth in the current Package Insert.

1.32"Tecan Instrument" means a Tecan Genesis 150/8 Instrument, sold by Chiron or
leased by a Third Party Lessor hereunder for use in the performance of the
assays using the Blood Screening Assays.

1.33"Territory" means the United States of America, including Puerto Rico, Guam
and all other protectorates.

1.34"Testing Centers" mean the locations identified on Exhibit 2 to the Member
Supplements.

1.35"Third Party" shall mean any Person other than ABC, its Members, Gen-Probe,
Chiron and their respective Affiliates.

1.36"Third Party Damages" means any liability arising out of a Third Party's
claim (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).

1.37"TMA Assay" shall mean an in vitro diagnostic assay based on or utilizing
transcription-mediated amplification.

15

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CONFIDENTIAL   REDACTED VERSION

SCHEDULE B-1

TERMS AND CONDITIONS FOR PURCHASE OF PROCLEIX™ HIV-1/HCV
BLOOD SCREENING ASSAY

Chiron will supply the Procleix™ HIV-1/HCV Blood Screening Assay to the
Participating Members on the following terms and conditions:

1.Description of Blood Screening Assays. The Procleix™ HIV-1/HCV Blood Screening
Assays that will be supplied by Chiron to the Participating Members hereunder
are described in the current Package Insert, included as Attachment B-1 to this
Schedule B-1 and include the following components:

Procleix™ HIV-1/HCV Assay

1000 Test Kit P/N 301031
5000 Test Kit P/N 301030

Internal Control Reagent
Target Capture Reagent
Amplification Reagent
Enzyme Reagent
Probe Reagent
Selection Reagent
Procleix™ Negative Calibrator
Procleix™ HIV-1 Positive Calibrator
Procleix™ HCV Positive Calibrator

2.Supply Obligation. During the term of this Agreement Chiron agrees to supply
to each Participating Member, at the prices specified in Schedule E, all Blood
Screening Assays necessary to permit each Participating Member to conduct
screening of blood donations for the presence of HIV-1 and /or HCV in the
Territory. Each Participating Member agrees to store and handle all Blood
Screening Assays in accordance with the Package Insert. Any Blood Screening
Assays lost or damaged due to failure to comply with such storage and handling
instructions will be replaced at the affected Participating Member's sole
expense, which expense reflects the Reagent Utilization Factor premium specified
in Schedule E.

3.Purchase Obligation. During the term of this Agreement, each Participating
Member agrees to acquire 100% of its requirements of Blood Screening Assays
necessary to conduct screening by nucleic acid testing of blood donations for
the presence of HIV-1 and/or HCV. However, nothing in this Agreement will
restrict the right of a Participating Member to evaluate new technologies or to
perform, in its discretion, any confirmatory and supplementary nucleic acid
testing.

4.Other Supplies. All supplies necessary for the conduct of tests using the
Blood Screening Assays, other than Blood Screening Assays, Blood Screening
Systems and such disposables and calibrators included with each Blood Screening
Assay Kit, shall be purchased separately by each Participating Member and the
price of such supplies is not included in the fees established by this
Agreement. Certain of such supplies and the associated prices thereof as of the
date of execution of this Agreement are identified in Schedule E. Such prices of
supplies shall increase from time to time in the event of, and in the amount of,
any price increases by the manufacturers of such supplies.

5.Packing and Delivery of Blood Screening Assays. All Blood Screening Assays
will be suitably packed and transported to ensure safe transport to the
Participating Members in accordance with the

16

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manufacturer's instructions and delivered Carriage and Insurance paid to the
Participating Member's designated Testing Centers, and each delivery will be
accompanied by a packing slip indicating the quantity delivered. Blood Screening
Assays will be delivered during normal business hours and accompanied by storage
instructions and arrive at the temperatures specified by the manufacturer and
set out in the Package Insert. The Blood Screening Assays will be delivered in
kit form, with appropriate distribution between screening tests, discriminatory
tests and related calibrators.

6.Shipping. Except as set forth below, all shipping and handling charges for the
Blood Screening Systems and the regular monthly shipments of Blood Screening
Assays will be borne entirely by Chiron on shipments to the Testing Centers. All
shipping and handling charges for shipping requests other than to a Testing
Center, and all incremental shipping and handling charges for Modified Orders
and Changed Orders, will be borne by the requesting Participating Member.

7.Forecasts and Orders.

7.1Each Participating Member will provide Chiron with a written twelve month
forecast of its requirements of Blood Screening Assays (each a "Product
Requirements Forecast") on an annual basis, including requested delivery dates,
which forecast shall constitute such Participating Member's standing firm
purchase order for each month contained therein. Not less than ninety (90) days
prior to each anniversary of the effective date of the applicable Member
Supplement, each Participating Member will provide such a Product Requirements
Forecast. Participating Members shall deliver any modifications to the standing
firm purchase order for Blood Screening Assays for delivery during the next
following month on or prior to the first day of the immediately preceding
calendar month (for example, a Participating Member will provide requested
modifications to the February standing firm purchase order—for deliveries to be
made during the month of February—prior to January 1). All purchase order
modification requests must be received at least 30 days prior to a requested
delivery date. Except as otherwise agreed, Chiron agrees to accept modifications
to standing firm purchase orders which do not differ by more than [**] from the
quantities forecast for delivery in the applicable month in the current Product
Requirements Forecast. Participating Members may adjust their Product
Requirements Forecast from time to time with the consent of Chiron, such consent
to not be unreasonably withheld.

7.2If the variance between the modification requested and the current Product
Requirements Forecast exceeds the [**] referenced in Section 7.1 of this
Schedule B-1, Chiron will notify the requesting Participating Member within five
(5) business days after receipt of the modification request as to whether it
accepts such modification request. If a modification request is accepted, Chiron
agrees to deliver such amounts of Blood Screening Assays on the delivery date(s)
stated. If a modification request is not accepted, the parties will use all
reasonable endeavors to agree on further modifications to the order and/or
delivery date (a "Modified Order"), subject to Chiron's manufacturer's
accommodating Chiron's requests for changes in forecasted amounts.

8.Changes to Orders. If a Participating Member requests any modifications to
quantities of Blood Screening Assays ordered or the delivery schedule or
locations reflected in such order within 30 days of a delivery date (a "Changed
Order"), Chiron will use reasonable commercial efforts to comply with such
request.

9.IQA Procedures. Prior to the initial delivery of Blood Screening Assays,
Chiron, ABC and the Participating Members shall mutually agree upon procedures
for quality assurance testing of Blood Screening Assays received by
Participating Members ("IQA Procedures"). Chiron agrees to replace Blood
Screening Assays which fail to conform to the Specifications as set forth in the
Package Insert. The IQA Procedures shall include procedures for notice to Chiron
and for implementing the return of Blood Screening Assays for replacement. If
testing by Chiron or its supplier confirms the non-conformity of the Blood
Screening Assays, Chiron will bear the shipping costs associated

17

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with replacement. If Chiron's testing provides reasonably acceptable evidence to
the applicable Participating Member that the Blood Screening Assays do conform
to the specifications in question, the shipping costs will be borne by the
applicable Participating Member.

10.Technical Support. Chiron will provide Participating Members with technical
support to facilitate the operation by Participating Members of the Blood
Screening Assays on the Blood Screening Systems.

11.Nature of Testing. Each Participating Member agrees that Blood Screening
Assays supplied by Chiron hereunder shall be used by the Participating Member
solely to conduct Pooled Testing with a pool size of 16. If a Participating
Member desires to change its testing from Pooled Testing using a pool size of 16
to Single Unit Testing or any other pool size, the Participating Member and
Chiron shall enter into an addendum to the applicable Member Supplement
reflecting any additional Blood Testing Systems, changes to the fees or prices
payable under Schedule E of this Agreement or any other amendments that may be
applicable by reason of such change in the nature of the Participating Member's
testing of blood donations.

12.Warranty; Limitation of Liability.

12.1All Blood Screening Assays supplied by Chiron shall be manufactured in
accordance with, and shall conform with, the Specifications, provided that ABC
uses the Blood Screening Assays in accordance with the instructions provided by
Chiron. Any Blood Screening Assays failing to meet such Specifications shall be
replaced by Chiron at Chiron's cost unless the defect was caused by an act or
omission of a Participating Member.

12.2Chiron disclaims all other warranties and further limits its liability in
accordance with Sections 7.4 and 7.12 of this Association Agreement,
respectively.

18

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ATTACHMENT B-1

Package Insert

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

Procleix™ HIV-1/HCV Assay

For In Vitro Diagnostic Use
1000 Test Kit, 5000 Test Kit

 
   
TABLE OF CONTENTS       INTENDED USE   1   SUMMARY AND EXPLANATION OF THE TEST  
2   PRINCIPLES OF THE PROCEDURE   2   MATERIALS PROVIDED   4   MATERIALS
REQUIRED, SOLD SEPARATELY   5   MATERIALS REQUIRED BUT NOT PROVIDED   6  
REAGENTS   7   STORAGE INSTRUCTIONS   8   PRECAUTIONS   9   REAGENT PREPARATION
  11   SPECIMEN COLLECTION, STORAGE, AND HANDLING   12   PROCEDURAL NOTES   13  
INSTRUCTIONS FOR USE   16     Target Capture   16     Amplification   18    
Hybridization Protection Assay (HPA)   19     Procleix HIV-1 and HCV
    Discriminatory Assays   20   QUALITY CONTROL PROCEDURES   21     Acceptance
Criteria for the Procleix
    HIV-1/HCV Assay and Procleix
    HIV-1 and HCV Discriminatory Assays   21       Acceptance Criteria for the
Calibration and Calculation of Cutoff   22   INTERPRETATION OF RESULTS   28  
PERFORMANCE CHARACTERISTICS   30   PERFORMANCE OF POOLED SAMPLE TESTING   32  
PERFORMANCE OF INDIVIDUAL DONATION TESTING   46   LIMITATIONS OF THE PROCEDURE  
48   CONCLUSIONS   49   BIBLIOGRAPHY   49

INTENDED USE

The Procleix™ HIV-1/HCV Assay* is a qualitative in vitro nucleic acid assay
system for the detection of human immunodeficiency virus type 1 and/or hepatitis
C virus RNA in human plasma from donations of whole blood and blood components
for transfusion. 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. This assay is intended to be used in conjunction with
licensed tests for detecting antibodies to HIV-1 and HCV.

This assay may be used as an alternative to licensed HIV-1 p24 antigen tests for
screening human plasma from donations of whole blood and blood components.

This assay is not intended for use as an aid in diagnosis.

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

IN0076 Rev. F

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SUMMARY AND EXPLANATION OF THE TEST

        Epidemiological studies identified human immunodeficiency virus type 1
(HIV-1) as the etiological agent of acquired immunodeficiency syndrome (AIDS)1-7
and hepatitis C virus (HCV)8-13 as the etiological agent for most blood-borne
non-A, non-B hepatitis (NANBH). Both viruses are transmitted primarily by
exposure to infected blood or blood products, certain body fluids or tissues,
and from mother to fetus or child.

        Current detection of HIV-1 infection in the blood bank setting is based
on serologic screening for anti-viral antibodies by enzyme immunoassay (EIA)
with confirmation by supplemental antibody tests such as Western blot or
immunofluorescence assays. Although sensitivity of HIV-1 antibody detection has
increased in the last few years and sensitive tests for p24 antigen (p24Ag) have
been developed and implemented, a window period between infection and detectable
serological markers still exists14,16-17. The screening of blood with current
EIA tests results, on average, in a 22-day seronegative window17. Although
addition of the p24Ag test allows earlier detection of HIV-1 infection,
implementation of the p24Ag test in the U.S. yielded a very modest number of
Ab(-)/Ag(+) donors with no significant reduction in the risk of infection.
Several studies suggest that addition of nucleic acid-based amplification tests
would reduce the window period of detection to 6-11 days, preventing more than
half of the HIV-1 infections by blood transfusion14.

        Nucleic Acid Testing (NAT) of whole blood donations has been in place in
the United States since early 1999. Stramer et al., have reported the results of
testing small pools of 16, 24 and 128 plasma samples15,30 under IND
(Investigational New Drug Application) clearances from the FDA. As of
November 2001, the major programs (pooled and individual donation testing) in
the U.S. have tested a total of 24.9 million donations for HCV RNA and HIV-1
RNA. A total of 89 donations (1:280,000 screened units) were confirmed to be
positive for HCV RNA and negative in serological testing. Similarly, nine HIV-1
RNA positive, serologically negative donations (1:2,767,000) were identified.
During this testing period, two specimens were reactive for HIV-1 RNA and p24 Ag
but nonreactive by HIV antibody testing.

        Detection of HCV is based on serologic screening for anti-viral
antibodies with enzyme-linked immunosorbent assays (ELISA) or enzyme
immunoassays (EIA) and confirmation with a Strip Immunoblot Assay (e.g., RIBA®
SIA). Even though the development of these tests has significantly reduced the
incidence of post transfusion HCV infection in the U.S., risk of contracting HCV
through transfusion still exists14,16-17. Recent studies indicate that nucleic
acid-based amplification tests for HCV RNA will allow detection of HCV infection
approximately 59 days earlier than the current antibody-based tests17.

        The Procleix HIV-1/HCV Assay utilizes target amplification nucleic acid
probe technology for the detection of HIV-1 and HCV RNA in voluntary blood
donors18. The assay contains reagents which may be used for simultaneous
detection of both viruses or individual viruses, HIV-1 and HCV. All three assays
incorporate an Internal Control for monitoring assay performance in each
individual specimen.

PRINCIPLES OF THE PROCEDURE

        The Procleix HIV-1/HCV Assay involves three main steps which take place
in a single tube: sample preparation; HIV-1 and HCV RNA target amplification by
Transcription-Mediated Amplification (TMA)19; and detection of the amplification
products (amplicon) by the Hybridization Protection Assay (HPA)20.

        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

IN0076 Rev. F

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regions of HIV-1 and HCV, are hybridized to the HIV-1 or HCV 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 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 HIV-1/HCV Assay utilizes the
TMA method to amplify regions of HIV-1 RNA and of HCV 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 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, or assay calibrator 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 HIV-1/HCV signal by the
differential kinetics of light emission from probes with different labels21.
Internal Control specific amplicon is detected using a probe with rapid emission
of light (termed flasher signal). Amplicon specific to HIV-1/HCV is detected
using probes with relatively slower kinetics of light emission (termed glower
signal). The Dual Kinetic Assay (DKA) is a method used to differentiate between
the signals from flasher and glower labels21. When used for the simultaneous
detection of HIV-1 and HCV, the Procleix HIV-1/HCV Assay differentiates between
Internal Control and combined HIV-1/HCV signals but does not discriminate
between individual HIV-1 and HCV signals.

        Specimens found to be reactive in the Procleix HIV-1/HCV Assay must be
run in individual HIV-1 and HCV Discriminatory Assays to determine if they are
reactive for HIV-1, HCV or both.

        The Procleix HIV-1 and HCV Discriminatory Assays utilize the same three
main steps as the Procleix HIV-1/HCV Assay (target capture, TMA and HPA); the
same assay procedure is followed with one difference: HIV-1-specific or
HCV-specific probe reagents are used in place of the Procleix HIV-1/HCV Assay
Probe Reagent.

IN0076 Rev. F

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MATERIALS PROVIDED

Procleix HIV-1/HCV Assay         1000 Test Kit P/N 301031
5000 Test Kit P/N 301030   Internal Control Reagent       Target Capture Reagent
      Amplification Reagent       Enzyme Reagent       Probe Reagent      
Selection Reagent       Procleix Negative Calibrator       Procleix HIV-1
Positive Calibrator       Procleix HCV Positive Calibrator    

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MATERIALS REQUIRED, SOLD SEPARATELY

 
   
Procleix HIV-1 and HCV
Discriminatory Probe Reagents   P/N 301026  
HIV-1 Discriminatory Probe Reagent
 
    HCV Discriminatory Probe Reagent    
Procleix Assay Fluids
 
P/N 301027   Wash Solution       Oil       Buffer for Deactivation Fluid    
Procleix Auto Detect Reagents
 
P/N 301038   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
TU0022   Ten Tip Cassettes   P/N 104578   Sealing Cards   P/N 102085
Procleix HIV-1/HCV
Proficiency Panel
 
P/N 301034   HIV-1 Positive Panel Members       HCV Positive Panel Members      
HIV-1 and HCV Positive Panel Member       Negative Panel Members    
Procleix HIV-1 and HCV
External Quality Controls
 
P/N 301035   HIV-1 Positive External Quality Control       HCV Positive External
Quality Control       Negative External Quality Control    
Procleix HIV-1/HCV
Assay Calibrators
 
P/N 301036   HIV-1 Positive Calibrator       HCV Positive Calibrator      
Negative Calibrator    
Chiron CPT (Correlated Pipetting Transfer)
Pooling Software (Only required for pooling)
 
P/N 10001970

        The Chiron CPT Pooling Software, used in combination with the TECAN
GENESIS RSP, performs sample scanning and pooling operations that combine
aliquots from 16 individual samples into a single Master Pool Tube, which may be
used for further testing.

IN0076 Rev. F

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Equipment

        All equipment is available from Chiron Corporation unless otherwise
noted.

