Exhibit 10.86


 


	
  AWARD/CONTRACT

  	
   

  	
  1
  THIS CONTRACT IS A RATED ORDER UNDER DPAS (15 CFR 700)

  	
   

  	
  RATING

  DO C9

  	
   

  	
  PAGE OF PAGES4

  1       I       29

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  2. CONTRACT (Proc. Inst. Indent.) NO.

  W9113M-10-C-0056

  	
   

  	
  3. EFFECTIVE DATE

      14
  July 2010

  	
  4. REQUISITION/PURCHASE
  REQUEST/PROJECT NO.

    SEE
  SCHEDULE

  
	
   

  	
   

  	
   

  	
   

  
	
  5. ISSUED BY

  	
  CODE

  	
   

  	
  W9113M   

  	
  6. ADMINISTERED BY (If other than Item 5)

  	
  CODE   

  	
   

  	
  S4801A

  
	
   

  	
   

  	
   

  	
   

  
	
  USASMDC/ARSTRAT

  SMDC-RDC-EB

  64 THOMAS JOHNSON DRIVE

  FREDERICK MD 21702

  	
   

  	
  DCM
  SEATTLE

  CORPORATE CAMPUS EAST III

  3009 112TH AVE., NE, SUITE 200

  BELLEVUE WA 98004-8019

  
	
   

  	
   

  
	
  7.
  NAME AND ADDRESS OF CONTRACTOR (No.,
  street, county, State and ZIP Code)

  	
   

  	
  8. DELIVERY

  
	
   

  	
   

  	
   

  
	
  AVIBIOPHARMA, INC.

  	
   

  	
  o  FOB
  ORIGIN         x  OTHER (See below)

  
	
  4575 SW RESEARCH WAY STE 200

  	
   

  	
   

  
	
  CORVALLIS OR 97333-1299

  	
   

  	
  9.  DISCOUNT FOR PROMPT PAYMENT

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
  10.  SUBMIT INVOICES

  	
   

  	
  ITEM

  
	
  CODE 49WU1

  	
  FACILITY CODE

  	
   

  	
  (4
  copies unless otherwise specified) TO THE ADDRESS SHOWN IN

  	
   

  	
  G

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  11.  SHIP TO/MARK FOR

  	
  CODE

  	
   

  	
   

  	
   

  	
  12.  PAYMENT WILL BE MADE BY

  	
   

  	
  CODE

  	
   

  	
  HQ0339

  
	
  See Schedule

  	
   

  	
   

  DFAS-COLUMBUS
  CETER

  DFAS-CO/WEST ENTITLEMENT OPERATION

  PO BOX 182381 COLUMBUS OH 43218-2381

  
	
   

  	
   

  	
   

  
	
  13,  AUTHORITY FOR USING OTHER THAN FULL AND
  OPEN COMPETITION:

  	
   

  	
  14.  ACCOUNTING AND APPROPRIATION DATA

  
	
   

  	
   

  	
   

  
	
  10 U.S.C.
  2304(c) (    )      I      141
  U.S.C. 253(c) (    )

  	
   

  	
  SEE
  SCHEDULE

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  15A. ITEM NO.

  	
   

  	
  1513, SUPPLIES/SERVICES

  	
   

  	
  15C. QUANTITY

  	
   

  	
  15D.UNIT

  	
   

  	
  15E. UNIT PRICE

  	
   

  	
  15F. AMOUNT

  
	
   

  	
   

  	
   

    SEE SCHEDULE

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
  15G. TOTAL AMOUNT
  OF CONTRACT  

  	
   

  	
  $

  	
  80396827.30

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  16. TABLE OF CONTENTS

  
	
   

  	
   

  	
   

  
	
  (X)

  	
   

  	
  SEC.

  	
   

  	
  DESCRIPTION

  	
   

  	
  PAGE(S)

  	
   

  	
  (X)

  	
   

  	
  SEC.

  	
   

  	
  DESCRIPTION

  	
   

  	
  PAGE(S)

  
	
   

  	
   

  	
   

  	
   

  	
  PART I - THE SCHEDULE

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  PART II -
  CONTRACT CLAUSES

  	
   

  	
   

  
	
  X

  	
   

  	
  A

  	
   

  	
  SOLICITATION/CONTRACT
  FORM

  	
   

  	
  1-2

  	
   

  	
  X

  	
   

  	
  I

  	
   

  	
  CONTRACT CLAUSES

  	
   

  	
  21-28

  
	
  X

  	
   

  	
  B

  	
   

  	
  SUPPLIES
  OR SERVICES AND PRICES/COSTS

  	
   

  	
  3-10

  	
   

  	
   

  	
   

  	
  PART III -
  LIST OF DOCUMENTS, EXHIBITS AND OTHER ATTACH.

  
	
  X

  	
   

  	
  C

  	
   

  	
  DESCRIPTION/SPECS./WORK
  STATEMENT

  	
   

  	
  11

  	
   

  	
  X

  	
   

  	
  J

  	
   

  	
  LIST OF ATTACHMENTS

  	
   

  	
  28

  
	
  X

  	
   

  	
  D

  	
   

  	
  PACKAGING
  AND MARKING

  	
   

  	
  12

  	
   

  	
   

  	
   

  	
  PART IV -
  REPRESENTATIONS AND INSTRUCTIONS

  
	
  X

  	
   

  	
  E

  	
   

  	
  INSPECTION
  AND ACCEPTANCE

  	
   

  	
  13

  	
   

  	
   

  	
   

  	
  K

  	
   

  	
  REPRESENTATIONS,
  CERTIFICATIONS AND OTHER STATEMENTS OF OFFERORS

  	
   

  	
   

  
	
  X

  	
   

  	
  F

  	
   

  	
  DELIVERIES
  OR PERFORMANCE

  	
   

  	
  14

  	
   

  	
   

  	
   

  
	
  X

  	
   

  	
  G

  	
   

  	
  CONTRACT
  ADMINISTRATION DATA

  	
   

  	
  15-17

  	
   

  	
   

  	
   

  	
  L

  	
   

  	
  INSTRS., CONDS., AND
  NOTICES TO OFFERORS

  	
   

  	
   

  
	
  X

  	
   

  	
  H

  	
   

  	
  SPECIAL
  CONTRACT REQUIREMENTS

  	
   

  	
  18-20

  	
   

  	
   

  	
   

  	
  M

  	
   

  	
  EVALUATION FACTORS FOR
  AWARD

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  CONTRACTING OFFICER WILL COMPLETE
  ITEM 17 OR 18 AS APPLICABLE

  
	
   

  
	
  17.  x     CONTRACTOR’S
  NEGOTIATED AGREEMENT (Contractor is
  required to sign this document and return 1 copies to issuing office.)  Contractor agrees to furnish and
  deliver all items or perform all the services set forth or otherwise
  identified above and on any continuation sheets for the consideration stated
  herein. The rights and obligations of the parties to this contract shall be
  subject to and governed by the following documents: (a) this
  award/contract, (b) the solicitation, if any, and (c) such
  provisions, representations, certifications, and specifications, as are
  attached or incorporated by  reference herein. (Attachments are listed herein.)

  	
   

  	
  18.  o    AWARD (Contractor is not required to sign this document.)
  Your offer on Solicitation Number W9113M-09-R-0008, including the
  additions or changes made by you which additions or changes are set forth in
  full above, is hereby accepted as to the terms listed above and on any
  continuation sheets. This award consummates the contract which consists of
  the following documents: (a) the Government’s solicitation and your
  offer, and (b) this award/contract. No further contractual document is
  necessary,

  
	
   

  	
   

  	
   

  
	
  19A. NAME AND
  TITLE OF SIGNER.(Type
  or Print)

  	
   

  	
  20A. NAME OF
  CONTRACTING OFFICER

  
	
   

  	
   

  	
   

  
	
  J. David Boyle II

  	
   

  	
   

  
	
  Interim
  President & CEO, SVP & CFO

  	
   

  	
  LYNN M. SELFRIDGE

  
	
   

  	
   

  	
   

  
	
  19A. NAME OF
  CONTRACTOR

  	
   

  	
  19C. DATE SIGNED

  	
   

  	
  20B. UNITED
  STATES OF AMERICA

  	
   

  	
  20 DATE SIGNED

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  BY:

  	
  /s/ J.
  David Boyle II

  	
   

  	
   

  	
  BY:

  	
  /s/ Lynn
  M. Selfridge

  	
   

  
	
  (Signature of person authorized
  to sign)

  	
   

  	
  July 13,
  2010

  	
   

  	
  (Signature of Contracting
  Officer)

  	
   

  	
  July 14 2010

  
	
   

  	
   

  	
   

  
	
  AUTHORIZED FOR
  LOCAL REPRODUCTION

  	
   

  	
  STANDARD FORM 26  (REV. 4/2008)

  
	
  Previous edition
  is usable

  	
   

  	
  Prescribed by GSA — FAR (48 CFR) 53.214(a)

  
																																																													



 






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TREATMENT FILED SEPARATELY WITH THE COMMISSION


 
















 


Section A - Solicitation/Contract Form


 


SECTION A


CONTINUATION OF FORM 26


 


Award is hereby made for the Advanced Development through licensure of
a Hemorrhagic Fever Virus Therapeutic.


 


The AVI Biopharma Inc. proposal dated 1/30/2010 and as revised on 3/11/2010
and 4/30/2010, is incorporated into contract No. W9113M-10-C-0056 in its
entirety with the following revisions:


 


1.               Section G has been
revised to include local WAWF clause to include the type and codes required for
payment purposes.


 


2.     Section H has been revised to include paragraphs H. 6,
requirements from the RFP at Section M.3.4 Post-Award Evaluations of
Contractors’ Performance and Down-Select Criteria.


 


3.     The following clauses are hereby added to Section I by
reference:


 


52.215-16 Facilities Capital Cost of Money (June 2003)


 


252.204-7008 Export Controlled Items (April 2010)


 


4.  The following clauses are hereby deleted from Section I:


 


52.232-25 Prompt Payment OCT 2008


 


5.  The following clause in Section I is hereby revised to remove
the last sentence: 52.217-7 Option for Increased quantity — Separately Priced
Line Item (MAR 1989)


 


6.  The AVI proposed IMS dates take precedence over any inconsistencies
contained within the SOW Attached in Section J, Attachments 1 and 2.


 


7.  CLINs 0001 through 0004 referenced in AVI SOW, Section J.
Attachment 2, are revised to read CLIN 0005 through 0008, respectively.


 


8.  As noted in Government Statement of Objectives Section 5.7, as
a condition of submitting a proposal under the solicitation W9113M-09-R-0008,
AVI agrees to the no cost termination, under FAR 52.249-6 of their current
Government contract, HDTRA1-07-C-0010, CLINs 000301, 000302, and 000303 only
for the performing efforts related to any or both of these products as a
condition of the award of this contract.


 






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TREATMENT FILED SEPARATELY WITH THE COMMISSION


 


2

















 


Section B - Supplies or Services and Prices


 


	
  ITEM NO

  	
   

  	
  SUPPLIES/SERVICES QUANTITY

  	
   

  	
  UNIT

  	
   

  	
  UNIT PRICE

  	
   

  	
  AMOUNT

  
	
  0001

  	
   

  	
   

  	
   

  	
  Lot

  	
   

  	
   

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  Advanced Development of Hemorrhagic

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  CPIF

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Fever virus Therapeutic - Ebola Virus. Delivery of the developmental
  therapeutic end item that has successfully achieved all activities associated
  with completing FDA [+] Clinical Trials exclusive of those required to
  achieve Technology Readiness Level 4, to include Pre-IND, IND, and Phase
  1 [+] Clinical Studies, including Management, Regulatory Affairs, all FDA
  submissions and official program reporting requirements (to include [+] if
  required) in accordance with the Contractor’s Statement of Work (SOW), dated
  3/11/10, Attachment 1 of Section J. (Note:  maturity level of candidate receiving award
  will determine the specific activities awarded.) Reporting requirements are
  delineated in Contract Data Requirements List DD Form 1423, attached as
  Exhibits A001 through A006 in Section J.

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  FOB: Destination

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  TARGET COST

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TARGET FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TOTAL TGT COST + FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MINIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MAXIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  SHARE RATIO ABOVE TARGET

  	
   

  	
  [+]

  
	
   

  	
   

  	
  SHARE RATIO BELOW TARGET

  	
   

  	
  [+]

  



 






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  ITEM NO

  	
   

  	
  SUPPLIES/SERVICES QUANTITY

  	
   

  	
  UNIT

  	
   

  	
  UNIT PRICE

  	
   

  	
  AMOUNT

  
	
  000101

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  Funding for CLIN 0001

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  CPIF

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  FOB: Destination

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  TARGET COST

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TARGET FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TOTAL TGT COST + FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MINIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MAXIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  SHARE RATIO ABOVE TARGET

  	
   

  	
   

  
	
   

  	
   

  	
  SHARE RATIO BELOW TARGET

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  ACRN AA

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  CIN: 000000000000000000000000000000

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  ITEM NO

  	
   

  	
  SUPPLIES/SERVICES QUANTITY

  	
   

  	
  UNIT

  	
   

  	
  UNIT PRICE

  	
   

  	
  AMOUNT

  
	
  0002

  	
   

  	
   

  	
   

  	
  Lot

  	
   

  	
   

  	
   

  	
  $[+]

  
	
  OPTION

  	
   

  	
  Advanced Development of Hemorrhagic

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  CPIF

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Fever Virus Therapeutic - Ebola Virus. Delivery of the developmental
  therapeutic end item that has successfully achieved [+]. This line item
  includes all associated Management, Regulatory Affairs, FDA submissions and
  Official program reporting requirements (to include [+] if required) in
  accordance with the Contractor’s Statement of Work (SOW), dated 3/11/10,
  Attachment 1 of Section J. Reporting requirements are delineated in
  Contract Data Requirements List DD Form 1423, attached as Exhibits A001
  through A006 in Section J.

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  FOB: Destination

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  TARGET COST

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TARGET FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TOTAL TGT COST + FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MINIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MAXIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  SHARE RATIO ABOVE TARGET

  	
   

  	
  [+]

  
	
   

  	
   

  	
  SHARE RATIO BELOW TARGET

  	
   

  	
  [+]

  



 






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DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT FILED SEPARATELY WITH THE COMMISSION


 


4

















 


	
  ITEM NO

  	
   

  	
  SUPPLIES/SERVICES QUANTITY

  	
   

  	
  UNIT

  	
   

  	
  UNIT PRICE

  	
   

  	
  AMOUNT

  
	
  0003

  	
   

  	
   

  	
   

  	
  Lot

  	
   

  	
   

  	
   

  	
  $[+]

  
	
  OPTION

  	
   

  	
  Advanced Development of
  Hemorrhagic

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  CPIF

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Fever Virus Therapeutic - Ebola Virus. Delivery of the developmental
  therapeutic end item that has successfully achieved [+] Clinical Studies.
  This line item includes all associated Management, Regulatory Affairs, FDA submissions
  and Official program reporting requirements (to include [+] if required). in
  accordance with the Contractor’s Statement of Work (SOW), dated (insert upon
  award), Attachment 1 of Section J. Reporting requirements are delineated
  in Contract Data Requirements List DD Form 1423, attached as Exhibits
  A001 through A006 in Section J.

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  FOB: Destination

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  TARGET COST

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TARGET FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TOTAL TGT COST + FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MINIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MAXIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  SHARE RATIO ABOVE TARGET

  	
   

  	
  [+]

  
	
   

  	
   

  	
  SHARE RATIO BELOW TARGET

  	
   

  	
  [+]

  



 






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DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT FILED SEPARATELY WITH THE COMMISSION


 


5

















 


	
  ITEM NO

  	
   

  	
  SUPPLIES/SERVICES QUANTITY

  	
   

  	
  UNIT

  	
   

  	
  UNIT PRICE

  	
   

  	
  AMOUNT

  
	
  0004

  	
   

  	
   

  	
   

  	
  Lot

  	
   

  	
   

  	
   

  	
  $[+]

  
	
  OPTION

  	
   

  	
  Advanced Development of Hemorrhagic

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  CPIF

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Fever Virus Therapeutic - Ebola Virus. New Drug Application and
  delivery of FDA licensed developmental therapeutic end item to include all
  New Drug Application and Licensure activities resulting in the delivery of at
  least [+] of an FDA approved therapeutic. This line item includes all
  associated Management, Regulatory Affairs, FDA submissions and Official
  program reporting requirements (to include [+] if required), in accordance
  with the Contractor’s Statement of Work (SOW), dated 3/11/10, Attachment 1 of
  Section J. Reporting requirements are delineated in Contract Data
  Requirements List DD Form 1423, attached as Exhibits A001 through A006
  in Section J.

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  FOB: Destination

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  TARGET COST

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TARGET FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TOTAL TGT COST + FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MINIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MAXIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  SHARE RATIO ABOVE TARGET

  	
   

  	
  [+]

  
	
   

  	
   

  	
  SHARE RATIO BELOW TARGET

  	
   

  	
  [+]

  



 






+           DESIGNATES PORTIONS OF THIS
DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT FILED SEPARATELY WITH THE COMMISSION


 


6
















 


	
  ITEM NO

  	
   

  	
  SUPPLIES/SERVICES QUANTITY

  	
   

  	
  UNIT

  	
   

  	
  UNIT PRICE

  	
   

  	
  AMOUNT

  
	
  0005

  	
   

  	
   

  	
   

  	
  Lot

  	
   

  	
   

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  Advanced Development of Hemorrhagic

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  CPIF

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Fever Virus Therapeutic - Marburg Virus. Delivery of the
  developmental therapeutic end item that has successfully achieved all
  activities associated with completing FDA [+] Clinical Trials exclusive of
  those required to achieve Technology Readiness Level 4, to include Pre-IND,
  IND, and Phase 1 [+] Clinical Studies, including Management, Regulatory
  Affairs, all FDA submissions and official program reporting requirements (to
  include [+] if required) in accordance with the Contractor’s Statement of
  Work (SOW), dated 3/11/10, Attachment 2 of Section J. (Note: maturity level
  of candidate receiving award will determine the specific activities awarded.)
  Reporting requirements are delineated in Contract Data Requirements List DD
  Form 1423, attached as Exhibits A001 through A006 in Section J.

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  FOB: Destination

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  TARGET COST

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TARGET FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TOTAL TGT COST + FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MINIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MAXIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  SHARE RATIO ABOVE TARGET

  	
   

  	
  [+]

  
	
   

  	
   

  	
  SHARE RATIO BELOW TARGET

  	
   

  	
  [+]

  



 






+           DESIGNATES PORTIONS OF THIS
DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT FILED SEPARATELY WITH THE COMMISSION


 


7

















 


	
  ITEM NO

  	
   

  	
  SUPPLIES/SERVICES QUANTITY

  	
   

  	
  UNIT

  	
   

  	
  UNIT PRICE

  	
   

  	
  AMOUNT

  
	
  000501

  	
   

  	
   

  	
   

  	
  Lot

  	
   

  	
   

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  Funding for CLIN 0005

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  CPIF

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  FOB: Destination

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  TARGET COST

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TARGET FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TOTAL TGT COST + FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MINIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MAXIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  SHARE RATIO ABOVE TARGET

  	
   

  	
   

  
	
   

  	
   

  	
  SHARE RATIO BELOW TARGET

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  ACRN AB

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $[+]

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  CIN: 000000000000000000000000000000

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  ITEM NO

  	
   

  	
  SUPPLIES/SERVICES QUANTITY

  	
   

  	
  UNIT

  	
   

  	
  UNIT PRICE

  	
   

  	
  AMOUNT

  
	
  0006

  	
   

  	
   

  	
   

  	
  Lot

  	
   

  	
   

  	
   

  	
  $[+]

  
	
  OPTION

  	
   

  	
  Advanced Development of Hemorrhagic

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  CPIF

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Fever Virus Therapeutic - Marburg Virus. Delivery of the
  developmental therapeutic end item that has successfully achieved [+]. This
  line item includes all associated Management, Regulatory Affairs, FDA
  submissions and Official program reporting requirements (to include [+] if required).
  in accordance with the Contractor’s Statement of Work (SOW), dated 3/11/10,
  Attachment 2 of Section J. Reporting requirements are delineated in Contract
  Data Requirements List DD Form 1423, attached as Exhibits A001 through A006
  in Section J.

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  FOB: Destination

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  TARGET COST

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TARGET FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TOTAL TGT COST + FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MINIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MAXIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  SHARE RATIO ABOVE TARGET

  	
   

  	
  [+]

  
	
   

  	
   

  	
  SHARE RATIO BELOW TARGET

  	
   

  	
  [+]

  



 






+           DESIGNATES PORTIONS OF THIS
DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT FILED SEPARATELY WITH THE COMMISSION


 


8

















 


	
  ITEM NO

  	
   

  	
  SUPPLIES/SERVICES QUANTITY

  	
   

  	
  UNIT

  	
   

  	
  UNIT PRICE

  	
   

  	
  AMOUNT

  
	
  0007

  	
   

  	
   

  	
   

  	
  Lot

  	
   

  	
   

  	
   

  	
  $[+]

  
	
  OPTION

  	
   

  	
  Advanced Development of Hemorrhagic

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  CPIF

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Fever Virus Therapeutic - Marburg Virus. Delivery of the
  developmental therapeutic end item that has successfully achieved [+]
  Clinical Studies. This line item includes all associated Management,
  Regulatory Affairs, FDA submissions and Official program reporting
  requirements (to include [+] if required). in accordance with the
  Contractor’s Statement of Work (SOW), dated 3/11/10, Attachment 2 of Section
  J. Reporting requirements are delineated in Contract Data Requirements List
  DD Form 1423, attached as Exhibits A001 through A006 in Section J.

