EXHIBIT 10.21
[LETTERHEAD OF ITC APPEARS HERE]
Joint Research and Development Agreement
This Agreement (the "Agreement") is made as of Oct 28, 1996 (the "Effective
Date") by and between Exigent Diagnostics, Inc. ("Exigent"), a Delaware
corporation having its principal place of business at 0000 Xxxxxxx Xxxxxxx
Xxxxxx Xxxx, Xxxxx, and International Technidyne Corporation ("ITC"), a Delaware
corporation having its principal place of business at 0 Xxxxx Xxxxxx, Xxxxxx, XX
00000.
WITNESSETH
WHEREAS, ITC has certain proprietary know-how, skilled laboratory
researchers and manufacturing expertise in the field of plasma coagulation and
other diagnostic assays; and
WHEREAS, Exigent has certain proprietary know-how and skilled laboratory
researchers in the field of diagnostic assays; and
WHEREAS, ITC and Exigent desire to enter into an agreement for the
research, development and evaluation of point-of-care coagulation assay test
cartridges and coagulation detector (the research, development and evaluation
hereafter referred to as "Research" and the procedures and processes resulting
from the Research hereafter referred to as the "Products").
NOW THEREFORE, for and in consideration of the promises and mutual
covenants and agreements hereinafter set forth and for other good and valuable
consideration, the receipt and sufficiency of which are hereby acknowledged and
accepted, the parties hereto agree as follows:
1. CONTRACT PURPOSE
1.1. The goal of the joint research, development and evaluation effort to
be conducted is to develop cost-effective point-of-care plasma coagulation
assays, for the benefit of both parties hereto. The principal objectives of the
research and development efforts are more particularly set forth in the
Coagulation Assays Development Plan attached hereto as Annex I and incorporated
herein by this reference. The parties may amend Annex I from time to time by
executing a revised, restated, dated Annex I and attaching it hereto.
1.2. The parties agree that ITC and Exigent, through the respective
employees of each will perform the tasks specified hereto and in Annex I. The
parties agree periodically, but not less frequently than quarterly, commencing
on the date three months from the Effective Date of
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this Agreement, to review and revise Annex I, as needed.
2. RESEARCH
2.1. The employees of each party hereto, in their respective laboratories,
shall perform the tasks specified in Annex I, collaborating at all times in such
performance by, without limitation, exchanging materials and information and
providing all relevant data, information and results useful to the purposes of
this Agreement, to each party hereto, without restriction, other than as
specified in this Agreement.
2.2. Exigent will reimburse ITC for each hour of Research work (as per
2.3.) performed by an ITC employee, representative or agent, at the rate of $100
per hour, plus expenses, including, without limitation, the cost of dedicated
equipment (inclusive of, without limitation, design, installation and validation
costs and exclusive of depreciation costs) and materials and research and
development expenses. ITC shall render an invoice each month for such services
and expenses and Exigent shall pay such invoice in full within 30 days of
receipt thereof. Exigent shall pay ITC interest at the rate of one and one half
(1 1/2%) percent per month on any amount not timely paid.
2.3. ITC agrees to responsibility for sections 22, 27, 53 and 68 of Annex
I except for subsection 60 of section 53, which is being developed by Battelle
Research as part of a contract with Exigent. The estimated budget for ITC based
on Annex I work totals $336,000 which includes $48,000 contingency. Approval of
use of any portion of the contingency requires the sole approval of Exigent.
2.4. Neither party hereto makes any representation or warranty to the
other with respect to the purity, activity, safety, accuracy or usefulness of
the materials or information exchanged under this Agreement.
3. PRODUCTS
3.1. Subject to the exclusivity provision of Sections 3.2. and 3.3. below
and the patent and other intellectual property provisions set forth in Section 4
below, either party hereto shall have the right to develop, make, use, license
and/or sell Products for the equal benefit of both parties hereto. Subject to
the exclusivity provisions of Sections 3.2. and 3.3. below and the Royalty
provision of section 4.2., any consideration accruing as a result of the
development, use, license or sale of Products shall be shared equally by the
parties hereto. Any sale or license arrangement or agreement relating to a
Product shall be subject to the approval of the party not originating such
arrangement or agreement, such approval shall not be unreasonably withheld,
delayed or conditioned. This right shall include the right to grant sublicenses
with respect to the use or sale of Products to third parties.
2
3.2. Exigent shall have the exclusive right to, and benefit of, the
inventions and discoveries, including Products, resulting from the Research in
the field of multitest device point-of-care testing. Multitest devices shall
mean those devices capable of performing more than one type of diagnostic assay
in a given run. As an example, a device which can test for blood chemistries and
coagulation time or combination of chemistry, electrochemistry, coagulation and
immunoassay, in which several samples are placed in the same device and the
device is instructed to perform the preprogrammed assay without reloading, is a
multitest device.