 
   
Procleix System   P/N 104955 (nominal 115V)
P/N 104954 (nominal 230V)

        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

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

IN0076 Rev. F

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REAGENTS

Procleix HIV-1/HCV Assay Kit:

P/N 301031 - 1000 Test Kit

P/N 301030 - 5000 Test Kit

CONTENTS

  Number of vials/
Volume per vial

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

Reagent Name

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

  1000
Test Kit

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

  5000
Test Kit

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

Internal Control Reagent
A HEPES buffered solution containing detergent and an RNA transcript.   2 X 5
mL   10 X 5
mL Store unopened reagent at –15° to –35°C.        
Target Capture Reagent
A HEPES buffered solution containing detergent, capture oligonucleotides and
magnetic microparticles.
 
2 X 280
mL
 
10 X 280
mL Store at 2° to 8°C. (Do not freeze)
Internal Control Reagent must be added to Target Capture Reagent before use in
the assay.        
Amplification Reagent
Primers, dNTPs, NTPs and co-factors in TRIS buffered solution containing PROCLIN
300 as preservative.
 
3 X 32
mL
 
15 X 32
mL Store unopened reagent at –15° to –35°C.        
Enzyme Reagent
MMLV Reverse Transcriptase and T7 RNA Polymerase in HEPES/TRIS buffered solution
containing 0.05% sodium azide as preservative.
 
2 X 18
mL
 
10 X 18
mL Store unopened reagent at –15° to –35°C.        
Probe Reagent
Chemiluminescent oligonucleotide probes in succinate buffered solution
containing detergent.
 
2 X 75
mL
 
10 X 75
mL Store unopened reagent at –15° to –35°C.        
Selection Reagent
Borate buffered solution containing surfactant.
 
2 X 180
mL
 
10 X 180
mL Store at 15° to 30°C.        
Procleix Negative Calibrator
Defibrinated normal human plasma, nonreactive for hepatitis B surface antigen
(HBsAg),
HIV-1 p24Ag, antibodies to human immunodeficiency virus type 1 (anti-HIV-1) and
type 2 (anti-HIV-2), and antibodies to human hepatitis C virus (anti-HCV) when
tested by FDA-licensed assays, containing gentamicin and 0.2% sodium azide as
preservatives.
Store at –15° to –35°C.
 
30 X 2
mL
 
90 X 2
mL

LOGO [g906999.jpg]         

IN0076 Rev. F

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Procleix HIV-1 Positive Calibrator
Inactivated HIV-1 positive plasma in defibrinated normal human plasma,
nonreactive for hepatitis B surface antigen (HBsAg), and antibodies to human
hepatitis C virus (anti-HCV) when tested by FDA-licensed assays, containing
gentamicin and 0.2% sodium azide as preservatives.
Store at –15° to –35°C.
 
30 X 2
mL
 
90 X 2
mL

LOGO [g871599.jpg]         
Procleix HCV Positive Calibrator
Inactivated HCV positive plasma in defibrinated normal human plasma, nonreactive
for hepatitis B surface antigen (HBsAg), and antibodies to human
immunodeficiency virus type 1 (anti-HIV-1) and type 2 (anti-HIV-2), when tested
by FDA-licensed assays, containing gentamicin and 0.2% sodium azide as
preservatives.
Store at –15° to –35°C.
 
30 X 2
mL
 
90 X 2
mL

LOGO [g884487.jpg]         

STORAGE INSTRUCTIONS

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

B. LOGO [g863231.jpg]

The Procleix HIV-1/HCV Assay Probe Reagent and the Discriminatory Probe Reagents
are light sensitive. Protect these reagents from light during storage and
preparation for use.

C.Target Capture Reagent (TCR) is stable when stored unopened at 2° to 8°C until
the expiration date. Do not use after expiration date. 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 until the
expiration date. Do not use after expiration date. 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 expiration date.

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.

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

Internal Control Reagent
Amplification Reagent
Enzyme Reagent
Probe Reagent
Procleix Negative Calibrator
Procleix HIV-1 Positive Calibrator
Procleix HCV Positive Calibrator
Procleix HIV-1 Discriminatory Probe Reagent
Procleix HCV Discriminatory Probe Reagent

        Do not use after expiration date.

H.After thawing, the Amplification Reagent, Enzyme Reagent, Probe Reagent, HIV-1
Discriminatory Probe Reagent and HCV Discriminatory 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 Amplification, Enzyme,
Probe, HIV-1 and HCV Discriminatory Probe Reagents after the initial thaw.

I.After thawing, Negative, HIV-1 and HCV Positive Calibrators may be kept at
room temperature up to 4 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, or HIV-1 and HCV Discriminatory Probe Reagents, 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.

PRECAUTIONS

For In Vitro Diagnostic Use.

A.Specimens may be infectious. Use Universal Precautions22,26 when performing
the assay. Proper handling and disposal methods should be established according
to local, state and federal regulations.23-25 Only personnel qualified as
proficient in the use of the Procleix HIV-1/HCV Assay, the use of the TECAN
GENESIS RSP and/or manual sample/TCR pipetting, and trained in handling
infectious materials should perform this type of diagnostic procedure.

B.CAUTION: Some components of this kit contain human blood products. The HIV-1
Positive Calibrator in this kit contains human plasma that is HIV-1 positive and
has been heat-treated to inactivate the virus. The HCV Positive Calibrator
contains human plasma that is HCV positive and has been heat-treated to
inactivate the virus. The Negative Calibrator has been assayed by FDA licensed
tests and found non-reactive for the presence of hepatitis B surface antigen
(HBsAg), HIV-1 p24Ag and antibodies to HIV-1/2 and HCV. No known test method can
offer

IN0076 Rev. F

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complete assurance that products derived from human blood will not transmit
infectious agents. All human blood sourced materials should be considered
potentially infectious and should be handled with Universal Precautions.22,26 If
spillage occurs, immediately disinfect, then wipe up with a 0.5% (final
concentration) sodium hypochlorite solution (diluted bleach) or follow
appropriate site procedures.

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.This product contains sodium azide as a preservative. Do not use metal tubing
for reagent transfer. If solutions containing azide compounds are disposed of in
a plumbing system, they should be diluted and flushed with generous amounts of
running water. These precautions are recommended to avoid accumulation of
deposits in metal piping in which explosive conditions could develop.

E.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.

F.Dispose of all materials that have come in contact with specimens and reagents
according to local, state and federal regulations.23,24 Thoroughly clean and
disinfect all work surfaces.

G.Use only supplied or specified required disposables.

H.Do not use this kit after its expiration date. DO NOT interchange, mix, or
combine reagents from kits with different master lot numbers.

I.Avoid microbial and ribonuclease contamination of reagents.

J.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.

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

L.Some reagents of this kit are labeled with risk and safety symbols according
to the European Directive 1999/45/EC and should be handled accordingly.

Material Safety Data Sheets are available upon request.

IN0076 Rev. F

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The following reagents contain 0.2% sodium azide as a preservative:

Procleix Negative Calibrator
Procleix HIV-1 Positive Calibrator
Procleix HCV Positive Calibrator

Xn. Harmful   GRAPHIC [g910687.jpg]

R22/R32/S2
S13/S36/S46

R22   Harmful if swallowed R32   Contact with acid liberates very toxic gas S2  
Keep out of reach of children S13   Keep away from food, drink, and animal
feeding stuffs S36   Wear suitable protective clothing S46   If swallowed, seek
medical advice immediately and show this container or label

M.Refer to PRECAUTIONS in other Procleix Assay package inserts and Procleix
System Operator's Manuals.

REAGENT PREPARATION

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

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, HIV-1 Discriminatory Probe Reagent or HCV
Discriminatory Probe Reagent above 30oC.

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

IN0076 Rev. F

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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 expiration date of
the working TCR in the space provided on the label.

8.Thaw calibrators at room temperature. These are single use vials and must be
thawed prior to each run. Once thawed, use calibrators within four 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 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 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.

IN0076 Rev. F

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Do not freeze whole blood.

Temperature
(°C)

LOGO [g897447.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.25

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 16
individual samples into a single Master Pool Tube, which may be used for further
testing.

PROCEDURAL NOTES

A.RUN SIZE

IN0076 Rev. F

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When the average run size is 55 tests or more, P/N 301030 should yield 5000
tests per kit. P/N 301031 should yield 1000 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 HIV-1 Positive Calibrator and
the HCV Positive Calibrator.

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 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. 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.

7.Setup procedures for the 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. The aliquoted reagents must be used the
same day the aliquoting was performed. DO NOT store reagents in the aliquot
conical tubes.

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.

E.TEMPERATURE

IN0076 Rev. F

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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
Procleix HIV-1/HCV 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 pipettors used in the Amplification and HPA steps must be dedicated. All
pipettors used for manual pipetting in the Target Capture steps must be
dedicated.

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

IN0076 Rev. F

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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.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:

PROCLEIX HIV-1/HCV 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 Procleix HIV-1/HCV Assay.

Per CLIA requirements (42 CFR 493), the Procleix HIV-1 and HCV External Quality
Controls or equivalent must be run every time a Procleix assay is performed.
Procleix HIV-1/HCV Assay Calibrators and Discriminatory Probe Reagents are to be
used with the corresponding master lot of the Procleix HIV-1/HCV Assays. The
operator must check to ensure that the Procleix HIV-1/HCV Assay Calibrators and
Discriminatory Probe Reagents are used with the corresponding master lot of kit
reagents as indicated on the master lot sheet enclosed with each shipment of
Procleix HIV-1/HCV Assay Calibrators and Discriminatory Probe Reagents.

To run the Procleix HIV-1/HCV Assay for the detection of HIV-1 and HCV RNA,
follow the steps below for Target Capture, Amplification and Hybridization
Protection Assay. To run the Procleix HIV-1/HCV Assay for discrimination between
HIV-1 and HCV RNA, see Section D, below, prior to proceeding.

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 HIV-1/HCV Assay has been validated using the TECAN GENESIS RSP
150/8. 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 150/8 PIPETTOR:

1.Start the Procleix 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

IN0076 Rev. F

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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 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.

5.Reference the Procleix Assay Software Operator's Manual for instructions on
pipetting. The TECAN GENESIS RSP will read bar codes of all carriers, TTUs,
Calibrators, and samples. The TECAN GENESIS RSP will pipette 400 µL of working
TCR into each reaction tube and then pipette 500 µL each of calibrators 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 Procleix 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 Procleix 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 Procleix TCS separation
bay and vortex to resuspend the microparticle pellets. See PROCEDURAL NOTES.

16.Place the rack of TTUs on the 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 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 Procleix TCS separation bay and proceed
directly to Amplification.

IN0076 Rev. F

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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 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 µL 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 µL of each calibrator, external quality control 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.

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

2.Deliver 75 µL 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 µL 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.

IN0076 Rev. F

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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 µL 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.

1.Hybridization

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

b.Add 100 µL 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 µL 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.

IN0076 Rev. F

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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.

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 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 "HIV-HCV" assay protocol from the Procleix 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 1 mL 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.

D.PROCLEIX HIV-1 AND HCV DISCRIMINATORY ASSAYS

1.All reactive individual specimens should be run in singlet in the HIV-1 and/or
HCV Discriminatory Assays.

2.To perform the discriminatory assays, make the following modifications to the
procedure above:

a.Perform all TARGET CAPTURE and AMPLIFICATION steps exactly as they are
outlined above. Set up separate runs for HIV-1 and HCV Discriminatory Assays.
Both Discriminatory Assays use the same Calibrators that are used in the
Procleix HIV-1/HCV Assay.

IN0076 Rev. F

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b.Substitute HIV-1 or HCV Discriminatory Probe Reagent for Probe Reagent, in
step C.1.b, when performing HYBRIDIZATION PROTECTION ASSAY.

c.Choose the appropriate Procleix System Software protocol: "dHIV-1" for HIV-1
DISCRIMINATORY ASSAY or "dHCV" for HCV DISCRIMINATORY ASSAY, in step C.3.b, when
performing the HYBRIDIZATION PROTECTION ASSAY.

QUALITY CONTROL PROCEDURES:

PROCLEIX HIV-1/HCV ASSAY ON INDIVIDUAL DONOR PLASMA SAMPLES OR ON POOLED PLASMA
SAMPLES

I.ACCEPTANCE CRITERIA FOR THE PROCLEIX HIV-1/HCV ASSAY AND PROCLEIX HIV-1 AND
HCV DISCRIMINATORY ASSAYS

Run Validity Criteria

A.A run is valid if the minimum number of calibrators is valid and calibrators
meet acceptance criteria (see II.A. below). In a run, no more than 2 of the 9
calibrators may be invalid. The Procleix System Software will invalidate a run
if more than 2 calibrators are invalid in a run. Cutoff values will be
calculated for Internal Control (flasher) and Analyte (glower) in valid runs
(see II.A. below). 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. All specimens in an invalid run are to be retested,
except as noted in step I.B. below.

B.Procleix HIV-1/HCV Assay. If more than 10% of calibrators plus specimen
results (overall interpretation) are invalid in the Procleix HIV-1/HCV Assay,
then the run is invalidated by the Procleix System Software and the run must be
repeated. 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
10% run validity criterion for the Procleix HIV-1/HCV Assay must be manually
recalculated.

Potential reactive specimens in an invalid run due to the 10% run validity
criterion must be identified by the user. Any reactive result serves as the test
of record and the sample should be resolved according to the resolution
algorithm for reactive specimens, as explained below in the INTERPRETATION OF
RESULTS section, step 4 or 5.

Nonreactive specimens in an invalid run due to the 10% run validity criterion
are to be re-tested, as explained below in the INTERPRETATION OF RESULTS
section, step 1.

C.Procleix HIV-1 and HCV Discriminatory Assays. For the Procleix HIV-1 and HCV
Discriminatory Assays, the Procleix System Software will only invalidate a
Procleix HIV-1 or HCV Discriminatory Assay run based on calibrator invalidity
criteria described in (A) above. Specimen results are not used to invalidate the
Procleix HIV-1 and HCV Discriminatory Assays. An assay run or an individual
sample may be invalidated by an operator if specific technical/ operator/
instrument difficulties were observed and documented.

D.When using the TECAN GENESIS RSP, specimens that are invalid due to
insufficient sample or TCR are not included in the calculation of the 10%
criterion.

II.ACCEPTANCE CRITERIA FOR THE CALIBRATION AND CALCULATION OF CUTOFF

A.Procleix HIV-1/HCV Assay

Negative Calibrator Acceptance Criteria

IN0076 Rev. F

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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 300,000 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.

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   124,000 2   126,000 3   125,000    

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

Total Internal Control RLU =   375,000

NCx (Internal Control) = Total Internal Control RLU = 125,000
            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

HIV-1 Positive Calibrator Acceptance Criteria

Individual HIV-1 Positive Calibrator (PC) Analyte values must be less than or
equal to 1,800,000 RLU and greater than or equal to 300,000 RLU. If one of the
HIV-1 Positive Calibrator values is outside these limits, the HIV-1 Positive
Calibrator mean (HIV-1 PCx) will be recalculated based upon the two acceptable
HIV-1 Positive Calibrator values. The run is invalid and must be repeated if two
or more of the three HIV-1 Positive Calibrator Analyte values are outside of
these limits. IC values may not exceed 475,000 RLU.

Determination of the mean of the HIV-1 Positive Calibrator (HIV-1 PCx) values
for Analyte [HIV-1 PCx(Analyte)].

IN0076 Rev. F

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Example:

HIV-1 Positive Calibrator

 
Analyte
Relative Light Units

1   690,000 2   700,000 3   710,000    

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

Total Analyte RLU =   2,100,000

HIV-1 PCx (Analyte) = Total Analyte RLU = 700,000
            3

HCV Positive Calibrator Acceptance Criteria

        Individual HCV Positive Calibrator Analyte values must be less than or
equal to 900,000 RLU and greater than or equal to 200,000 RLU. If one of the HCV
Positive Calibrator values is outside these limits, the HCV Positive Calibrator
mean (HCV PCx) will be recalculated based upon the two acceptable HCV Positive
Calibrator values. The run is invalid and must be repeated if two or more of the
three HCV Positive Calibrator Analyte values are outside these limits. IC values
may not exceed 475,000 RLU.

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

Example:

HCV Positive Calibrator

  Analyte
Relative Light Units

1   350,000 2   360,000 3   340,000    

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

Total Analyte RLU =   1,050,000

HCV PCx (Analyte) = Total Analyte RLU = 350,000
        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 (125,000)

Internal Control Cutoff Value = 62,500 RLU

Calculation of the HIV-1/HCV Analyte Cutoff Value

Analyte Cutoff Value = NCx (Analyte) + [0.02 X HIV-1 PCx
(Analyte)]+ [0.04 X HCV PCx (Analyte)]

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

Analyte Cutoff Value = 15,000 + (0.02 X 700,000) + (0.04 X 350,000)

Analyte Cutoff Value = 43,000 RLU

IN0076 Rev. F

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Summary of Acceptance Criteria for Procleix HIV-1/ HCV Assay

Acceptance Criteria:    
Negative Calibrator
 
  Analyte   > 0 and < 40,000 RLU Internal Control   > 75,000 and < 300,000 RLU
HIV-1 Positive Calibrator     Analyte   > 300,000 and < 1,800,000 RLU Internal
Control   < 475,000 RLU
HCV Positive Calibrator
 
  Analyte   > 200,000 and < 900,000 RLU Internal Control   < 475,000 RLU

Summary of Cutoff Calculations for Procleix HIV-1/HCV Assay

Analyte Cutoff =   NC Analyte Mean RLU     + 0.02 X (HIV-1 PC Analyte Mean RLU)
    + 0.04 X (HCV PC Analyte Mean RLU)                 Internal Control Cutoff =
0.5 X (Negative Calibrator IC Mean RLU)

B.Procleix HIV-1 Discriminatory 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 300,000 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 Analyte value that is 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.