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  FOB: Destination

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  TARGET COST

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TARGET FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TOTAL TGT COST + FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MINIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MAXIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  SHARE RATIO ABOVE TARGET

  	
   

  	
  [+]

  
	
   

  	
   

  	
  SHARE RATIO BELOW TARGET

  	
   

  	
  [+]

  



 






+           DESIGNATES PORTIONS OF THIS
DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT FILED SEPARATELY WITH THE COMMISSION


 


9

















 


	
  ITEM NO

  	
   

  	
  SUPPLIES/SERVICES QUANTITY

  	
   

  	
  UNIT

  	
   

  	
  UNIT PRICE

  	
   

  	
  AMOUNT

  
	
  0008

  	
   

  	
   

  	
   

  	
  Lot

  	
   

  	
   

  	
   

  	
  $[+]

  
	
  OPTION

  	
   

  	
  Advanced Development of Hemorrhagic

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  CPIF

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Fever Virus Therapeutic - Marburg Virus. New Drug Application and
  delivery of FDA licensed developmental therapeutic end item to include all
  New Drug Application and Licensure activities resulting in the delivery of at
  least [+] of an FDA approved therapeutic. This line item includes all associated
  Management, Regulatory Affairs, FDA submissions and Official program
  reporting requirements (to include [+] if required), in accordance with the
  Contractor’s Statement of Work (SOW), dated 3/11/10, Attachment 2 of Section
  J. Reporting requirements are delineated in Contract Data Requirements List
  DD Form 1423, attached as Exhibits A001 through A006 in Section J.

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  FOB: Destination

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  TARGET COST

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TARGET FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  TOTAL TGT COST + FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MINIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  MAXIMUM FEE

  	
   

  	
  $[+]

  
	
   

  	
   

  	
  SHARE RATIO ABOVE TARGET

  	
   

  	
  [+]

  
	
   

  	
   

  	
  SHARE RATIO BELOW TARGET

  	
   

  	
  [+]

  



 






+           DESIGNATES PORTIONS OF THIS
DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT FILED SEPARATELY WITH THE COMMISSION


 


10

















 


Section C - Descriptions and Specifications


 


SECTION C


Contractor’s Statement of Work, dated 3/11/10, Attachment 1 and 2,
Section J.


 






+           DESIGNATES PORTIONS OF THIS
DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT FILED SEPARATELY WITH THE COMMISSION


 


11

















 


Section D - Packaging and Marking


 


SECTION D


Packaging and Marking shall be in accordance with FDA regulations as
described in Contractor’s Statement of Work, dated 3/11/10, Attachment 1and 2
in Section J.


 






+           DESIGNATES PORTIONS OF THIS
DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT FILED SEPARATELY WITH THE COMMISSION


 


12
















 


Section E - Inspection and Acceptance


 


INSPECTION AND ACCEPTANCE TERMS


 


Supplies/services will be inspected/accepted at:


 


	
  CLIN

  	
   

  	
  INSPECT AT

  	
   

  	
  INSPECT BY

  	
   

  	
  ACCEPT AT

  	
   

  	
  ACCEPT BY

  
	
  0001

  	
   

  	
  Destination

  	
   

  	
  Government

  	
   

  	
  Destination

  	
   

  	
  Government

  
	
  000101

  	
   

  	
  N/A

  	
   

  	
  N/A

  	
   

  	
  N/A

  	
   

  	
  Government

  
	
  0002

  	
   

  	
  Destination

  	
   

  	
  Government

  	
   

  	
  Destination

  	
   

  	
  Government

  
	
  0003

  	
   

  	
  Destination

  	
   

  	
  Government

  	
   

  	
  Destination

  	
   

  	
  Government

  
	
  0004

  	
   

  	
  Destination

  	
   

  	
  Government

  	
   

  	
  Destination

  	
   

  	
  Government

  
	
  0005

  	
   

  	
  Destination

  	
   

  	
  Government

  	
   

  	
  Destination

  	
   

  	
  Government

  
	
  000501

  	
   

  	
  N/A

  	
   

  	
  N/A

  	
   

  	
  N/A

  	
   

  	
  Government

  
	
  0006

  	
   

  	
  Destination

  	
   

  	
  Government

  	
   

  	
  Destination

  	
   

  	
  Government

  
	
  0007

  	
   

  	
  Destination

  	
   

  	
  Government

  	
   

  	
  Destination

  	
   

  	
  Government

  
	
  0008

  	
   

  	
  Destination

  	
   

  	
  Government

  	
   

  	
  Destination

  	
   

  	
  Government

  



 


CLAUSES INCORPORATED BY REFERENCE


 


	
  52.246-8

  	
   

  	
  Inspection Of Research And Development Cost Reimbursement

  	
   

  	
  MAY 2001

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  52.246-16

  	
   

  	
  Responsibility For Supplies

  	
   

  	
  APR 1984

  



 


CLAUSES INCORPORATED BY FULL TEXT


 


52.246-11 HIGHER-LEVEL CONTRACT QUALITY (FEB 1999)


 


The Contractor shall comply with the higher-level quality standard
selected below. (If more than one standard is listed, the offeror shall
indicate its selection by checking the appropriate block.)


 


	
  Title

  	
   

  	
  Number

  	
   

  	
  Date

  	
   

  	
  Tailoring

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  



 


ISO 9001/2000 or higher;


X              Quality System in compliance with FDA quality
requirements


 


(End of clause)


 






+    DESIGNATES PORTIONS OF THIS DOCUMENT THAT
HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED
SEPARATELY WITH THE COMMISSION


 


13

















 


Section F - Deliveries or Performance


 


DELIVERY INFORMATION


 


	
  CLIN

  	
   

  	
  DELIVERY DATE

  	
   

  	
  QUANTITY

  	
   

  	
  SHIP TO ADDRESS

  	
   

  	
  UIC

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  0001

  	
   

  	
  25-MAR-2012

  	
   

  	
  Lot

  	
   

  	
  Transformational Medical Technologies Initiative Defense Threat
  Reduction Agency

  8725 John J. Kingman Road, stop 6201

  Fort Belvoir, VA, 22060-6201

  FOB: Destination

  	
   

  	
  HDTRA1

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  000101

  	
   

  	
  N/A

  	
   

  	
  N/A

  	
   

  	
  N/A

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  0002

  	
   

  	
  09-FEB-2015

  	
   

  	
  Lot

  	
   

  	
  Same As Above

  FOB: Destination

  	
   

  	
  HDTRA1

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  0003

  	
   

  	
  08-NOV-2015

  	
   

  	
  Lot

  	
   

  	
  Same As Above

  FOB: Destination

  	
   

  	
  HDTRA1

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  0004

  	
   

  	
  07-SEP-2016

  	
   

  	
  Lot

  	
   

  	
  Same As Above

  FOB: Destination

  	
   

  	
  HDTRA1

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  0005

  	
   

  	
  01-APR-2012

  	
   

  	
  Lot

  	
   

  	
  Same As Above

  FOB: Destination

  	
   

  	
  HDTRA1

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  000501

  	
   

  	
  N/A

  	
   

  	
  N/A

  	
   

  	
  N/A

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  0006

  	
   

  	
  09-FEB-2015

  	
   

  	
  Lot

  	
   

  	
  Same As Above

  FOB: Destination

  	
   

  	
  HDTRA1

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  0007

  	
   

  	
  08-NOV-2015

  	
   

  	
  Lot

  	
   

  	
  Same As Above

  FOB: Destination

  	
   

  	
  HDTRA1

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  0008

  	
   

  	
  07-SEP-2016

  	
   

  	
  Lot

  	
   

  	
  Same As Above

  FOB: Destination

  	
   

  	
  HDTRA1

  



 


CLAUSES INCORPORATED BY REFERENCE


 


	
  52.242-15 Alt I

  	
   

  	
  Stop-Work Order (Aug 1989) - Alternate I

  	
   

  	
  APR 1984

  
	
  52.247-34

  	
   

  	
  F.O.B. Destination

  	
   

  	
  NOV 1991

  



 






+           DESIGNATES PORTIONS OF THIS
DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT FILED SEPARATELY WITH THE COMMISSION


 


14

















 


Section G - Contract Administration Data


 


SECTION G 


PAYMENTS:


 


Detailed Copies of all payment requests will be provided electronically
to the Government points of contact listed below at the same time of submission
to WAWF:


 


Contracting Office:


 


USASMDC


Attn: SMDC-RDC-EB/S. O’Connell 64 Thomas Johnson Drive


Frederick, MD 21702


Telephone: 301-619-2895


Fax: 301-619-5069


Email: sandra.oconnell@us.army.mil


 


Contracting Officers Representative (COR):


 


CLINS 0001-0004


John Anderson


8725 John J. Kingman Road, stop 6201

Fort Belvoir, VA 22060-6201


Telephone: (703)767-2908


Email: John.anderson@dtra.mil


 


CLINS 0005-0008

Adekunle Famodu

8725 John J. Kingman Road, stop 6201


Fort Belvoir, VA 22060-6201


Telephone: (703)767-7935


Email: Adekunle.famodu@dtra.mil


 


ACCOUNTING AND APPROPRIATION DATA


 


AA: 970040026TM5YTMW61D255999BD33800000S49012 DODAAC: HD1115


AMOUNT: $[+]


CIN 000000000000000000000000000000: $[+]


 


ACCOUNTING AND APPROPRIATION DATA


 


AB: 970040026TM5YTMW61D255999BD337801000S49012 DODAAC: HD1115


AMOUNT: $[+]


CIN 000000000000000000000000000000: $[+]


 


CLAUSES INCORPORATED BY REFERENCE


 






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DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT FILED SEPARATELY WITH THE COMMISSION


 


15

















 


	
  252.201-7000

  	
   

  	
  Contracting Officer’s Representative

  	
   

  	
  DEC 1991

  



 


CLAUSES INCORPORATED BY FULL TEXT


 


INVOICING INSTRUCTIONS


 


a.  The contractor shall submit payment request electronically in
accordance with DFARS 252.232-7003 utilizing Wide Area Work Flow (WAWF). The
WAWF application allows DOD vendors to submit and track invoices and
receipt/acceptance documents electronically. The contractor shall register with
WAWF at https://wawf.eb.mil and ensure an electronic business point of contract
(POC) is designated in the Central Contractor Registration site at
http://www.ccr.gov within ten (10) days after award of this contract. Payments
made under this contract shall be via Electronic Funds Transfer (EFT) and shall
be based on the EFT information contained in the Central Contractor Registration
(CCR) database. The contractor shall ensure that its EFT information in the CCR
database remains current and correct.


 


b. Multiple pricing structures may be utilized for this contract or, if
a task ordering contract, for individual task orders issued thereunder. In
order to ensure the successful flow of WAWF documents, the type of payment
request submitted shall be based on the following as applicable:


 


o            Invoice and Receiving Report (COMBO): applicable to
Firm-Fixed-Price (FFP) contracts/task orders that include the delivery of
supplies/hardware.


 


o            Invoice as 2-in-1: applicable to Labor Hour
and FFP contracts/task orders for services only.


 


x           Cost Voucher: applicable to Time and
Material (T&M) and Cost-Reimbursement type contracts/task orders.


 


o            Construction Invoice: applicable to
contracts/task orders for construction.


 


c.  WAWF requires the following
data for each payment request: (To be
provided by the Government. If a task ordering contract, each awarded task
order shall identify this information)


 


Contract/Task Order Data


 


Contractor CAGE Code: 49WU1

Issue by DODAAC: W9113M

Admin by DODAAC: S4801A

Inspect by DODAAC: S4801A

Accept by DODAAC: S4801A

Ship to DODAAC: HD1115

Payment by DODAAC: HQ0339


 


Email Points of Contact Listing


 


Inspector: TBD


Acceptor: TBD


Contracting Specialist: sandra.oconnell@us.army.mil


Contracting Officer:


Contracting Officer’s Technical Representative: John.anderson@dtra.mil
(CLINs 1-4)

Adekunle.famodu@dtra.mil (CLINs 5-8)


 






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d. Questions concerning payments shall be directed to the Defense
Finance and Accounting Service (DFAS). The appropriate DFAS office is
indentified in the “PAYMENT WILL BE MADE BY” block on the contract award
coversheet. Please have your contract and, if applicable, task order number
ready when calling about payments. Payment and receipt information may be
accessed using the DFAS web site MyInvoice. MyInvoice is a web-based
application developed specifically for contractors/vendors and Government/
Military employees to obtain invoice status. It is an interactive web-based
system, accessible 24/7. Users must allow pop-up messages within this system.
Your contract and, if applicable, task order number or invoice number will be
required to inquire about the status of your payment. For additional
information, see the MyInvoice website at https://myinvoice.csd.disa.mil/ or
visit http://www.dfas.mil/contractorpay/ electroniccommerce/myinvoice.html.


 


e.  The contractor may submit requests for payment through WAWF not
more frequently than monthly (or bi-weekly if a small business).


 


f.  For Labor Hour and T&M contracts/task orders, payment requests
for labor shall be based on the total labor hours/DPPH expended thereunder for
the applicable billing period. These labor charges shall be derived by applying
the total hours expended for each labor category multiplied by the applicable
fixed-labor rates specified in the contract/task order. Labor charges for
cost-reimbursement contracts/task orders shall be based on the total hours
expended for each labor category multiplied by actual direct labor rates plus
applicable indirect burdens and fee. Travel and ODC/material under T&M and
Cost-Reimbursement type contracts/task orders shall be billed at actual costs.
For each payment request, the contractor shall attach/upload into WAWF
sufficient documentation as to how the billed amounts were derived/calculated.


 


g. For Firm-Fixed-Price contracts/task orders, payments on the total
contract price (excluding any unexercised options) may be requested in equal
monthly (or bi-weekly if a small business) amounts calculated over the life of
the contract/task order unless alternative payment schedules (e.g.,
performance-based payments) are specified elsewhere in the contract, or if
applicable, in individual task orders.


 


h. For each payment request, the contractor shall maintain sufficient
documentation to substantiate the submitted charges. Such documentation shall
include evidence of actual expenditures/payment such as individual daily job timecards,
subcontractor/vendor invoices and payment receipts, or other substantiation
specified by the Contracting Officer. Such data shall be maintained and readily
available for audit purposes, but shall not be included with the WAWF
submission. The contractor shall provide such documentation within 7 days of
request by the Procuring Contracting Officer, Administrative Contracting
Officer, or DCAA auditor.


 


i.   The contractor shall ensure that each payment request submitted in
WAWF denotes that the Contracting Officer and Contract Specialist will receive
a copy of the payment request notice.


 


j.   Except for FFP contracts/task orders, the contractor and each
assignee under an assignment entered into under this contract or, if
applicable, an individual task order and in effect at the time of final payment
on this contract or, if applicable, an individual task order issued under this
contract, shall execute and deliver, at the time of and as a condition
precedent to, any final payment thereunder, a release discharging the
Government, its officers, agents, and employees, of and from all liabilities,
obligations, and claims arising out of, or under, the specific contract/task
order. These closing documents shall be submitted with the final payment
request.


 


k.  The contractor shall submit final payment requests for Labor Hour
and FFP contracts/task orders within 120 days (or longer if approved in writing
by the Contracting Officer) after contract/order completion. For T&M or
Cost-Reimbursement type contracts/task orders, the contractor shall prepare a
final payment request within 120 days (or longer if approved in writing by the
Contracting Officer) after settlement of the final annual indirect cost rates
to reflect the settled amounts and rates for the performance period covered.
The cognizant DCAA shall perform a final audit on the contractor’s final
payment request to determine allowable costs. The Administrative Contracting
Officer may utilize the cumulative allowable worksheets included with the DCAA
incurred cost audit reports in lieu of


 






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17

















 


requesting DCAA to perform the final closeout audit to determine the
final costs on the cost reimbursable portions of the contract/task order.


 






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Section H - Special Contract Requirements


 


SECTION H


 


H. 1 SECURITY CONSIDERATIONS


 


At this time, there are no anticipated classified
materials or performance required for this acquisition. However, if mandated by
a program and/or contractual requirements in the future, the selected
contractor(s) may need to have a Facility Security Clearance and Personnel
Security Clearances to maintain a safeguarding capability through SECRET
clearance level in accordance with the Industrial Security Regulation, DoD
5220.22-R and the National Industrial Security Program Operating Manual, DoD
5220.22-M. Following contract award, should classified information be required,
it will be safeguarded in accordance with these documents, including submission
of a DD Form 254 and Government generation of a Security Classification
Guide. The contractor(s) will receive routine Government audits of their
industrial security management system to ensure adequate security safeguards
have been established and maintained. The Government’s assigned Industrial
Security Representative will determine the frequency of such formal reviews,
but a review will normally be conducted on an annual basis.


 


Although not anticipated at this time, should
performance of the contract(s) require physical access to a
Federally-controlled facility, the contractor(s) shall comply with the
Office of Management and Budget Guidance M-05-24, dated August 5, 2005, Implementation
of Homeland Security Presidential Directive 12-Policy for a Common
Identification Standard for Federal Employees and Contractors. The Government
will coordinate all actions necessary for access to a Federally-controlled
facility to ensure proper and only essential access is provided to the
contractor(s).


 


Ebola and Marburg viruses are category A select
agents as classified by the CDC and require BSL-4 containment facilities.
Therefore, this contract will involve access to Biological Select Agents and
Toxins (BSAT). The Contractors will be required to certify they are registered
in accordance with Federal, State, and local regulations, including with the
CDC and the Animal and Plant Health Inspection Service. The Contractor will be
required to comply with DoD Directive 5210.88, Safeguarding Biological Select
Agents and Toxins; DoDI 5210.89, Minimum Security Standards for Safeguarding
Biological Select Agents and Toxins; Army Regulation (AR) 50-1, Biological
Surety; and AR 190-17, Biological Select Agents and Toxins Security Program;
and AR 190-51, Army Physical Security Program.


 


The HFV Class will not generate or require the
use of classified information or classified material of any kind. The data
generated in the projects would be considered “unclassified controlled
information” at best. The Contractor must meet the requirements for working
with unclassified controlled information set forth by DoDD 5200.1.


 


The Contractor will comply with DoDD 5200.1 Appendix
C in the marking of all documents and media items, safeguarding of all information,
accessing of all information, storage of all project data, reproduction and
disposal of all information, handling and transport of all information,
management of the Information Security Program, and limited control and
distribution of some project documents.


 






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H.2 TEST AND EVALUATION


 


The HFV Class of Therapeutics will be developed
in full accordance with FDA regulations and guidelines established by CFR 21,
the Pure Food and Drug Act. The FDA mandates test and evaluation processes that
follow a series of phases that establish the effectiveness and safety of new
drugs. The FDA issues extensive mandatory guidance and requires submission of
substantive evidence for FDA review. Only after FDA approval can work proceed
from one phase to the next. The FDA process is mandatory for licensure. The
Government will utilize the Contractor’s validated information and FDA process
documentation in evaluating progress and conformance with TPP Guidelines.


 


H.3.       PROHIBITION OF USE OF LABORATORY ANIMALS

Information and guidance is provided at the following web site:

https://mrmc.amedd.army.mil/index.cfm?pageid=research_protections.acuro


 


https://mrmc.amedd.army.mil/rodorpaurd.asp


 


** PROHIBITION — READ
FURTHER FOR DETAILS **


 


Notwithstanding any other provisions contained in this award or
incorporated by reference herein, the recipient is expressly forbidden to use
or subcontract for the use of laboratory animals in any manner whatsoever
without the express written approval of the US Army Medical Research and
Materiel Command, Animal Care and Use Office. You will receive written approval
to begin research under the applicable protocol proposed for this award from
the US Army Medical Research and Materiel Command, Animal Care and Use Office
under separate letter to the recipient and Principal Investigator. A copy of
this approval will be provided to the US Army Space and Missile Defense Command
for the official file. Non-compliance with any provision of this clause may
result in the termination of the award.


 


H.4.       PROHIBITION OF USE OF HUMAN SUBJECTS

Information and guidance is provided at the following web site:


 


https://mrmc.amedd.army.mil/rodorphrpo.asp


 


** PROHIBITION — READ
FURTHER FOR DETAILS **


 


Research under this award involving the use of human subjects may not
begin until the U.S. Army Medical Research and Materiel Command’s Office of
Research Protections, Human Research Protections Office (HRPO) approves the
protocol. Written approval to begin research or subcontract for the use of
human subjects under the applicable protocol proposed for this award will be
issued from the US Army Medical Research and Materiel Command, HRPO, under
separate letter to the funded institution and the Principal Investigator. A
copy of this approval will be provided to the US Army Space and Missile Defense
Command for the official file. Non-compliance with any provision of this clause
may result in withholding of funds and or the termination of the award.


 






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H.5. PROHIBITION OF USE OF HUMAN ANATOMICAL SUBSTANCES

Information and guidance is provided at the following web site:


 


https://mrmc.amedd.army.mil/rodorphrpo.asp


 


** PROHIBITION — READ FURTHER
FOR DETAILS**


 


Research at funded institutions using human anatomical substances may
not begin until the U.S. Army Medical Research and Materiel Command’s Office of
Research Protections, Human Research Protections Office (HRPO) approves the
protocol. Written approval to begin research or subcontract for the use of
human anatomical substances under the applicable protocol proposed for this
award will be issued from the US Army Medical Research and Materiel Command,
HRPO, under separate letter to the funded institution and the Principal
Investigator. A copy of this approval will be provided to the US Army Space and
Missile Defense Command for the official file. Non-compliance with any
provision of this clause may result in withholding of funds and or the
termination of the award.