3.3. ITC shall have the exclusive right to, and benefit of, the inventions
and discoveries, including Products, resulting from the Research, as it pertains
to coagulation in the field of single patient point-of-care testing. Single
patient point-of-care testing shall mean cartridge technology with single or
multiple coagulation assays or such multiple assays in a single cartridge for a
single patient. The Agreement does not restrict ITC from performing coagulation,
chemistry, immunoassay or hematology tests, on whole blood or plasma, in
cartridges of ITC design provided that if the coagulation cartridge designed as
part of this project is used, a royalty will be paid to Exigent as per section
4.2.
3.4. For purposes of this Agreement, point-of-care shall mean a diagnostic
test performed in the vicinity of a patient (regardless of species) at the time
a sample is obtained from the patient and is expressly contrasted with, and
distinguished from, testing performed at a central laboratory within a hospital,
or commercial laboratory.
4. PROPRIETARY RIGHTS
4.1. The parties hereto agree promptly to disclose to the other party any
and all inventions or discoveries, including Products, made by it in the course
of or as a result of the Research, whether discovered or conceived by an
employee, agent or representative. The parties hereto acknowledge that the
Research and Products will result from the collaboration between the parties and
that the right, title and interest in the Research and Products, including the
right to domestic and foreign copyright, copyright renewal, trademark and/or
patent protection therein and the right to register and claim priority therein
under any applicable law, treaty or conventions, shall be equally and jointly
owned. Each party hereto will equally share the expenses of prosecuting any
patent or otherwise developing or protecting any intellectual property right
related to the Research or Products. The processes and strategies of development
or protection of intellectual property rights related to the Research and/or
Products, including without limitation the scope of protection and/or
international activity, shall be the responsibility of both parties equally and
each party shall use its best efforts to agree on such processes and strategies.
4.2. Each party hereto shall have, subject to the contrary provisions in
Sections 3.2. and 3.3. of this Agreement, the irrevocable right to use all
inventions and discoveries (including Products) resulting from the Research.
Exigent's rights shall be royalty free. ITC's rights shall be royalty free after
ITC has compensated Exigent in cash for 50% of the technology development costs
for coagulation assays as contained in this Agreement which payment shall be
made prior to ITC's commercialization of inventions and discoveries. Each party
hereto shall ensure that the individuals under the control of each shall assign
to such party, or to the parties hereto jointly,
3
all right, title and interest in each invention and/or discovery, such that the
parties hereto become the joint owner of any such invention and/or discovery,
including all patent or other proprietary rights relating thereto.
4.3. The parties hereto each agree to execute and deliver to the other all
reasonable copyright, patent and other applications, assignments and instruments
tendered by the other and perform such acts as may be reasonably necessary or
advisable for obtaining such rights and/or of vesting and maintaining the title
to the rights as specified in this Agreement.
4.4. The parties will keep a monthly schedule of all costs incurred which
will be subject to audit if desired by the other party and which will form the
basis of calculating the total Research and Development Cost. Any change to the
Research and Development Cost that results in changes exceeding $336,000 will
require approval of both parties before incurring the cost. Such cost will
include all expenses, capital costs, material costs and interest charged. This
cost, once the project is complete, will form the basis to set the Royalty
payment due Exigent by ITC if ITC chooses to use the inventions and discoveries.
4.5. The provisions of Section 4 hereof shall survive the expiration or
other termination of this Agreement.
5. CONFIDENTIALITY
5.1. The term "Confidential Information" shall mean all confidential,
proprietary or non-public information of either party hereto, including all
materials and technical information exchanged in connection with the Research,
information developed as a result of the Research known-how, data and/or trade
secrets, regardless of form, however disclosed, and all samples or prototypes of
any Products, furnished by one party to the other, either directly or
indirectly. Confidential Information shall not include information or materials
which (i) at the time of disclosure are in the public domain, (ii) after
disclosure become part of the public domain by publication or otherwise, other
than by reason of a breach of this Agreement, (iii) the recipient can establish
by reasonable proof were in its possession at the time of disclosure or were
subsequently and independently developed by the recipient, by persons not having
access to the Confidential Information or (iv) the recipient receives from a
third party who has the right to disclose such information.
5.2. Neither party receiving Confidential Information of the other (the
"Recipient") shall use the Confidential Information for any purpose other than
to fulfill the purposes and/or obligations of this Agreement and shall not
disclose the information to any person other than a person over whom Recipient
has control, who has a need to know the information in order for Recipient to
fulfill the purposes and/or obligations of this Agreement and who agrees to be
bound by the terms of this confidentiality provision.