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

Example:

Negative Calibrator

  Internal Control Relative Light Units

1   124,000 2   126,000 3   125,000    

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

Total Internal Control RLU =   375,000

NCx (Internal Control) = Total Internal Control RLU = 125,000
3

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

IN0076 Rev. F

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Example:

Negative Calibrator

  Analyte
Relative Light Units

1   12,000 2   11,000 3   13,000    

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

Total Analyte RLU =   36,000

NCx (Analyte) = Total Analyte RLU = 12,000
    3

HIV-1 Positive Calibrator Acceptance Criteria

Individual HIV-1 Positive Calibrator (PC) Analyte values must be less than or
equal to 1,800,000 RLU and greater than or equal to 300,000 RLU. If one of the
HIV-1 Positive Calibrator values is outside these limits, the HIV-1 Positive
Calibrator mean (HIV-1 PCx) will be recalculated based upon the two acceptable
HIV-1 Positive Calibrator values. The run is invalid and must be repeated if two
or more of the three HIV-1 Positive Calibrator Analyte values are outside these
limits. IC values may not exceed 475,000 RLU.

Determination of the mean of the HIV-1 Positive Calibrator (HIV-1 PCx) values
for Analyte [HIV-1 PCx (Analyte)].

Example:

HIV-1 Positive Calibrator   Analyte
Relative Light Units 1   690,000 2   700,000 3   710,000    

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

Total Analyte RLU =   2,100,000

(HIV-1 PCx) (Analyte) = Total Analyte RLU = 700,000
3

HCV Positive Calibrator Acceptance Criteria

In the HIV-1 Discriminatory Assay, each individual HCV Positive Calibrator must
have Analyte values less than or equal to 40,000 RLU and greater than or equal
to 0 RLU. Each HCV Positive Calibrator must also have IC values greater than or
equal to 75,000 RLU and less than or equal to 300,000 RLU. The run is invalid
and must be repeated if two or more of the three calibrator values have IC
values or Analyte values that are outside these limits.

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 (125,000)

Internal Control Cutoff Value = 62,500 RLU

Calculation of the Analyte Cutoff Value

Analyte Cutoff Value = NCx (Analyte) + [0.04 X HIV-1 PCx (Analyte)]

IN0076 Rev. F

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Using values given in the Negative Calibrator and HIV-1 Positive Calibrator
examples above:

Analyte Cutoff Value = 12,000 + (0.04 X 700,000)

Analyte Cutoff Value = 40,000 RLU

Summary of Acceptance Criteria for the Procleix HIV-1 Discriminatory Assay

Acceptance Criteria:    
Negative Calibrator
 
  Analyte   > 0 and < 40,000 RLU Internal Control   > 75,000 and < 300,000 RLU
HIV-1 Positive Calibrator
 
  Analyte   > 300,000 and < 1,800,000 RLU Internal Control   < 475,000 RLU
HCV Positive Calibrator*
 
  Analyte   > 0 and < 40,000 RLU Internal Control   < 75,000 and < 300,000 RLU

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

*Note that the HCV Positive Calibrator performs similarly to the Negative
Calibrator in the HIV-1 Discriminatory Assay.

Summary of Cutoff Calculations for the Procleix HIV-1 Discriminatory Assay

Analyte Cutoff = NC Analyte Mean RLU + 0.04 X (HIV-1 PC Analyte Mean RLU)
                Internal Control Cutoff = 0.5 X (Negative Calibrator IC Mean
RLU)

C.Procleix HCV Discriminatory Assay

Negative Calibrator Acceptance Criteria

Each individual Negative Calibrator must have an Internal Control (IC) value
greater than or equal to 75,000 RLU and less than or equal to 300,000 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 or an IC or Analyte value is 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.

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   124,000 2   126,000 3   125,000    

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

Total Analyte RLU =   375,000

NCx (Internal Control) = Total Internal Control RLU = 125,000
3

IN0076 Rev. F

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

Example:

Negative Calibrator

 
Analyte
Relative Light Units

1   20,000 2   22,000 3   18,000    

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

Total Analyte RLU =   60,000

NCx (Analyte) = Total Analyte RLU = 20,000
3

HIV-1 Positive Calibrator Acceptance Criteria

In the HCV Discriminatory Assay, each individual HIV-1 Positive Calibrator must
have Analyte values less than or equal to 40,000 RLU and greater than or equal
to 0 RLU. Each HIV-1 Positive Calibrator must also have IC values greater than
or equal to 75,000 RLU and less than or equal to 300,000 RLU. The run is invalid
and must be repeated if two or more of the three calibrator values have IC
values or Analyte values that are outside of these limits.

HCV Positive Calibrator Acceptance Criteria

Individual HCV Positive Calibrator value must be less than or equal to 2,700,000
RLU and greater than or equal to 400,000 RLU. If one of the HCV Positive
Calibrator values is outside these limits, the HCV Positive Calibrator mean (HCV
PCx) will be recalculated based upon the two acceptable HCV Positive Calibrator
values. The run is invalid and must be repeated if two or more of the three HCV
Positive Calibrator values are outside these limits. IC values may not exceed
475,000 RLU.

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

Example:

HCV Positive Calibrator

  Analyte
Relative Light Units

1   900,000 2   1,000,000 3   1,100,000    

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

Total Analyte RLU =   3,000,000

HCV PCx (Analyte) = Total Analyte RLU = 1,000,000
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 (125,000)

Internal Control Cutoff Value = 62,500

Calculation of the Analyte Cutoff Value

IN0076 Rev. F

27

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Analyte Cutoff Value = NCx(Analyte) + [0.04 X HCV PCx(Analyte)]

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

Analyte Cutoff Value = 20,000 + (0.04 X 1,000,000)

Analyte Cutoff Value = 60,000 RLU

Summary of Acceptance Criteria for the Procleix HCV Discriminatory Assay

Acceptance Criteria:    
Negative Calibrator
 
  Analyte   > 0 and < 40,000 RLU Internal Control   > 75,000 and < 300,000 RLU
HIV-1 Positive Calibrator*
 
  Analyte   > 0 and < 40,000 RLU Internal Control   > 75,000 and < 300,000 RLU
HCV Positive Calibrator
 
  Analyte   > 400,000 and < 2,700,000 RLU Internal Control   < 475,000 RLU

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

*Note that the HIV-1 Positive Calibrator performs similarly to the Negative
Calibrator in the HCV Discriminatory Assay.

Summary of Cutoff Calculations for the Procleix HCV Discriminatory Assay

Analyte Cutoff =   NC Analyte Mean RLU     + 0.04 X (HCV 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 Procleix System Software.
Two cutoffs are determined for each 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 475,000 RLU. The sample will automatically be reported as
Invalid with the Procleix System Software.

IN0076 Rev. F

28

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Summary of Sample Validity:

Sample
Interpretation

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

 
Internal Control
Result

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

 
 
Nonreactive   Valid   Analyte S/CO < 1 and IC
> IC Cutoff and IC <
475,000 RLU Reactive   (Not used)   Analyte S/CO > 1and IC
< 475,000 RLU

1.Any specimen with an invalid Procleix HIV-1/HCV Assay, Procleix HIV-1
Discriminatory Assay or Procleix HCV Discriminatory Assay result must be
retested in the same assay in singlet, except as noted in step 6 below.

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 (e.g.,
plasma unit or serology tube) 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
HIV-1/HCV Assay are considered Nonreactive for HIV-1 and HCV RNA. If the
Nonreactive specimen is a pool of 16, each of the 16 individual specimens
comprising the pool is considered Nonreactive and no further testing is
required.

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

IF THE REACTIVE SPECIMEN IS A POOL, then each of the individual specimens
comprising the pool is tested with the HIV-1/HCV Assay.

a.If an individual specimen tests Nonreactive with the HIV-1/HCV Assay, then the
specimen is considered Nonreactive for HIV-1 and HCV RNA and no further testing
is required.

b.If an individual specimen tests Reactive with the HIV-1/HCV Assay, then the
specimen must be tested with the HIV-1 Discriminatory and HCV Discriminatory
Assays.

(1)If an individual specimen then tests Reactive with one or both Discriminatory
tests, then the specimen is considered Reactive-Discriminated and may be
confirmed as described in (7) below.

(2)If an individual specimen then tests Nonreactive with both Discriminatory
tests, then the specimen is considered Non-Discriminated. Further clarification
of Non-Discriminated specimens may be obtained by testing an alternate specimen
from the index donation with the Procleix Assays and/or by follow-up testing.

5.IF THE REACTIVE SPECIMEN IS FROM AN INDIVIDUAL DONATION, then the specimen
must be tested with the HIV-1 Discriminatory and HCV Discriminatory Assays.

a.If an individual specimen then tests Reactive with one or both Discriminatory
tests, then the specimen is considered Reactive-Discriminated and may be
confirmed as described in (7) below.

b.If an individual specimen then tests Nonreactive with both Discriminatory
tests, then the specimen is considered Non-Discriminated. The Non-Discriminated
specimen may be retested in the HIV-1/HCV Assay if sufficient sample is
available.

IN0076 Rev. F

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

(1)If the individual specimen tests Nonreactive in the repeated HIV-1/HCV Assay,
then the specimen is considered Nonreactive for HIV-1 and HCV RNA and no further
testing is required.

(2)If the individual specimen tests Reactive in the repeated HIV-1/HCV Assay,
then the specimen is considered Repeatedly Reactive, Non-Discriminated for HIV-1
and HCV RNA. Further clarification of these specimens may be obtained by testing
an alternate specimen from the index donation with the Procleix Assays and/or by
follow-up testing.

6.Potential reactive specimens in an invalid run due to the 10% run validity
criterion must be identified by the user, by viewing the run report, and become
the test of record. Any reactive result (analyte signal/cutoff > 1) serves as
the test of record and the sample should be resolved according to the resolution
algorithm for reactive specimens, as explained in the INTERPRETATION OF RESULTS
section, step 4 or 5.

Nonreactive specimens in an invalid run due to the 10% run validity criterion
are to be retested in the same assay in singlet.

7.HIV seroreactive specimens found to be Reactive-HIV-1 Discriminated in the
Procleix tests may be considered positive for HIV-1 nucleic acid. HCV
seroreactive specimens found to be Reactive-HCV Discriminated in the Procleix
tests may be considered positive for HCV nucleic acid. The interpretation of
Reactive-Discriminated specimen results on specimens that are Nonreactive by
serology is unclear. Further clarification may be obtained by testing an
alternate specimen from the index donation with the Procleix Assays (to
eliminate false positives due to possible specimen contamination) and/or by
follow-up testing to determine if the NAT reactivity of the index donation
represents early pre-seroconversion infection.

PERFORMANCE CHARACTERISTICS

REPRODUCIBILITY

Procleix HIV-1/HCV Assay reproducibility was determined at three blood testing
laboratories. The reproducibility study evaluated both automated pipetting using
TECAN GENESIS RSP, and manual pipetting of the specimen and Target Capture
Reagent (TCR) into the reaction tube. The reproducibility of the HIV-1/HCV Assay
was assessed with a seven member reproducibility panel; 16 individual specimens
were pipetted with the Chiron CPT Pooling Software to create each of the seven
panel members (each panel member is a 16 member pool). Each pool contained from
zero to three HIV-1 and/or HCV RNA positive specimens with the remaining
specimens in the pool being HIV-1 and HCV RNA negative (Table I).

For determination of the reproducibility of the Procleix HIV-1 Discriminatory
Assay and the Procleix HCV Discriminatory Assay, nine panel members were tested
as individual specimens and not in a pool. Eight of these panel members were
HIV-1 and/or HCV RNA positive, and one was HIV-1 and HCV RNA negative (Tables
IIa, IIb).

The reproducibility panels were tested by a total of six operators (two at each
site) with three different Clinical Lots over at least 18 nonconsecutive days.
Inter- and intra-assay variability and inter-lot variability were determined.
Mean S/CO, standard deviation (SD) and coefficient of variation (%CV) results
are shown for panel members and for the Negative, HIV-1 Positive and HCV
Positive Calibrators. Since no significant difference in assay reproducibility
was observed between automated pipetting and manual pipetting, results for the
two methods are combined in the Tables below (Tables I, IIa, IIb). Also, since
HCV RNA positive and HIV-1 RNA positive samples containing 90 copies/mL or
greater gave high (saturated) signals in all three assays, results on multiple
panel members are combined.

IN0076 Rev. F

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Table I. Reproducibility of the Procleix HIV-1/HCV Assay

 
   
   
   
   
   
  Intra-Assay

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

  Inter-Assay

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

  Inter-Lot

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

Specimen

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

   
  Concentration
Copies/mL

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

  Number of
replicates

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

  %
Agreement

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

  Mean
S/CO

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

  N

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

  SD

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

  %CV

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

  SD

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

  %CV

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

  SD

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

  %CV

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

Nonreactive   1   0   320   100.00   0.23   0.054   23.5   0.034   14.7   0.041
  17.7 HIV-1   3   190, 620, 720   965   99.90   18.75   1.864   9.9   1.191  
6.4   2.351   12.5 HIV-1/HCV   2   620,720/90   641   100.00   27.42   2.374  
8.7   1.840   6.7   2.743   10.0 HCV   1   190   321   100.00   8.70   1.074  
12.3   0.615   7.1   0.743   8.5

 
   
   
   
  Intra-Assay

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

  Inter-Assay

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

  Inter-Lot

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

Specimen

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

  Number of
replicates

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

  %
Agreement

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

  Mean
RLU

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

  SD

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

  %CV

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

  SD

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

  %CV

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

  SD

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

  %CV

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

Negative Calibrator   323   N/A   10363   2023   19.5   1740   16.8   1606  
15.5 HIV-1 Positive Calibrator   324   N/A   858644   34660   4.0   55020   6.4
  141285   16.5 HCV Positive Calibrator   316   N/A   398939   17511   4.4  
15926   4.0   41127   10.3

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

N = Number of panel members combined for this analysis.

Table IIa. Reproducibility of the Procleix HIV-1 Discriminatory Assay (excludes
10 false positive results)

 
   
   
   
   
   
  Intra-Assay

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

  Inter-Assay

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

  Inter-Lot

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

Specimen

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

   
  Concentration
Copies/mL

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

  Number of
replicates

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

  % Agreement

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

  Mean
S/CO

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

  N

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

  SD

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

  %CV

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

  SD

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

  %CV

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

  SD

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

  %CV

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

Nonreactive   1   0   322   100.00   0.19   0.050   26.3   0.029   15.3   0.024
  12.3 HIV-1   4   150, 500,   1289   100.00   19.69   2.391   12.1   1.114  
5.7   0.883   4.5         1500, 10000                                    
HIV-1/HCV   1   500/500   318   100.00   19.44   1.225   6.3   1.373   7.1  
1.045   5.4 HCV   3   150, 500, 1500   955   100.00   0.18   0.054   29.7  
0.038   20.9   0.029   16.1

 
   
   
   
  Intra-Assay

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

  Inter-Assay

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

  Inter-Lot

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

Specimen

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

  Number of
replicates

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

  % Agreement

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

  Mean
RLU

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

  SD

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

  %CV

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

  SD

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

  %CV

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

  SD

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

  %CV

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

Negative Calibrator   323   N/A   8900   2121   23.8   1824   20.5   1470   16.5
HIV-1 Positive Calibrator   320   N/A   894464   57091   6.4   63756   7.1  
30695   3.4 HCV Positive Calibrator   322   N/A   8686   2381   27.4   1572  
18.1   783   9.0

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

N = Number of panel members combined for this analysis.

IN0076 Rev. F

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Table IIb. Reproducibility of the Procleix HCV Discriminatory Assay (excludes 3
false positive results)

 
   
   
   
   
   
  Intra-Assay

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

  Inter-Assay

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

  Inter-Lot

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

Specimen

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

   
  Concentration
Copies/mL

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

  Number of
replicates

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

  % Agreement

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

  Mean
S/CO

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

  N

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

  SD

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

  %CV

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

  SD

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

  %CV

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

  SD

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

  %CV

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

Nonreactive   1   0   323   100.00   0.13   0.051   39.0   0.031   24.1   0.010
  8.0 HIV-1   4   150, 500,   1288   100.00   0.13   0.073   55.0   0.042   31.5
  0.018   13.3         1500, 10000                                     HIV-1/HCV
  1   500/500   323   100.00   21.32   1.965   9.2   1.000   4.7   0.510   2.4
HCV   3   150, 500, 1500   966   99.90   21.48   1.884   8.8   1.211   5.6  
0.479   2.2

 
   
   
   
  Intra-Assay

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

  Inter-Assay

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

  Inter-Lot

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

Specimen

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

  Number of
replicates

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

  %
Agreement

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

  Mean
RLU

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

  SD

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

  %CV

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

  SD

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

  %CV

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

  SD

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

  %CV

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

Negative Calibrator   320   N/A   8132   2861   35.2   1893   23.3   81   1.0
HIV-1 Positive Calibrator   321   N/A   7937   3089   38.9   2240   28.2   929  
11.7 HCV Positive Calibrator   323   N/A   1243692   57818   4.6   92720   7.5  
36728   3.0

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

N = Number of panel members combined for this analysis.