 


H.6 Post-Award Evaluations of Contractors’ Performance
and Down-Select Criteria


 


H.6.1 This acquisition provides
that Contractors with products that fail in development or in default of
contract requirements will not be continued by option exercise (if not
defaulted sooner).


 


H.6.2 All other performing
Contractors will not be denied the opportunity to continue performance under an
option clause by the Government’s decision to exercise or not exercise an
option, or otherwise, absent a best value comparative evaluation using
established RFP evaluation criteria. The criteria shall include, but not be
limited to, post-award performance, the Government’s preference to avoid
therapeutics addressing duplicative indications and the Anti-Viral TPP
Guidelines. Trade-offs can be considered at down-select points in the
evaluation of each candidate against the evaluation criteria. The Government’s
right to unilaterally decide not to exercise all options and to discontinue the
development of all HFV therapeutics is paramount.


 


H.6.3 In the event a best value
comparative evaluation becomes necessary or is desired at a down-select point,
selection shall be based on evaluation of the contractors’ actual post-award
contract performance against evaluation criteria established in the RFP to
include the Anti-Viral TPP Guidelines and the Government’s preference to avoid
therapeutics addressing duplicative indications.


 


CLAUSES INCORPORATED BY REFERENCE


 


	
  252.234-7002

  	
   

  	
  Earned Value Management System

  	
   

  	
  APR 2008

  



 






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21

















 


Section I - Contract Clauses


 


CLAUSES INCORPORATED BY REFERENCE


 


	
  52.202-1

  	
   

  	
  Definitions

  	
   

  	
  JUL 2004

  
	
  52.203-3

  	
   

  	
  Gratuities

  	
   

  	
  APR 1984

  
	
  52.203-5

  	
   

  	
  Covenant Against Contingent Fees

  	
   

  	
  APR 1984

  
	
  52.203-6

  	
   

  	
  Restrictions On Subcontractor Sales To The Government

  	
   

  	
  SEP 2006

  
	
  52.203-7

  	
   

  	
  Anti-Kickback Procedures

  	
   

  	
  JUL 1995

  
	
  52.203-8

  	
   

  	
  Cancellation, Rescission, and Recovery of Funds for Illegal or
  Improper Activity

  	
   

  	
  JAN 1997

  
	
  52.203-10

  	
   

  	
  Price Or Fee Adjustment For Illegal Or Improper Activity

  	
   

  	
  JAN 1997

  
	
  52.203-12

  	
   

  	
  Limitation On Payments To Influence Certain Federal Transactions

  	
   

  	
  SEP 2007

  
	
  52.203-14

  	
   

  	
  Display of Hotline Poster(s)

  	
   

  	
  DEC 2007

  
	
  52.204-4

  	
   

  	
  Printed or Copied Double-Sided on Recycled Paper

  	
   

  	
  AUG 2000

  
	
  52.204-7

  	
   

  	
  Central Contractor Registration

  	
   

  	
  APR 2008

  
	
  52.204-10

  	
   

  	
  Reporting Subcontract Awards

  	
   

  	
  SEP 2007

  
	
  52.209-6

  	
   

  	
  Protecting the Government’s Interest When Subcontracting With
  Contractors Debarred, Suspended, or Proposed for Debarment

  	
   

  	
  SEP 2006 

  
	
  52.211-5

  	
   

  	
  Material Requirements

  	
   

  	
  AUG 2000

  
	
  52.215-2

  	
   

  	
  Audit and Records—Negotiation

  	
   

  	
  MAR 2009

  
	
  52.215-2  Alt I

  	
   

  	
  Audit and Records—Negotiation (Mar 2009) Alternate I

  	
   

  	
  MAR 2009

  
	
  52.215-8

  	
   

  	
  Order of Precedence—Uniform Contract Format

  	
   

  	
  OCT 1997

  
	
  52.215-10

  	
   

  	
  Price Reduction for Defective Cost or Pricing Data

  	
   

  	
  OCT 1997

  
	
  52.215-11

  	
   

  	
  Price Reduction for Defective Cost or Pricing Data—Modifications

  	
   

  	
  OCT 1997

  
	
  52.215-12

  	
   

  	
  Subcontractor Cost or Pricing Data

  	
   

  	
  OCT 1997

  
	
  52.215-13

  	
   

  	
  Subcontractor Cost or Pricing Data—Modifications

  	
   

  	
  OCT 1997

  
	
  52.215-15

  	
   

  	
  Pension Adjustments and Asset Reversions

  	
   

  	
  OCT 2004

  
	
  52.215-16

  	
   

  	
  Facilities Capital Cost of Money

  	
   

  	
  JUN 2003

  
	
  52.215-19

  	
   

  	
  Notification of Ownership Changes

  	
   

  	
  OCT 1997

  
	
  52.215-23

  	
   

  	
  Limitations on Pass-Through Charges

  	
   

  	
  OCT 2009

  
	
  52.216-7

  	
   

  	
  Allowable Cost And Payment

  	
   

  	
  DEC 2002

  
	
  52.219-6

  	
   

  	
  Notice Of Total Small Business Set-Aside

  	
   

  	
  JUN 2003

  
	
  52.219-8

  	
   

  	
  Utilization of Small Business Concerns

  	
   

  	
  MAY 2004

  
	
  52.219-14

  	
   

  	
  Limitations On Subcontracting

  	
   

  	
  DEC 1996

  
	
  52.222-19

  	
   

  	
  Child Labor — Cooperation with Authorities and Remedies

  	
   

  	
  AUG 2009

  
	
  52.222-20

  	
   

  	
  Walsh-Healey Public Contracts Act

  	
   

  	
  DEC 1996

  
	
  52.222-21

  	
   

  	
  Prohibition Of Segregated Facilities

  	
   

  	
  FEB 1999

  
	
  52.222-26

  	
   

  	
  Equal Opportunity

  	
   

  	
  MAR 2007

  
	
  52.222-35

  	
   

  	
  Equal Opportunity For Special Disabled Veterans, Veterans of the
  Vietnam Era, and Other Eligible Veterans

  	
   

  	
  SEP 2006 

  
	
  52.222-36

  	
   

  	
  Affirmative Action For Workers With Disabilities

  	
   

  	
  JUN 1998

  
	
  52.222-37

  	
   

  	
  Employment Reports On Special Disabled Veterans, Veterans Of The
  Vietnam Era, and Other Eligible Veterans

  	
   

  	
  SEP 2006 

  
	
  52.222-39

  	
   

  	
  Notification of Employee Rights Concerning Payment of Union Dues or
  Fees

  	
   

  	
  DEC 2004

  
	
  52.222-50

  	
   

  	
  Combating Trafficking in Persons

  	
   

  	
  FEB 2009

  
	
  52.223-3

  	
   

  	
  Hazardous Material Identification And Material Safety Data 

  	
   

  	
  JAN 1997

  
	
  52.223-6

  	
   

  	
  Drug-Free Workplace

  	
   

  	
  MAY 2001

  
	
  52.223-14

  	
   

  	
  Toxic Chemical Release Reporting

  	
   

  	
  AUG 2003

  



 






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  52.225-13

  	
   

  	
  Restrictions on Certain Foreign Purchases

  	
   

  	
  JUN 2008

  
	
  52.227-1

  	
   

  	
  Authorization and Consent

  	
   

  	
  DEC 2007

  
	
  52.227-2

  	
   

  	
  Notice And Assistance Regarding Patent And Copyright Infringement

  	
   

  	
  DEC 2007

  
	
  52.227-11

  	
   

  	
  Patent Rights—Ownership By The Contractor

  	
   

  	
  DEC 2007

  
	
  52.227-14

  	
   

  	
  Rights in Data—General

  	
   

  	
  DEC 2007

  
	
  52.227-23

  	
   

  	
  Rights to Proposal Data (Technical)

  	
   

  	
  JUN 1987

  
	
  52.228-7

  	
   

  	
  Insurance—Liability To Third Persons

  	
   

  	
  MAR 1996

  
	
  52.232-1

  	
   

  	
  Payments

  	
   

  	
  APR 1984

  
	
  52.232-17

  	
   

  	
  Interest

  	
   

  	
  OCT 2008

  
	
  52.232-20

  	
   

  	
  Limitation Of Cost

  	
   

  	
  APR 1984

  
	
  52.232-22

  	
   

  	
  Limitation Of Funds

  	
   

  	
  APR 1984

  
	
  52.232-23

  	
   

  	
  Assignment Of Claims

  	
   

  	
  JAN 1986

  
	
  52.232-33

  	
   

  	
  Payment by Electronic Funds Transfer—Central Contractor Registration

  	
   

  	
  OCT 2003

  
	
  52.233-1

  	
   

  	
  Disputes

  	
   

  	
  JUL 2002

  
	
  52.233-3  Alt I

  	
   

  	
  Protest After Award (Aug 1996) - Alternate I

  	
   

  	
  JUN 1985

  
	
  52.233-4

  	
   

  	
  Applicable Law for Breach of Contract Claim

  	
   

  	
  OCT 2004

  
	
  52.242-1

  	
   

  	
  Notice of Intent to Disallow Costs

  	
   

  	
  APR 1984

  
	
  52.242-3

  	
   

  	
  Penalties for Unallowable Costs

  	
   

  	
  MAY 2001

  
	
  52.242-4

  	
   

  	
  Certification of Final Indirect Costs

  	
   

  	
  JAN 1997

  
	
  52.242-13

  	
   

  	
  Bankruptcy

  	
   

  	
  JUL 1995

  
	
  52.242-15  Alt I

  	
   

  	
  Stop-Work Order (Aug 1989) - Alternate I

  	
   

  	
  APR 1984

  
	
  52.242-17

  	
   

  	
  Government Delay Of Work

  	
   

  	
  APR 1984

  
	
  52.243-2

  	
   

  	
  Changes—Cost-Reimbursement

  	
   

  	
  AUG 1987

  
	
  52.243-2  Alt V

  	
   

  	
  Changes—Cost-Reimbursement (Aug 1987) - Alternate V

  	
   

  	
  APR 1984

  
	
  52.244-2

  	
   

  	
  Subcontracts

  	
   

  	
  JUN 2007

  
	
  52.244-5

  	
   

  	
  Competition In Subcontracting

  	
   

  	
  DEC 1996

  
	
  52.244-6

  	
   

  	
  Subcontracts for Commercial Items

  	
   

  	
  AUG 2009

  
	
  52.249-6

  	
   

  	
  Termination (Cost Reimbursement)

  	
   

  	
  MAY 2004

  
	
  52.249-14

  	
   

  	
  Excusable Delays

  	
   

  	
  APR 1984

  
	
  52.253-1

  	
   

  	
  Computer Generated Forms

  	
   

  	
  JAN 1991

  
	
  252.203-7000

  	
   

  	
  Requirements Relating to Compensation of Former DoD Officials

  	
   

  	
  JAN 2009

  
	
  252.203-7001

  	
   

  	
  Prohibition On Persons Convicted of Fraud or Other Defense-
  Contract-Related Felonies

  	
   

  	
  DEC 2008

  
	
  252.204-7004  Alt A

  	
   

  	
  Central Contractor Registration (52.204-7) Alternate A

  	
   

  	
  SEP 2007

  
	
  252.204-7006

  	
   

  	
  Billing Instructions

  	
   

  	
  OCT 2005

  
	
  252.204-7008

  	
   

  	
  Export-Controlled Items

  	
   

  	
  APR 2010

  
	
  252.205-7000

  	
   

  	
  Provision Of Information To Cooperative Agreement Holders

  	
   

  	
  DEC 1991

  
	
  252.209-7004

  	
   

  	
  Subcontracting With Firms That Are Owned or Controlled By The
  Government of a Terrorist Country

  	
   

  	
  DEC 2006

  
	
  252.211-7003

  	
   

  	
  Item Identification and Valuation

  	
   

  	
  AUG 2008

  
	
  252.215-7000

  	
   

  	
  Pricing Adjustments

  	
   

  	
  DEC 1991

  
	
  252.215-7004

  	
   

  	
  Excessive Pass-Through Charges

  	
   

  	
  MAY 2008

  
	
  252.223-7001

  	
   

  	
  Hazard Warning Labels

  	
   

  	
  DEC 1991

  
	
  252.225-7004

  	
   

  	
  Report of Contract Performance Outside the United States and
  Canada—Submission after Award

  	
   

  	
  MAY 2007

  
	
  252.225-7006

  	
   

  	
  Quarterly Reporting of Actual Contract Performance Outside the United
  States

  	
   

  	
  MAY 2007

  
	
  252.225-7012

  	
   

  	
  Preference For Certain Domestic Commodities

  	
   

  	
  DEC 2008

  
	
  252.227-7039

  	
   

  	
  Patents—Reporting Of Subject Inventions

  	
   

  	
  APR 1990

  



 






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  252.232-7003

  	
   

  	
  Electronic Submission of Payment Requests and Receiving Reports

  	
   

  	
  MAR 2008

  
	
  252.232-7010

  	
   

  	
  Levies on Contract Payments

  	
   

  	
  DEC 2006

  
	
  252.235-7002

  	
   

  	
  Animal Welfare

  	
   

  	
  DEC 1991

  
	
  252.235-7004

  	
   

  	
  Protection of Human Subjects

  	
   

  	
  JUL 2009

  
	
  252.243-7002

  	
   

  	
  Requests for Equitable Adjustment

  	
   

  	
  MAR 1998

  
	
  252.244-7000

  	
   

  	
  Subcontracts for Commercial Items and Commercial Components (DoD
  Contracts)

  	
   

  	
  AUG 2009

  
	
  252.247-7023

  	
   

  	
  Transportation of Supplies by Sea

  	
   

  	
  MAY 2002

  
	
  252.247-7024

  	
   

  	
  Notification Of Transportation Of Supplies By Sea

  	
   

  	
  MAR 2000

  



 


CLAUSES INCORPORATED BY FULL TEXT


 


52.216-10 INCENTIVE FEE (MAR 1997)


 


(a) General. The Government shall pay the Contractor for
performing this contract a fee determined as provided in this contract.


 


(b) Target cost and target fee. The target cost and target fee
specified in the Schedule are subject to adjustment if the contract is modified
in accordance with paragraph (d) below.


 


(1)  “Target cost,” as used in this contract, means the estimated cost
of this contract as initially negotiated, adjusted in accordance with paragraph
(d) below.


 


(2)  “Target fee,” as used in this contract, means the fee initially
negotiated on the assumption that this contract would be performed for a cost
equal to the estimated cost initially negotiated, adjusted in accordance with
paragraph (d) below.


 


(c) Withholding of payment. Normally, the Government shall pay the
fee to the Contractor as specified in the Schedule. However, when the
Contracting Officer considers that performance or cost indicates that the
Contractor will not achieve target, the Government shall pay on the basis of an
appropriate lesser fee. When the Contractor demonstrates that performance or
cost clearly indicates that the Contractor will earn a fee significantly above
the target fee, the Government may, at the sole discretion of the Contracting
Officer, pay on the basis of an appropriate higher fee. After payment of 85
percent of the applicable fee, the Contracting Officer may withhold further
payment of fee until a reserve is set aside in an amount that the Contracting
Officer considers necessary to protect the Government’s interest. This reserve
shall not exceed 15 percent of the applicable fee or $100,000, whichever is
less. The Contracting Officer shall release 75 percent of all fee withholds
under this contract after receipt of the certified final indirect cost rate
proposal covering the year of physical completion of this contract, provided
the Contractor has satisfied all other contract terms and conditions, including
the submission of the final patent and royalty reports, and is not delinquent
in submitting final vouchers on prior years’ settlements. The Contracting
Officer may release up to 90 percent of the fee withholds under this contract
based on the Contractor’s past performance related to the submission and
settlement of final indirect cost rate proposals.


 


(d) Equitable adjustments. When the work under this contract is
increased or decreased by a modification to this contract or when any equitable
adjustment in the target cost is authorized under any other clause, equitable
adjustments in the target cost, target fee, minimum fee, and maximum fee, as
appropriate, shall be stated in a supplemental agreement to this contract.


 


(e) Fee payable. (1) The
fee payable under this contract shall be the target fee increased by [+]
[Contracting Officer insert Contractor’s participation] cents for every dollar
that the total allowable cost is less than the target cost or decreased by [+]
[Contracting Officer insert Contractor’s participation] cents for every dollar
that the total allowable


 






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cost exceeds the target cost. In no event shall the
fee be greater than [+][Contracting Officer insert percentage] percent or less
than . . . .[+] . . . . . . [Contracting Officer insert percentage] percent of
the target cost.


 


(2) The fee shall be subject to adjustment, to the
extent provided in paragraph (d) above, and within the minimum and maximum fee
limitations in subparagraph (1) above, when the total allowable cost is
increased or decreased as a consequence of (i) payments made under assignments or
(ii) claims excepted from the release as required by paragraph (h)(2) of the
Allowable Cost and Payment clause.


 


(3) If this contract is terminated in its entirety,
the portion of the target fee payable shall not be subject to an increase or
decrease as provided in this paragraph. The termination shall be accomplished
in accordance with other applicable clauses of this contract.


 


(4) For the purpose of fee adjustment, “total
allowable cost” shall not include allowable costs arising out of—


 


(i)   Any of the causes covered by the Excusable
Delays clause to the extent that they are beyond the control and without the
fault or negligence of the Contractor or any subcontractor;


 


(ii)   The taking effect, after negotiating the
target cost, of a statute, court decision, written ruling, or regulation that
results in the Contractor’s being required to pay or bear the burden of any tax
or duty or rate increase in a tax or duty;


 


(iii)  Any direct cost attributed to the Contractor’s
involvement in litigation as required by the Contracting Officer pursuant to a
clause of this contract, including furnishing evidence and information
requested pursuant to the Notice and Assistance Regarding Patent and Copyright
Infringement clause;


 


(iv)  The purchase and maintenance of additional
insurance not in the target cost and required by the Contracting Officer, or
claims for reimbursement for liabilities to third persons pursuant to the
Insurance Liability to Third Persons clause;


 


(v) Any claim, loss, or damage resulting from a
risk for which the Contractor has been relieved of liability by the Government
Property clause; or


 


(vi)  Any claim, loss, or damage resulting from a
risk defined in the contract as unusually hazardous or as a nuclear risk and
against which the Government has expressly agreed to indemnify the Contractor.


 


(5) All other allowable costs are included in “total
allowable cost” for fee adjustment in accordance with this paragraph (e),
unless otherwise specifically provided in this contract.


 


(f)  Contract modification. The total allowable
cost and the adjusted fee determined as provided in this clause shall be
evidenced by a modification to this contract signed by the Contractor and
Contracting Officer.


 


(g) Inconsistencies. In the event of any language
inconsistencies between this clause and provisioning documents or Government
options under this contract, compensation for spare parts or other supplies and
services ordered under such documents shall be determined in accordance with
this clause.


 


(End of clause)


 


52.217-7 OPTION FOR INCREASED QUANTITY—SEPARATELY
PRICED LINE ITEM (MAR 1989)


 


The Government may require the delivery of the
numbered line item, identified in the Schedule as an option item, in the
quantity and at the price stated in the Schedule. The Contracting Officer may
exercise the option by written notice to the Contractor within 30 days. In
Accordance with Section H.6.


 


(End of clause)


 






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52.219-28 POST-AWARD SMALL BUSINESS PROGRAM
REREPRESENTATION (APR 2009)


 


(a) Definitions. As used in this clause—


 


Long-term contract means a contract of more than
five years in duration, including options. However, the term does not include
contracts that exceed five years in duration because the period of performance
has been extended for a cumulative period not to exceed six months under the
clause at 52.217-8, Option to Extend Services, or other appropriate authority.


 


Small business concern means a concern, including
its affiliates, that is independently owned and operated, not dominant in the
field of operation in which it is bidding on Government contracts, and qualified
as a small business under the criteria in 13 CFR part 121 and the size standard
in paragraph (c) of this clause. Such a concern is “not dominant in its field
of operation” when it does not exercise a controlling or major influence on a
national basis in a kind of business activity in which a number of business
concerns are primarily engaged. In determining whether dominance exists,
consideration shall be given to all appropriate factors, including volume of
business, number of employees, financial resources, competitive status or
position, ownership or control of materials, processes, patents, license
agreements, facilities, sales territory, and nature of business activity.


 


(b) If the Contractor represented that it was a
small business concern prior to award of this contract, the Contractor shall
rerepresent its size status according to paragraph (e) of this clause or, if
applicable, paragraph (g) of this clause, upon the occurrence of any of the
following:


 


(1)  Within 30 days after execution of a novation
agreement or within 30 days after modification of the contract to include this
clause, if the novation agreement was executed prior to inclusion of this
clause in the contract.


 


(2)  Within 30 days after a merger or acquisition
that does not require a novation or within 30 days after modification of the
contract to include this clause, if the merger or acquisition occurred prior to
inclusion of this clause in the contract.


 


(3)  For long-term contracts—


 


(i)   Within 60 to 120 days prior to the end of the fifth year of the
contract; and


 


(ii)  Within 60 to 120 days prior to the date specified in the contract
for exercising any option thereafter.


 


(c) The Contractor shall rerepresent its size status
in accordance with the size standard in effect at the time of this
rerepresentation that corresponds to the North American Industry Classification
System (NAICS) code assigned to this contract. The small business size standard
corresponding to this NAICS code can be found at
http://www.sba.gov/services/contractingopportunities/sizestandardstopics/.