5.3. All originals and copies of any of the foregoing however and whenever
produced, shall be the sole property of the originator of such Confidential
Information, subject to Sections 3 and 5 hereto regarding the ownership of the
results of the Research. Upon the expiration or
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earlier termination of this Agreement, each party shall promptly surrender to
the other party all Confidential Information of such other party that is reduced
to one or more writings, drawings, schematics, tapes, disks, or other form of
documentation, together with any documents, materials and equipment belonging to
the other party and such party shall not thereafter retain or deliver to any
other person or entity any of the foregoing or any summary or memorandum
thereof.
5.4. Each party hereby agrees that it shall be responsible for the
obligations of its employees, representatives and agents hereunder and executes
this Agreement on behalf of itself and such employees, representatives and
agents. In addition to its other obligations under this Section 5, each party
shall use at least the same degree of care (which at a minimum shall be
reasonable) to avoid unauthorized dissemination of Confidential Information as
it employs for its own information of a similar nature that it does not want to
have disseminated. The parties shall not put the Confidential Information of the
other to commercial use, except as expressly provided under this Agreement.
5.5 The provisions of Section 5 shall survive expiration or earlier
TERMINATION OF THIS AGREEMENT.
6. LAWS AND REGULATIONS
6.1. The parties hereto agree that each will conduct the research, provide
materials, develop and manufacture Products strictly in compliance with all
applicable federal, state and local laws, regulations, ordinances.
6.2. Each party hereto shall obtain and maintain, at its own expense, any
non-United States governmental consents, authorizations, approvals, filings,
permits or licenses required for it to export any Product it develops and for
which it arranges a foreign sale and for it to exercise its rights and to
discharge its obligation under this Agreement, including, without limitation,
all consents and filings with any non-United States governmental body. Each
party acknowledges that the Products and all related technical information,
documents and material are subject to export controls under the US Export
Administration Act of 1969, as amended, and the rules and regulations
promulgated from time to time thereunder (collectively the "Export Act"),
restricting exports and reexports of technical data, direct products of
technical data and software media. Each party hereto will, with respect to
Products it develops and for which it arranges a foreign sale, (i) comply
strictly with all legal requirements established under the Export Act, (ii)
cooperate fully with the other party in any official or unofficial audit or
inspection relating to the Export Act and (iii) not distribute or supply any
Product to any person if there is reason to believe that such person intends to
export, reexport or otherwise take such Products to, or use such Products in,
any country in violation of the Export Act.
Each party agrees not to knowingly export or re-export the Products or any
party thereof, directly or indirectly, without first obtaining permission to do
so from the United States Office of Export Administration and other appropriate
governmental agencies, into any of those countries listed, from time to time at
the time of any shipment of Products, in Title 15 of the Code of Federal
Regulations of the United States of America (or any successor or additional
5
provision) as "prohibited or restricted" countries or any other country to which
such exports or re-exports may be restricted (collectively the "Restricted
Countries"). Each party hereto agrees not to distribute the Products or any
part thereof to any person if it has reason to believe that such person intends
to export, re-export or otherwise take the same to, or to use the same in, any
of the Prohibited Countries and each such party agrees to seek reasonable
written assurances in the form of binding covenants from customers as may from
time to time be requested by the other party hereto.
7. TERM AND TERMINATION
7.1. The term of this Agreement shall be for a period of one year
commencing on the Effective Date hereof and end on the one year anniversary of
the Effective Date; provided that this agreement shall be renewed automatically
for one year increments unless terminated by either party hereto upon one-month
written notice to the other, which may be given at any time after the one year
anniversary of the Effective Date.
7.2. ITC may terminate this Agreement upon 30 days written notice to
Exigent within the first year of the Agreement upon the occurrence of any
termination event as follows: (i) Exigent or any of its employees,
representatives or agents breaches any material obligation under this Agreement,
including, without limitation, violation of any payment terms, if such breach is
not cured to ITC's satisfaction within the 30 day notice period, (ii) Exigent
ceases to conduct business in the the normal course, becomes insolvent, enters
into suspension of payments, moratorium, reorganization or bankruptcy, makes a
general assignment for the benefit of creditors, admits in writing its inability
to pay debts as they mature, suffers or permits the appointment of a receiver
for its business or assets, or avails itself of or becomes subject to any other
judicial or administrative proceeding related to insolvency or protection of
creditors' rights (and, if such action or proceeding is involuntary on the part
of Exigent, such action or proceeding is not dismissed within 90 days), (iii)
the failure of Exigent to obtain any required permit or consent required to
perform the Research.
7.3. Exigent may terminate this Agreement upon 30 days written notice to
ITC within the first year of the Agreement upon the occurrence of any
termination event as follows: (i) ITC or any of its employees breaches any
material obligation under this Agreement, if such breach is not cured to
Exigent's satisfaction within the 30 day notice period, or (ii) ITC ceases to
conduct business in the normal course, becomes insolvent, enters into suspension
of payments, moratorium, reorganization or bankruptcy, makes a general
assignment for the benefit of creditors, admits in writing its inability to pay
debts as they mature, suffers or permits the appointment of a receiver for its
business or assets, or avails itself of or becomes subject to any other judicial
or administrative proceeding related to insolvency or protection of creditors'
rights (and, if such action or proceeding is involuntary on the part of ITC,
such action or proceeding is not dismissed within 90 days).