PERFORMANCE OF POOLED SAMPLE TESTING

Specificity of the Procleix HIV-1/HCV Assay

The HIV-1/HCV Assay was used to screen plasma pools comprised of 16 donor
specimens and individual donor specimens (IDS). These specimens were tested at
eight volunteer blood donor sites using three Clinical Lots of reagents. This
population derived from approximately 103 geographically diverse blood donor
sites in the continental US and five others which were US military blood donor
sites located in Hawaii (one), Japan (two), Germany (one), and Guam (one). Pools
or individual specimens with S/CO<1.0 are considered Nonreactive (NR).
Individual specimens that are Reactive (R) by the HIV-1/HCV Assay and Reactive
by either the HIV-1 or HCV Discriminatory Assay or both are termed
Reactive-Discriminated. Individual specimens that are reactive by the HIV-1/HCV
Assay but Nonreactive by both the HIV-1 or HCV Discriminatory Assays are termed
Reactive-Non-Discriminated. A non-discriminated specimen which tested again as
HIV-1/HCV Reactive was termed Repeatedly Reactive-Non-Discriminated. A
non-discriminated specimen which tested again as HIV-1/HCV Assay Nonreactive was
considered Nonreactive for HIV-1 and HCV RNA.

At the time the study was performed there was no recognized standard for
establishing the presence or absence of HIV-1 RNA or HCV RNA in blood.
Specificity was based on testing of blood donations from random volunteer blood
donors. For the purpose of specificity calculations, specimens testing
seroreactive for anti-HIV-1 and anti-HCV antibody (Ab) or HIV p24 antigen (Ag)
were eliminated from the analysis.

In the pooling specificity study, 11,978 pools (191,648 donor specimens) were
tested (Table III and Table IV). Specificity of pool testing relative to
serology testing was 99.67% (11,625/11,663). Specificity was defined as number
of pools containing all serology and Procleix HIV-1/HCV Assay nonreactive
specimens (True negative, TN) divided by the sum of TN and False positive pools.
False positive pools were defined as pools Reactive by the HIV-1/HCV Assay and
that contained all specimens nonreactive by serology.

There were 175 (1.46%) pools initially reactive by the HIV-1/HCV Assay. All 16
individual donor specimens from each reactive pool were tested. There were 33
pools containing all Nonreactive

IN0076 Rev. F

32

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

individual donor specimens. One hundred and sixty-six individual donor specimens
derived from the remaining 142 pools were Reactive in the HIV-1/HCV Assay. No
significant differences among sites or Clinical Lots were observed.

Of the 166 HIV-1/HCV Assay reactive individual donor specimens, 138 (83.1%) were
Reactive in the HCV Discriminatory Assay, 13 (7.8%) were Reactive in the HIV-1
Discriminatory Assay and 15 (9.0%) were Nonreactive in both discriminatory
tests. The 15 Reactive-Non-Discriminated specimens were seronegative for HIV and
HCV and were Nonreactive when retested in the HIV-1/HCV Assay. The adjusted
reactive rate after removal of reactive pools containing true positive samples
was 0.31% (37/11,841).

A total of 49,054 specimens (total of pooled and individual donor specimens)
were run in the HIV-1/HCV Assay during these specificity studies and 185 (0.38%)
specimens tested as initially invalid due to an Internal Control failure. All
185 specimens giving initially invalid results gave valid repeat testing results
in the HIV-1/HCV Assay.

Table III. Procleix HIV-1/HCV Assay Reactivity in Volunteer Blood Donors

 
  Procleix HIV-1/HCV Assay
Plasma Pool of 16

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

Samples Tested*   11,978 Initial Reactive   175 Initial Reactive Rate   1.46%
Adjusted Reactive Rate   0.31% Combined Mean S/CO on Negative Analytes   0.21 ±
0.10

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

*Combined data across all sites and Clinical Lots.

No significant differences among Clinical Lots of reagents were observed for
either the Negative population Analyte mean S/CO or mean Internal Control S/CO
in the negative population distribution.

Results of deconvolution of all 16 member pools are shown in Table IV. In these
pivotal specificity studies (pooled and individual donation testing), no
specimen was identified as a yield specimen based on the HIV-1/HCV Assay
reactivity, HIV-1 and/or HCV Discriminatory Assay reactivity, reactivity by
Alternative NAT and lack of HCV or HIV-1 antibody reactivity. The finding of no
HIV-1 or HCV RNA yield donors in 226,205 specimens is consistent with published
yields15. Rates of specimens testing reactive for both HCV RNA and HCV antibody
in volunteer donors was 1 in 1,508 donors and rates of specimens testing
reactive for both HIV-1 RNA and HIV-1 antibody was 1 in 14,138 donors.

IN0076 Rev. F

33

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Table IV. Deconvoluted Pooling Results

 
  N (%)

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

  Sero-RR*

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

   
   
Total pools tested   11,978 (100.0 ) N/A         HIV-1/HCV Assay Nonreactive
pools   11,803 (98.54 ) N/A         HIV-1/HCV Assay Reactive pools   175 (1.46 )
N/A        
Pools with all HIV-1/HCV Assay Nonreactive IDS
 
33 (18.9
)
N/A
 
 
 
  Pools with > 1 HIV-1/HCV Assay Reactive IDS   142 (81.1 ) N/A        
HIV-1/HCV Assay Reactive IDS
 
166 (100.0
)
120
 
 
 
  HIV-1 and HCV Discriminatory Reactive IDS   0 (0.0 ) 0         HIV-1
Discriminatory Reactive IDS   13 (7.8 ) 13         HCV Discriminatory Reactive
IDS   138 (83.1 ) 131         HIV-1 and HCV Discriminatory Nonreactive IDS   15
(9.0 ) 0        
Repeat HIV-1/HCV Assay Nonreactive IDS
 
15 (100.0
)
0
 
 
 
  Repeat HIV-1/HCV Assay Reactive IDS   0 (0.0 ) 0        

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

*EIA repeatedly reactive, supplemental serology positive or indeterminate.

IDS = Individual Donor Specimen.

Specificity of the Procleix HIV-1 and HCV Discriminatory Assays

In the HIV-1 and HCV Discriminatory Assays specificity study, the HIV-1
Discriminatory and HCV Discriminatory assays were run only on individual donor
specimens which had previously tested as Nonreactive by the HIV-1/HCV assay. The
initial reactive rates for the HIV-1 Discriminatory and HCV Discriminatory
Assays were 0.24% (6/2508) and 0.29% (7/2443), respectively. In this study
initially reactive specimens were not retested.

Comparison with Serology

Results generated from the pooled and individual donation testing specificity
studies allow comparison of the HIV-1/HCV Assay with serology reactivity (Table
V). Sixteen of 17 HIV-1 seroreactive, Western blot positive specimens were also
Procleix HIV-1/HCV Assay Reactive (Table V). The one discordant specimen was
Nonreactive when tested as a pool by the Procleix HIV-1/HCV Assay but was
Reactive by the Procleix HIV-1/HCV Assay when tested as an individual donor
specimen. All of the HIV seroreactive specimens which were Indeterminate or
negative by Western Blot (91.7% of total HIV seroreactive specimens) were
Nonreactive by the Procleix HIV-1/HCV Assay. Overall agreement between the
Procleix HIV-1/HCV Assay and Western blot was 100% (226/226) if testing at an
individual donor level is compared.

77.3% (150/194) of HCV seroreactive, Chiron RIBA HCV 3.0 (RIBA) Positive
specimens were Reactive by the HIV-1/HCV Assay. 3.3% (2/60) of HCV seroreactive,
RIBA Indeterminate specimens were reactive by the Procleix HIV-1/HCV Assay. All
163 RIBA Negative specimens were also Nonreactive by the Procleix HIV-1/HCV
Assay. Overall agreement between the Procleix HIV-1/HCV Assay and RIBA was 89.0%
(371/417). These data are consistent with previous reports that about 20% of HCV
seropositives will have undetectable HCV RNA27 and estimates that approximately
20% of HCV seropositive individuals may have resolved infection28.

IN0076 Rev. F

34

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

Table V. Comparison of Serologic and Procleix HIV-1/HCV Assay Reactives from the
Specificity Studies

 
   
  Procleix HIV-1/HCV

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

  Serology

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

  Reactive

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

  Nonreactive

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

  HIV Ab RR   POS   16 (7.0 %) 1* (0.4 %) Western Blot   IND   0 (0 %) 74 (32.5
%) (N = 228)   NEG   0 (0 %) 135 (59.2 %)     N/A   0 (0 %) 2 (0.9 %) HCV Ab RR
  POS   150 (35.8 %) 44 (10.5 %) RIBA   IND   2 (0.5 %) 58 (13.8 %) (N = 419)  
NEG   0 (0.0 %) 163 (38.9 %)     N/A   1 (0.2 %) 1 (0.2 %)

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

*Sample contained < 50 copies/mL of HIV-1 RNA and was Procleix HIV-1/HCV
negative in pool testing but reactive in individual sample testing.

Non-Specificity Studies

When tested with the Procleix HIV-1/HCV Assay, no cross-reactivity or
interference was observed for naturally occurring icteric, hemolyzed or lipemic
specimens or plasma containing the following substances: serum albumin (up to
225 g/L), hemoglobin (up to 5000 mg/L), billirubin (up to 200 mg/L) and lipids
(up to 2,752 mg/dL).

No cross-reactivity or interference was observed in specimens from patients with
autoimmune diseases or with liver diseases not caused by HCV infection.
Autoimmune conditions included rheumatoid arthritis (n = 10), rheumatoid factor
(n = 10), antinuclear antibody (n = 10), multiple sclerosis (n = 10), lupus (n =
10) and multiple myeloma (n = 9). Also tested were flu vaccinees (n = 10),
hepatitis B vaccinees (n = 10), elevated IgM (n = 6), elevated IgG (n = 11),
alcoholic liver cirrhosis (n = 10) and elevated ALT (n = 10).

No cross-reactivity or interference was observed in bacterially contaminated
plasmas or in plasmas infected with other blood borne pathogens, including
herpes simplex virus-1 (n = 10), herpes simplex virus-2 (n = 1), CMV (n = 10),
EBV (n = 10), hepatitis A virus (n = 10), HTLV-I (n = 10), HTLV-II (n = 10),
hepatitis B virus (n = 10), HIV-2 (n = 10), rubella (n = 10) and parvovirus B-19
(n = 10).

CLINICAL SENSITIVITY

Testing of Whole Blood Donor Specimens

A total of 24,764,889 donations were screened as part of pooled sample testing
since early 199930. As of November 2001, eighty-eight Procleix HCV yield cases
(1:281,419) and seven HIV-1 yield cases (1:3,537,841) were identified across the
ten Procleix pooled testing sites. Yield cases were confirmed to be positive for
either HIV-1 or HCV RNA, but negative in serology testing.

Two of the nine HIV-1 yield cases were reactive for HIV-1 RNA and p24 Ag but
Nonreactive by HIV antibody testing (Table VI).

IN0076 Rev. F

35

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

Table VI. Summary of Procleix Assay Yield Cases

Pooled Sample Testing

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

Number of Donations Tested   24,764,889 Procleix HCV
Yield Cases   88
(1:281,419) Procleix HIV-1   7 Yield Cases   (1:3,537,841)

Testing of Specimens from HIV-1 and/or HCV Infected Individuals

A total of 2014 specimens positive by commercial HIV-1 RNA and HCV RNA assays
(sensitivity >100 copies/mL) were obtained from four commercial vendors. Three
Clinical Lots were used for all testing. These specimens were classified as
HIV-1 RNA positives (n = 867), HCV RNA positives (n = 967) and both HIV-1 and
HCV RNA (coinfected) positives (n = 180) based on alternate nucleic acid testing
(Table VII). These specimens were also classified by disease category as
described below and as shown in Table VIII. These positive samples were tested
undiluted (neat) with the Procleix HIV-1/HCV Assay, HIV-1 Discriminatory Assay
and the HCV Discriminatory Assay, and tested diluted 1:16 with the Procleix
HIV-1/HCV Assay. All dilutions were made with processed human serum that was
negative for HIV-1 RNA and antibody/antigen, and HCV RNA and antibody.

During the study, specimens known to contain <100 copies/mL of viral RNA were
excluded from this analysis and therefore the sensitivity presented herein is
for samples with viral RNA concentrations equal to or greater than 100
copies/mL, or of unknown viral concentration.

The sensitivity for the Procleix HIV-1/HCV and HIV-1 Discriminatory Assays for
undiluted (neat) HIV-1 positive samples was 99.9% (95% CI: 99.4-100%) and 100%
(95% CI: 99.6-100%), respectively. The sensitivity for the Procleix HIV-1/HCV
Assay for diluted (1:16) HIV-1 positive samples was 99.0% (95% CI: 98.0-99.5%).

The sensitivity for both the Procleix HIV-1/HCV Assay and the HCV Discriminatory
Assay for undiluted (neat) HCV positive samples was 99.6% (95% CI: 98.9-99.9%).
The sensitivity for the Procleix HIV-1/HCV Assay for diluted (1:16) HCV
positives was 99.6% (95% CI: 98.9-99.9).

The sensitivity for the Procleix HIV-1/HCV Assay, HIV-1 Discriminatory Assay and
HCV Discriminatory Assay for undiluted HIV-1/HCV coinfected specimens was 100%
(95% CI: 98.0-100%), 100% (95% CI: 97.9-100%) and 100% (95% CI: 92.6-100%),
respectively. The sensitivity for the Procleix HIV-1/HCV Assay for HIV-1/HCV
coinfected specimens was 98.9% (95% CI: 96.0-99.9) when tested at 1:16 dilution.

The overall clinical sensitivity for the Procleix HIV-1/HCV Assay, which takes
into account all samples (RNA concentrations > 100 copies/mL or unknown viral
concentration) tested, is 99.8% (95% CI: 99.4-99.9), that for the HIV-1
Discriminatory Assay is 100% (95% CI: 99.6-100%), and that for the HCV
Discriminatory Assay is 99.6% (95% CI: 99.0-99.9%).

IN0076 Rev. F

36

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Table VII. The Sensitivity of the Procleix HIV-1/HCV, HIV-1 and HCV
Discriminatory Assays for HIV-1 and HCV Positive Specimens with RNA
Concentrations > 100 Copies/mL or Unknown

HIV-1/HCV Assay

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

   
  Sensitivity for Neat Specimens

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

  Sensitivity for 1:16 Diluted Specimens

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

  Sample

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

    N

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

  TP

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

  %

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

  (95% C. I.)

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

  N

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

  TP

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

  %

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

  (95% C. I.)

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

  All   2014   2009   99.8   (99.4—99.9 ) 2012   1997   99.3   (98.8—99.6 ) HIV
Only   867   866   99.9   (99.4—100.0 ) 866   857   99.0   (98.0—99.5 ) HCV Only
  967   963   99.6   (98.9—99.9 ) 966   962   99.6   (98.9—99.9 ) HIV & HCV  
180   180   100   (98.0—100.0 ) 180   178   98.9   (96.0—99.9 )

HIV-1 Discriminatory Assay

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

   
  Sensitivity

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

  Sample

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

    N

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

  TP

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

  %

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

  (95% C. I.)

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

  All   1042   1042   100   (99.6—100.0 ) HIV Only   868   868   100  
(99.6—100.0 ) HIV & HCV   174   174   100   (97.9—100.0 )

HIV Discriminatory Assay

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

   
  Sensitivity

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

  Sample

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

    N

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

  TP

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

  %

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

  (95% C. I.)

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

  All   1014   1010   99.6   (99.0—99.9 ) HCV Only   966   962   99.6  
(98.9—99.9 ) HIV & HCV   48   48   100   (92.6—100.0 )

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

C. I. = Confidence interval.

The data from the above study were further analyzed according to the disease
stages of the patients from whom the specimens were obtained as shown in Table
VIII. A total of 296 samples were from AIDS patients (as defined by
AIDS-indicative conditions and/or a CD4 count of <200/mm3), 338 from
asymptomatic patients (asymptomatic, persistent generalized lymphadenopathy, or
acute HIV infection), 168 from symptomatic but non-AIDS patients (not AIDS and
not asymptomatic) and 240 from individuals with unknown HIV disease state29.
Most of these patients were on HIV anti-viral medication. The sensitivity for
HIV detection with the Procleix HIV-1/HCV Assay ranged from 99.6 to 100% for
neat specimens and from 96.4 to 100% for 1:16 diluted specimens. The sensitivity
for the HIV-1 Discriminatory Assay was 100%. All HIV-1 p24 Ag reactive specimens
were also reactive with the Procleix HIV-1/HCV Assay when tested as undiluted
(neat) or as 1:16 diluted samples, and with HIV-1 Discriminatory Assay when
tested as neat samples. This was also true of all specimens excluded from the
study due to low viral RNA concentrations (<100 copies/mL).

Similarly, the specimens from HCV infected patients were segregated as shown in
Table IX. A total of 887 specimens were from volunteer blood donors whose
donations were HCV reactive with PCR-based NAT, 53 specimens were from patients
with chronic HCV infection that was first identified by blood donation screening
and 75 specimens were not categorized by the vendor other than being HCV NAT or
antibody positive. The sensitivity for HCV testing with the Procleix HIV-1/HCV
Assay ranged from 99.5 to 100% (95% CI: 98.9-99.9%) with neat samples and 97.3
to 100% (95% CI: 93.3-100%) with 1:16 diluted samples. The sensitivity for HCV
Discriminatory Assay ranged from 99.5 to 100% (95% CI: 95.2-100%) for neat
samples.