 


(d) The small business size standard for a
Contractor providing a product which it does not manufacture itself, for a
contract other than a construction or service contract, is 500 employees.


 


(e) Except as provided in paragraph (g) of this
clause, the Contractor shall make the rerepresentation required by paragraph
(b) of this clause by validating or updating all its representations in the
Online Representations and Certifications Application and its data in the
Central Contractor Registration, as necessary, to ensure that they reflect the
Contractor’s current status. The Contractor shall notify the contracting office
in writing within the timeframes specified in paragraph (b) of this clause that
the data have been validated or updated, and provide the date of the validation
or update.


 






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(f)    If the Contractor represented that it was
other than a small business concern prior to award of this contract, the
Contractor may, but is not required to, take the actions required by paragraphs
(e) or (g) of this clause.


 


(g)   If the Contractor does not have
representations and certifications in ORCA, or does not have a representation
in ORCA for the NAICS code applicable to this contract, the Contractor is
required to complete the following rerepresentation and submit it to the
contracting office, along with the contract number and the date on which the
rerepresentation was completed:


 


The Contractor represents
that it ( ) is, ( ) is not a small business concern under NAICS Code 541711-
assigned to contract number             .


 


(Contractor to sign and date and insert authorized
signer’s name and title).



(End of clause)


 


52.252-2 CLAUSES INCORPORATED BY REFERENCE (FEB
1998)


 


This contract incorporates one or more clauses by
reference, with the same force and effect as if they were given in full text.
Upon request, the Contracting Officer will make their full text available.
Also, the full text of a clause may be accessed electronically at this/these
address(es):


 


http://farsite.hill.af.mil


 


(End of clause)


 


252.204-7000 DISCLOSURE OF INFORMATION (DEC 1991)


 


(a) The Contractor shall not release to anyone
outside the Contractor’s organization any unclassified information, regardless
of medium (e.g., film, tape, document), pertaining to any part of this contract
or any program related to this contract, unless—


 


(1)   The Contracting Officer has given prior written approval; or


 


(2)   The information is otherwise in the public domain before the date
of release.


 


(b) Requests for approval shall identify the
specific information to be released, the medium to be used, and the purpose for
the release. The Contractor shall submit its request to the Contracting Officer
at least 45 days before the proposed date for release.


 


(c) The Contractor agrees to include a similar
requirement in each subcontract under this contract. Subcontractors shall
submit requests for authorization to release through the prime contractor to
the Contracting Officer.


 


(End of clause)


 


252.235-7010 Acknowledgment of Support and
Disclaimer. (MAY 1995)


 


(a) The Contractor shall include an acknowledgment
of the Government’s support in the publication of any material


 






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based on or developed under this contract, stated in
the following terms: This material is based upon work supported by the US Army
Space and Missile Defense Command under Contract No. [Insert upon award]


 


(b) All material, except scientific articles or
papers published in scientific journals, must, in addition to any notices or
disclaimers by the Contractor, also contain the following disclaimer: Any
opinions, findings and conclusions or recommendations expressed in this material
are those of the author(s) and do not necessarily reflect the views of the
[name of contracting agency(ies)].


 






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Section J - List of Documents, Exhibits and Other Attachments


 


SECTION J


LIST OF ATTACHMENTS


 


	
  Attachment No.

  	
   

  	
  Description

  	
   

  	
  Date

  	
   

  	
  Number of Pages

  
	
  1

  	
   

  	
  Contractor’s Statement of Work — Ebola Virus

  	
   

  	
  3/11/10

  	
   

  	
  57

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  2

  	
   

  	
  Contractor’s Statement of Work — Marburg Virus

  	
   

  	
  3/11/10

  	
   

  	
  57

  



 


Exhibit No.


A001 Contract Work Breakdown Structure (CWBS)


A002 Contractor’s Progress, Status, & Management Report


A003 Contract Funds Status Report, DD Form 1586


A004 Integrated Master Schedule


A005 Contract Performance Report


A006 In Process Review


 






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  AVI BioPharma, Inc.

  	
   

  	
   

  
	
  HFV-ZEBOV

  	
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  Revised Statement of Work

  	
   

  



 


Appendix B:
Revised Statement of Work


 


3.0 CONTRACT


 


AVI BioPharma (AVI) Statement of Work for AVI-6002 as an effective
therapeutic for ebolavirus:


 


3.2 CLIN0001 Technology
Development (Part 1): AVI will deliver the developmental
therapeutic end item that has completed [+] clinical trials, with all the
associated preclinical and regulatory requirements sufficient and in place to
support its delivery. This will comprise all those activities necessary for our
candidate drug product to complete the US GOVERNMENT (USG) Statement of
Objectives for CLIN0001. We will complete the planning (including assessment
and mitigation of risk) for manufacturing the drug supply, and execute process
development to enable scale up from the current [+] batch GLP material, through
a [+] batch cGMP engineering development scale, in anticipation of an ultimate
[+] modular manufacturing scale; includes analytical methods development and
validation ([+], drug substance) and method qualification (drug product), and
development of specifications for lot release.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Drug product on which [+]
clinical trials have been completed.


 


3.2.2 [+] Process Development and Qualification: AVI will
prepare drug substance for use in subsequent [+] studies (includes the use of
previously manufactured components outside this RFP to prepare drug substance).
The [+] development program will improve process reproducibility and prepare
for manufacturing at larger scales. AVI will investigate several steps that
have shown variability [+], and examine steps that have challenges in scale-up
[+]. The overall goal of drug substance development is to design a [+] process
that is highly reproducible, and that can be demonstrated at [+] scale, and
usable in the final manufacturing [+] scale. [+]. A stable, [+] form of the
drug substance will be produced.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Design scalable processes
for [+] and drug substance.


 


3.2.2.1 [+] Process Development and Qualification: The [+]
development program is aimed at improving reproducibility and scalability, and
ensuring the quality of the product. The overall goal is to design [+] process that is highly reproducible and
easily scalable.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Finalization of a highly
reproducible and easily scalable [+] process in preparation for manufacturing
at larger scales.


 


3.2.2.1.1 Synthesis and Characterization of
Authentics: This project will help ensure a consistent quality
of product. [+]. These authentics
will be used as markers in the analytical method validation to check the
resolution of the methods.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Preparation of authentic
impurity markers


 


	
   

  	
  Use
  or disclosure of data contained on this sheet is subject to the

  	
   

  
	
  W9113M-09-R-0008

  	
  restriction
  on the title page of this proposal.

  	
   

  



 






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3.2.2.1.2 [+] Process Development: The [+]
development program is aimed at improving reproducibility and scalability. It
will investigate several steps that have shown [+]. The overall goal is to design a [+] process that is highly
reproducible and easily scalable.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Improvement of specific
steps and finalization of a highly reproducible and easily scalable [+]
process.


 


3.2.2.1.3 Project Management, Operations and
Oversight: Project management will oversee the CROs that are
performing [+] process development and will also manage the in-house
development effort


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.2.2.2 Drug Substance [+] Process Development: The drug
substance [+] process development program will involve optimization of the [+]
components of the manufacturing process. The overall goal is to design a highly
reproducible and scalable [+] drug substance manufacturing process that can be
demonstrated at an [+] and is usable in the final manufacturing [+] scale.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+].


 


Deliverable: Demonstration of a
reproducible and scalable manufacturing process for drug substance.


 


3.2.2.2.1 Drug Substance [+] Process Development: Development
activities are to include optimization of [+] to produce a scalable synthesis
process as well as optimization of current [+] process to increase efficiency
of [+]. Investigation of alternative [+] methods [+] will also be conducted.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Optimization of the
synthesis and [+] components of the manufacturing process.


 


3.2.2.2.2 Project Management, Operations and
Oversight: This element entails oversight and guidance of the
development activities, as well as management of technical personnel.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.2.3 Manufacturing for Nonclinical Studies**: [+] production
will occur at [+], and will supply all the [+] needed for CLIN0001 drug
substance manufacture, plus a contingency plan for any drug substance batch
needing to be repeated (this is essential to ensureconcordance with the
timeline). Any excess [+] will be used during the scale up in CLIN0002. The
current [+] drug substance process will be transferred to a contract
manufacturing organization (CMO) accomplished in the [+] manufacture of
oligomeric therapeutic drugs. The CMO will perform scaling of process to [+],
plus process development and Reduction to Practice (RtP) run(s). Material for
toxicology studies will be made.


 






**Drug Product for the [+] clinical trial has already been manufactured
and is currently stored awaiting final preparations for the start of the study.


 


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Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Produce drug substance for
[+] studies using [+] scale drug substance process.


 


3.2.3.1 Manufacture [+]: This production
is planned to occur at [+]. It will produce all the [+] needed for CLIN0001
drug substance manufacture plus a contingency if a drug substance batch needs
to be repeated. Any excess [+] will be used during the scale up in CLIN0002.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Timely supply of [+] to
support CLIN0001 drug substance development and manufacture.


 


3.2.3.1.1 Contract Negotiation, Material Acquisition: Finalize and
sign contracts for production. Order long lead time and custom reagents to
support upcoming campaign.


 


Period of Work: Approximately [+] month
from time of award (e.g. [+]).


 


Deliverable: Contract and materials in
place for [+] manufacture.


 


3.2.3.1.2 Manufacture [+]: Produce all the
[+] needed for CLIN0001 drug substance development and manufacture.


 


Period of Work: Approximately [+] months from
time of award (e.g. [+]).


 


Deliverable: Timely supply of [+] to
support CLIN0001 drug substance development and manufacture.


 


3.2.3.1.3 Quality Audits and Review: Quality audits
are managed by the Director of QA and scheduled in accordance with the Audit
Master Schedule. Automatic audit reminders are issued by the EDMS. Auditors
schedule travel to and from audits, write audit reports, provide lists of
findings and make recommendations. The Director of QA oversees all operational
aspects of audits, procedures connected with audits and audit reports. Audit
findings, recommendations and responses are reviewed by the Director of QA, the
VP of Regulatory Affairs and QA. Non-compliance issues are brought to the
attention of the Chief Executive Officer (CEO), personally, by the Director of
QA on a biweekly basis. In addition, a QA Unit and Compliance Report is written
monthly by the Director of QA and presented to the CEO in a 1:1 meeting.
Functional management and staffing of the QA Unit is the responsibility of, and
managed by, the VP of Regulatory Affairs and QA.


 


Quality Audits include non-cGMP, non-GLP, cGMP or GLP audits, depending
on the process step and may include audits of non-regulated facilities
(non-cGMP and non-GLP facilities) or audits of facilities that are required to
comply with cGMP or GLP. These are Direct Impact audits of Contract
Manufacturing Organizations (CMOs), quality control testing , storage and
distribution facilities connected with the manufacture of [+] and activated
tails. Audit documentation includes a list of questions directly suited to the
service provided by the CMO and an ICH Q7-compliant audit checklist. All CMOs
must be audited and approved by QA and, when applicable, readiness for
Pre-Approval Inspection (PAI) by the FDA or other regulatory agency is
evaluated at an appropriate time during an audit. Audit records have limited,
controlled review access for authorized departmental and senior management
staff, and are


 






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reviewed through and archived using the EDMS.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: QA approved CMO (vendor)
and release of manufactured [+] for AVI-6002 program. Audit report completed
and satisfactory resolution of responses to findings for CMO providing [+]. Lot
release of [+] for drug substance manufacturing program in accordance with
QA-approved specifications using analytical methods.


 


3.2.3.1.4 Project Management, Operations and
Oversight: Project management will oversee the CMO that is
doing the CLIN0001 production.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.2.3.2 Manufacture Drug Substance: Select CMO
experienced in [+] synthesis of [+] drugs. Tech transfer of [+] scale process
for drug substance; scale-up of process to [+], process development and RtP
run(s); determine stable [+] form for drug substance.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Achieve [+] scale drug
substance process and produce material for [+] studies.


 


3.2.3.2.1 Select and Contract CMO: CMOs capable of
performing [+] synthesis have been reviewed for suitability for the API
manufacture, [+], and isolation. Site visits will be performed followed by
quality audits, contract negotiations, technical transfer, and Quality
agreement execution.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+])


 


Deliverable: Selection and completion of
contracts with a suitable CMO for API manufacture.


 


3.2.3.2.2 Manufacturing Tech Transfer at 8L: Production will
be introduced at the current [+] scale to allow comparability of previous lots
and to transfer knowledge to the new CMO. Each API will be made and purified at
this scale with the objective being to produce material suitable for
toxicological studies.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Demonstration of successful
tech transfer of current [+] sale and production of material suitable for [+]
studies.


 


3.2.3.2.3 Process Development, Reduction to Practice
at [+]: After the [+] tech transfer campaigns, the process
size will be adapted to a [+] size as part of normal development in order to
produce more material suitable for [+] studies. At this point process changes
may be introduced to make the process more efficient as long as the impurity
profiles remain unchanged.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 






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Deliverable: Demonstration of
scalability of manufacturing process to [+] scale by successful completion of
RtP run(s).


 


3.2.3.2.4 Project Management, Operations and
Oversight: As part of the normal course of outsourcing
production, regular team meetings will be held and updates provided. Production
oversight from site visits and data review will be shared and discussed.
Regular conference calls with the CMO will be established to review progress
and results.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget


 


3.2.4 Develop and Validate Analytical Assays and Lot
Release Specifications: Existing analytical methods will be refined
and validated for each [+]. Methods for drug substance will be developed and
validated to meet characterization criteria set with the FDA for release. For
the drug product assays, development will utilize synergies with drug substance
methods to reduce time and cost of method qualification. For both drug substance
and drug product, AVI will qualify vendors, facilities and conduct audits.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Validated assays for [+]
and drug substance, qualification of the drug product assays, and development
of lot release specifications for [+], drug substance and drug product.


 


3.2.4.1 [+] Analytical Method Development and
Validation: Existing analytical methods will be refined and
validated for each [+].


 


Period of Work: Approximately [+] days from
time of award (e.g. [+])


 


Deliverable: Audited report for
validated analytical methods for each [+].


 


3.2.4.1.1 Method Development and Validation: Methods
confirming process consistency will be developed by a qualified subcontractor.
Methods for assay and impurity profile will be validated to established
criteria for cGMP starting materials.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Audited report for
validated analytical methods for each [+].


 


3.2.4.1.2 Identify Impurities above ID Threshold: Process-critical
impurities will be synthesized and included in the validation process. Markers
for known impurities will be synthesized as part of the impurity profile.
Chromatograms of historic lots will be generated using the refined analytical
methods. A team of chemists will work on identifying and synthesizing all
impurities that occur [+].


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Identification and
preparation of markers for all impurities that occur above the [+].


 


3.2.4.1.3 Develop (Assess and Refine) Lot Release
Specifications: To ensure consistent quality, a team will assess and
refine all the [+] lot release specifications.


 






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Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: Preparation of a lot
release specification for each [+].


 


3.2.4.1.4 cGMP Audits: See section 3.2.3.1.3
Quality Audits and Review for general description of Quality Audits. cGMP
audits are performed by experienced auditors for the Contract Manufacturing
Organizations (CMOs), quality control testing and storage and distribution
facilities. Audits employ a checklist approach, based on regulatory
requirements and ICH Q7 guidelines, which are customized to comply with
requirements for each subcontractor site and circumstance. When applicable, the
readiness for a Pre-Approval Inspection by the FDA or other regulatory agency
(PAI) of cGMP and GLP subcontractors is also evaluated. Under the Quality
System, batch release specifications, test methods and quality control test
results, protocols for stability studies and analytical methods and study
reports or data are reviewed for compliance with regulations and guidelines and
approved by the Director of QA.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Audit report completed and
satisfactory resolution of responses to findings by subcontract laboratories
testing [+] for drug substance for subsequent clinical use.


 


3.2.4.1.5 Project Management, Operations and
Oversight: Track progress and manage issues as they arise.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]). 


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.2.4.2 Drug Substance (DS) Analytical Method
Development and Validation: Drug substance analytical
methods will be developed and validated to meet characterization criteria set
forth by regulatory agency for release. Impurities will be isolated and identified.
Subcontractors will be qualified, and audits performed, by AVI QA Unit.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Audited report for
validated analytical methods for drug substance release.


 


3.2.4.2.1 Method Development and Validation: Methods,
compliant with regulatory expectations, will be developed for impurity profile,
assay, identity and description. Method validation will be performed by
qualified vendor.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Methods for impurity
profile, assay, identity and description, validated and audited report as
appropriate.


 


3.2.4.2.2 Identify Impurities above [+]: Impurities will be identified and the
identity verified by synthesis of authentic compounds. Detection level of
impurities will be established.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Establish identity and
detection levels of impurities.


 






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3.2.4.2.3 Develop (Assess and Refine) Lot Release
Specifications: Release specifications will be established that
ensure consistency between production lots. RTP batches will be used to refine
release specifications and assess the analytical method capability to meet the
specification threshold according to ICH Q6A recommendations. Director of QA
participates in review and approval of specifications that are compliant with
cGMP and compendial requirements.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: cGMP-compliant lot release
specifications are approved for drug substance for subsequent clinical use.


 


3.2.4.2.4 Quality Audits and review: Documentation
for drug substance (DS) analytical method development and validation will be
reviewed by QA for compliance with regulatory requirements. See section
3.2.3.1.3 Quality Audits and Review and section 3.2.4.1.4 cGMP Audits. Audits
occur, reports are completed and satisfactory responses are received to audit
findings. Director of QA reviews and approves validation protocols and
validation reports for the analytical methods.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Audits occur, audit reports
are completed audit findings are resolved and validated analytical tests and
methods are approved for drug substance.


 


3.2.4.2.5 Project Management, Operations and
Oversight: Track progress and manage issues as they arise.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.2.4.3 Drug Product (DP) Analytical Method
Development and Qualification: Drug product analytical
method development and qualification will characterize phosphate buffered
saline filled drug product. Method development will utilize synergies with drug
substance methods to reduce time and cost of method qualification. Includes
subcontractor qualification and audits by AVI QA Unit.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Qualified analytical test
methods (validated assay method) that comply with the FDA’s quality and
regulatory requirements for release of drug product.


 


3.2.4.3.1 Method Development and Qualification: Methods,
compliant with regulatory expectations, will be developed for impurity profile,
assay, identity, and description. Method qualification will be performed by
qualified vendor. A contract analytical development laboratory will be chosen,
and methods for drug product analysis and release will be developed that comply
with the FDA’s quality and regulatory requirements.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Audited reports for
qualified methods for impurity profile, identity, and description and validated
method for assay


 


3.2.4.3.2 Identify Impurities above ID Threshold: Impurities will
be identified and the identity verified by synthesis of authentic compounds.
Detection level of impurities will be established.


 






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Period of Work: Approximately [+] months
(e.g. [+])


 


Deliverable: Establish identity and
detection levels of impurities.


 


3.2.4.3.3 Develop (Assess and Refine) Lot Release
Specifications: Release specifications will be established that
ensure consistency between production lots. RTP batches will be used to refine
release specifications and assess the analytical method capability to meet the
specification threshold according to ICH Q6A recommendations.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: Lot release specification
in compliance with the FDA’s quality and regulatory requirements for drug
product for subsequent clinical use.


 


3.2.4.3.4 cGMP Audits: Documentation for drug
product (DP) analytical method development and validation will be reviewed by
QA for compliance with regulatory requirements. See section 3.2.4.1.4 above.
Audit occurs, report completed and satisfactory resolution of responses to
findings by subcontract testing laboratories developing analytical methods and
testing drug product for subsequent clinical use. Lot release will occur using
QA-approved validated analytical methods and specifications compliant with
compendia and other regulatory requirement.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Completed and QA reviewed
validation reports. Audit report completed and satisfactory resolution of
responses to findings by subcontract testing laboratories. Lot release tests
and specifications that comply with the FDA’s quality and regulatory requirements
are approved by the Director of QA.


 


3.2.4.3.5 Project Management, Operations and
Oversight: Track progress and manage issues as they arise.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.2.5 Nonclinical Toxicology: AVI will
conduct [+] studies [+]. A new assay will be used for the determination of drug
levels in biological matrices, and each component of the study drug will be
assayed independently. The method will be validated (GLP) in plasma as is
required for study protocols for pharmacokinetic analysis. An existing [+] will
be transferred and validated (GLP) for the analysis of dosing solutions, over a
[+]. The single dose [+] will evaluate the effect of a single dose on target
organs observed. Quality Audits will be conducted on the contract research
organization (CRO) and the audit records maintained by the AVI EDMS.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Completed GLP-compliant
non-clinical toxicology study reports for studies in [+], including [+]
reports.


 


3.2.5.1 [+] Method Validation: Feasibility
studies have proven a [+] method acceptable for the determination of drug
levels in 


biological matrices. Each component of the study drug is assayed 


 






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independently. The method will be validated (GLP) in matrices
corresponding to samples specified by study protocols for pharmacokinetic
analysis [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audited final report on
validated [+] method for detection of drug levels in biological matrices.


 


3.2.5.2 Analytical Method Validation for Determination
of Dose Solution Concentration: An existing [+] method will
be transferred and validated (GLP) for the analysis of dosing solutions. The
method will be validated over a concentration range suitable for determination
of concentration, homogeneity, and stability of the dose formulations for the
non-clinical toxicology studies.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: Audited final report on
validated method for concentration of drug levels.


 


3.2.5.3 [+]: The single dose [+] study
will evaluate the effect of a [+]. The results will have an impact on the
dosages and escalation in the [+] trial. This study requires validation of the
analytical method.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audited final report for
[+] study.