7.4. The provisions of Sections 3, 4, 5 and 7 shall survive the expiration
or earlier termination of this Agreement. From and after the date of any such
expiration or earlier
6
termination, neither party shall have any further rights, privileges or
obligations hereunder except that: (i) such expiration or earlier termination
shall not relieve either party of any liability or obligation accrued prior to
the expiration or termination date, including without limitation, Exigent's
obligation to purchase the components and/or raw materials purchased or
manufactured pursuant to Exigent's forecasts, if any, (ii) such expiration or
earlier termination shall not affect the continued operation or enforcement of
any provision of this Agreement which is to survive expiration or termination,
and (iii) upon such expiration or earlier termination, each party shall
immediately return to the other party all Confidential Information as required
by Section 5 of this Agreement. In no event upon the expiration or termination
of this Agreement shall the terminating party (or in the event of an expiration,
either party) be liable to the other party for any damages, indemnities, loss of
profits, loss of revenues, or other losses by reason of any such expiration or
termination.
8. MISCELLANEOUS
8.1 Exigent's representative with respect to Exigent's rights and
obligations hereunder shall be Xx. Xxx Xxxxx, or such other representative as
Exigent designates to ITC, in writing, and Exigent represents that Xx. Xxxxx is
authorized to bind Exigent in connection with this Agreement. Likewise, ITC's
representative is Xxxxxx Xxxxxxx who has the same authority within ITC as
affects the execution and operation of this Agreement. Each party hereto
represents and warrants to the other that it has the right and has obtained all
necessary corporate approvals, to enter into this Agreement and perform the
obligations to be performed by it under this Agreement and that this Agreement
constitutes its valid, binding and enforceable obligation, enforceable against
it in accordance with its terms.
8.2 The failure of either party hereto to perform any obligation under
this Agreement (except any payment obligation hereunder of Exigent to ITC) due
to acts of God, acts of government, civil disturbances, wars, strikes,
transportation problems, unreasonable delays by ITC's vendors in delivery,
failure to provide products or material to ITC by its vendors, or other causes
beyond its reasonable control shall not be deemed to be a breach of this
agreement; provided, however, that the party so prevented from complying
herewith shall immediately give notice thereof to the other party and shall
continue to take all commercially reasonable action to comply as fully as
possible herewith. After removal of the basis for the non-performance, the party
failing to perform shall resume performance within a reasonable time.
8.3 This Agreement, together with its Annexes, constitutes the sole and
entire agreement between the parties relating to the subject matter herein, does
not operate as an acceptance of any conflicting terms or provisions of any
Exigent purchase orders or any other instrument or document and terminates and
supersedes any and all prior agreements and understandings between the parties.
8.4 No change in, addition to, or waiver of any of the terms and
provisions herein shall be binding upon any party unless approved by it in
writing.
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8.5. The failure by either party to exercise or to enforce any of the terms
or condition of this Agreement shall not constitute or be deemed a waiver of
that party's right thereafter to enforce each and every term and condition of
this Agreement.
8.6. Should a court of law or arbitrator hold that any one or more of the
provisions in this Agreement is invalid, illegal or unenforceable, no other
provision of this Agreement shall be affected thereby, and the remaining
provision of this Agreement shall be both construed and reformed and shall
continue with the same effect as if such unenforceable, illegal or invalid
provision shall not have been inserted in this Agreement.
8.7. This Agreement and the respective rights and obligations of the
parties hereto shall be governed by and determined in accordance with the
domestic internal laws of the Commonwealth of Pennsylvania, without giving
effect to conflict of laws principles thereof.
8.8. ITC and Exigent are independent parties. It is understood and agreed
that neither party hereto is, by this Agreement or anything herein contained,
constituted or appointed the legal representative of the other, nor shall either
party hereto have the right or authority to make any representation, warranty,
covenant, guarantee or commitment or assume, create or incur any liability or
any obligation of any kind, expressed or implied, in the name of or otherwise on
behalf of the other, whether directly or indirectly. This Agreement is not
intended to create a joint venture, partnership or agency relationship between
the parties hereto.
8.9. All notices and other communications which are required or permitted
under this agreement shall be in writing and sent by facsimile (confirmed by
mail), overnight courier, or registered or certified mail, postage prepaid, to
the receiving party at the following addresses:
If to ITC: International Technidyne Corporation
0 Xxxxx Xxxxxx
Xxxxxx, XX 00000
Attention: Xx. Xxxxxxx Xxxxxxxxxx
with a copy to: Thermo Electron Corporation
00 Xxxxx Xxxxxx
Xxxxxxx, XX 00000
Attention: General Counsel
with copy to Xxxxxx Xxxxxxxx Xxxxxxx LLP
0000 Xxx Xxxxx Xxxxxx
Xxxxxxxxxxxx, XX
00000
Attn: Xxxxx Abelso
If to Exigent: Exigent Diagnostics, Inc.