During this clinical study, in which a total of 1014 HCV RNA-positive samples
were tested, two of these samples were consistently reactive when tested at 1:16
dilution, but nonreactive when tested neat.

IN0076 Rev. F

37

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

In the same study, 13 sero-positive samples with low copy numbers of HIV or HCV
(or both) were non-reactive when tested at 1:16 dilution, and reactive when
tested neat.

In summary, it appears that the disease stages for HIV-1 or HCV infected
individuals did not significantly affect the sensitivity for the Procleix
Assays, although some low copy number HCV antibody positive specimens (2/967)
were non-reactive when tested neat but reactive when tested at 1:16 dilution.

The clinical sensitivity claims of the assay are still met with the inclusion of
these specimens.

IN0076 Rev. F

38

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

Table VIII. Sensitivity of the Procleix HIV-1/HCV and HIV-1 Discriminatory
Assays for HIV-1 Positive Specimens from Individuals at Various Disease States*

 
  Procleix HIV-1/HCV Assay

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

  HIV-1 Discriminatory

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

  HIV-1 Antibody

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

  HIV-1 p24 Ag

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

 
  Neat

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

  1:16 Dilution

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

  Neat

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

   
   
   
   
   
   
Disease

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

  N
Tested

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

  N
R

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

  %
R

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

  N
Tested

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

  N
R

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

  %
R

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

  N
Tested

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

  N
R

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

  %
R

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

  N
Tested

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

  N
R

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

  %
R

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

  N
Tested

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

  N
R

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

  %
R

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

AIDS   295   295   100.0   296   295   99.7   296   296   100.0   296   296  
100.0   226   44   19.5 Symptomatic**   168   168   100.0   167   161   96.4  
168   168   100.0   168   168   100.0   138   14   10.1 Asymptomatic***   338  
338   100.0   338   338   100.0   338   338   100.0   338   297   87.9   234  
73   31.2 Unknown   240   239   99.6   240   238   99.2   240   240   100.0  
236   234   99.2   202   29   14.4    

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

Total   1041   1040   99.9   1041   1032   99.1   1042   1042   100.0   1038  
995   95.9   800   160   20.0

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

N = Number        R = Reactive

*Samples with confirmed viral loads < 100 copies/mL excluded.

**Symptomatic (not asymptomatic and not AIDS).

***Asymptomatic (asymptomatic, persistent generalized lymphadenopathy, or acute
HIV infection).

Table IX. Sensitivity of the Procleix HIV-1/HCV and HCV Discriminatory Assays
for HCV Positive Specimens From Individuals at Various Disease States*

 
  Procleix HIV-1/HCV Assay

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

  HIV Discriminatory Assay

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

  HIV Antibody

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

 
  Neat

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

  1:16 Dilution

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

  Neat

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

   
   
   
Disease

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

  N
Tested

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

  N
R

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

  %
R

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

  N
Tested

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

  N
R

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

  %
R

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

  N
Tested

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

  N
R

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

  %
R

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

  N
Tested

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

  N
R

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

  %
R

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

First Time Blood   887   883   99.5   886   882   99.5   886   882   99.5   886
  886   100 Chronic HCV   53   53   100   53   53   100   53   53   100   53  
53   100 Unknown   75   75   100   75   73   97.3   75   75   100   52   20  
38.5    

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

 

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

Total   1015   1011   99.6   1014   1008   99.4   1014   1010   99.6   991   959
  96.8

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

N = Number        R = Reactive

*Samples with confirmed viral loads < 100 copies/mL excluded.

Sensitivity for Pooled Samples

        The clinical sensitivity of the Procleix HIV-1/HCV Assay with pooled
samples was determined by testing 102 sixteen-member pools composed of one HIV-1
or HCV positive sample and 15 negative samples, and 102 sixteen-member pools
composed of two HIV-1 and/or HCV positive samples and 14 negative samples. The
viral load of the HIV-1 positive samples used to make the pools ranged from 1060
copies/mL to 10,018,200 copies/mL with a median of 27,490 copies/mL. The viral
load of the HCV positive samples used to make the pools ranged from 1660
copies/mL to 20,200,000 copies/mL with a median of 327,000 copies/mL. All 204
(100%; 95% CI: 98.2-100%) pools containing at least one HIV-1 and/or HCV RNA
positive specimen were reactive with the HIV-1/HCV Assay.

Prospective Study of Individuals at High Risk for HIV-1 and HCV Infection

        Specimens from 539 individuals at high risk for infection with HIV-1
and/or HCV were tested as undiluted (neat) samples with the Procleix HIV-1/HCV,
HIV-1 Discriminatory and HCV Discriminatory Assays. These samples were also
tested at 1:16 dilution with the Procleix HIV-1/HCV Assay. Results

IN0076 Rev. F

39

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

are shown in Table X. 72.5% (391/539) had IV drug use (IVDU) as one of their
risk factors. Risk factors other than IVDU included having unprotected sex, men
having sex with men, occupational exposure, having sex with positive partner,
and having transfusion of blood or blood products. Sensitivity was determined by
comparing the Procleix Assays with an HIV-1 or HCV PCR-based assay that has a
claimed analytical sensitivity of ³100 copies viral RNA /mL.

        Both the Procleix HIV-1/HCV Assay and HIV-1 Discriminatory Assay
detected all 23 samples, either undiluted or 1:16 diluted, that were tested
reactive for HIV-1 with the PCR NAT test. Of these 23 HIV-1 reactive specimens,
11 were also reactive with the HCV Discriminatory Assay and are considered
samples from individuals coinfected with HIV-1 and HCV.

        There was one confirmed HIV-1 yield case that appeared to be in the
window period. This specimen was reactive with the Procleix HIV-1/HCV and HIV-1
Discriminatory Assays as an undiluted sample, and with the Procleix HIV-1/HCV
Assay as a 1:16 diluted sample. The specimen was HIV antibody seronegative, HIV
p24 Ag positive and was positive with an alternate HIV-1 nucleic acid test
(NAT).

        There were 268 HCV antibody and/or alternate HCV NAT positive specimens
among the 520 high-risk specimens that were tested with Procleix HIV-1/HCV and
HCV Discriminatory Assays. When tested as undiluted (neat) samples, 266 of the
268 positive specimens (99.3%, 95% CI: 97.3-99.9%) were reactive with both the
Procleix HIV-1/HCV and HCV Discriminatory Assays. When tested as diluted
samples, 254 of 259 (98.1%, 95% CI: 95.6-99.4%) were reactive with the Procleix
HIV-1/HCV Assay. There were 44 HCV seropositive specimens that were nonreactive
in all Procleix Assays. Of the 44, 37 were tested by an alternate HCV NAT and 34
were found to be NAT negative (considered Procleix TN for sensitivity
calculations), two were equivocal, and one was positive (Procleix FN). This
study resulted in three confirmed HCV yield cases that were considered true
positives for the Procleix assay. These specimens were HCV antibody negative;
two of which were alternate HCV NAT positive and one was QNS for alternate NAT.
All three subjects later seroconverted.

Table X. Clinical Sensitivity of the Procleix HIV-1/HCV Assay in a High Risk
Population

 
   
   
   
   
   
   
  Sensitivity

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

Disease

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

   
   
   
   
   
   
  Specimen

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

  Number

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

  TP

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

  FP

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

  TN

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

  FN

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

  %

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

  (95% C. I.)

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

HIV-1*   Neat   530   23   0   507   0   100   (85.2 - 100.0)     Diluted   520
  23   0   497   0   100   (85.2 - 100.0)
HCV**
 
Neat
 
520
 
266
 
3
 
249
 
2
 
99.3
 
(97.3 - 99.9)     Diluted   508   254   2   247   5   98.1   (95.6 - 99.4)

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

*Reactive in the HIV-1/HCV Assay and the HIV-1 Discriminatory Assay.

**Reactive in the HIV-1/HCV Assay and the HCV Discriminatory Assay.

Analytical Sensitivity

        To determine the analytical sensitivity of the Procleix HIV-1/HCV Assay
and HIV-1 and HCV Discriminatory Assays for detection of HIV-1 and HCV viral
RNA, HIV-1 panel members were prepared by serial dilution of negative human
plasma spiked with HIV-1 (type B isolate) tissue culture supernatant. HCV panel
members were made by serial dilution of a patient plasma specimen containing HCV
(subtype 1a). The RNA levels in viral stocks used to make the HIV-1 panel and
high titer HCV plasma used to make the HCV panel were value assigned using an
in-house quantitative HIV-1 assay calibrated to the VQA standard obtained from
Dr. James Bremer (Rush-Presbyterian

IN0076 Rev. F

40

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

Hospital, Chicago, IL) or quantitative HCV assay compared to HCV RNA WHO
standard. (1 WHO IU/mL is equivalent to 2.7 copies/mL).

        The panel members were tested with ten clinical lots of reagents and the
test results are presented in Table XI. The Procleix HIV-1/HCV Assay and HIV-1
and HCV Discriminatory Assays achieved 100% detection for panel members
containing 300 copies/mL, and > 99% detection for those members containing 100
copies/mL of HIV-1 or HCV RNA. The lower bound of 95% CI for both HIV-1 and HCV
at 100 and 300 copies/mL for all assays exceeded 95%, which is consistent with a
claimed analytical sensitivity of 100 copies RNA/mL. The Procleix HIV-1/HCV and
Discriminatory Assays were able to detect 30 copies/mL of HIV-1 or HCV RNA at a
frequency greater than 90%, with the lower bound of 95% CI ranging from 90% to
97.3%.

Table XI. Detection of HIV-1 B RNA and HCV 1a RNA in Analytical Sensitivity
Panels

 
  Procleix HIV-1/HCV Assay

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

  HIV-1 Discriminatory Assay

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

 
   
   
  95%
Confidence Limits

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

   
   
  95%
Confidence Limits

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

HIV-1
Copies/mL

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

  Number of
reactive/
tested*

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

  %
Positive

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

  Number of
reactive/
tested*

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

  %
Positive

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

  Lower

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

  Upper

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

  Lower

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

  Upper

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

300   716/716   100   99.5   100   715/715   100   99.5   100 100   719/719  
100   99.5   100   718/718   100   99.5   100 30   707/720   98.2   96.9   99.0
  702/713   98.5   97.3   99.2 10   573/718   79.8   76.7   82.7   592/717  
82.6   79.6   85.3 3   297/718   41.4   37.7   45.1   305/717   42.5   38.9  
46.3 1   112/717   15.6   13.0   18.5   139/718   19.4   16.5   22.4

 

 
Procleix HIV-1/HCV Assay

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

 
HIV Discriminatory Assay

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

 
   
   
  95%
Confidence Limits

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

   
   
  95%
Confidence Limits

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

HIV 1a
Copies/mL

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

  Number of
reactive/
tested*

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

  %
Positive

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

  Number of
reactive/
tested*

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

  %
Positive

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

  Lower

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

  Upper

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

  Lower

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

  Upper

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

300   718/718   100   99.5   100   720/720   100   99.5   100 100   720/720  
100   99.5   100   745/746   99.9   99.3   100 30   669/718   93.2   91.1   94.9
  660/716   92.2   90.0   94.0 10   470/719   65.4   61.8   68.9   458/717  
63.9   60.2   67.4 3   231/718   32.2   28.8   35.7   258/717   36.0   32.5  
39.6 1   70/716   9.8   7.7   12.2   104/719   14.5   11.0   17.3

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

*Invalid reactions were not re-tested.

CBER HIV-1 RNA Panel

        Panel A (5 members) and Panel B (8 members) were tested in duplicate
with 5 Clinical Lots using both the HIV-1/HCV Assay and the HIV-1 Discriminatory
Assay. Results for both Panel A and B are shown in Table XII. For Panel A,
testing with the HIV-1/HCV Assay showed reproducible detection of HIV-1 RNA at
copy levels ranging from 250,000 to 100 copies/mL; the panel member at 0
copies/mL was non-reactive. Results for Panel B demonstrated reproducible
detection of HIV-1 RNA at copy levels ranging from 250,000 to 50 copies/mL and
non-reactive results with both negative panel members (B4 and B8). Similar
results were obtained with the Discriminatory Assays.

IN0076 Rev. F

41

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

CBER HCV RNA Panel

        This panel consisted of 10 panel members with copy levels ranging from
100,000 to 0 copies/mL. This panel was tested in duplicate with 5 Clinical Lots
using both the HIV-1/HCV and HCV Discriminatory Assays. Results are shown in
Table XII. Reproducible detection of HCV was obtained down to 50 copies/mL with
both assays.

Table XII. Detection of HIV-1 RNA and HCV RNA in CBER panel members

 
  Panel members tested and positivity rates

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

   
  A1

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

  A2

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

  A3

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

  A4

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

  A5

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

  B1

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

  B2

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

  B3

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

  B4

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

  B5

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

  B6

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

  B7

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

  B8

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

  CBER HIV-1 RNA Panel (copies/mL)   250,00   25,000   1,000   100   0   2,500  
10   250,000   0   100   50   25,000   0   HIV-1/HCV Assay*   100 % 100 % 100 %
100 % 0 % 100 % 60 % 100 % 0 % 100 % 100 % 100 % 0 % HIV-1 Discriminatory
Assay**   100 % 100 % 100 % 100 % 0 % 100 % 100 % 100 % 0 % 100 % 100 % 100 % 0
%

 

 
Panel members tested and positivity rates

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

   
  1

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

  2

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

  3

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

  4

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

  5

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

  6

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

  7

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

  8

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

  9

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

  10

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

  CBER HCV RNA Panel (copies/mL)   1,000   0   100,000   10,000   0   500   200
  50   10   5   HIV-1/HCV Assay*   100 % 0 % 100 % 100 % 0 % 100 % 100 % 100 %
90 % 30 % HCV Discriminatory Assay**   100 % 0 % 100 % 100 % 0 % 100 % 100 % 100
% 100 % 50 %

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

* n=10; ** n=6

WHO International Standard for HIV-1

        The WHO International Standard for HIV-1 RNA (NIBSC code 97/656) with a
concentration of 100,000 IU/mL was serially diluted and tested with the
HIV-1/HCV Assay and the HIV-1 Discriminatory Assay. The results obtained are
shown in Table XIII.

WHO International Standard for HCV

        The WHO International Standard for HCV RNA (96/790) with a concentration
of 100,000 international units (IU)/mL was serially diluted and tested with the
HIV-1/HCV Assay and the HCV Discriminatory Assay. The results obtained are shown
in Table XIII.

IN0076 Rev. F

42

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Table XIII. Testing of International Standards for HIV-1 RNA (NIBSC code 97/656)
and HCV RNA (NIBSC 96/790)

 
  Concentrations tested and positivity rates

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

WHO HIV-1 (97/656)   300
IU/mL   100
IU/mL   33.3
IU/mL   11.1
IU/mL   3.7
IU/mL   1.23
IU/mL   0
IU/mL HIV-1/HCV Assay*   100%   100%   100%   77.5%   50%   32.5%   0% HIV-1
Discriminatory Assay**   100%   100%   100%   80%   27.6%   26.6%   0%

 

 
Concentrations tested and positivity rates

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

WHO HCV (96/790)   110
IU/mL   37
IU/mL   11
IU/mL   3.7
IU/mL   1.1
IU/mL   0.37
IU/mL   0.11
IU/mL   0.04
IU/mL   0.00
IU/mL HIV-1/HCV Assay*   100%   100%   100%   100%   50%   25%   0%   0%   0%
HCV Discriminatory Assay**   100%   100%   100%   95%   60%   25%   0%   0%   0%

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

* n=40; ** n=30

Reactivity in Seroconverting Donors

        Commercially available seroconversion panels collected from
plasmapheresis donors were tested with the Procleix HIV-1/HCV Assay (neat and
1:16 diluted), HIV-1 Discriminatory (neat only) and HCV Discriminatory (neat
only) Assays. Ten seroconversion panels for HIV-1 and ten panels for HCV were
tested with one Clinical Lot. The test results were compared with those of the
Ortho HCV 3.0 ELISA test or the Abbott Anti-HCV 2.0 test for HCV seroconversion
panels, or with those of Abbott HIV-1/-2 antibody and Abbott or Coulter HIV-1
p24 antigen test for HIV-1 seroconversion panels. The Procleix HIV-1/HCV Assay
was able to detect the infection with median values of 12 and 7 days earlier
than the Abbott HIV-1/-2 antibody and HIV-1 p24 Ag assays, respectively, when
specimens were tested neat (Table XIV). The Procleix HIV-1/HCV Assay was able to
detect the infection with median values of 10 and 3 days earlier than the Abbott
HIV-1/-2 antibody and HIV-1 p24 Ag tests, respectively, when specimens were
tested at a 1:16 dilution. The HIV-1 Discriminatory Assay was able to detect
infection with median values of 12 and 6 days earlier than the Abbott HIV-1/-2
antibody and HIV-1 p24 Ag tests, respectively, when specimens were tested neat.
Reduction of the window period was observed in 9 of 10 panels when the Procleix
HIV-1/HCV and HIV-1 Discriminatory Assays were used as compared to the use of
the Abbott HIV Ab test alone. When compared to the HIV-1 p24 Ag assay, the
Procleix HIV-1/HCV Assay detected the infection earlier in 8 of 10 panels and at
the same time as HIV-1 p24 Ag in the other two panels. In all cases, HIV-1 p24
Ag reactive specimens were reactive with the Procleix HIV-1/HCV Assay and the
HIV-1 Discriminatory Assay.