 


3.2.5.4 [+]: This study provides supportive data for the repeat dose
study [+] that has been completed. Allow correlation of observed effects with
exposure.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audited final report for
[+] study.


 


3.2.5.5 [+]: In vitro study to assess the
effects of the test article on [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audited final report for
[+] study.


 


3.2.5.6 [+]: To investigate the actions
of the test article/vehicle on action potential [+] methods. This study will identify
potential risk of [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audited final report for
[+] study.


 


3.2.5.7 [+] with Long Recovery: [+]. This study
will determine [+] in multidose
clinical trial


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audited final report for
[+] Study with Long Recovery.


 






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3.2.5.8 cGLP Audits: Quality Audits conducted in
this arena are Direct Impact audits of our Contract Research Organizations
(CRO). Audits include a list of questions directly suited to the CRO and a
GLP/cGMP [+] checklist. All CROs (through audits) are approved (or rejected) by
QA and audit records are maintained by the AVI EDMS. See section 3.2.3.1.3 for
general description of Quality Audits. Audits of [+] facilities, [+] laboratories,
and related study data will be conducted by experienced auditors from the
Quality Unit. Audits employ a checklist approach, based on regulatory
requirements (21 CFR Part 58 for GLP compliance) and ICH guidelines. The
checklists are customized to comply with requirements applicable for each
subcontractor facility and type of testing. When applicable, the readiness for
a Pre-Approval Inspection by the FDA or other regulatory agency (PAI) of GLP
subcontractors is also evaluated.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audit and audit report
completed and acceptable responses to findings received from subcontract [+]
facilities and [+] laboratories testing AVI-6002 for [+]. GLP studies will
occur using QA-approved protocols that meet regulatory and IUCAC and USG
requirements and validated [+] methods are used.


 


3.2.5.9 Project Management, Operations and Oversight: Track progress
and manage issues as they arise.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.2.6 Pilot [+] Studies: [+].


 


** [+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Complete [+] studies.


 


3.2.6.1 [+]: [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, conduct and receive
report for single vs combination agent AVI-6002 study.


 


3.2.6.2 GLP Audits: Quality Audits conducted in
this arena are Direct Impact audits of our Contract Research Organizations
(CRO). Audits include a list of questions directly suited to the CRO and a
GLP/GMP (animal) checklist. All CROs (through audits) are approved (or
rejected) by QA and audit records are maintained by the AVI EDMS. See section
3.2.5.8 above. See section 3.2.3.1.3 for general description of Quality Audits.
Audits of animal testing facilities, bioanalytical laboratories, and related
study data will be conducted by experienced auditors from the Quality Unit.
Audits employ a checklist approach, based on regulatory requirements (21 CFR Part 58
for GLP compliance) and ICH guidelines. the checklists are customized to comply
with requirements applicable for each subcontractor facility and type of
testing. When applicable, the readiness for a Pre-Approval Inspection by the
FDA or other regulatory agency (PAI) of GLP subcontractors is also evaluated.


 






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Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable:. Audit and
report completed and satisfactory responses to audit findings received from [+]
facilities and [+] testing drug product for nonclinical studies. GLP studies
will occur using QA-approved protocols that meet regulatory and IUCAC and USG
requirements and validated bioanalytical methods are used


 


3.2.6.3 Project Management, Operations and Oversight: The antiviral
team will meet regularly to review the protocol, monitor progress of the
studies and evaluate observations. In addition, weekly conference calls with
[+] will provide coordination of effort and timing.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.2.7 Contract Program Management**: AVI will track
progress on each element in the contract, including all financial and reporting
requirements; ensure compliance with contract and all government regulations.
AVI will manage all subcontracts and ensure that their timelines are met, and
the components contributed by each to the overall study are coordinated, on
budget, and that they are compliant with all contract and Government
regulations that are applicable.


 






**Work will continue during period [+] on this
program — namely [+] and regulatory to prepare for [+] clinical study. Program
management will be required to oversee those tasks.


 


Period of Work: Concurrent with all
CLIN0001 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide contract management
and financial oversight ensuring compliance.


 


3.2.7.1 Program Management: Track progress
and manage issues as they arise.


 


Period of Work: Concurrent with all
CLIN0001 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide project management
ensuring compliance.


 


3.2.7.2 Finance and [+]: Track financial work process and reporting.


 


Period of Work: Concurrent with all
CLIN0001 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide project financial
management ensuring compliance.


 


3.2.7.3 Contract and Subcontract Management: Manage our
compliance with contract and USG regulations; manage subcontractors and
relationship with them.


 


Period of Work: Concurrent with all
CLIN0001 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide contract and
subcontract management ensuring compliance.


 


3.2.7.4 EDMS Installation, Validation, Implementation,
Training and QA: AVI will implement enhancements to the Quality
Systems Approach already in place, including installation of a secure 21CFR Part 11
compliant EDMS and preparation for electronic document submission to the FDA.
AVI will train all pertinent staff on EDMS and Quality Assurance.


 






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Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: EDMS system will have been
selected, installed and fully operational. QA audits of all vendors will have
been performed and any follow up action items identified and tracked.


 


3.3 CLIN0001 Technology Development — [+] Clinical
Study (Part 2): Using the currently filed IND, and [+] data
obtained subsequently, AVI will establish agreement with the FDA for the
acceptable protocol** [+], such as [+] review and approval. AVI will conduct
and report the [+] clinical study in healthy [+].


 






**Discussions with the FDA are planned for [+] which
will cover the [+] and additional input to the proposed [+] study may be
requested.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Final study report for [+]
clinical study agreed upon by the government.


 


3.3.1 Support [+] Submission: An [+] cannot be granted until the appropriate
legislative order has been given by Congress, however, AVI will submit a
Request for Consideration for an [+]
and briefing document (per Section 564(c) of the FD&C Act),
amendments under Project Bioshield Act of 2004, and draft FDA Guideline of June 2005.
The Request for Consideration will contain data from all available research and
nonclinical studies together with draft protocol synopses for the [+] studies and the first clinical study.
The FDA will be asked to provide advice on the additional requirements to
achieve an [+].


 


As requested by the FDA in the meeting, AVI will continue to submit
additional scientific, [+] and [+] study data in final study reports as [+] when the final reports are available
with the intention of fulfilling all requirements for an [+] before such use is required.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Letter to the FDA requesting
a meeting to discuss the Request for Consideration as an [+] and Briefing
Document submitted as an [+]. In addition, after the meeting with the FDA the
company’s notes of the meeting with the FDA will be submitted as an [+].


 


3.3.1.1 Support [+] Submission, Meeting with FDA and USG: AVI’s regulatory affairs
staff will prepare the Meeting Request Letter and Briefing Document for the
Request for Consideration as an [+] Meeting with the FDA and submit them as
[+]. After the Meeting with the FDA, AVI’s regulatory affairs staff will
prepare notes of the meeting and submit them as an [+].


 


The Request for Consideration as an [+] submissions will be planned,
prepared and managed by AVI’s regulatory affairs staff, using FDA compliant
electronic templates, e-publishing techniques and the EDMS. Meeting
arrangements and follow-up Meeting Minutes will also be prepared and managed by
RA. Oversight will be provided by AVI’s senior management.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: Letter to the FDA requesting
a meeting to discuss a Request for Consideration as an [+] and Briefing
Document submitted as an [+]. After the meeting with the FDA the company’s
notes of the [+] with the FDA will be submitted as an [+].


 






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3.3.1.2 Project Management, Operations and Oversight: Consideration
as an [+] request managed by AVI regulatory affairs, using FDA compliant
electronic templates, electronic document management and e-submission. Meeting
arrangements and follow-up meeting minutes also managed by RA. Oversight is
provided by AVI’s senior management.


 


Period of Work: Approximately [+] month
from meeting date being offered with FDA (e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones to timeline and budget.


 


3.3.2 [+] Clinical Study: The [+] will be
conducted with [+] to this award. The timeline will not allow AVI to wait for
full manufacturing scale [+] cGMP drug product material, however the drug
product used will be comparable and the assay method validated. The study and
discussions with the FDA will be based on the IND already opened for drug
product. Dosing will start at the [+]. Based on the pharmacokinetics, safety
and general tolerability, [+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: [+] clinical study report;
study conducted with research scale cGMP drug product.


 


3.3.2.1 Clinical Site and Local Laboratory Activities:
The study will be planned and executed at an audited, selected [+]
Clinical Research Facility with support from a fully CLIA accredited
laboratory. From initiation onward the site(s) will be monitored through
to study completion and site close out.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Plan, conduct and complete
[+] clinical study. Provide all required data to the CRO for final study
report.


 


Final report describing [+] clinical study conducted with research
scale cGMP drug product manufactured at a cGMP-compliant facility.


 


3.3.2.1.1 Contracts and Budget: Contract and
budget will be negotiated and agreed with the [+] CRO and supporting
laboratories.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: All contracts (site and
laboratories) to permit study to be executed are agreed and signed.


 


3.3.2.1.2 Final Protocol to FDA; [+] submissions: Final [+] protocol submitted
to FDA, [+]; feedback received and incorporated prior to study initiation.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: All approvals received
before initiation of clinical study.


 


3.3.2.1.3 Site Activities: First Subject In to Last
Subject Out: The study will be planned and executed at an
audited, selected [+] Clinical Research Facility. Site will be involved with
review of study specific documentation and trained prior to first subject first
visit. All interactions with site will be documented. Regular site monitoring
will be planned and documented to ensure data has been verified and entered in
a timely fashion, while ensuring subject safety. Any compliance issues will be
raised to the clinical


 






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team for response.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: [+] clinical study
conducted under cGCP and completed on schedule, within budget.


 


3.3.2.1.4 Site Close Out: After
completion of the last subject last visit, all data queries will be completed
by the site and/or laboratory, previously validated database locked, analyses
run, and draft study report prepared. In parallel formal close out of the
clinical site, with disposal of unused drug supplies and completion of all outstanding
documentation will occur.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: All open queries and action
items associated with clinical study execution are completed and documented in
a site close out visit report.


 


3.3.2.2 Outsource Services: Identify,
select and qualify subcontractors needed to execute clinical study. Assigned
vendor personnel will participate in a kick off meeting in which study
expectations and needs, including timelines, will be discussed. Protocol and
procedure training will occur. A communication plan and reports will be
developed prior to first subject enrolled.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Training records, meeting
minutes confirming that subcontractors are trained to the study and ready to
perform services.


 


3.3.2.2.1 [+] Method Validation: Feasibility
studies have proven a [+] method acceptable for the determination of drug
levels in [+] matrices. Each component of the study drug is assayed
independently. The method will be validated (GLP) in matrices corresponding to
samples specified by the clinical study protocol for pharmacokinetic analysis
[+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Validated [+] assay for
drug levels in [+] matrices.


 


3.3.2.2.2 Clinical Research Organization and Data
Management: The CRO is key to study success. Their team along
with AVI personnel is responsible for site start up activities, site training,
and study execution, including data collection and management. The statistical
support is part of the CRO. This group and Data Management will develop the
plans necessary for data collection, query management, data analysis and
quality checks. They will prepare reports for the [+] reviews. The final
clinical study report will be written by CRO personnel.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Executed contract between
AVI and CRO.


 


3.3.2.2.3 Central Laboratory Services and Data
Transfer: Exploratory [+] accessioning and analyses will each
be conducted at a central lab facility. Data from each will be sent to data
management vendor for inclusion in final study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 






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Deliverable: Laboratory data report.


 


3.3.2.2.4 [+]: An independent [+] will be appointed to oversee and confirm
dose escalation decisions. A [+]
charter will be prepared and agreed with [+]
members, a contract developed and a kickoff meeting and then dose escalation
meetings with open and closed sessions. Members of the [+] will be available to review safety data
and confirm or reject dose escalation to the next higher dose.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Decision to dose escalate;
continue or stop study as documented in meeting minutes.


 


3.3.2.2.5 Provide Electronic Data Management with
Access to US Government: Enable [+]
web portal with secure access to assigned study, company, vendor and USG
personnel.


 


Period of Work: Approximately [+] months
(e.g. [+]). 


 


Deliverable: Functional secure EDC
portal access.


 


3.3.2.2.6 Drug Warehousing and Distribution: Store clinical
trial material at refrigerated conditions in secure, temperature controlled and
monitored unit. Implement traceable distribution system with chain of custody
documentation.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Provide clinical trial
material on time to site(s) and keep adequate records.


 


3.3.2.3 Study Documents for Clinical Sites and Final
Study Report: The Clinical Research Organization (CRO) is
responsible for preparing and providing to AVI for review all appropriate study
specific documents, except the clinical protocol. Upon AVI authorization the
CRO will send these documents to the sites in preparation for study start.
Additionally, should any unexpected or serious safety events be reported, the
CRO will document, discuss with AVI medical monitor, and complete the
appropriate forms. At the study end, the CRO will prepare the tables, listings
and figures and draft the final study report which will then be finalized with
AVI input.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Shipping receipts showing
what was sent to whom and when.


 


3.3.2.3.1 Prepare and Distribute Study Documents: CRO, lab vendors
and drug warehouse provide complete set of documents and forms to effectively
and efficiently conduct study, including but not limited to: study specific
data collection forms (electronic case report forms), the study operations
manual, training on the protocol, clinical trial material storage, inventory
and administration, use of [+], safety reporting, and Good Clinical Practice
regulations.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: All study related documents
including but not limited to: study plan and timeline, eCRF completion
guidelines, monitoring reports, protocol compliance tracking, communication
plan, meeting minutes, training materials and logs, drug accountability logs
and final study report.


 


3.3.2.3.2 Final Study Report: Prepare
compliant and complete final clinical study report


 






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Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Submission ready final
clinical study report.


 


3.3.2.4 Regulatory Submissions and Templates: The near final
draft clinical protocol, FDA Form 1571, FDA Form 3674, FDA Form 1572,
information on the investigators (including a copy of the CV of the Principal
Investigator), study facility, and [+] will be submitted as an [+] for review
by the FDA. An electronic template that is compliant with electronic submission
requirements will be used for the protocol. Other “Essential Documents”
specified by the ICH guideline on Good Clinical Practice and 21 CFR will be
collected and reviewed for compliance. The clinical study will be registered on
www.Clinicaltrials.gov or an equivalent public access database.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: FDA Letter confirming that
it is “Safe to Proceed” with the clinical study.


 


3.3.2.5 GCP Audits: Clinical data and document
quality checks are carried out by clinical monitors during routine monitoring
of each clinical study, as required under GCP. See section 3.2.1.3 for general
description of quality Audits and Review. Quality Audits performed by
experienced auditors from the QA Unit at clinical investigational sites
(hospitals, etc.) are Direct Impact audits that will be specifically
designed to verify compliance with GCP requirements and local and international
regulatory regulations and guidelines. Audits will include contractor site
selection audit, study audits during the study and an end of study audit. Audit
documentation will be managed and archived in the EDMS


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audit and audit report are
completed and satisfactory responses to audit findings are received from CRO’s
clinical facilities and [+] laboratories testing drug product in clinical
studies. GCP-compliant clinical studies will occur using QA-approved protocols
that meet regulatory and Institutional Review Board, HIPAA and USG
requirements. Validated [+] methods are used for testing clinical samples.


 


3.3.2.6 Project Management, Operations and Oversight: Develop
timeline, manage vendors, anticipate and resolve problems, track protocol
compliance, report progress as part of the normal course of conducting clinical
trials, regular team meetings will be held with each vendor and held
internally. This team is responsible for the study plan. Study progress and any
issues relative to the study plan will be documented and addressed with the
Product Development Team on at least a monthly basis. Regular conference calls
with the TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.3.3 Store Drug Product from Clinical Lot for 2 Years
Past End of Study: Samples from the drug product batches used in the
[+] clinical study will be stored under specified controlled storage conditions
for 2 years past the completion of the study.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 






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Deliverable: Store samples of drug
product used in [+] clinical study.


 


3.3.3.1 Initiate Drug Product Storage at Drug
Distributor Warehouse: Drug product from the clinical trial will be
retained for at least 2 years past the end of the clinical study end. These
samples will be held at the recommended storage temperature in a secured
refrigerated unit that is calibrated and monitored.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Store samples of drug
product used in [+] clinical study.


 


3.3.3.2 cGMP Audits: See section 3.2.3.1.3
Quality Audits and Review for general description of quality audits and section
3.2.4.1.4 for description of cGMP audits. Audits occur, audit reports are
completed and satisfactory responses to audit findings are received from the
subcontract facility storing and distributing AVI-6002 drug product for
subsequent clinical use. Release and shipping of clinical supplies to clinical
facilities will occur using QA-approved procedures that are compliant with GCP
and local and international regulatory requirements.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Audit and audit report are
completed and satisfactory responses to audit findings are received from the
CMO drug product storage facility and conditions are acceptable for drug
product lots for subsequent distribution for clinical use.


 


3.3.3.3 Project Management, Operations and Oversight: Oversight of
warehouse storage of drug product will be managed by AVI personnel through site
visits, audits, and records review.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.3.4. Stability Studies: Samples from
the [+] (drug substance and drug product) and [+] scale (drug substance), will
be placed on a stability study at recommended storage temperature and an
elevated temperature as per ICH guidelines for a minimum of [+] consistent with
the RFP. A final stability report will be written by the Contract organization
that performs the stability studies.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Samples of drug substance
and drug product set up for [+] stability studies.


 


3.3.4.1 Contract Analytical Lab, Method Transfer,
Short Term Stability of Drug Product at Dilutions for Clinical Study: Identify
infusion sets, short term stability for at least [+].


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Report on short term
stability of drug product under conditions of clinical study.


 


3.3.4.2 Contract and Initiate [+]: These studies
will confirm the stability of the regular [+].
These studies are expected to confirm result from previous stability studies.


 










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Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Ongoing stability studies
of [+].


 


3.3.4.3 Refine Stability Indicating Analytical Methods
for Drug Substance and Drug Product: Forced degradation studies
will identify degradants using HPLC/mass spectrometry. Once peak retention
times are matched to degradant/impurity ID, stability program will utilize
validated HPLC methods.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Completion of analytical
method development for Drug Substance and Drug Product.


 


3.3.4.4 24 Months Stability Studies Drug Product: Drug substance
and the resultant drug product will be placed on a stability study at
recommended storage temperature and an elevated temperature as per ICH
guidelines for a minimum of [+] consistent with the RFP. This is applicable to
cGMP materials made at both the [+] scales. A final stability report will be
written by the Contract organization that performs the stability studies.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Ongoing [+] study with drug
product prepared for [+] clinical study in CLIN0001.


 


3.3.4.5 Ongoing Quality Audits and Review including [+] Stability Programs: Drug substance and
the resultant drug product will be placed on a stability study at recommended
storage temperature and an elevated temperature as per ICH guidelines for a
minimum of [+] consistent with the RFP. This is applicable to cGMP materials
made at both the [+] scales. A final stability report will be written by the
Contract organization that performs the stability studies See section 3.2.3.1.3
Quality Audits and Review for a general description of quality audits and
section 3.2.4.1.4 for a description of cGMP audits. cGMP audits occur, reports
are completed and satisfactory responses to audit findings are received from subcontract
laboratories conducting stability studies. Analytical testing occurs using
QA-approved validated analytical methods and stability specifications compliant
with compendia and other regulatory requirements.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: Audit report completed and
satisfactory responses to audit findings received. Stability data are reported
at regular intervals and reviewed by AVI.


 


3.3.4.6 Ongoing Program Management, Operations and
Oversight including [+] Stability
Programs: Develop timeline, manage vendors, anticipate and resolve
problems, track protocol compliance, report progress As part of the normal
course of conducting clinical trials, regular team meetings will be held with
each vendor and held internally. Study progress and any issues relative to the
study plan will be documented and addressed with the Product Development Team
on at least a [+] basis. Regular conference calls with the TMTI will be
established to review progress and results.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 






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3.3.5 End of [+] FDA Meeting: AVI will
request an End of [+] Meeting to discuss the future development plan including
design of the [+] and the application of the [+] as soon as the data from the
first clinical study is available, and appropriate questions of the agency can
be formulated to enable the further clinical development. Agreement will be
sought on fixed dose combination drug products, toxicology, toxicokinetics,
clinical and pharmaceutical development of the drug substance and drug product,
[+] development and review, with advanced notification of USG Program Office.
The scheduling will depend on FDA, but the meeting should occur within 75 days
of the formal request, and the briefing book will be sent to the FDA, at least
4 weeks ahead of the meeting. FDA feedback will be incorporated into the
subsequent development plans. AVI’s regulatory affairs staff will plan, prepare
and compile the submission documents using electronic templates and
e-publishing techniques; documents will be managed and stored electronically
using the EDMS.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: AVI submits an End of [+]
Meeting Request Letter and Briefing Document to the FDA, participates in the
meeting with FDA and prepares meeting notes. AVI reviews the FDA’s official
Meeting Minutes to assure that key elements of the discussions and agreements reached
are documented. The FDA’s requirements and expectations for the appropriate
regulatory procedural enhancements leading to a potential [+] are clear.


 


3.3.5.1 [+] FDA Meeting Request [+],
Preparation of Briefing Documents: Just before the completion of
[+], AVI’s regulatory affairs staff will manage, prepare and compile the [+]
Meeting Request Letter and Briefing Document, with key components being
provided by the research and development staff and subcontractors. The
submission will be prepared using electronic templates, published using
e-publishing techniques and all documents will be managed and controlled in the
EDMS. The [+] Meeting will be planned and held, then AVI will prepare Meeting
Notes that will be submitted to the FDA. The FDA’s official Meeting Minutes
will be reviewed for clarity and agreement with AVI’s understanding of the
outcomes. As necessary, AVI will continue proactive dialogue with the FDA by
mutually convenient means.