0000 Xxxxxxx Xxxxxxx
Xxxxxx Xxxx Xxxxx
00000
Attention: Xx. Xxx Xxxxx
or to any other address that the receiving party may have provided to the
sending party in writing as provided aforesaid. Any notice or other
communication delivered by facsimile shall
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be deemed to have been received the day it is sent, if sent before 5:00 p.m. on
a business day and the next business day thereafter, if sent on a weekend,
holiday or after 5:00 p.m. Any notice or other communication sent by overnight
courier shall be deemed to have been received on the business day after it is
delivered to the courier. Any notice or other communication sent by registered
or certified mail shall be deemed to have been received on the third business
day after its date of posting. The facsimile number to which notices should be
sent are:
ITC (000) 000-0000
Thermo (000) 000-0000
Exigent (000) 000-0000
Xxxxxx Xxxxxxxx 000 000-0000
8.10. This Agreement and each and every covenant, term and condition shall
be binding upon and inure to the benefit of both parties hereto and their
respective successors. Neither this Agreement nor any right hereunder may be
assigned or otherwise transferred by either party without first receiving the
express prior written consent of the other party, except that ITC may transfer
or assign this Agreement, or any of the rights and/or obligations thereunder to
any parent, sister, subsidiary or sister entity.
8.11. This Agreement may be executed in one or more counterparts, each of
which shall be deemed an original, but all of which together shall constitute
one and the same instrument.
8.12. It is expected that upon completion of this Research and Development
Agreement, Exigent will enter into a manufacturing agreement with ITC for
production of coagulation reagents in a cuvette, subject to competitive pricing
as offered by ITC.
IN WITNESS WHEREOF, ITC and Exigent have caused this Agreement to be
executed by their duly authorized representatives as of the date first set forth
above.
Exigent Diagnostics, Inc. International Technidyne Corporation
By: /s/ X. Xxxxxxx Stoughton By: /s/ Xxxxxx Xxxxxxx
----------------------------- ----------------------------------
Name: X. Xxxxxxx Stoughton Name: Xxxxxx Xxxxxxx
--------------------------- --------------------------------
Title: Chairman & CEO Title: President
-------------------------- -------------------------------
Date: Oct 26, 1996 Date: Oct 27, 1996
--------------------------- --------------------------------
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Annex I REV.2 Coagulation Tests Development Plan - Confidential Information
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ID TASK NAME TIME RESOURCE DEVELOP. $ BILLED $
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1 COAGULATION TESTS DEVELOPMENT PLAN (4 METHODS) APTT, PT, THROMBIN TIME, FIBRINOGEN 190D $336,000.00 $463,000.00
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2
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3 NOTE: THE RESOURCE ESTIMATES ARE NOT RELATED TO ELAPSED TIME. MORE THAN ONE PERSON
CAN BE ASSIGNED 1D $0.00 $0.00
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4 TO A TASK TO SHORTEN THE ELAPSED TIME. 1D $0.00 $0.00
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5
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6
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7 PROOF OF CONCEPT - COAGULATION ASSAYS BY REFLECTOMETRY - EXIGENT (COMPLETE) OD $0.00 $0.00
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8 Reflectance spectra of clotted and unclotted plasma samples Od $0.00 $0.00
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9 Preliminary evaluation of CORE System detection angles Od $0.00 $0.00
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10 Evaluate reference titles to zero and/or blank the Xxxx reflectometer Od $0.00 $0.00
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11 DETERMINE CLOTTING TIME FOR PT AND APTT USING COMMERCIAL COAGULATION REAGENTS
(LIQUID) OD $0.00 $0.00
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12 Evaluate incubation temperature vs. clot time Od $0.00 $0.00
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13 Evaluate incubation temperature vs. clot time Od $0.00 $0.00
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14 Evaluate commercial coagulation reagents and sample mixing vs. clot time Od $0.00 $0.00
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15 Evaluate commercial coagulation reagents and sample volumes vs. clot time Od $0.00 $0.00
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16 Estimate precision - Ortho PT and APTT controls Od $0.00 $0.00
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17 Perform method comparison (MLA vs. Reflectometry) Od
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18
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19
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20
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21
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22 SELECTION OF COAGULATION REAGENTS (PRELIMINARY STUDIES) - ITC 25D $40,000.00 $40,000.00
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23 Create experimental lots & evaluate dried or lyophilized PT and APTT reagents 5w ITC $20,000.00 $20,000.00
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24 REVIEW DIFFERENCES BETWEEN APTT AND PT (HOMOGENEOUS REAGENTS) 25D $20,000.00 $20,000.00
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25 Determine mixing and/or homogeneity requirements 5w ITC $20,000.00 $20,000.00
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Annex I Rev.2 Coagulation Tests Development Plan - Confidential Information
------------------------------------------------------------------------------------------------------------------------------
ID TASK NAME TIME RESOURCE DEVELOP. $ BILLED $
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26
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27 DIAGNOSTIC PRODUCT SPECIFICATIONS - ITC/EXIGENT 0.63D $0.00 $2,000.00
------------------------------------------------------------------------------------------------------------------------------
28 APTT 5h ITC $0.00 $500.00