IN0076 Rev. F

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

Table XIV. Testing for HIV-1 RNA with the Procleix HIV-1/HCV and HIV-1
Discriminatory Assays on HIV-1 Seroconversion Panels

 
  Days Earlier Detection Than HIV Antibody

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

  Days Earlier Detection Than HIV-1 p24 Ag

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

 
   
   
  HIV-1 Discriminatory

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

   
   
  HIV-1 Discriminatory

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

 
  HIV-1/HCV

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

  HIV-1/HCV

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

Panel ID

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

  Neat

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

  1/16

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

  Neat

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

  Neat

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

  1/16

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

  Neat

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

BCP 6240   12   7   12   7   2   7 BCP 6248   14   11   11   7   4   4 PRB923*  
12   17   17   2   7   7 PRB926**   27   25   27   7   5   7 PRB929***   11   11
  11   0   0   0 PRB932^   0   0   0   0   0   0 PRB943   9   9   9   2   2   2
PRB945**   13   10   13   13   10   13 PRB946^^   11   7   7   7   3   3
PRB950**   28   10   28   18   0   18    

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

 

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

 

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

 

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

 

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

 

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

Median   12   10   12   7   3   6

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

*Intermittent HIV-1/HCV reactivity at 11 and 35 days prior to ramp up is not
used for this calculation.

**HIV-1/HCV positive in first bleed of seroconversion panel.

***Single reactive in the HIV-1 Discriminatory Assay 14 days prior to ramp up is
not used for this calculation.

^HIV antibody was negative at day 78 of the seroconversion series during
HIV-1/HCV reactivity.

^^No seroconversion to HIV antibody in this panel which spans 11 days.

        The Procleix HIV-1/HCV and HCV Discriminatory Assays were able to detect
infection with a median value of 25 days earlier than the HCV antibody tests
(Table XV) when tested diluted or undiluted. Reduction of the seroconversion
window period by the Procleix HIV-1/HCV and HCV Discriminatory Assays was
observed in 10 of 10 panels compared to the HCV antibody test.

IN0076 Rev. F

44

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

Table XV. Testing for HCV RNA with the Procleix HIV-1/HCV and HCV Discriminatory
Assays on HCV Seroconversion Panels

 
  Days Earlier Detection Than HCV Antibody

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

 
   
   
  HCV Discriminatory

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

Panel ID

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

  HIV-1/HCV
  Neat

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

  1/16

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

  Neat

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

BCP 6213   26   26   26 BCP 6225   39   33   39 BCP 6226*   39   39   39 BCP
6228*   31   31   31 BCP 9045*   41   41   41 PHV904*   14   14   14 PHV907*  
21   21   21 PHV908*   19   19   19 PHV914*   24   24   24 PHV916*   23   23  
23    

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

 

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

 

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

Median   25   25   25

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

*HIV-1/HCV Assay reactive in first bleed of seroconversion panel vs. Ortho HCV
3.0.

Subtype Detectability

        Since there are no recognized international standards for HCV or HIV-1
other than HCV subtype 1a and HIV-1 subtype B, multiple specimens and isolates
(59 different HIV-1 and 53 different HCV specimens) were tested to determine
detectability of these viral subtypes31. HIV-1 specimens of subtypes A, B, C, D,
E, F, and G were quantified for HIV-1 RNA concentrations using commercial
quantitative HIV-1 RNA assays or an in-house developed quantitative test, the
latter using the same technology as the Procleix assays. HIV-1 subtypes N and O
were quantified with an in-house quantitative HIV-1 RNA test. Specimens were
diluted into negative human plasma to target viral concentrations of 300 or 100
copies/mL and diluted specimens were tested in the HIV-1/HCV and HIV-1
Discriminatory Assays. All HIV-1 subtypes were reactive with both the Procleix
HIV-1/HCV and HIV-1 Discriminatory Assays at 300 and 100 copies/mL (Table XVI).

        HCV specimens of subtypes 1, 2, 3, 4, 5 and 6 were quantified for HCV
RNA using commercially available quantitative HCV RNA assays. Specimens were
diluted into negative human plasma to target viral concentrations of 300 or 100
copies/mL and diluted specimens were tested with the HIV-1/HCV and HCV
Discriminatory Assays. All HCV subtypes were reactive by the HIV-1/HCV and HCV
Discriminatory Assays at 300 and 100 copies/mL, except one HCV subtype 2
specimen which was reactive at 300 copies/mL, but nonreactive at 100 copies/mL
(Table XVI).

IN0076 Rev. F

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Table XVI. HIV-1 and HCV Subtype Detectability

Specimen

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

  Subtype

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

  Copies/mL

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

  HIV-1/HCV
Reactive/Total

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

  HIV-1 Discriminatory
Reactive/Total

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

HIV   A*   300
100   11/11
9/9   11/11
9/9     B   300
100   10/10
10/10   11/11
11/11     C   300
100   9/9
9/9   9/9
9/9     D   300
100   6/6
6/6   6/6
6/6     E   300
100   8/8
8/8   8/8
8/8     F   300
100   5/5
5/5   5/5
5/5     G   300
100   3/3
3/3   3/3
3/3     N   300
100   1/1
1/1   1/1
1/1     O   300
100   6/6
6/6   6/6
6/6

Specimen

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

 
Subtype

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

 
Copies/mL

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

 
HIV-1/HCV
Reactive/Total

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

 
HIV Discriminatory
Reactive/Total

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

HCV   1   300
100   10/10
10/10   10/10
10/10     2   300
100   13/13
12/13   13/13
13/13     3   300
100   11/11
11/11   11/11
11/11     4   300
100   10/10
10/10   11/11
11/11     5   300
100   4/4
4/4   4/4
4/4     6   300
100   4/4
5/5   4/4
5/5

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

* Two samples were quantified at < 1000 copies/mL and were reactive when tested
undiluted and at 1:3 dilution.

PERFORMANCE OF INDIVIDUAL DONATION TESTING

Clinical Sensitivity

        The clinical sensitivity of the HIV-1/HCV Assay, HIV-1 Discriminatory
and HCV Discriminatory Assays were evaluated by testing clinical samples without
dilution (neat). The HIV-1/HCV Assay was used to test a total of 867 confirmed
HIV positive, 967 HCV positive and 180 HIV and HCV positive samples. As
summarized in Table VII, the overall sensitivity based on this study was 99.8%
(95% CI: 99.4-99.9). Specifically, the sensitivity for HIV positive samples was
99.9% (95% CI: 99.4-100.0) while

IN0076 Rev. F

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that for HCV positive samples and HIV and HCV positive samples was 99.6% (95%
CI: 98.9-99.9) and 100% (95% CI: 98.0-100.0), respectively. Three HCV positive
samples tested non-reactive as undiluted samples, but reactive at 1:16 dilution.
However, one of the three showed a viral load lower than the Limit of Detection
for the Procleix HIV-1/HCV Assay as determined by an alternate nucleic acid
test. The other two consistently tested reactive at 1:16 dilution but
non-reactive with the undiluted sample and the nature of this discordance is
under investigation.

        The sensitivity for the discriminatory assays was evaluated as well. As
shown in Table VII, the sensitivity for the HIV-1 Discriminatory Assay was 100%
(95% CI: 99.6-100.0) for HIV positive samples and 100% (95% CI: 97.9-100.0) for
HIV and HCV positive samples. The HCV Discriminatory Assay showed a sensitivity
of 99.6% (95% CI: 98.9-99.9) for HCV positive samples and 100% (95% CI:
92.6-100.0) for HIV and HCV positive samples.

        The data in the aforementioned studies were re-analyzed according to the
disease stages and the results are presented in Tables VIII (for HIV/AIDS) and
IX (for HCV). Overall, the assays showed similar sensitivity for samples from
various disease stages.

Seroconversion Panel Testing

        When a limited number of HIV-1 seroconversion panel members were tested
as undiluted (neat), an average of two days earlier detection was observed as
compared to 1:16 dilution (Table XIV). No difference was observed between the
HIV-1/HCV Assay and HIV-1 Discriminatory Assay. Both assays were more sensitive
for detecting window period samples as compared to the HIV-1 p24 Antigen assay.

        For HCV seroconversion panels, no differences were observed between the
Procleix HIV-1/HCV Assay and the HCV Discriminatory Assay when testing was
performed on undiluted samples or 1:16 diluted samples (Table XV). Both assays
were able to detect HCV infection on average 25 days earlier than the antibody
test.

Clinical Specificity

        The clinical specificity for individual donation testing was determined
for the HIV-1/HCV assay by testing individual donor specimens that were never
pooled (Table XVII). Seventy-one of 34,557 (0.21%) individual donor specimens
were initially reactive in the Procleix HIV-1/HCV assay. Twenty-one of these 71
specimens were also reactive in the HCV Discriminatory Assay and were
seropositive for HCV. Three of the 71 were reactive in the HIV-1 Discriminatory
Assay and seropositive for HIV-1/HIV-2. Forty-five specimens were nonreactive by
both the HCV and HIV-1 Discriminatory Assays and HCV and HIV-1/HIV-2 antibody
assays yielding an adjusted (false) reactive rate of 0.13% (45/34,533). One
specimen had incomplete assay results and could not be discriminated. One
specimen was Procleix HCV Discriminated, HCV EIA repeatedly Reactive with no
RIBA available. Seventeen samples with Nonreactive Procleix assay results had
incomplete serologic results and were excluded from the specificity
calculations, yielding a specificity in individually tested donor samples of
99.87% (34,229/34,274).

IN0076 Rev. F

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Table XVII. Procleix HIV-1/HCV Assay Reactivity in Volunteer Blood Donors

 
  Procleix HIV-1/HCV Assay
Individual Donation

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

Samples Tested*   34,557 Initial Reactive   71 Initial Reactive Rate   0.21%
Adjusted Reactive Rate   0.13% Combined Mean S/CO on Negative Analytes   0.17 ±
0.07

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

* Combined data across all sites and Clinical Lots.

        This specificity study was conducted primarily in three military sites.
The military donor population may differ from the civilian donor population.
However, when sub-analyses were conducted across donor age groups, gender and
race, comparable clinical specificity was observed across all categories ranging
from 99.7% to 100% (all 95% confidence intervals overlapped). These sub-analyses
included evaluation of 5,743 females; 1,102 donors over the age of 50; and at
least 2,900 donors in each of the race categories of Black/Non-Hispanic,
White/Hispanic, and White/Non-Hispanic. These results suggest that the
specificity of the Procleix HIV-1/HCV Assay with individual donations is not
affected by race, age or gender.

Table XVIII. Summary of Procleix Assay Yield Under IND Testing

Individual Donation Testing

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

Number of Donations Tested   103,357 Procleix HCV
Yield Case   1
(1:103,357) Procleix HIV-1
Yield Case   0

        A total of 103,357 individual donations were screened under IND from
April 2000 to November 2001 (Table XVIII). One Procleix HCV yield case
(1:103,357) was identified across the three Procleix individual donation test
sites. The yield case was confirmed to be positive for HCV RNA, but negative in
serology testing. No HIV-1 yield cases were identified with individual donation
testing.

LIMITATIONS OF THE PROCEDURE

•This assay has been evaluated with the Procleix instrument only.

•The concentrations for HIV-1 subtype N and group O virus used for assessing
analytical sensitivity were determined by an in-house quantitative test, which
used the same technology as the Procleix assays. This may result in inaccurate
assessment of analytical sensitivity for these viral subtypes.

•The Procleix Assay may not be used to replace antibody-detection tests such as
an EIA test for HIV-1 or HCV, a Western Blot for HIV-1, or a RIBA for HCV.

•The clinical sensitivity for the Procleix HIV-1/HCV assay has been evaluated
only for specimens with viral concentrations equal to or greater than 100 copies
RNA/mL or those with unknown viral concentration.

IN0076 Rev. F

48

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CONCLUSIONS

        Overall specificity for the Procleix HIV-1/HCV Assay (16-member pools,
single donors), HIV-1 Discriminatory Assay (single donors) and HCV
Discriminatory Assay (single donors) is shown in Table XIX. Sensitivity for the
Procleix HIV-1/HCV Assay (based on known HIV-1 and HCV RNA positives run neat
and diluted 1:16), HIV-1 Discriminatory Assay (based on known HIV-1 RNA
positives run neat), and HCV Discriminatory Assay (based on known HCV RNA
positives run neat) are also shown in Table XIX.

Table XIX. Overview

 
   
  Specificity (95% C.I.)

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

  Sensitivity (95% C.I.)

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

Procleix HIV-1/HCV   16-member Pool   99.67% (99.55-99.77%)   99.3%
(98.8-99.6%)*     Individual donation   99.87% (99.83-99.91%)   99.8%
(99.4-99.9%) HIV-1 Discriminatory   Individual donation   99.76% (99.48-99.91%)
  100%
(99.6-100%) HCV Discriminatory   Individual donation   99.71% (99.41-99.88%)  
99.6% (99.0-99.9%)

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

C.I. = Confidence intervals.

*Sensitivity in 2,012 known-positive samples diluted 1:16; Sensitivity was 100%
in 204 pools.

BIBLIOGRAPHY

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and L. Montagnier. 1983. Isolation of a T-lymphotropic retrovirus from a patient
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5.Sarngadharan, J. G., M. Popovic, L. Broch, J. Scupbach, and R. C. Gallo. 1984.
Antibodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the
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6.Gallo, D., J. S. Kimpton, and P. J. Dailey. 1987. Comparative studies on use
of fresh and frozen peripheral blood lymphocyte specimens for isolation of human
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7.Clavel, F., D. Guetard, F. Brun-Vezinet, S. Chamaret, M. Rey, M. O.
Santos-Ferraira, A. G. Laurent, C. Dauguet, C. Katlama, C. Rouzioux, D.
Klatzmann, J. L. Champalimaud, and L.

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Montagnier. 1986. Isolation of a new human retrovirus from West African patients
with AIDS. Science. 233:343-346.

8.Alter, H. J., R. H. Purcell, J. W. Shih, J. C. Melpolder, M. Houghton, Q-L.
Choo, and G. Kuo. 1989. Detection of antibody to hepatitis C virus in
prospectively followed transfusion recipients with acute and chronic non-A,
non-B hepatitis. N Engl J Med. 321:1494-1500.

9.Esteban, J. I., A. Gonzalez, J. M. Hernandez, et al. 1990. Evaluation of
antibodies to hepatitis C virus in a study of transfusion-associated hepatitis.
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10.Van der Poel, C. L., H. W. Reesink, P. N. Lelie, A. Leentvaar-Kuypers, Q-L.
Choo, G. Kuo, and M. Houghton. 1989. Anti-hepatitis C antibodies and non-A,
non-B post-transfusion hepatitis in the Netherlands. Lancet. 2:297-298.

11.Choo, Q-L., G. Kuo, A. J. Weiner, et al. 1989. Isolation of a cDNA clone
derived from a blood-borne non-A, non-B viral hepatitis genome. Science.
244:359-362.

12.Alter, H. J., P. V. Holland, Ag. Morrow, et al. 1975. Clinical and
serological analysis of transfusion associated hepatitis. Lancet. 2:838-841.

13.Kuo, G., Q-L. Choo, H. J. Alter, et al. 1989. An assay for circulating
antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science.
244:362-364.

14.Busch, M. P., S. L. Stramer, and S. H. Kleinman. 1997. Evolving applications
of nucleic acid amplification assays for prevention of virus transmission by
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Biology to Blood Transfusion Medicine. AABB. Bethesda, MD. 123-176.

15.Stramer, S. L., S. Caglioti, and D. M. Strong. 2000. NAT of the United States
and Canadian Blood Supply. Transfusion. 40:1165-1168.

16.Busch, M. P., L. L. L. Lee, G. A. Satten, D. R. Henrard, H. Farzadegan, K. E.
Nelson, S. Read, R. Y. Dodd, and L. R. Petersen. 1995. Time course of detection
of viral and serologic markers preceding human immunodeficiency virus type 1
seroconversion: implications for screening of blood and tissue donors.
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17.Schreiber, G. B., M. P. Busch, S. H. Kleinman, and J. J. Korelitz. 1996. for
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18.McDonough, S., C. Giachetti, Y. Yang, D. Kolk, B. Billyard, and L. Mimms.
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immunodeficiency virus (HIV-1) and hepatitis C virus (HCV). Infusion Therapy and
Transfusion Medicine. 25:164-169.

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

20.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.

21.Nelson, N. C., A. BenCheikh, E. Matsuda, and M. Becker. 1996. Simultaneous
detection of multiple nucleic acid targets in a homogeneous format. Biochem.
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laboratory hazardous waste; proposed guidelines. NCCLS Document GP5-P.
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management. Washington, DC: U.S. Environmental Protection Agency, Publication
No. EPA/530-SW-86-014, 1986.

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Rule, Federal Register/ Vol. 56, No. 235/ December 6, 1991.

27.Valinsky, J.E., C. Bianco. 2000. Supplemental testing for HCV: To what extent
could nucleic acid amplification testing (NAT) replace HCV RIBA 3.0.
Transfusion. 40, 10S, 32S.

28.Damen, M., H.L. Zaijjer, H.T.M. Cuypers, H. Vrielink, CL van der Poel, HW
Reesink, PN Lelie. 1995. Reliability of the third-generation recombinant
immunoblot assay for hepatitis C virus. Transfusion. 35, 745-749.

29.MMWR. 1992. 41:1-9.

30.Stramer, S.L. et al. Application of Nucleic Acid Testing to Blood Borne
Pathogens and Emerging Technologies OBRR/CBER/FDA Workshop—December 4, 2001.