 


Period of Work: Approximately [+] weeks
(e.g. [+]).


 


Deliverable: [+] Meeting Request Letter
and Briefing Document submitted to the FDA. A meeting date is agreed and the
meeting (with participation of appropriate USG representatives) is planned.


 


3.3.5.2 FDA Meeting, Minutes, Follow up: AVI and USG
representatives will attend the End of [+] Meeting. Agreement will be sought on
a variety of development and regulatory procedural topics including for example
applicability of fixed dose combination drug product requirements, toxicology,
toxicokinetics, clinical and pharmaceutical development of the drug substance
and drug product, [+] development and review FDA feedback will be incorporated
into the subsequent development plans.


 


Period of Work: Approximately [+] weeks
(e.g. [+]).


 


Deliverable: The [+] Meeting with the FDA
occurs. AVI’s Meeting Notes and the FDA’s Meeting Minutes are prepared and
reflect mutual agreements and understandings of the requirements for further
development and the applicable regulatory procedures.


 


3.3.6 Complete [+] Clinical Trial and [+]: AVI will complete a [+] study to assess
safety, tolerability and pharmacokinetics in [+] (RFP 3.3.2). The results from
this first clinical study will be submitted to


 






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FDA as a supplement to the IND as soon as the data is available and the
appropriate study reports are prepared.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Conduct and complete [+]
clinical trial Submission of an [+] containing the Final Study Report of the
[+] Clinical Trial and other [+] as needed to support continuing nonclinical,
pharmaceutical and clinical research and development.


 


3.3.6.1 Prepare for and Meet with FDA to Discuss [+]: Due to the complexity and uncertainty
about the FDA’s expectations and requirements for [+] approval using the [+],
AVI’s regulatory affairs group will plan, request and manage a specific, [+]
Meeting with the FDA and other interested USG agencies to discuss the
application of the [+]. A Meeting Request Letter and Briefing Document will be
prepared and submitted at least 4 weeks ahead of the meeting. AVI will prepare
Meeting Notes and will review the FDA’s official Meeting Minutes to assure
agreement on the issues discussed. If necessary, further clarifications may be
requested in writing. AVI will continue an open dialogue with the FDA and USG
agencies involved and document those discussions.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Meeting Request and
Briefing Document, attendance at the [+] Meeting, AVI’s Meeting Notes and FDA’s
official Meeting Minutes. Agreement with the FDA and USG agencies regarding the
applicability and requirements for developing oligomeric drug products under
the [+], and for [+] approval.


 


3.3.6.2 Prepare and Submit [+] and [+]:
AVI will submit [+] containing appropriate research and development
data to the FDA and provide notifications to USG Program Office The agreement
of the FDA will be sought to submit the protocols for the [+] studies as well
as the [+] safety study for [+] and the relevant protocols will be submitted.
AVI’s regulatory affairs staff will plan, prepare and manage all submissions as
electronic documents using electronic templates, e-publishing techniques and
the EDMS.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: [+] will be submitted as
[+] and the FDA’s review comments will be incorporated before finalizing study
protocols. [+] will be submitted as research and development data reports are
available in order to keep the IND as current as possible. Copies of major
submissions and correspondence will be forwarded to USG, as required.


 


3.3.6.3 Project Management, Operations and Oversight: 


 


Develop timeline, manage vendors, anticipate and resolve problems,
track protocol compliance, report progress as part of the normal course of
conducting clinical trials, regular team meetings will be held with each vendor
and held internally. This team is responsible for the study plan. Study
progress and any issues relative to the study plan will be documented and
addressed with the Product Development Team on at least a monthly basis.
Regular conference calls with the TMTI will be established to review progress
and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 






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3.3.7 Deliver [+] of Clinical Material to US Government:
A sample of the drug product used in the [+] clinical study will be provided to the USG.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Deliver sample drug product
used in [+] clinical safety study to USG.


 


3.3.7.1 Ship [+] to US Government: At the end of
CLIN0001 at least [+] of the drug
product(s) will be delivered to the recipient specified by the USG.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Deliver sample of drug
product used in [+] clinical safety study to USG.


 


3.3.7.2 Project Management, Operations and Oversight: Oversight of
inventory and distribution will be managed by AVI personnel through site
visits, audits, and records review.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4 CLIN0002: AVI will
deliver the developmental therapeutic end item that has achieved [+] clinical trials, based upon CLIN0001,
additional prior studies and all the associated regulatory requirements
sufficient and in place to support this. This will comprise all those
activities necessary for our candidate product to complete the USG Statement of
Objectives in CLIN0002.


 


Period of Work: Approximately [+] days (e.g. [+]).


 


Deliverable: Drug product on which [+]
clinical trials have been completed.


 


3.4.1 Refine [+]: The critical goal of these
studies is to obtain concurrence with FDA on the [+] study to be conducted under the [+]. Critical viral parameters will be addressed in PK/PD
studies of [+], and in monitoring
[+], both conducted at USAMRIID.
The correlation of the [+] from
natural infections, will guide the format and goals of the [+] study. The [+] study will be discussed and refined with the FDA. AVI will
submit the protocols for the [+]
prior to subcontracting the studies to USAMRIID (the proposed vendor to be
pre-qualified as acceptable for GLP-compliant studies). The final protocols and
final study reports will be submitted to FDA as [+].


 


Period of Work: Approximately [+] days (e.g.
[+]).


 


Deliverable: Establish model for [+]
Studies with FDA.


 


3.4.1.1 Delayed Time to Treatment in [+]: Critical efficacy parameters will be
addressed in a study with various preplanned delays between exposure of [+] and
initiation of treatment. The work will be conducted at USAMRIID. The final
protocols and final study reports will be submitted to FDA as [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Complete Delayed Time to
Treatment Efficacy Study.


 










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3.4.1.2 [+]: Critical viral parameters
will be addressed in [+],
conducted at USAMRIID. The final protocols and final study reports will be
submitted to FDA as [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Complete [+].


 


3.4.1.3 Viral Time Course in [+]: Critical viral parameters will be
addressed in this study conducted at USAMRIID. The final protocols and final
study reports will be submitted to FDA as [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Complete viral timecourse
study in [+].


 


3.4.1.4 [+]: Critical viral parameters
will be addressed in [+],
conducted at USAMRIID. The final protocols and final study reports will be
submitted to FDA as [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Complete [+].


 


3.4.1.5 Quality Audits: See section 3.2.3.1.3 for a
general description of Quality Audits. Audits of [+] facilities, [+] laboratories, and related study data will
be conducted by experienced auditors from the Quality Unit. Audits employ a
checklist approach, based on regulatory requirements (21 CFR Part 58 for GLP
compliance) and ICH guidelines; the checklists are customized to address the
quality and regulatory requirements for each subcontractor facility and type of
testing. When applicable, the readiness for a Pre-Approval Inspection by the
FDA or other regulatory agency (PAI) of GLP subcontractors is also evaluated.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audit and audit reports are
completed and satisfactory responses to audit findings are received from
subcontract [+] laboratories testing drug product for nonclinical studies. GLP
studies will occur using QA-approved protocols that meet regulatory and IUCAC
and USG requirements and validated [+] methods are used for analysis of test
articles.


 


3.4.1.6 Project Management, Operations and Oversight:  


 


Develop timeline, manage vendors, anticipate and resolve problems,
track protocol compliance, report progress as part of the normal course of
conducting clinical trials, regular team meetings will be held with each vendor
and held internally. This team is responsible for the study plan. Study
progress and any issues relative to the study plan will be documented and
addressed with the Product Development Team on at least a monthly basis.
Regular conference calls with the TMTI will be established to review progress
and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.2 Develop and Validate Analytical Assays for Drug
Product: AVI will complete analytical


 






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methods development and validation for drug product and finalization of
specifications for lot release of drug product. The development and validation
of formulated product analytical test methods utilize the analytical test
methods developed and validated for therapeutic drug substance, where
applicable. The addition of compendial tests and limits for sterility,, to those
for appearance, identification, assay and impurities will meet the regulatory
requirements for lot release and for the product lots in ICHcompliant stability
testing programs. The Director of QA will participate in the review and
approval of analytical test methods, analytical validation protocols and
reports, and drug product specifications that comply with compendia and other
regulatory requirements.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Complete development of
analytical methods, validation and specifications for drug product.


 


3.4.2.1 Drug Product Analytical Method Development and
Validation: Drug product analytical development will exploit
similarities between the drug substance and the drug product to accelerate
development and minimize validation time. As with drug substance, multiple HPLC
methods are required for purity identification. Includes vendor qualification,
facilities and API process audits of batch records by AVI QA Unit. AVI will
complete analytical methods development and validation for drug product and
finalization of specifications for lot release of drug product. The addition of
methods for sterility, to those for appearance, identification, assay and
impurities will meet the regulatory scrutiny required for cGMP release and ICH
stability.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Complete development of
analytical methods for drug product, and audited validation report.


 


3.4.2.2 Refine Drug Product Lot Release Specification:
Based upon the results from the CLIN0001 manufacturing experience
product specifications for each of the drug substances and the drug product
will be developed. For the individual drug substances these will be similar to
those developed in CLIN0001 since [+] studies will have been based upon these
specifications that were used in the IND. Refinement of the specifications will
be made based upon new assay development and analysis of lots used in the [+]
studies and clinical trials.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Develop specifications for
each drug substance and drug product.


 


3.4.2.3 Quality Audits: Documentation
for analytical assay method development and validation will be reviewed by QA
for compliance with regulatory requirements. See section 3.2.3.1.3 Quality
Audits and Review and section 3.2.4.1.4 cGMP Audits. Audits occur, audit
reports are completed and satisfactory responses to audit findings are received
from subcontract analytical testing laboratories developing and validating
analytical methods for drug product for subsequent clinical use. The Director
of QA participates in the review and approval of validation protocols and
validation reports.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audits occur, audit reports
are completed and satisfactory responses to audit findings are


 






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received from the test facilities. Validated analytical methods are
developed and approved.


 


3.4.2.4 Project Management, Operations and Oversight: Develop
timeline, manage vendors, anticipate and resolve problems, track protocol
compliance, report progress as part of the normal course of conducting clinical
trials, regular team meetings will be held with each vendor and held
internally. This team is responsible for the study plan. Study progress and any
issues relative to the study plan will be documented and addressed with the
Product Development Team on at least a monthly basis. Regular conference calls
with the TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.3 Scale-up Manufacturing, Qualification and
Validation of cGMP Manufacturing Process: Manufacturing goals will
include scale-up of the raw material supply [+], as well as that of drug
substance. Further suppliers will be qualified. AVI will manufacture the drug
substance and drug product supply at [+] batch scale for the [+] clinical
studies (. AVI will also initiate the development of the full manufacturing
scale of [+] manufacturing, and initiate validation of [+], including for
stability at this full [+] scale. The manufacturing facilities will be audited
for compliance with cGMP and other quality and regulatory requirements by
experienced auditors. The Director of QA will participate in the review and
approval of process validation protocols and reports.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Drug product for [+] clinical
trials and validated drug substance for [+] clinical trials will be prepared.
Release drug product lots for [+] clinical trials manufactured using a
validated process at a cGMP-compliant facility. Lots meet the AVI-approved drug
product specification and have been tested using validated analytical methods.


 


3.4.3.1 [+] Manufacturing Scale-Up: As part of the
scale up process the [+] manufacturing supply chain needs to be established to
produce [+] on the scale required to support the intended manufacturing
scale-up. The current production capacity [+] multiple manufacturers will be
utilized. However, even this effort will require expansion of [+] facilities
for [+] of the activated [+]. [+] are needed to be made at the [+] to support
scale up activities.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Assured supply for [+] and
other raw materials.


 


3.4.3.1.1 Contract Additional [+] Manufacturing and
[+] Sites: Negotiate and sign contracts with the additional [+]
manufacturing and [+] CMOs.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Selection and contract
finalization of additional [+] CMOs.


 


3.4.3.1.2 Manufacture of [+]: Complete tech
transfer with all new CMOs. Scale-up the [+] production process and manufacture
the required [+] to support the drug substance manufacture.


 










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Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Timely supply of [+] to
support drug substance manufacture.


 


3.4.3.1.3 [+] Development and Validation: Evaluate the
feasibility of [+] recovery. The Director of QA participates in the review and
approval of process protocols and reports.


 


Period of Work: Approximately [+] months
(e.g. [+].


 


Deliverable: Report on feasibility and
impact on cost of [+].


 


3.4.3.1.4 Quality Audits and Review: See section
3.2.3.1.3 Quality Audits and Review and section 3.2.4.1.4 cGMP Audits. Audits
occur, audit reports are completed and satisfactory responses to audit findings
are received from the CMO.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Completed audit reports.
Audits occur, audit reports are completed and satisfactory responses to audit
findings are received from the CMO. Approved master batch records are developed
for manufacturing [+] at the approved scale.


 


3.4.3.1.5 Project Management, Operations and
Oversight: Develop timeline, manage vendors, anticipate and
resolve problems, track project plan compliance, report progress. Progress and
any issues will be documented and addressed with the Product Development Team
on at least a monthly basis. Regular conference calls with the TMTI will be
established to review progress and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.3.2 Manufacturing Scale-Up, Large Scale
Manufacturing and Validation: GMP drug product for [+]
clinical trial will be manufactured from cGMP drug substance prepared at [+]
scale previously demonstrated in CLIN0001. The process will be scaled from the
[+]. The drug substance process will undergo process validation in which [+]
lots of drug substance are made at the [+] commercial scale and placed on
stability. Material from the first validation lot will be used to manufacture
drug product for [+] clinical trial. Quality Audits conducted in this arena are
Direct Impact audits of our Contract Manufacturing Organization (CMOs) first
cGMP run. It will include observation of the manufacturing process per cGMP/Q7
guidelines and will be documented with a report that will be added to the
initial CMO audit and filed within EDMS. The Director of QA participates in the
review and approval of process validation protocols and reports.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Audited validation report
for large scale manufacturing at a suitably qualified CMO.


 


3.4.3.2.1 Manufacture and release cGMP drug substance
and drug product Based on experience from CLIN0001, the APIs will be
produced under cGMP conditions at the [+] scale at this stage and drug product
will be manufactured for [+] clinical trial. Production and QA oversight will
be given and data generated carefully reviewed. The Director of QA participates
in the review and approval of batch records and in the review of analytical
testing of drug substance prior to approving lot


 






+ DESIGNATES PORTIONS OF THIS
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release


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Drug product for [+]
clinical trial.


 


3.4.3.2.2 Drug Substance Manufacturing Scale Up to [+]: From the [+] scale, the process will be
increased to a [+]. The purpose of using a smaller reaction size in a larger
capacity reactor is to control costs during clinical development, but enable
future scale increases in already qualified equipment. This allows minimization
of costs during the program and later enables production of RFP threshold
quantities for commercial production.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Demonstration of [+] scale
manufacturing process by successful completion of RtP run(s).


 


3.4.3.2.3 Validation of cGMP Drug Substance
Manufacturing Process: Once the [+] scale is established, a process
validation protocol will be written and executed under the guidance of the CMO
with direct input from AVI. Results of this validation will be reviewed and, if
acceptable, approved. The protocol will contain acceptance criteria in order to
evaluate the success. The Director of QA participates in the review and
approval of validation protocols, validation reports, and master batch records,


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Audited validation report
for drug substance manufacturing process at [+] scale.


 


3.4.4 Refine and Select Drug Product Formulation: AVI will work
with a formulation contract CRO, and a drug product CMO to formulate a [+] drug
product that will show enhanced stability without cold storage conditions.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Decision on final
formulation for drug product formulation.


 


3.4.4.1 [+] Product Screening Studies: Determine
important physicochemical parameters leading to design of solution [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Data to support decision on
final lyophilized formulation.


 


3.4.4.2 Accelerated Stability Studies Leading to
Selection of Lyophilized Drug Product Formulation: [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Data to support decision on
final [+] formulation.


 


3.4.4.3 Determine Extractables and Leachables: Determine if
any chemical components are extracted


 






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or leached from containers, closures, or materials used in
administration of the drug.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Data to support decision on
final [+] formulation.


 


3.4.4.4 Quality Audits: Perform
audit/review of all documentation See section 3.2.3.1.3 Quality Audits and
Review for a general description of quality audits. The CMO developing the drug
product formulation is audited to qualify the contractor as acceptable. An
audit report is completed and satisfactory responses to audit findings are
received. The formulation study protocols, draft batch records and data
obtained during manufacture of the new formulation, and the results of
analytical testing are reviewed by the Director of QA. The Director of QA
participates in the review and approval of a master batch record, analytical
test methods and their validation and proposed specifications derived from the
development of a new formulation.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Completed Audit reports.
Master batch record, analytical test methods and their validation protocols and
reports and revised specifications for the new formulation reviewed and
approved by the Director of QA.


 


3.4.4.5 Project Management, Operations and Oversight: Track progress
and manage issues as they arise.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.5 Manufacture cGMP Material at Scale for
Nonclinical and Clinical Studies and Consistency Lots: AVI will
prepare cGMP drug product for the [+] clinical safety studies from the first
validation batch of [+] scale drug substance. Three drug product batches will
be validated, and all will provide material for stability studies.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: [+] scale cGMP drug product
manufactured for [+].


 


3.4.5.1 Drug Product Engineering Runs: Drug product
configuration and process will be transferred to CMO; engineering runs will be
performed to confirm successful transfer.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Process suitable for GMP
drug manufacture.


 


3.4.5.1.1 Drug Product Engineering Run 1 An engineering
run is planned with the first drug substance of the combination product
manufactured in CLIN0002 for the purposes of testing all fill finish
capabilities including [+], formulation testing, and product testing for
adherence to product specifications.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Successful tech transfer
and final process suitable for GMP drug manufacture.


 










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DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
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3.4.5.1.2 Drug Product Engineering Run 2 An engineering
run is planned with the first drug substance of the combination product
manufactured in CLIN0002 for the purposes of testing all fill finish
capabilities including [+], formulation testing, and product testing for adherence
to product specifications.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Successful tech transfer
and final process suitable for GMP drug manufacture.


 


3.4.5.2 Manufacture, Release, Label 3 Consistency Lots
of Drug Product: Material produced at scale will be filled for the
clinical lots and for the consistency lots at a size commensurate with the
production scale of the contract manufacturing organization.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Released, labeled drug
product for clinical trials.


 


3.4.5.3 cGMP Audits: All manufacturing sites for
which a scale up is required has been previously audited and approved by QA.
The actual scale up of drug product manufacturing includes a review of all
relevant documentation for any pertinent quality issues, content uniformity,
completion and an onsite QA “for cause” visit if required. See section
3.2.3.1.3 Quality Audits and Review for general description of quality audits
and section 3.2.4.1.4 for description of cGMP audits. Full cGMP audits occur,
audit reports are completed and satisfactory responses to audit findings are
received from the CMO. Batch records and analytical test data for lot release
are reviewed by the Director of QA. Release and shipping procedures for
clinical supplies to clinical facilities are reviewed.


 


The Director of QA reviews and approves batch records, batch production
data and results of analytical testing for lot release.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Completed audit reports.
Audits occur, audit reports completed, satisfactory responses are received for
any audit findings, master batch records and other documents are reviewed and
approved for manufacturing and release of drug product.


 


3.4.5.4 Project Management, Operations and Oversight: The program
will be managed by AVI personnel and consist of initial technology transfer and
reduction to practice lots prior to cGMP production. Hands on training may be
provided initially but after establishment of the process and successful
manufacturing the program will be managed through conference calls, sites
visits, audits, data and document review including specifications and
comparison of release data with those specifications.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.6 Stability Studies: Drug product
will be evaluated according to ICH stability requirements. The duration of the
stability program is [+], and it will exceed the minimum requirement in the
statement of objectives and Target Product Profile (TPP) threshold. The
stability program includes full term aging studies at [+] will not be performed
on the drug substance, but will be performed on the lyophilized drug product.


 










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Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Stability studies of [+]
and validated drug substance have been initiated. Stability studies set up for
[+] scale cGMP drug product material manufactured for [+] safety studies.


 


3.4.6.1 Stability on [+] and Drug Substance ([+] Stability Program Starts): Follow ICH
guideline Q1A to acquire data to justify retest date at defined storage
condition.


 


Period of Work: Approximately [+] days (e.g.
[+]).


 


Deliverable: Completion of stability
studies from CLIN0001 and initiation of studies on [+] and validated drug
substance.


 


3.4.6.1.1 Ongoing Stability on [+]: This is the
completion of the [+] stability program started in CLIN0001.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Completion of stability
studies of [+].


 


3.4.6.1.2 Stability Studies Drug Substance ([+]
Stability Program Starts): Each drug substance
manufactured will be placed on a [+]
stability program in order to demonstrate the long term product characteristics
of the material. Since these drug substances are at a new scale of production
stability needs to be performed until a suitable quantity of lots have been
made to demonstrate shelf life. All lots made in CLIN0002 will be placed on
stability.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Initiation of stability
program for drug substance.


 


3.4.6.2 Stability on Drug Product ([+] Stability
Program Starts): Follow ICH guideline Q1A to acquire data to justify
expiration date at defined storage condition.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Initiation of stability
program for drug product.


 


3.4.6.2.1 Ongoing Drug Product Stability Studies: Continue ICH
guideline Q1A to acquire data to justify expiration date at defined storage
conditions. Drug product manufactured prior to the start of CLIN0002 will
continue on stability and final reports will be issued at the end of the study.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Ongoing stability data for
drug product.