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29 PT 5h ITC $0.00 $500.00
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30 Fibrinogen 5h ITC $0.00 $500.00
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31 Thrombin Time 5h ITC $0.00 $500.00
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32
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33
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34
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35
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36
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37 TEST CUVETTE DESIGN AND EVALUATION - ITC/BATTELLE/EXIGENT 15D $0.00 $0.00
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38 model coag cuvette - ITC/Battelle 3w $0.00 $0.00
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39 Sample volume accuracy studies - Battelle 1d $0.00 $0.00
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40 Select and evaluate cuvette materials - ITC/Battelle 2w $0.00 $0.00
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41 TEST REFLECTANCE OF CUVETTE MATERIALS - EXIGENT 0D $0.00 $0.00
------------------------------------------------------------------------------------------------------------------------------
42 Evaluate detection angles 0d $0.00 $0.00
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43 Wavelengths (420, 505, 540, 600, 625, 650, 800 and "X" nm) 0d $0.00 $0.00
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44 Zero or blank reference 0d $0.00 $0.00
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45 Sample size (thickness) vs. ramp time vs. delta reflectance 0d $0.00 $0.00
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46 Detection of temperature of cuvette 0d $0.00 $0.00
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47 Develop CORE system for ITC 0d $0.00 $0.00
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48 TEST CUVETTE DESIGN ON CORE SYSTEM WITH LIQUID REAGENTS &
PLASMA 15D $0.00 $0.00
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49 APTT 3w $0.00 $0.00
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50 PT 3w $0.00 $0.00
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Annex I REV.2 Coagulation Tests Development Plan - Confidential Information
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ID TASK NAME TIME RESOURCE DEVELOP. $ BILLED $
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51 Fibrinogen (if std. reagents 2w; if novel reagents add 4w) 3w $ 0.00 $ 0.00
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52 Thrombin time 3w $ 0.00 $ 0.00
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53 DESIGN CUVETTE MANUFACTURING PROCESS - ITC/;BATTELLE 50D $ 0.00 $ 99,000.00
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54 Pilot manufacturing process description/definition - Battelle 0d $ 0.00 $ 0.00
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55 Preliminary cuvette design documents - Battelle 0d ITC $ 0.00 $ 0.00
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56 Preliminary manufacturing process design/layout/capital estimates - ITC 2w ITC $ 0.00 $ 8,000.00
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57 PRELIMINARY COST ESTIMATES 3.75D $ 0.00 $ 3,000.00
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58 5 year forecast - Exigent 0d $ 0.00 $ 0.00
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59 cost estimate - ITC 30h ITC $ 0.00 $ 3,000.00
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60 Design the integration of the cuvette into test cartridge assemble
line - ITC/Battelle 6w BAT $ 0.00 $ 0.00
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61 NOTE: THESE NEXT 2 ITEMS ARE NOT WELL DEFINED, ROUGH ESTIMATE 1d $ 0.00 $ 0.00
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62 Design process equipment - Battelle/ITC ?? 6w ITC $ 0.00 $ 24,000.00
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63 Prepare tooling - Battelle/ITC ?? 10w ITC $ 0.00 $ 40,000.00
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64 Produce test lots (proof of manufacturing equipment) - ITC ?? 6w ITC $ 0.00 $ 24,000.00
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65
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66
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67
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68 FORMULATE COAGULATION REAGENTS IN A DRY FORMAT (4 METHODS) - ITC 190D $248,000.00 $248,000.00
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69 Determine the need for any liquid reagents 2w ITC $ 8,000.00 $ 8,000.00
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70 If so, utilize test cartridge reagent pouch ??? (assume not
necessary, if required then add 12w) 0d ITC $ 0.00 $ 0.00
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71 Formulate and optimize reagent combinations 38w ITC $152,000.00 $152,000.00
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72 Test stabilizers and preservative 10w ITC $ 40,000.00 $ 40,000.00
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73 Define stability and storage conditions - (part of spec.) 0d ITC $ 0.00 $ 0.00
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74 Design calibration procedure - how does the reflection system get
calibrated 4w ITC $ 16,000.00 $ 16,000.00
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75 Design reagent manufacturing process following GMP guidelines 8w ITC $ 32,000.00 $ 32,000.00
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Annex I REV.2 Coagulation Tests Development Plan - Confidential Information
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ID TASK NAME TIME RESOURCE DEVELOP. $ BILLED $
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76
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77
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78
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79 DEVELOP COAGULATION ASSAYS USING DRIED REAGENTS ON CORE SYSTEM - EXIGENT/ITC 25D $0.00 $0.00
------------------------------------------------------------------------------------------------------------------------------------
80 Determine reflectance spectra of clotted and unclotted samples - Exigent 1d $0.00 $0.00
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81 CONFIRM DETECTION ANGLES AND WAVELENGTH(S) - EXIGENT 1D $0.00 $0.00