31.Linnen, J.M., J.M. Gilker, A. Menez, A. Vaughn, A. Broulik, J. Dockter, K.
Gillote-Taylor, K. Greenbaum, D.P. Kolk, L. T. Mimms, C. Giachetti. 2002.
Sensitive detection of genetic variants of HIV-1 and HCV with an HIV-1/HCV assay
based on transcription-mediated amplification. J. Virol. Methods. 102, 135-139.

Gen-Probe U.S. LICENSE 1592

IN0076 Rev. F
2002-02

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

Chiron Blood Testing Technical Support:
(North America)
Telephone: (800) 452-6877
FAX: (800) 462-3938

(Europe, Middle East, Latin America, Africa)
Telephone: +33 (4) 78 37 99 04
FAX: +33 (4) 78 37 99 04

IN0076 Rev. F

51

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(Asia/Pacific)
Telephone: +61 (4) 1044 5810
FAX: +61 (2) 9974 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. 5,030,557; 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; 5,714,596; 5,750,338; 5,756,011; 5,756,709; 5,766,890; 5,827,656;
5,840,873; 5,863,719; 5,888,779; 5,948,899; 5,955,261; 6,004,745; 6,031,091;
6,074,816; 6,090,591; 6,110,678; 6,245,519; 6,252,059; 6,280,952; and
international counterparts.

© 2000, 2001, 2002 Gen-Probe Incorporated

IN0076 Rev. F

52

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CONFIDENTIAL   REDACTED VERSION

SCHEDULE C

TERMS AND CONDITIONS FOR USE OF BLOOD SCREENING SYSTEMS

Chiron will make available Blood Screening Systems to ABC on the following terms
and conditions:

1.Sale of Blood Screening Systems. Chiron shall sell the Blood Screening Systems
currently installed and in use by Participating Members as listed in Exhibit 4
to each Member Supplement (the "Transferred Instruments"), subject to the
provisions hereof. Each Participating Member will acquire, at it's sole expense,
any additional instrumentation it wishes to use in connection with the conduct
of testing of blood donations, including any instruments required to perform
pooling operations and sample archiving.

2.Location & Use of Blood Screening Systems. Participating Members shall use the
Blood Screening Systems only at the Testing Centers identified in Exhibit 2 to
the applicable Member Supplements. Participating Members shall not remove,
customize, or alter the Blood Screening Systems, including Software, without the
prior written consent of Chiron. Blood Screening Systems shall only be used to
perform testing of the Participating Member's blood donations using Blood
Screening Assays sold by Chiron. Chiron bears no responsibility with respect to
any use of such Blood Screening Systems with Blood Screening Assays other than
those supplied by Chiron hereunder. Any such alternate use shall invalidate all
warranties with respect to the Blood Screening Systems.

3.Title to the Blood Screening Systems. As between Chiron and each Participating
Member, upon payment of the amount specified in the applicable Member
Supplement, Chiron shall transfer all right, title and interest held by it in
and to the Transferred Instruments to the applicable Participating Member. Each
Participating Members acquiring Transferred Instruments shall remove any
markings from the Transferred Instruments which identify Chiron as the owner. If
a Participating Member selects the installment payment option, title to the
Transferred Instruments will transfer on execution, but the Participating Member
will grant a security interest in such Transferred Instruments to Chiron as
further described in the applicable Member Supplement.

4.Warranties; Limitation of Liability. Chiron represents and warrants that the
Blood Screening Systems will operate in accordance with their Specifications and
will be free from defects in materials and workmanship. This warranty does not
apply to Blood Screening Systems (a) not installed by a Chiron representative;
(b) not used or maintained in accordance with the instructions provided by
Chiron or their manufacturer, including without limitation of the maintenance
obligations set forth in Schedule D; (c) damaged by alteration, misuse,
tampering or abuse; or (d) for which the Participating Member has failed to pay
the Services Fee. Except to the extent of Chiron's obligations under Section 7.7
of this Association Agreement, Chiron's sole liability with respect to a breach
of the foregoing warranty is to repair or replace the Blood Screening System.
Participating Members will be responsible for all other repairs or replacements
of Blood Screening Systems that fail to operate in accordance with their
Specifications, including by reason of (i) any loss or damage caused by or
attributable to the Participating Members or their agents (ii) a failure by the
Participating Members to use the Blood Screening Systems in accordance with the
manufacturer's instructions, (iii) any negligence on the part of the
Participating Members or (iv) any failure by the Participating Members to carry
out their obligations hereunder. Chiron disclaims all other warranties and
further limits its liability in accordance with Sections 7.4 and 7.12 of this
Association Agreement, respectively.

53

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5.Software. Chiron shall provide to Participating Members, at no additional
charge, the Software and Documentation, pursuant to the following terms and
provisions:

5.1Title.

(a)Chiron or the applicable licensor shall own and retain title to the Software,
including all intellectual property rights embodied therein. Any copy which a
Participating Member makes of the Software, in whole or in part, is and shall
remain the property of Chiron or the applicable licensor.

(b)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 or work
product in order to give effect to such ownership terms.

5.2Grant of Rights and Restrictions on Use

(a)Grant of Rights. Chiron hereby grants, and each Participating Member hereby
accepts, subject to the terms and conditions of this Agreement including this
Schedule C, a nonexclusive, nontransferable and nonassignable (except as
permitted under Section 12.4 [Assignment] of this Association Agreement) object
code license to use the Software at the Testing Centers solely for Participating
Member's own use in connection with the operation of the Blood Screening Assays
on the Blood Screening Systems during the term of the applicable Member
Supplement, and to copy the Software solely for the purposes expressly
authorized under this Section 5 of this Schedule C. In addition, Chiron hereby
grants to each Participating Member the right to use the Documentation in
connection with its use of the Software hereunder. Documentation may not be
copied. Additional copies may be obtained from Chiron at Chiron's 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.

(b)Restrictions on Use. The grant of rights stated in Section 5.2(a) of this
Schedule C is subject to the terms and conditions of this Agreement as well as
the following restrictions:

(i)Use of the Software may be subsequently transferred to other Testing Centers
maintained by a Participating Member, provided (A) the total number of Testing
Centers at which the Software is used by such Participating Member does not
exceed the number of Testing Centers specified in the applicable Member
Supplement and (B) such Participating Member provides Chiron with written notice
thirty (30) days before such transfer.

(ii)In the event that disaster or other circumstances prevent Participating
Member from using the Software at the Testing Centers identified in the
applicable Member Supplement, the effected Participating Member 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)Participating Members 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 Participating Members allow access to the Software through terminals
located outside Participating

54

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Member's business premises by persons who are not Participating Member's
employees or authorized agents, contractors or representatives.

(iv)Participating Members 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 12.4 [Assignment] of this
Association Agreement.

(v)Participating Members 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 void all representations and warranties with regard to the
Software and shall be deemed a breach of this Agreement.

(vii)Upon expiration or termination of a Member Supplement, the applicable
Participating Member 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). The applicable Participating
Member 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).

5.3Warranties; Limitation of Liability.

(a)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.

(b)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 (other than as set forth in the Documentation) 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 a Participating
Member.

(c)Right to License. Chiron warrants that it has, and on the effective date of
each Member Supplement of the Software will have, full rights and authority to
license the Software to Participating Members and otherwise as needed for it to
perform its obligations hereunder, or has the authority to do so without
infringing the rights of any Third Party.

(d)Limitation of Liability. Chiron disclaims all other warranties and further
limits its liability in accordance with Sections 7.4 and 7.12 of this
Association Agreement.

5.4Source Code Escrow.

CHIRON agrees that it will provide that Participating Member will be a named
beneficiary under Chiron's Source Code Escrow Agreement.

55

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CONFIDENTIAL   REDACTED VERSION

SCHEDULE D

BLOOD SCREENING SYSTEMS AND SOFTWARE
SERVICE & SUPPORT

1.Maintenance & Troubleshooting.

1.1The Participating Member shall operate and maintain the Blood Screening
Systems in accordance with Chiron and manufacturer guidelines and
recommendations, which may be amended from time to time.

1.2In the event that any Testing Center resolves a problem with a Blood
Screening System, such problem shall be logged in writing, including a
description of the problem and the steps taken by the Participating Member to
resolve it. The Participating Member shall maintain a log for each Blood
Screening System and make available all such logs to Chiron Technical Support
upon request.

1.3If a Testing Center is unable to resolve a problem, the Testing Center shall
refer the problem to Chiron Technical Support for resolution in accordance with
Section 2 of this Schedule D.

1.4Except for routine maintenance and troubleshooting activities of Primary
Operators as provided in this Schedule D, 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 Blood Screening Systems. Chiron may
inspect the Blood Screening Systems at reasonable times upon reasonable notice.
Chiron will assure that activities of Primary Operators authorized under this
Schedule D will not invalidate any manufacturers' warranties with respect to the
Blood Screening Systems.

2.Technical Support and Service.

2.1Installation. Chiron support personnel will provide installation and set up
of all Blood Screening Systems, and shall ensure that the Blood Screening
Systems operate in conformance with all relevant Specifications. Without
limiting the foregoing, such setup and installation shall include the
installation of the Software and 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
Participating Member shall acknowledge the completion of such setup and
installation and its acceptance of the Blood Screening Systems in writing.

2.2Project Management. Chiron will provide reasonable project management support
to assist the Participating Member project manager in coordinating the
activities of Chiron and the Participating Member in connection with testing
blood using the Blood Screening Assays and the Blood Screening Systems.

2.3Data & Materials. The Participating Member 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 6.4 of the Association 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 Participating
Member, if the Participating Member fails to provide the same in accordance with
Chiron reasonable requests.

56

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2.4Preventative Maintenance.

(a)Chiron shall carry out scheduled Preventative Maintenance (PM) visits at six
month intervals (2 per year). The PM services will be arranged at least two
weeks before the due date for PM service at a time mutually agreeable between
Chiron and the Participating Member. The Participating Member will be required
to make the Blood Screening Systems available at a reasonable time within the
working day (Monday to Friday excluding Holidays) to allow PM services to be
completed within normal working hours.

(b)Each PM service will cover thorough cleaning, lubrication, replacement of
tubing and other parts, electronic/mechanical adjustments and safety checks, all
in accordance with the Blood Screening Systems manufacturers' recommended
procedures, as detailed in the applicable manufacturer's approved checklist/s.
Defective components discovered during PM services will be replaced at no
charge. Parts used to perform PM service will be provided by Chiron at its
expense.

(c)Appropriate testing will be performed in order to return the Blood Screening
Systems back to the user. Tecan instruments will be "certified" as fully
functional with required testing performed according to the manufacturers'
specifications. Liquid precision checks will utilize the appropriate volume for
testing.

(d)Documentation of PM service performed will be provided to each site upon
completion of all maintenance tasks. Information will be reviewed and signed by
Participating Member personnel before Chiron service personnel leave the
facility.

(e)Additional PM service may be performed at the request of the Participating
Member for an additional charge.

2.5Support and Service.

(a)Chiron Technical Support is available 24 hours a day, 7 days a week including
weekends and holidays via telephone. The Participating Member will refer
problems to Chiron Technical Support through a central toll-free telephone
number [**]. A service 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"). Messages left outside Normal Support Hours (including weekends and
holidays) will automatically page the on-call Technical Support personnel.
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 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

57

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escalation, Chiron Technical Support will be dispatched to the Testing Center to
provide service in accordance with the Priority/Response Time Schedule set forth
below.

Priority

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

  Response*

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

Priority 1:   Instrument not operating and alternate or back-up equipment not
available; tests cannot be performed   • Immediate telephone support
• Support Technician on site ASAP but no later than next morning
• Resolution within 24 hours (may be temporary workaround)
Priority 2:
 
Instrument operational but testing process (processing time) is affected
 
• Telephone support within 2 hours
• Support Technician on site within 24 hours
• Resolution within 48 hours
Priority 3:
 
Instrument is operational; no impact on testing 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 FDA regulation.

2.6.Replacement Parts.

(a)Chiron agrees to maintain at each Testing Center a suitable stock of
replacement parts for use in Blood Screening System minor repair and maintenance
at each Testing Center in the Territory. The Participating Member shall provide
Chiron a secure facility at each Testing Center for storage of such replacement
parts.

(b)Replacement parts not available from existing on-site inventory will be
delivered within the resolution timeframes in accordance with the
Priority/Response time Schedule set forth above.

(c)The Participating Member will document and inform Chiron if any replacement
parts are used by Participating Member personnel and return to Chiron (at
Chiron's expense) the part that was replaced. An inventory of replacement parts
will be performed quarterly by Chiron personnel. The cost of replacement part(s)
not in inventory that have not been reported used by the Participating Member
will be charged to the Participating Member. Replacement parts to be placed into
on site inventory will be agreed upon by Chiron and the Participating Member
management. The initial inventory of replacement parts will be provided at
Chiron's expense.

2.7.Replacement Instruments. If during the performance of any repair of a Blood
Screening System Chiron determines in its sole discretion to substitute an
entire instrument or instrument component in order to complete service in
accordance with the Priority/Response Time Schedule, Chiron will remove and
repair the failing instrument or instrument component. Chiron may substitute
reconditioned, refurbished and/or serviceable used instrument or instrument
component (tested to Chiron's quality assurance standards) for this purpose.
Following completion of such repair, Chiron will replace the substituted
instrument or instrument component with the repaired instrument or instrument
component at the next scheduled PM service, or earlier if requested by the
Participating Member.

58

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3.Warranty; Limitation of Liability.

3.1Chiron 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. Chiron warrants
that any replacement part or substituted instrument or instrument component
installed by Chiron during the performance of the Services shall function in
accordance with all applicable Specifications and be free from defects. Chiron
reserves the right to use reconditioned, refurbished and/or serviceable used
parts (tested to Chiron's quality assurance standards) for service hereunder.

3.2The Services shall cover wear and tear and defects in design, material or
workmanship, and shall include version updates to all Software for which Chiron
has the right to license or sublicense, 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 Blood Screening Systems that have been
tampered with, disassembled, altered, changed or modified, maintained by anyone
other than Primary Operators, or repaired (or attempts have been so made) by
anyone other than Chiron-authorized personnel; (iv) movement or rearrangement of
the Blood Screening Systems after initial installation not authorized and
supervised by Chiron personnel; and (v) service for any other equipment not
manufactured or supplied by Chiron. In the case of (ii), (iii) and (iv) above, a
Participating Member may request that Chiron provide service comparable to the
Services described herein, and Chiron will make such services available at the
then-current commercial rate for services of this type. If such service is
provided, Chiron expressly disclaims any representation or warranty as to the
performance of such service or the operability of the Blood Screening Systems on
which such service is performed.

3.3Chiron disclaims all other warranties and further limits its liability in
accordance with Sections 7.4 and 7.12 of the Association Agreement,
respectively.

3.4If 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.

59

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CONFIDENTIAL   REDACTED VERSION

SCHEDULE E

PRICES

1.Fees 1.1Blood Screening Assay Fee. Each Participating Member agrees to pay to
Chiron an amount equal to the number of Reportable Results achieved by such
Participating Member each month, multiplied by the applicable Per Result Fee
from the chart set forth in their applicable Member Supplement (the "Assay
Pricing Chart"), as adjusted pursuant to Section 2 of this Schedule E. The
applicable Per Result Fee for each Participating Member is set on an annual
basis using the Product Requirements Forecast provided by the Participating
Member for that year.

POOLED TESTING

 
   
  Aggregate Participating Members Reportable Results
For Prior Calendar Year2

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

Three Year Term1

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

  [**]

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

  [**]

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

  [**]

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

  [**]

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

  [**]

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

  [**]

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

        Per Reportable Result

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

Individual Participating Member
Reportable Results

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

  A

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

  B

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

  C

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

  D

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

  E

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

  F

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

P1
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
P2
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
P3
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
P4
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
P5
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
P6
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]

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

1Discount applicable to Three Year Grid, [**]

2Includes all testing performed by Members; e.g., Pooled Testing and Single Unit
Testing.

60

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POOLED TESTING

 
   
  Aggregate Participating Members Reportable Results
For Prior Calendar Year4

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

Four Year Term3

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

  [**]

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

  [**]

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

  [**]

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

  [**]

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

  [**]

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

  [**]

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

        Per Reportable Result

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

Individual Participating Member
Reportable Results

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

  A

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

  B

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

  C

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

  D

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

  E

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

  F

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

P1
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
P2
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
P3
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
P4
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
P5
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
P6
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]

POOLED TESTING

 
   
  Aggregate Participating Members Reportable Results
For Prior Calendar Year4

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

Five Year Term3

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

  [**]

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

  [**]

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

  [**]

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

  [**]

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

  [**]

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

  [**]

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

        Per Reportable Result

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

Individual Participating Member
Reportable Results

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

  A

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

  B

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

  C

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

  D

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

  E

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

  F

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

P1
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
P2
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
P3
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
P4
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
P5
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
P6
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]

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

3Discount applicable to the Four and Five Year Grid [**].

4Includes all testing performed by Members; e.g., Pooled Testing and Single Unit
Testing.