 


3.4.6.2.2 Stability Studies Drug Product ([+] Stability Program): New drug product
stability studies will be set up for [+]. Multiple temperature storage
conditions will be examined to provide the storage conditions for optimal use.


 


Period of Work: Approximately [+] week
(e.g. [+]).


 






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Deliverable: Initiation of stability
program for drug product.


 


3.4.6.3 cGMP Audit: Stability Study Audits are
Direct Impact audits. Audits include a list of questions directly suited to the
supplier and a cGMP, GLP (Analytical) checklist (again dependent on supplier).
All suppliers (through audits) are approved (or rejected) by QA and audit
records are maintained by the AVI EDMS. See section 3.2.3.1.3 Quality Audits
and Review for general description of quality audits and section 3.2.4.1.4 for
description of cGMP audits. Full cGMP audits occur, audit reports are completed
and satisfactory responses to audit findings are received from the CMO
conducting stability studies for AVI. The Director of QA reviews and approves
stability study protocols as well as reports on stability data.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Audited final report on
stability and shelf life of drug product. Full cGMP audits occur, audit reports
are completed and satisfactory responses to audit findings are received in
order to qualify the CMO. Stability study protocols are reviewed and approved.


 


3.4.6.4 Project Management, Operations and Oversight: Track progress
and manage issues as they arise.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.7 Stability Testing to Define Operational Storage
(Time Temperature Indicator): Each drug product is [+],
which makes room temperature storage feasible and reduces cold chain
requirements, exceeding minimum requirement in the statement of objectives and
TPP threshold. The scope of the stability studies will establish the Time
Temperature Indicator (TTI), since it includes full term accelerated
conditions. Based upon the results, a TTI can be established to support the
product shipments. As part of the operational storage and distribution
criteria, product shipments will be monitored for excursions during shipment
using temperature monitoring devices.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Stability studies set up
for [+] scale cGMP product material to establish TTI.


 


3.4.7.1 Conduct Stability Studies under [+]: These studies will be conducted at [+]
temperature than the recommended storage condition to determine additional time
that the material may exposed to harsher conditions without risk.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Stability studies completed
to establish TTI.


 


3.4.7.2 Conduct Shipping and Transport Stability
Studies: These studies will show that the drug product is
stable under the actual conditions of shipping.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Stability studies completed
to establish TTI.


 










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3.4.7.3 Quality Audits: Stability Study
Audits are Direct Impact audits. Audits include a list of questions directly
suited to the supplier and a cGMP, GLP (Analytical) checklist (again dependent
on supplier). All suppliers (through audits) are approved (or rejected) by QA
and audit records are maintained by the AVI EDMS. The Director of QA reviews
and approves stability study protocols as well as reports on stability data.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Documented audit findings
Approved stability study protocol and approved study data and reports.


 


3.4.7.4 Project Management, Operations and Oversight: Track progress
and manage issues as they arise.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.8 Conduct Nonclinical Studies: In addition
to the multiple studies completed to date and forming the basis for the open
IND, the studies since then and prior to this award that will supplement that
IND, AVI will also complete further [+] studies, for example [+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Conduct [+] scale cGMP
product material.


 


3.4.8.1 [+]: [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Final Report on [+].


 


3.4.8.2 [+]: [+] to provide data necessary for registration.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Sufficient [+].


 


3.4.8.3 [+] Mass Balance: Mass balance study required to show fate of
drug in [+]; required data for registration.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Final report from CRO on
mass balance in the [+].


 


3.4.8.4 [+] in vivo Metabolism: Provide data
on metabolism of drug in [+] model. Required for registration and determination
if any metabolites are present that need to be monitored in preclinical and
clinical trials.


 


Period of Work: Approximately [+] months
(e.g. [+]). 


 


Deliverable: Final report from CRO on in
vivo metabolism in the [+].


 


3.4.8.5 [+]: [+].


 






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Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Final report from CRO on
protein binding.


 


3.4.8.6 [+] Dose Range Finding Study: To determine
the effect of treatment on the [+] development, with determination of
appropriate dose levels for the definitive [+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Audited final report on [+]
study.


 


3.4.8.7 [+] Study: The definitive study to determine the effect of
treatment on the [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audited final report on [+]
study.


 


3.4.8.8 Quality Audits: All preclinical
studies will be monitored by AVI during critical in-life phases to assure
adherence to GLPs and protocol; monitoring will also be done by CRO QA unit.
Study reports reviewed by CRO QA unit and by AVI to assure accuracy See section
3.2.3.1.3 Quality Audits and Review for a general description of quality
audits. GLP audits occur, reports are completed and satisfactory responses to
audit findings are required from CROs conducting AVI-6002 nonclinical studies
and [+] testing facilities. Analytical testing occurs using AVI’s QA-approved
validated analytical methods. The Director of QA participates in the review and
approval of [+] method validation protocols and validation reports. All
nonclinical studies will be monitored by AVI during critical in-life phases to
assure adherence to GLP requirements. Study monitoring will also be done by the
CRO’s QA unit. Study reports and data listings will be reviewed by the CRO’s QA
unit and by AVI’s monitor and QA Unit to assure accuracy.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audits will occur, audit
reports completed and satisfactory responses to audit findings will be required
from nonclinical CROs and [+] testing facilities. Study reports and data
listings will be reviewed and approved by the CRO’s QA unit and by AVI’s
monitor and QA Unit.


 


3.4.8.9 Project Management, Operations and Oversight: Track progress
and manage issues as they arise.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.9 [+] Efficacy Studies in [+]: The
[+] studies will confirm therapeutic efficacy at specific dose levels and
expected exposures that will be mimicked in [+]. Using the currently filed IND,
clinical safety and any animal data obtained during CLIN0001, any additional
preclinical data, and based on the protocol developed with FDA as to the
studies necessary under the [+], AVI will conduct the [+] studies, necessary to
show protection against an [+] challenge by injection.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Conduct NHP [+] studies
using [+] scale cGMP product material.


 










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3.4.9.1 [+] Efficacy Studies in [+] #1: The [+] studies will confirm therapeutic
efficacy at specific dose levels and expected exposures that will be mimicked
in [+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Conduct NHP [+] studies using [+] scale AVI-6002 cGMP
product material


 


3.4.9.1.1 [+] Acquisition and Acclimation: Prior to [+] protocols are reviewed by [+]. Once
protocols are approved, [+]. [+] are held in quarantine to ensure acclimation
to the laboratory setting and receive a final health evaluation. Finally,
randomization and cage arrangements are finalized.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Sufficient [+] acclimated
and released for first pivotal study to begin.


 


3.4.9.1.2 Conduct Study, Laboratory Analyses, Viral
Sequencing: This is the “in-life” phase of the study involving
[+].


 


Period of Work: Approximately [+] months (e.g. [+]).


 


Deliverable: Completion of the [+]
portion of the first [+] study.


 


3.4.9.1.3 Data Analyses, Final Study Report: Compile
observations and unblind data. Statistical analysis and preparation of a final
study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Presentation of final study
report.


 


3.4.9.2 [+] Studies in [+]: The
[+] studies will confirm therapeutic efficacy at specific dose levels and
expected exposures that will be mimicked in [+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Conduct NHP [+] studies
using [+] scale AVI-6002 cGMP product material


 


3.4.9.2.1 [+] Acquisition and Acclimation: Prior to [+]
protocols are reviewed by [+]. Once protocols are approved, [+] acquisition can
take place. [+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Sufficient [+] acclimated
and released for second pivotal study to begin.


 


3.4.9.2.2 Conduct Study, Laboratory Analyses, [+]: This is the [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Completion of the [+]
portion of the [+] study.


 


3.4.9.2.3 Data Analyses, Final Study Report: Compile
observations and unblind data. Statistical analysis and preparation of a final
study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 










+ DESIGNATES PORTIONS OF THIS
DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
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Deliverable: Presentation of final study
report.


 


3.4.9.3 Data Management: Full data
management and statistical analysis plans will be developed by a qualified
Contract Research Organization, and shared with the FDA (and USG) before
studies completed. The CRO will monitor source documents (to the extent
possible in a BSL4 environment), collect data, ensure all data queries are
clarified, lock database, analyze and then reveal treatment allocation.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Conduct analyses of pivotal
efficacy studies for study reports.


 


3.4.9.4 GLP Audits: See section 3.2.3.1.3
Quality Audits and Review for a general description of quality audits. GLP
audits occur, reports are completed and satisfactory responses to audit
findings are required from CROs conducting nonclinical studies and [+] testing
facilities. Analytical testing occurs using AVI’s QA-approved validated
analytical methods. The Director of QA participates in the review and approval
of [+] method validation protocols and validation reports. All nonclinical
studies will be monitored by AVI during critical in-life phases to assure
adherence to GLP requirements. Study monitoring will also be done by the CRO’s
QA unit. Study reports and data listings will be reviewed by the CRO’s QA unit
and by AVI’s monitor and QA Unit to assure accuracy


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audits will occur, audit
reports completed and satisfactory responses to audit findings will be required
from nonclinical CROs and [+] testing facilities. Study reports and data
listings will be reviewed and approved by the CRO’s QA unit and by AVI’s
monitor and QA Unit.


 


3.4.9.5 Project Management, Operations and Oversight: Develop
timeline, manage vendors, anticipate and resolve problems, track project plan
compliance, report progress. Progress and any issues will be documented and
addressed with the Product Development Team on at least a monthly basis.
Regular conference calls with the TMTI will be established to review progress
and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.10 Activities to Achieve Pivotal Efficacy Studies:
AVI will prepare and submit [+]. The Final Protocols for the [+]
studies will also be submitted after the FDA responses are received from the
[+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: [+] submitted to the FDA.


 


3.4.10.1 [+] (Clinical, Nonclinical): [+] will be
submitted as soon as study reports are available to keep the [+]. The Final Protocols for the [+] studies will also be submitted as [+] after the FDA responses are received
from the [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: [+] submitted to the FDA.


 


3.4.10.2 [+] (Drug Substance, Drug Product): [+] will be
submitted as soon as data are available on the lots of drug substance and drug
product that will be used in the [+]
Studies are available.


 






+ DESIGNATES PORTIONS OF THIS
DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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Additional [+] will be
submitted as reports and data are available to keep the [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Prepare and submit [+].


 


3.4.10.3 Project Management, Operations and Oversight:
Develop timeline, manage vendors, anticipate and resolve problems,
track project compliance, report progress. As part of the normal course of
executing project, regular team meetings will be held with each vendor and held
internally. This team is responsible for the project plan. Project progress and
any issues relative to the project plan will be documented and addressed with
the Product Development Team on at least a monthly basis. Regular conference calls
with the TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.11 Request and Conduct [+] Meeting with the FDA: AVI will
request an [+] to provide a
summary of results of the [+]
clinical studies and to discuss the [+]
clinical development plan. The topic of designation as a [+]. A Meeting Request Letter and Briefing
Document will be submitted to the FDA. Advanced notification of the meeting,
plus copies of all meeting-related documents will be provided to the USG
Program Office in a timely manner. After the meeting AVI’s regulatory affairs
staff will prepare and submit notes of the meeting as an [+]. The FDA’s official
Meeting Minutes will be reviewed to ensure that they reflect the same meeting
outcomes and agreements as those documented by AVI.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: [+] Request and Briefing
Document submitted to the FDA. Participate in [+] meeting with FDA. Prepare
notes of the meeting and review the FDA’s official Meeting Minutes to assure
that both the FDA and AVI agree on the outcomes of the discussion and
agreements.


 


3.4.11.1 Prepare Meeting Request and Briefing Document:
The Meeting Request Letter and Briefing Document will be prepared as
soon as is feasible and submitted to the FDA at least one month in advance of
the requested meeting date. . Advanced notification of the meeting, plus copies
of all meeting-related documents will be provided to the USG Program Office in
a timely manner.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: [+] Meeting Request Letter
and Briefing Document submitted to the FDA.


 


3.4.11.2 [+]: [+].


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: Submit request for [+] to
the FDA.


 


3.4.11.3 FDA Meeting, Minutes and Follow Up: AVI will attend
the [+] with the FDA. AVI will submit notes of the meeting to the FDA and
ensure that the company is in agreement with the outcomes and agreements
recorded in the FDA’s official Meeting Minutes. Clarifications will be


 






+ DESIGNATES PORTIONS OF THIS
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requested, as necessary. AVI will continue an open dialogue with the
FDA as development continues.


 


Period of Work: Approximately [+] week
(e.g. [+]).


 


Deliverable: AVI will provide copies of
the company’s notes and the FDA’s official Meeting Minutes to the USG Program
office.


 


3.4.11.4 Project Management, Operations and Oversight:
Develop timeline, manage vendors, anticipate and resolve problems,
track compliance, report progress. Project progress and any issues relative to
the development plan will be documented and addressed with the Product
Development Team on at least a monthly basis. Regular conference calls with the
TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] months
(e.g. [+])


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.12 [+]: [+].


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Deliver sample of drug
product used in [+] clinical safety study to USG


 


3.4.12.1 Ship [+] to US Government: At the end of CLIN0002 at least [+] of the
drug product(s) will be delivered to the recipient specified by the US
Government.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Deliver sample of drug
product used in [+] clinical safety study to USG


 


3.4.12.2 Project Management, Operations and Oversight:
Track progress and manage issues as they arise.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.13 Phase 2 Multidose Dose Escalation Clinical
Study: A [+] Volunteers. A goal for this study is to establish a [+], the
intended therapeutic schedule. [+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Complete [+] clinical study
and issue final clinical study report.


 


3.4.13.1 Clinical Site and Local Laboratory
Activities: The study will be planned and executed at audited,
selected [+] Clinical Research site(s) with support from selected, fully [+]
accredited laboratory. Site and laboratory will have had satisfactory GCP/GLP
audits and then site will be initiated, monitored through to study completion
and close out.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 






+ DESIGNATES PORTIONS OF THIS
DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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Deliverable: Plan, conduct and complete
[+] clinical study. Provide all required data to the CRO for final study
report.


 


3.4.13.1.1 Contracts and Budgets: Contracts will
be negotiated with vendors for the execution of this study.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Signed contracts in place
with all vendors before initiation of [+] clinical study.


 


3.4.13.1.2 Protocol [+] Approval: Full [+] in parallel; AVI will answer any
questions and amend protocol if necessary. The Amended protocol will be
submitted to the [+] for approval prior to and notification of site(s) start
study. All required information about the investigator, site, testing laboratories
and CRO responsibilities will be submitted to the FDA prior to study start at
any site.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: FDA, Ethics Committee and
[+] approvals received before study start.


 


3.4.13.1.3 Site Activities First Patient First Visit
to Last Patient Last Visit: The study will be planned
and executed at an audited, selected [+] Clinical Research Facility. Site will
be involved with review of study specific documentation and trained prior to
first subject first visit. All interactions with the site will be documented.
Regular site monitoring will be planned and documented to ensure data has been
verified and entered in a timely fashion, while ensuring subject safety. Any
compliance issues will be raised to the clinical team for response.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Complete [+] study and
complete electronic case report forms on schedule and within budget.


 


3.4.13.1.4 Site(s) Close Out: After
completion of the last subject last visit, all data queries will be completed
by the site and/or laboratory, previously validated database locked, analyses
run, and draft study report prepared. In parallel formal close out of the
clinical site, with disposal of unused drug supplies and completion of all
outstanding documentation will occur.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: All open queries and action
items associated with clinical study execution are completed and documented in
a site close out visit report.


 


3.4.13.2 Outsource Services: Identify,
select and qualify subcontractors needed to execute clinical study. Assigned
vendor personnel will participate in a kick off meeting in which study
expectations and needs, including timelines, will be discussed. Protocol and
procedure training will occur. A communication plan and reports needed will be
developed prior to first subject enrolled.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Training records, meeting
minutes confirm that subcontractors are trained to the study and ready to
perform services.


 










+ DESIGNATES PORTIONS OF THIS
DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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3.4.13.2.1 Clinical Research Organization and Data
Management: The CRO is key to study success. Their team, along
with AVI personnel, is responsible for site start up activities, site training,
and study execution, including data collection and management. The statistical
support is part of the CRO. This group and Data Management will develop the
plans necessary for data collection, query management, data analysis and
quality checks. They will prepare reports for the [+] reviews. The final
clinical study report will be written by CRO personnel.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Executed contract between
AVI and CRO.


 


3.4.13.2.2 Central Laboratory Services and Data
Transfer: [+] and analyses will each be conducted at a central
lab facility. Data from each will be sent to data management vendor for
inclusion in final study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Laboratory data reports
provided to data management vendor.


 


3.4.13.2.3 [+]: An independent [+] will be appointed to oversee and confirm
dose escalation decisions. A [+]
will be prepared and agreed with [+]
members, a contract developed and a kickoff meeting and then [+] meetings with open and closed session.
Members of the [+] will be
available to [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Decisions to [+] as documented in meeting minutes.


 


3.4.13.2.4 Provide Electronic Data Management with
Access to US Government: Enable Medidata web portal with secure access
to assigned study, company, vendor, and USG personnel.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Functional secure EDC
portal access.


 


3.4.13.2.5 Drug Warehousing and Distribution: Store clinical
trial material at [+] in secure, temperature controlled and monitored unit.
Implement traceable distribution system with chain of custody documentation.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Provide clinical trial
material on time to site(s) and keep adequate records.


 


3.4.13.3 Provide Documents to Clinical Sites and
Complete Study Reports: CRO, lab vendors and drug warehouse provide
complete set of documents and forms to effectively and efficiently conduct
study, including but not limited to: study specific data collection forms
(electronic case report forms), the study operations manual, training on the
protocol, clinical trial material storage, inventory and administration, use of
[+], and Good Clinical Practice regulations.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 






+ DESIGNATES PORTIONS OF THIS
DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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Deliverable: Shipping receipts showing
what was sent to whom and when.


 


3.4.13.3.1 Prepare and Distribute Study Documents: CRO, lab
vendors and drug warehouse provide complete set of documents and forms to
effectively and efficiently conduct study.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable:. All study
related documents including but not limited to: study plan and timeline, [+]
completion guidelines, monitoring reports, protocol compliance tracking,
communication plan, meeting minutes, training materials and logs, drug
accountability logs and final study report.


 


3.4.13.3.2 Final Study Reports: Prepare
submission ready final clinical study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable:Submit compliant and
complete [+] will be submitted to the FDA as an [+].


 


3.4.13.4 GCP Audits: Audits will be performed of
Clinical Study Sites.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audits will occur, audit
reports completed and satisfactory responses to audit findings will be required
from clinical sites. Study reports and data listings will be reviewed and
approved by the CRO’s QA unit and by AVI’s monitor and QA Unit.


 


3.4.13.5 Project Management, Operations and Oversight:
Develop timeline, manage vendors, anticipate and resolve problems,
track protocol compliance, report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.14 [+] Clinical Study: AVI will
conduct a [+]. A specialized [+], is expected to support efficient
enrollment and evaluation. Subject accrual and treatment is scheduled for less
than [+] months. The results will be available for the planning of the expanded
[+] trial.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Conduct [+] clinical study using [+] scale cGMP drug
product material and issue final clinical study report.


 


3.4.14.1 Clinical Site and Local Laboratory Activities: Clinical
sites and laboratories will be audited for compliance with GCP, selected and
then initiated, monitored through to study completion and close out. The study
will be planned and executed at audited, selected [+] Clinical Research site(s) with support from a fully [+] accredited laboratory. From initiation
forward the site(s) will be monitored through to study completion and site
close out.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Plan, conduct and complete
[+] clinical study. Provide all
required data to the CRO for final study report.


 






+ DESIGNATES PORTIONS OF THIS
DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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3.4.14.1.1 Contracts and Budgets: Contracts will
be negotiated with vendors for the execution of this study.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Signed contracts in place
with all vendors before initiation of [+] clinical study.


 


3.4.14.1.2 [+] Approval: Full protocol
will be submitted to [+] in parallel; AVI with CRO will answer any questions
and amend protocol if necessary to ensure final ethics approval, and
notification of site(s) prior to study start.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: All approvals received
before initiation of clinical study.


 


3.4.14.1.3 Site Activities First Patient in to Last
Patient Out: The study will be planned and executed at an
audited, selected [+] Clinical Research Facility. Site will be involved with
review of study specific documentation and trained prior to first subject first
visit. All interactions with the site will be documented. Regular site
monitoring will be planned and documented to AVI (or Contract Research
Organization staff) will monitor conduct of the [+] study to ensure data has
been verified and entered in a timely fashion, while ensuring subject safety.
Any compliance issues will be raised to the clinical team for response.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Complete in life portion of
[+] study and complete electronic case report forms on schedule and within
budget.


 


3.4.14.1.4 Site(s) Close Out: After
completion of the last subject last visit, all data queries will be completed
by the site and/or laboratory, previously validated database locked, analyses
run, and draft study report prepared. In parallel formal close out of the clinical
site, with disposal of unused drug supplies and completion of all outstanding
documentation will occur.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: All open queries and action
items associated with clinical study execution are completed and documented in
a site close out visit report.


 


3.4.14.2 Outsource Services: Identify,
select and qualify subcontractors needed to execute clinical study. Assigned
vendor personnel will participate in a kick off meeting in which study
expectations and needs, including timelines, will be discussed. Protocol and
procedure training will occur. A communication plan and reports needed will be
developed prior to first subject enrolled.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Training records, meeting
minutes confirm that subcontractors are trained to the study and ready to
perform services.