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82 Complementary with chemistry slides 1d $0.00 $0.00
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83 Evaluate bandwidth - enhance precision, delta R and ramp time 1d $0.00 $0.00
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84 Check interferences 1d $0.00 $0.00
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85 Set algorithm to calculate clotting time - Exigent 1d $0.00 $0.00
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86 Evaluate incubation temperature and time profiles: compare temperature/time
vs. clot time vs. delta R vs. ramp time - Exigent 1d $0.00 $0.00
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87 HYDRATING DRIED REAGENTS (IF REQUIRED ITC/EXIGENT WORK TOGETHER) 25D $0.00 $0.00
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88 Evaluate volumes of sample and/or diluent (if requires diluent, work
with Battelle) 5w $0.00 $0.00
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89 Formulate and optimize diluent (if required) - ITC 5w $0.00 $0.00
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90 AGITATION FORCE AND TIME OD $0.00 $0.00
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91 Preliminary mixing studies - ITC/Battelle/Exigent 3w $0.00 $0.00
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92 Sample size (thickness, depended on the cuvette design) vs. clot time vs. delta
R vs. ramp time - Exigent 1d $0.00 $0.00
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93 Sample types - compare clot time of citrated blood and citrated plasma of same
individuals - Exigent 1d $0.00 $0.00
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94 Establish assay imprecision - Exigent 1d $0.00 $0.00
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95 Method comparison study - Exigent 1d $0.00 $0.00
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96
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97
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98
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99
------------------------------------------------------------------------------------------------------------------------------------
100
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Annex I REV.2 Coagulation Tests Development Plan - Confidential Information
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ID TASK NAME TIME RESOURCE DEVELOP. $ BILLED $
------------------------------------------------------------------------------------------------------------------------------------
101 INSTRUMENT/SOFTWARE CONTROL - EXIGENT/UMM/BATTELLE/ITC 10D $0.00 $0.00
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102 TEMPERATURE CONTROL 37 degrees C+/0.25 degrees C - UMM 1D $0.00 $0.00
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103 Time to reach 37 degrees C - less than 2 min 1d $0.00 $0.00
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104 Verify temperature 1d $0.00 $0.00
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105 Control time of adding plasma and/or reagent into cuvette - Battelle 1d $0.00 $0.00
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106 Control plasma and/or reagent volumes - Battelle 1d $0.00 $0.00
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107 Control mixing (speed and time) - UMM/Battelle 1d $0.00 $0.00
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108 Control light sources and detection angles - UMM 1d $0.00 $0.00
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109 DETERMINE THE CLOT TIME - EXIGENT/ITC 10D $0.00 $0.00
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110 Reference samples - Exigent 1d $0.00 $0.00
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111 Guard interval 2d $0.00 $0.00
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112 Clot formation 3d $0.00 $0.00
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113 Initial and final sensitivity settings 1w $0.00 $0.00
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114 Clot verification 2w $0.00 $0.00
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115 Default settings: minimum and maximum observation times 2w $0.00 $0.00
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116 Test throughput 1d $0.00 $0.00
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117 Detect overfill or underfill of cartridge - Battelle 1d $0.00 $0.00
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118 Detect foaming or air bubbles in sample - Battelle 1d $0.00 $0.00
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119
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120
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121 1d $0.00 $0.00
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122 SAMPLE COLLECTION - EXIGENT 1D $0.00 $0.00
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123 Follow the ITC methods for collecting specimens 1d $0.00 $0.00
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124 Evaluate blood volumes to sodium citrate volumes (10.9-12.9 mmol/L dehydrate
trisodium citrate) vs. clot time vs. delta R vs. ramp xxx 1d $0.00 $0.00
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125 Mixing method 1d $0.00 $0.00
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Annex I REV.2 Coagulation Tests Development Plan - Confidential Information
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ID TASK NAME TIME RESOURCE DEVELOP.$ BILLED $
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126 Evaluate closed tube sampling 1d $0.00 $0.00
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127 Evaluate sample handling, transport temperature, storage and time prior to assay
(cold and glass activation) recovery after storage? 1d $0.00 $0.00
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128 EVALUATE CENTRIFUGE SPEED AND TIME TO OBTAIN PLATELET-FREE CITRATE PLASMA-(WORK
WITH UMM) 1D $0.00 $0.00
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129 Hemolyzed samples-lipidemia, diluted samples, icteric samples 1d $0.00 $0.00
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130 Check and remove clot 1d $0.00 $0.00
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131 EVALUATE CENTRIFUGATION TEMPERATURE (WORK WITH UMM) 1D $0.00 $0.00