61

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Single Donor Testing

 
   
  Aggregate Participating Members Reportable Results
For Prior Calendar Year4

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

          

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

  [**]

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

  [**]

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

  [**]

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

  [**]

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

  [**]

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

  [**]

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

Individual Participating Member
Reportable Results

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

  A

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

  B

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

  C

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

  D

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

  E

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

  F

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

S0
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
S1
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
S2
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
S3
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
S4
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
S5
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
S6
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
S7
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]

        On or prior to the 5th of each month, each Participating Member shall
provide Chiron with a report showing the Reportable Results and Reagent
Utilization Factor for the prior month for each of its Testing Centers. On or
prior to the 15th of each month, Chiron shall prepare and deliver an invoice to
each Participating Member based on such report, calculating the Blood Screening
Assay Fee by multiplying the Reportable Results by the applicable Per Result
Fee, determined in accordance with the then current Product Requirements
Forecast. If a Participating Member's report is not timely received by Chiron,
Chiron will prepare the invoice substituting one-twelfth of the then current
Product Requirements Forecast and the parties shall "true-up" payments made to
the actual Reportable Results achieved on a calendar quarter basis, rectifying
any under- or over-payment on the next subsequent invoice, without application
of interest. Each Participating Member shall make payment on invoices in
accordance with Section 5.3 of the Association Agreement, except where modified
by the applicable Member Supplement.

1.2Blood Screening Systems Fee. Each Participating Member agrees to pay to
Chiron the Blood Screening Systems Fee set forth in their Member Supplement.
Such amount will be due and payable in a lump sum on the effective date of the
applicable Member Supplement. If a Participating Member elects to lease its
Blood Screening Systems, payments will be invoiced by Chiron on a monthly basis,
together with the Blood Screening Assay Fee described above. Each Participating
Member shall make payment on invoices in accordance with Section 5.3 of the
Association Agreement, except where modified by the applicable Member
Supplement. The applicable purchase price for Blood Screening Systems will be
set on a Member-by-Member basis based on the specific requirements of each
Participating Member. The pricing information set forth below is provided for
informational purposes only.

Blood Screening System Components

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

  Unit Price

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

  Monthly Lease
Payment5

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

Pooling TECAN6   [**]   $  
Assay TECAN7
 
[**]
 
$
 
Procleix™ System8
 
[**]
 
$
 

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

5Based on 36 month lease. Subject to credit approval.

62

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6Includes CPT-16 Pooling Software, ver. 2.0.0.2

7Includes Procleix™ Assay Software, ver. 2.0.0.76 and Procleix™ Assay Software
LHP, ver. 2.1

8Includes Procleix™ System Software, ver. 3.0.3.4, Procleix™ Protocol,
ver. 2.1.0.0, and Procleix™ Worklist Editor, ver. 3.0.3.2

1.3.Services Fee. Each Participating Member agrees to pay to Chiron the Services
Fee set forth in their Member Supplement. Such amount will be due and payable
annually in a lump sum on each anniversary of the effective date of the
applicable Member Supplement. If a Participating Member elects to lease its
Blood Screening Systems, payments will be invoiced by Chiron on a monthly basis,
together with the Blood Screening Assay Fee and Blood Screening Systems Fee
described above. Each Participating Member shall make payment on invoices in
accordance with Section 5.3 of the Association Agreement, except where modified
by the applicable Member Supplement. The applicable purchase price for Services
will be set on a Member-by-Member basis based on the specific requirements of
each Participating Member. The pricing information set forth below is provided
for informational purposes only.

Blood Screening System Components

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

  Price/Year/Unit

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

  Monthly
Installment
Payment

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

Pooling TECAN9   [**]   $  
Assay TECAN10
 
[**]
 
$
 
Procleix™ System11
 
[**]
 
$
 

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

9Includes all version updates to CPT-16 Pooling Software, ver. 2.0.0.2

10Includes all version updates to Procleix™ Assay Software, ver. 2.0.0.76 and
Procleix™ Assay Software LHP, ver. 2.1

11Includes all version updates to Procleix™ System Software, ver. 3.0.3.4,
Procleix™ Protocol, ver. 2.1.0.0, and Procleix™ Worklist Editor, ver. 3.0.3.2

1.4.NAT Tracker Fee. Each Participating Member electing to purchase the NAT
Tracker software solution agrees to pay to Chiron the NAT Tracker Fee set forth
in their Member Supplement. Such amount will be due and payable annually in a
lump sum on the effective date of the applicable Member Supplement and on each
anniversary thereafter. Participating Members electing to purchase the NAT
Tracker software solution will enter into a separate software license agreement
with Chiron.

2.Adjustments to Fees.

2.1Reagent Utilization Factor.

(a)Chiron and each Participating Member agree to monitor the Reagent Utilization
Factor at each Testing Center during the term of this Agreement. If the Reagent
Utilization Factor for any Testing Center set forth on the report provided by a
Participating Member pursuant to Section 1.1 of this Schedule E exceeds that
Participating Member's target Reagent Utilization Factor, set forth in the
applicable Member Supplement (the "Target RUF"), [**], Chiron and each
Participating Member shall use their best endeavors to identify and correct the
cause of the excess.

(b)The Reagent Utilization Factor shall be calculated for each Participating
Member promptly following each successive 52 week period commencing on the
Effective Date of the applicable Member Supplement (each, an "Annual RUF
Measuring Period"),

63

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aggregating all Testing Centers. If the Reagent Utilization Factor for a
Participating Member for any Annual RUF Measuring Period exceeds the applicable
Target RUF, Chiron shall invoice the Participating Member on the next subsequent
monthly invoice, and the Participating Member agrees to pay, the additional fee
set forth in their Member Supplement.

2.2.[**].

3.[**].

4.Effect of Change in Nature of Testing. If a Participating Member elects to
move from Pooled Testing to Single Unit Testing, or from Single Unit Testing to
Pooled Testing, pursuant to Section 11 of Schedule B-1, (i) the price per
donation shall be adjusted pursuant to the then current Assay Pricing Chart and
(ii) the Target RUF will be recalculated.

5.Additional Supplies. The following additional supplies are available from
Chiron at the prices set forth below. Chiron reserves the right to increase or
decrease these prices at any time, without notice to each Participating Member:

[**]                [**]

[**]                [**]

[**]                [**]

64

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

EXHIBIT 10.317

 
   
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.

MEMBER SUPPLEMENT

        This Member Supplement (this "Member Supplement"), dated as
of                        (the "Effective Date"), is by and between Chiron
Corporation, a Delaware corporation ("Chiron"), and                        ("ABC
Member").

RECITALS

A.Chiron and America's Blood Centers, an association of non-profit
community-based blood centers ("ABC"), have entered into that certain
Association Agreement dated as of May 1, 2002 (the "Association Agreement");

B.Pursuant to and in accordance with the terms of the Association Agreement,
Chiron has agreed to sell Blood Screening Assays and sell or arrange for the
lease of Blood Screening Systems to ABC members, for use to conduct nucleic acid
amplification tests to detect the presence of certain viruses in blood donation
samples;

C.                              , an ABC member, wishes to acquire Blood
Screening Assays and Blood Screening Systems to conduct nucleic acid
amplification tests to detect the presence of certain viruses in blood donation
samples, in accordance with the terms of the Association Agreement, subject to
the following additional terms and conditions.

AGREEMENT

        NOW, THEREFORE, in consideration of the foregoing and the mutual
covenants and agreements herein contained, and for other good and valuable
consideration, the receipt and sufficiency of which is hereby acknowledged, the
parties hereto agree as follows:

1.Definitions. All capitalized terms used but not otherwise defined in this
Member Supplement shall have the meanings set forth in the Association
Agreement.

2.Association Agreement. The terms and conditions of the Association Agreement,
attached as Exhibit 1 to this Member Supplement, are adopted by the parties
hereto and incorporated by reference. For the purpose of the Association
Agreement and this Member Supplement, ABC MEMBER shall be deemed to be a
Participating Member. In the event of any conflict between the terms and
conditions of this Member Supplement and the terms and conditions of the
Association Agreement, the terms and conditions of the Association Agreement
govern.

3.Blood Screening Assays. In accordance with Schedule B of the Association
Agreement, Chiron shall supply ABC MEMBER with its requirements of Blood
Screening Assays to permit ABC MEMBER to conduct Pooled Testing or Single Unit
Testing of blood donations in the Territory at the Testing Centers listed on
Exhibit 2 to this Member Supplement. ABC MEMBER's initial Product Requirement
Forecast is attached as Exhibit 3 to this Member Supplement.

1

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

4.Blood Screening Systems. In accordance with Schedule C of the Association
Agreement, Chiron shall sell ABC MEMBER the Blood Screening Systems described on
Exhibit 4 to this Member Supplement.

5.Fees. In accordance with Schedule E to the Association Agreement, ABC MEMBER
agrees to the following fees:

5.1Blood Screening Assay Fee. The applicable Per Result Fee is set on an annual
basis from the Assay Pricing Chart below using the Product Requirements Forecast
provided for that year. For the first year of the term of this Member
Supplement, the applicable Per Result Fee for ABC MEMBER is            .

                        TESTING

 
   
  Aggregate Participating Members Reportable Results
For Prior Calendar Year2

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

                        -Year Term1

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

  [**]

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

  [**]

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

  [**]

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

  [**]

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

  [**]

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

  [**]

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

        Per Reportable Result

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

Individual Participating Member
Reportable Results

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

  A

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

  B

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

  C

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

  D

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

  E

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

  F

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

[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]
 
[**]

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

1Discount of [**].

2Includes all testing performed by Members; e.g., Pooled Testing and Single Unit
Testing.

5.2Blood Screening Systems Fee. The Blood Screening Systems Fee for the purchase
of Blood Screening Systems set forth on Exhibit 4 to this Member Supplement is
$                        , payable in a lump sum in accordance with Section 1.2
of Schedule E. Additional components will be available to the Participating
Member at the then current list price for such components.

5.3Services Fee. The Services Fee for the Blood Screening Systems set forth on
Exhibit 4 to this Member Supplement is
$                                           , payable annually in accordance
with Section 1.3 of Schedule E. The purchase of additional components will
result in an increase in the Services Fee from and after the installation of the
additional component(s). The Services Fee shall not be due or payable for Blood
Screening Systems purchased new until the expiration of the applicable
manufacturers' warranties.

5.4NAT Tracker Fee. The applicable license fee for the NAT Tracker software
solution is based on the number of Testing Centers operating the NAT Tracker
software, as set forth below, and payable annually in a lump sum in accordance
with Section 1.4 of Schedule E. Additional Testing Centers may be licensed to
use the NAT Tracker software at the then current license fee.

Software

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  Price/Year

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  Number of
Testing Centers

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  Extended License
Fee

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NAT Tracker3   $ [**]       $  

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3Includes all version updates to NAT Tracker Software, ver. 1.0E.

6.Reagent Utilization Factor. In accordance with Schedule E to the Association
Agreement, for each [**] increment by which the actual Reagent Utilization
Factor during each Annual RUF

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Measuring Period exceeds ABC MEMBER's Target RUF of            , ABC MEMBER
agrees to pay an additional fee [**]; provided that no additional fee shall be
payable hereunder to the extent that the cause of the Reagent Utilization Factor
exceeding such amount is attributable to a breach by Chiron of the limited
warranty set forth in Section 12 of Schedule B-1.

7.Training. Chiron agrees to provide the following training program for ABC
MEMBER personnel.

7.1Initial Training. Chiron shall provide, at Chiron's sole expense, initial
training to            technical personnel from ABC MEMBER. Initial training
includes assay training on the Blood Screening System and Pooled Testing
training, if applicable. Training will include theory, practical training and
operation/maintenance on all required equipment. Upon successful completion of
training, individuals will be certified as Primary Operators. Chiron will
provide an additional week of "train-the-trainer" courses for up
to            Primary Operators from ABC MEMBER. Upon successful completion of
these courses, these Primary Operators will be issued trainer certifications.
Primary Operators with trainer certifications may train Secondary Operators in
accordance with Section 7.2 of this Member Supplement. Chiron also agrees to
provide, at Chiron's expense, Bio Medical Instrument Technician ("BMIT")
training to            Primary Operators from ABC MEMBER. BMIT training includes
training on the Tecan Genesis instrumentation and includes theory, diagnostic
tests, troubleshooting and basic instrument repair. Upon successful completion
of the course, trainees will be certified as Bio Medical Instrument Technicians.
BMIT-certified Primary Operators must be re-certified annually by Chiron.

7.2On Site Training. Training of Secondary Operators will be performed on site
at the Testing Centers, by Primary Operators or by Chiron support personnel.
Each Secondary Operator will be required to pass proficiency certification prior
to reporting results. Without limiting Section 7.1 of this Member Supplement, if
the Participating Member later requires training of additional personnel due to
employee turnover, such additional training will be the responsibility of the
Participating Member, using Primary Operators previously trained by Chiron
pursuant to this Section 7 of this Member Supplement. Chiron undertakes to
co-operate with the Participating Member and if requested by the Participating
Member, provide technical personnel to assist in training such additional
personnel.

7.3Proficiency Panels. Chiron will provide, at no cost to the Participating
Member, one proficiency panel for initial proficiency certification of each of
the operators trained pursuant to Section 7.1 of this Member Supplement. If,
following initial certification, the Participating Member wishes to re-certify
an operator, or the Participating Member wishes to obtain proficiency panels for
ongoing quality control or future training purposes, the Participating Member
shall purchase such proficiency panels as may be necessary for such purposes.
The Participating Member agrees to provide forecasts of its needs for
proficiency panels in the same manner as is set forth in Section 7 of
Schedule B-1 to this Agreement.

7.4Manuals and Documentation. The training provided under Sections 7.1 and 7.2
of this Member Supplement shall include copies of training materials, operator
manuals and documentation, including maintenance and troubleshooting
documentation.

7.5Changes to Blood Screening Assays, Blood Screening Systems, Software. If, in
accordance with Section 6.7 of the Association Agreement, mandatory changes are
made by the manufacturer to the Blood Screening Assays, Blood Screening Systems
or Software during the term of this Agreement, and as a result further staff
training is required, the training must be carried out by Chiron at its cost at
the Testing Centers, unless the parties otherwise agree. Chiron must provide
proficiency panels at its cost for any additional proficiency certification
required as a result of the changes referred to in this Section 7.5 of this
Member Supplement. For clarity of understanding, unless otherwise agreed the
Participating Member will bear any additional

3

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training costs and costs of proficiency panels arising from any optional change
which the Participating Member elects to implement pursuant to Section 6.7 of
the Association Agreement.

8.Insurance.

8.1ABC MEMBER shall obtain and maintain at its sole cost, a policy or policies
of insurance with the following coverages, which shall be in full force and
effect for the term of this Agreement and thereafter through two years following
the termination of the Agreement: a) a Commercial General Liability policy
including Products and Completed Operations Liability in an amount of not less
than $                        combined single limit for each occurrence;
b) Workers' Compensation coverage with statutory limits for each jurisdiction
where the work required of such party under this Agreement is performed and an
employers' liability policy with at least the following limits,
$                        per accident, $                        per disease
(policy limit), and $                        disease (each employee); and
c) Professional Liability (Errors & Omissions) Insurance in an amount not less
than $                        each claim specifically insuring claims arising
from obligations of ABC MEMBER.

8.2ABC MEMBER shall provide Chiron with certificates of insurance evidencing the
coverage required herein upon execution of this Agreement, and renewal
certificates on request from Chiron. ABC MEMBER must notify Chiron within a
reasonable time if there is a material change to any of the insurance policies
referred to in this Section. Such certificates shall provide for thirty
(30) days prior written notice to the certificate holder in the event of
non-renewal of the policies, cancellation or material change in the coverage
provided.

9.Term. This Member Supplement shall become effective on the Effective Date of
this Member Supplement, and shall terminate on the earlier to occur of
(i)             (            ) months from the Effective Date of this Member
Supplement, or (ii) the termination or expiration of the Association Agreement.
ABC MEMBER shall have the right to extend the term of this Member Supplement,
subject to the continued effectiveness of the Association Agreement, by two
extension periods, each one year in length. ABC MEMBER shall elect an extension
by delivering written notice to Chiron not less than ninety (90) days prior to
the expiration of the initial term or extension.

10.Notices. Notices, requests, waivers and other communications made pursuant to
this Member Supplement or the Association Agreement shall be made in accordance
with Section 12.6 of the Association Agreement and, if to ABC MEMBER, shall be
addressed to ABC MEMBER as set forth below:

ABC MEMBER
                                                         
                                                         
Fax: (              )                                 
Attn:                                                  

11.[**]. 12.Survivability. Sections 2 and 9 of this Member Supplement shall
survive any expiration or termination of this Member Supplement.

[SIGNATURE PAGE FOLLOWS]

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        IN WITNESS WHEREOF, the parties hereto, acting through their duly
authorized officers, have executed this Agreement as of the date first set forth
above.

 
   
   
    CHIRON CORPORATION
 
 
By:
 

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    ABC MEMBER
 
 
By:
 

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EXHIBITS

1Association Agreement

2Testing Centers

3Products Requirements Forecast

4Blood Screening Systems

6

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QuickLinks

EXHIBIT 10.317

Association Agreement Regarding the Sale and Servicing of Blood Screening
Products
SCHEDULE A Definitions
SCHEDULE B-1 TERMS AND CONDITIONS FOR PURCHASE OF PROCLEIX™ HIV-1/HCV BLOOD
SCREENING ASSAY
ATTACHMENT B-1 Package Insert
SCHEDULE C TERMS AND CONDITIONS FOR USE OF BLOOD SCREENING SYSTEMS
SCHEDULE D BLOOD SCREENING SYSTEMS AND SOFTWARE SERVICE & SUPPORT
SCHEDULE E PRICES

EXHIBIT 10.317

MEMBER SUPPLEMENT
RECITALS
AGREEMENT
EXHIBITS