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132 Instrument 1d $0.00 $0.00
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133 Blood and citrate plasma stability as RT and 2-8 degreesC (for every assay) 1d $0.00 $0.00
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134 PATIENTS ON HEPARIN/WARFARIN THERAPY (WORK WITH ITC) 1D $0.00 $0.00
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135 Half-life of heparin in blood and plasma 1d $0.00 $0.00
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136 Baseline value (clot time) before therapy 1d $0.00 $0.00
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137 Clot time 1d $0.00 $0.00
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138 Sample drawn through an in-dwelling catheter 1d $0.00 $0.00
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139
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140 QUALITY CONTROL MATERIAL - ITC 60D $0.00 $0.00
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141 FORMULATE/PREPARE NORMAL AND ABNORMAL CONTROLS FOR EVERY ASSAY 60D $0.00 $0.00
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142 DEVELOP 8 PLASMA CONTROLS (4 METHODS *2 CONTROLS) 60D $0.00 $0.00
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143 note: assumes minor modification to existing controls & repackage Od $0.00 $0.00
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144 Negative for HBsAg and antibody to HIV Od $0.00 $0.00
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145 Modification of existing formulation and testing on CORE system 4w $0.00 $0.00
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146 Develop manufacturing documentation following GMP guidelines 3w $0.00 $0.00
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147 manufacturing pilots and scale-up 4w $0.00 $0.00
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148 Establish clot times on mercury system 60d $0.00 $0.00
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149 Preparation, manufacturing and packaging - GMP guidelines 1d $0.00 $0.00
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150 Stability and storage (definition and testing) 10w $0.00 $0.00
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ANNEX I REV.2 COAGULATION TESTS DEVELOPMENT PLAN - CONFIDENTIAL INFORMATION
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ID TASK NAME TIME RESOURCE DEVELOP. $ BILLED $
--------------------------------------------------------------------------------------------------------------------------------
151
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152
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153 IN-HOUSE VALIDATION OF THREE LOTS OF COAGULATION TEST
CARTRIDGE ON "MERCURY" ANALYZER - EXIGENT 10D $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
154 Determine reference intervals and compare to literature values 1d $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
155 PERFORM METHOD COMPARISON STUDY 1D $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
156 vs. SBCL - Ortho kits (MLA-1000) 1d $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
157 vs. ITC 1d $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
158 vs. other reference methods 1d $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
159 DETERMINE INTERFERING SUBSTANCES 1D $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
160 Analytical specificity - hemolyzed, icteric or lipemic specimens,
anticoagulants, aspirin, vitamin K antagonists, estrogen therapy, ? 1d $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
161 Clinical specificity - liver disease, Factor deficiencies etc. 1d $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
162 PERFORM ANALYTICAL AND CLINICAL VALIDATION FOR REGULATORY APPROVAL
FOR INTENDED USE IN HOSPITALS AND AT ALTERNATIVE SITES SUCH 1D $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
163 Physiological or hereditary coagulation abnormalities - hemophilia
and von Willebrand's disease 1d $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
164 Drug induced coagulation abnormalities - warfarin, heparin, Coumadin 1d $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
165 DETERMINE STABILITY AND STORAGE CONDITIONS (WORK WITH ITC) 0.25D $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
166 Sample (blood and Plasma) 2h $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
167 Reagents and test cartridges 2h $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
168 Determine assay imprecision (inter and intra) 2h $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
169 Determine analytical sensitivity and linearity 2d $0.00 $0.00
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170 Determine procedural and diagnostic limitations 1w $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
171 Clinical utility (intended use) 1w $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
172 REPORTING 6D $0.00 $0.00
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173 Clot time to nearest 10th of a second 1d $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
174 International normalized ratio (PT assay) 1w $0.00 $0.00
--------------------------------------------------------------------------------------------------------------------------------
175 International sensitivity index or each lot of PT reagents - ITC 1w $0.00 $0.00
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ANNEX I REV.2 COAGULATION TESTS DEVELOPMENT PLAN - CONFIDENTIAL INFORMATION
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ID TASK NAME TIME RESOURCE DEVELOP. $ BILLED $
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176 Quality control and quality assurance procedure 2w $0.00 $0.00
----------------------------------------------------------------------------------------------------------------------------
177 Calibration procedure 1w $0.00 $0.00
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178 Labeling 1w $0.00 $0.00
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179
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180
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181 Contingency estimate 30w $48,000.00 $74,000.00
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