 


3.4.14.2.1 Clinical Research Organization and Data
Management: The CRO is key to study success. Their team, along
with AVI personnel, is responsible for site start up activities, site training,
and study execution, including data collection and management. The statistical
support is part of the CRO. This


 






+ DESIGNATES PORTIONS OF THIS
DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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group and Data Management will develop the plans necessary for data
collection, query management, data analysis and quality checks. They will
prepare reports for the [+] reviews. The final clinical study report will be
written by CRO personnel.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Executed contract between
AVI and CRO.


 


3.4.14.2.2 Central Laboratory Services and Data
Transfer: [+] and analyses will each be conducted at a central
lab run at one facility. Data from each will be sent to data management vendor
for inclusion in final study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Laboratory data reports
provided to data management vendor.


 


3.4.14.2.3 [+]: An independent [+] will be appointed to oversee and
confirm dose escalation decisions. A [+]
charter will be prepared and agreed with [+]
members, a contract developed and a kickoff meeting and then dose escalation
meetings with open and closed session. Members of the [+] will be available to review safety data
and confirm or reject escalation to the next higher dose.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Decisions to dose escalate,
continue or stop study as documented in meeting minutes.


 


3.4.14.2.4 Provide Electronic Data Management with
Access to US Government: Enable [+]
with secure access to assigned study, company, vendor and USG personnel.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Functional secure [+]
access.


 


3.4.14.2.5 Drug Warehousing and Distribution: Store clinical
trial material at refrigerated conditions in secure, temperature controlled and
monitored unit. Implement traceable distribution system with chain of custody
documentation.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Provide clinical trial
material on time to site(s) and keep adequate records.


 


3.4.14.3 Provide Documents to Clinical Sites and
Complete Study Reports: CRO, lab vendors and drug warehouse provide
complete set of documents and forms to effectively and efficiently conduct
study, including but not limited to: study specific data collection forms
(electronic case report forms), the study operations manual, training on the
protocol, clinical trial material storage, inventory and administration, use of
[+], and Good Clinical Practice regulations.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Shipping receipts showing
what was sent to whom and when.


 


3.4.14.3.1 Prepare and Distribute Study Documents: CRO, lab
vendors and drug warehouse provide


 






+ DESIGNATES PORTIONS OF THIS DOCUMENT
THAT HAVE BEEN OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED
SEPARATELY WITH THE COMMISSION.


 


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complete set of documents and forms to effectively and efficiently
conduct study.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: All study related documents
including but not limited to: study plan and timeline, [+] guidelines, monitoring
reports, protocol compliance tracking, communication plan, meeting minutes,
training materials and logs, drug accountability logs and final study report.


 


3.4.14.3.2 Final Study Report: Prepare
Submission ready final clinical study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: The Final Study Report will
be submitted to the FDA as an [+]. Submit compliant and complete final clinical
study report.


 


3.4.14.4 GCP Audits: Audits will be performed of
Clinical Study Sites.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audits will occur, audit
reports completed and satisfactory responses to audit findings will be required
from clinical sites. Study reports and data listings will be reviewed and
approved by the CRO’s QA unit and by AVI’s monitor and QA Unit.


 


3.4.14.5 Project Management, Operations and Oversight:
Track progress and manage issues as they arise.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.15 Contract Program Management: AVI will track
progress on each element in the contract, including all financial and reporting
requirements; ensure compliance with contract and all government regulations.
AVI will manage all subcontracts and ensure that their timelines are met, and
the components contributed by each to the overall program are coordinated, on
budget, and that they are compliant with all contract and Government
regulations that are applicable. In addition AVI will continue to implement
enhancements to the Quality Systems Approach already in place, including
installation of a secure 21 CFR Part 11 compliant EDMS and preparation for
electronic submission of documents to the FDA. The EDMS will be utilized for
document management and control, including collaborative authoring of study
reports and eCTD text for the [+], revision and versioning control with
metadata for audit trails, and secure document repository. The EDMS will
provide authorized representatives of USG electronic access to program status
information. The use of eCTD compliant document templates and completed reports
for electronic submissions to the FDA will be managed, controlled, archived and
regulated under the Quality System in the EDMS.


 


Period of Work: Concurrent with all
CLIN0002 activities. Approximately [+] days (e.g. [+]).


 


Deliverable: Provide contract management
and financial oversight ensuring compliance.


 


3.4.15.1 Program Management: Track progress
and manage issues as they arise.


 






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Period of Work: Concurrent with all
CLIN0002 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide project management
ensuring compliance.


 


3.4.15.2 Finance and [+]: Track financial work process and reporting.


 


Period of Work: Concurrent with all
CLIN0002 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide project financial
management ensuring compliance.


 


3.4.15.3 Contract and Subcontract Management: Manage our
compliance with contract and USG regulations; manage subcontractors and
relationship with them.


 


Period of Work: Concurrent with all
CLIN0002 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide contract and
subcontract management ensuring compliance.


 


3.4.15.4 EDMS and QA: AVI will continue to store
all documents on the validated EDMS and preparation for electronic document
submission to the FDA. AVI will train all pertinent staff on EDMS and Quality
Assurance.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: EDMS system fully
operational. QA audits of all vendors will have been performed and any follow
up action items identified and tracked.


 


3.5 CLIN0003: AVI will
deliver the developmental therapeutic end item that has achieved [+] Clinical
Study, based upon CLIN0001 and CLIN0002 (recognizing that some activities will
be concurrent), additional prior studies and all the associated regulatory
requirements sufficient and in place to support this. This will comprise all those
activities necessary for our candidate drug product to complete the USG
Statement of Objectives in CLIN0003.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Drug product on which [+]
Clinical Study has been completed.


 


3.5.1 Complete Pivotal Efficacy Studies: This has been
moved to CLIN0002 3.4.9.1 and 3.4.9.2.


 


3.5.2 [+]: Continue to implement
enhancements to the Quality Systems Approach already in place, including
installation of a secure 21CFR Part 11 compliant EDMS and preparation for
electronic submission of documents to the FDA.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Submit the quality
amendment to FDA as a supplement to the AVI-6002 [+].


 


3.5.2.1 Write and Submit [+]: Update information stored on EDMS and
preparation for electronic submission of documents to the FDA.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Submit the quality
amendment to FDA as an [+].


 


3.5.2.2 Respond to FDA Questions: Develop and
provide response to any questions or


 






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recommendations from FDA following filing of [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Submit to FDA as an [+].


 


3.5.2.3 Project Management, Operations and Oversight: Develop
timeline, manage vendors, anticipate and resolve problems, track protocol
compliance, report project progress. As part of the normal course of conducting
clinical trials, regular team meetings will be held with each vendor and held
internally. This team is responsible for the project plan. Project progress and
any issues relative to the project plan will be documented and addressed with
the Product Development Team on at least a monthly basis. Regular conference
calls with the TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.5.3 [+] Study: Using the currently filed
AVI-6002 [+], clinical safety and any [+] data obtained during
CLIN0001 and CLIN0002, AVI will initiate the [+] Study in [+]
using the protocols agreed with FDA, while ensuring all necessary [+]
study requirements such as [+] review and approval. AVI will
conduct this [+]. FDA concurrence that this will be
sufficient for the safety database to [+] will be sought.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Conduct and audit [+] study and issue final study report.


 


3.5.3.1 Clinical Site and Local Laboratory Activities:
The study will be planned and executed at audited, selected [+] Clinical Research site(s) with support
from a fully [+] accredited
laboratory. From initiation forward the site(s) will be monitored through to
study completion and site close out.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Plan, conduct and complete
[+] clinical study. Provide all
required data to the CRO for final study report.


 


3.5.3.1.1 Contracts and Budgets: Contracts will
be negotiated with vendors for the execution of this study.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Signed contracts in place
with all vendors before initiation of [+] clinical study


 


3.5.3.1.2 [+] Approval: Full protocol
will be submitted to [+] in
parallel; AVI with the CRO will answer any questions and amend protocol if
necessary to ensure final ethics approval and notification of site(s) prior to
study start.


 


Period of Work: Approximately [+] months
(e.g. [+])


 


Deliverable: FDA, Ethics Committee and [+] approvals received before initiation of
the [+] safety study.


 






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3.5.3.1.3 Site Activities First Patient in to Last
Patient Out: The study will be planned and executed at an
audited, selected clinical sites. Sites will be involved with review of study
specific documentation and trained prior to first subject first visit. All
interactions with the sites will be documented. Regular site monitoring will be
planned and documented to AVI (or Contract Research Organization staff) will
monitor conduct of the [+] study to
ensure data have been verified and entered in a timely fashion, while ensuring
subject safety. Any compliance issues will be raised to the clinical team for
response.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Complete in life portion of
pivotal safety study and complete electronic case report forms on schedule and
within budget.


 


3.5.3.1.4 Site(s) Close Out: After
completion of the last subject last visit, all data queries will be completed
by the site and/or laboratory, previously validated database locked, analyses
run, and draft study report prepared. In parallel formal close out of the
clinical site, with disposal of unused drug supplies and completion of all
outstanding documentation will occur.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: All open queries and action
items associated with clinical study execution are completed and documented in
a site close out visit report.


 


3.5.3.2 Outsource Services: Identify,
select and qualify subcontractors needed to execute clinical study. Assigned
vendor personnel will participate in a kick off meeting in which study
expectations and needs, including timelines, will be discussed. Protocol and
procedure training will occur. A communication plan and reports needed will be
developed prior to first subject enrolled.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Training records, meeting
minutes confirm that subcontractors are trained to the study and ready to
perform services.


 


3.5.3.2.1 Clinical Research Organization and Data
Management: The CRO is key to study success. Their team, along
with AVI personnel, is responsible for site start up activities, site training,
and study execution, including data collection and management. The statistical
support is part of the CRO. This group and Data Management will develop the
plans necessary for data collection, query management, data analysis and
quality checks. They will prepare reports for the [+] reviews. The final clinical study report will be written by
CRO personnel.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Executed contract between
AVI and CRO.


 


3.5.3.2.2 Central Laboratory Services and Data
Transfer: [+] and
analyses will each be conducted at a central lab facility. Data from each will
be sent to data management vendor for inclusion in final study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Laboratory data reports
provided to data management vendor.


 










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3.5.3.2.3 [+]: An independent [+] will be appointed to oversee and confirm
dose escalation decisions. A [+]
will be prepared and agreed with [+]
members, a contract developed and a kickoff meeting and then dose escalation
meetings with open and closed session. Members of the [+] will be available to review safety data
and confirm or reject escalation to the next higher dose.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Provide safety oversight
for pivotal safety study. Decisions to dose escalate, continue or stop study as
documented in meeting minutes.


 


3.5.3.2.4 Provide Electronic Data Management with
Access to US Government: Enable [+]
with secure access to assigned study, company, vendor and USG personnel.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Functional, secure [+]
access.


 


3.5.3.2.5 Drug Warehousing and Distribution: Store clinical
trial material at refrigerated conditions in secure, temperature controlled and
monitored unit. Implement traceable distribution system with chain of custody
documentation.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Provide clinical trial
material on time to site(s) and keep adequate records.


 


3.5.3.3 Provide Documents to Clinical Sites and
Complete Study Reports: CRO, lab vendors and drug warehouse provide
complete set of documents and forms to effectively and efficiently conduct
study, including but not limited to: study specific data collection forms
(electronic case report forms), the study operations manual, training on the
protocol, clinical trial material storage, inventory and administration, use of
[+], and Good Clinical Practice regulations.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Shipping receipts showing
what was sent to whom and when.


 


3.5.3.3.1 Prepare and Distribute Study Documents: CRO, lab
vendors and drug warehouse provide complete set of documents and forms to
effectively and efficiently conduct study.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: All study related documents
including but not limited to: study plan and timeline, eCRF completion
guidelines, monitoring reports, protocol compliance tracking, communication
plan, meeting minutes, training materials and logs, drug accountability logs
and final study report.


 


3.5.3.3.2 Final Study Report: Prepare
submission ready final clinical study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Submit compliant and
complete final clinical study report.


 


3.5.3.4 GCP Audits: Audits will be performed of
Clinical Study Sites.


 










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Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audits will occur, audit
reports completed and satisfactory responses to audit findings will be required
from clinical sites. Study reports and data listings will be reviewed and
approved by the CRO’s QA unit and by AVI ‘s monitor and QA Unit.


 


3.5.3.5 Project Management, Operations and Oversight: Track progress
and manage issues as they arise.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.5.4 Refine and Select Formulation and Delivery
System: AVI will continue the assessment of stability for
the validation lots prepared in CLIN0002. The drug kit per treatment will
comprise [+]. The storage of the kit will be [at room temperature (15°C to
30°C)]. This drug product kit meets the [+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Finalize the drug kit components
for drug product.


 


3.5.4.1 Determine Configuration for Market: All details of
the commercial formulation are finalized ([+]).


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Finalize the drug kit
components for AVI-6002 product.


 


3.5.4.2 Identify Manufacturer for Packaging Final
Product: Establish contract for assembling final marketing
packages.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Finalize the vendor for
manufacture, labeling and packaging of AVI-6002 product.


 


3.5.4.3 Continue Drug Substance and Drug Product
Stability Studies: Continue drug substance and drug product stability
studies.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Continue stability for drug
substance and drug product.


 


3.5.4.4 Project Management, Operations and Oversight: Track progress
and manage issues as they arise.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.5.5 Deliver [+] to US Government: Deliver at least [+] of product, from the lot used for the [+] study.


 






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Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Deliver sample of drug
product used in [+] study to USG.


 


3.5.5.1 Deliver [+] to US Government: At the end of
CLIN0003 at least [+] of the drug
product(s) will be delivered to the recipient specified by the USG.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Deliver sample of drug
product used in [+] study to USG


 


3.5.5.2 Project Management, Operations and Oversight: Oversight of
inventory and distribution will be managed by AVI personnel through site
visits, audits, and records review.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.5.6 Contract Program Management: AVI will track
progress on each element in the contract, including all financial and reporting
requirements; ensure compliance with contract and all government regulations.
AVI will manage all subcontracts and ensure that their timelines are met, and
the components contributed by each to the overall program are coordinated, on
budget, and that they are compliant with all contract and Government regulations
that are applicable.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Provide contract management
and financial oversight ensuring compliance. 


 


3.5.6.1 Program Management: Track progress
and manage issues as they arise.


 


Period of Work: Concurrent with all
CLIN0003 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide project management
ensuring compliance.


 


3. 5.6.2 Finance and [+]: Track financial
work process and reporting.


 


Period of Work: Concurrent with all
CLIN0002 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide project financial
management ensuring compliance.


 


3.5.6.3 Contract and Subcontract Management: Manage our
compliance with contract and USG regulations; manage subcontractors and
relationship with them.


 


Period of Work: Concurrent with all
CLIN0003 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide contract and
subcontract management ensuring compliance.


 


3.5.6.4 EDMS and QA: AVI will continue to store
all documents on the validated EDMS and preparation for electronic document
submission to the FDA. AVI will train all pertinent staff on EDMS and Quality
Assurance.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: EDMS system fully
operational. QA audits of all vendors will have been performed and


 






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any follow up action items identified and tracked.


 


3.6 CLIN0004:AVI will deliver
the FDA approved therapeutic end item including all New Drug Application and
Approval activities resulting in the delivery of at least [+], based upon CLIN0001, CLIN0002 and
CLIN0003 (recognizing that some activities will be concurrent), additional
prior studies and all the associated regulatory requirements sufficient and in
place to support this. This will comprise all those activities necessary for [+] drug product to complete the USG
Statement of Objectives in CLIN0004.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Drug product approved by FDA.


 


3.6.1 [+] Meeting with the FDA: A [+] Meeting with the FDA will be requested
and a Briefing Document submitted approximately one month in advance of the
meeting. The FDA will schedule the meeting within 60 days of the request. The
purpose of the [+] Meeting is to
reach agreement on the electronic format and content of the [+]. The [+]
will also be discussed at this meeting. AVI will prepare notes of the meeting
that will document the discussion and agreements with the FDA; the notes will
be submitted to the FDA. The FDA will issue official Meeting Minutes. AVI will
follow up to request clarifications, as needed.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: AVI prepares and submits
Request Letter and Briefing Document, participates in the [+] meeting with the FDA, prepares notes of
the meeting that are submitted to the FDA.


 


3.6.1.1 Prepare Meeting Request and Briefing
Documents: The [+]
Meeting Request Letter and Briefing document will be prepared and submitted as
soon as is feasible after the completion of dosing in the clinical trials
approximately [+] ahead of the
meeting. Advanced notification of the meeting, plus copies of all
meeting-related documents will be provided to the USG in a timely manner.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: AVI [+] Meeting Request Letter and Briefing
Document are submitted to the FDA.


 


3.6.1.2 [+] Meeting, Minutes and Follow Up: AVI will
participate in the [+] with FDA,
take notes and obtain official minutes, following up on any action items due.
AVI will provide copies of the FDA’s Meeting Minutes to USG.


 


Period of Work: Approximately [+] weeks
(e.g. [+]).


 


Deliverable: AVI’s [+] Meeting notes and the FDA’s official
Meeting Minutes.


 


3.6.1.3 Project Management, Operations and Oversight: Develop
timeline, manage vendors, anticipate and resolve problems, track project
compliance, report project progress. As part of the normal course of executing
project, regular team meetings will be held with each vendor and held
internally. This team is responsible for the project plan. Project progress and
any issues relative to the project plan will be documented and addressed with
the Product Development Team on at least a monthly basis. Regular conference
calls with the TMTI will be established to review progress and results.


 






+ DESIGNATES PORTIONS OF THIS
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Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.6.2 Prepare, Submit and FDA Review of [+]: AVI will electronically submit an [+] that meets the USG’s Target Product
Profile. By using eligibility as a small business enterprise, and employing
regulatory procedural relief benefits due [+],
AVI is planning for the [+] to be
prior to the completion of the contractual period proposed. During the FDA’s
review, AVI will remain ready to respond promptly to any questions that arise
by using secure email correspondence. The USG will be kept fully informed of
progress.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: AVI prepares and
electronically submits an [+] that
meets the FDA’s requirements for review and validation.


 


3.6.2.1 Complete and Submit [+] and Respond to FDA
Review Comments: AVI will complete and submit an [+] to the FDA; and respond in a timely
fashion to Information Requests and other comments from the FDA reviewers.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: An [+] that has been submitted electronically
to the FDA and accepted for filing as an appropriately structured electronic
submission. Responses to Requests for Information and the [+] from the FDA will be answered promptly.


 


3.6.2.2 Project Management and Oversight: Develop
timeline, manage vendors, anticipate and resolve problems, track project
compliance, report project progress. As part of the normal course of executing
project, regular team meetings will be held with each vendor and held
internally. This team is responsible for the project plan. Project progress and
any issues relative to the project plan will be documented and addressed with
the Product Development Team on at least a monthly basis. Regular conference
calls with the TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.6.3 [+] and Response to FDA [+]: Given the
issues faced by the FDA [+], it is
likely that the FDA [+]. AVI will
attend and participate in an ACM, and respond promptly to any questions in the
[+] approval occurs.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Responses to Requests for
Information from the FDA will be submitted promptly. AVI will prepare a
Briefing Document and presentation materials for an [+]. Draft notes of the [+]
will be prepared.


 


3.6.3.1 [+]: AVI will plan and prepare
and, once confirmed, attend and participate at [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 






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Deliverable: AVI will prepare a
presentation and Briefing Document in advance of the ACM.


 


3.6.3.2 Prepare and Submit Complete Response to [+]: At the
conclusion of their review, the FDA will issue a [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Complete Response will be
made to any questions asked by the FDA.


 


3.6.3.3 Project Management and Oversight: Develop
timeline, manage vendors, anticipate and resolve problems, track project
compliance, report project progress. As part of the normal course of executing
project, regular team meetings will be held with each vendor and held
internally. This team is responsible for the project plan. Project progress and
any issues relative to the project plan will be documented and addressed with
the Product Development Team on at least a monthly basis. Regular conference
calls with the TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.6.3.4 [+]: AVI will receive formal
confirmation [+]. AVI will submit
[+] and participate in the final
negotiations of the [+].


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Receipt of the [+]. A copy will be sent to the USG Program
office.


 


3.6.4 [+] in Compliance with FDA Requirements: The [+]. The [+],
or in the electronic format required by the FDA at that time. The [+] will have been submitted to the FDA in
the [+] at that time.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Prepare [+].


 


3.6.4.1 Structured [+] Review and Responses: Preparation of the draft [+] (i.e. the
physician’s information and patient information leaflet) will be started before
[+] to facilitate discussion with the FDA and information will continue to be
added up [+]. Two versions are required to be submitted in the [+], one of
which is annotated with the source data for each statement. Both versions are
submitted electronically in the required XML format. During review by the FDA
Division and by [+], AVI will respond to comments promptly. At the conclusion
of the FDA review, AVI will resubmit [the final version of the agreed labeling
as an SPL (XML) format]. [+] will be sent to the USG Program Office at time of
submission [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Prepare draft labeling in
[+] and discussion with the FDA.


 


3.6.4.2 [+]: During the review of the [+] by the FDA Division and by
[+], AVI will respond promptly


 






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to comments. Recommendations of the FDA will be discussed and
incorporated and the finalized files will be resubmitted immediately prior to
[+].


 


Period of Work: Approximately [+] weeks
(e.g. [+]).


 


Deliverable: Final approved [+] to the
FDA immediately prior to [+]. Copy of the draft [+] is sent to USG Program
Office.


 


3.6.5 [+] by the FDA to US Government: Deliver [+] by the FDA, to the
USG office immediately after the [+].


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: [+] configuration approved
by the FDA will be delivered to the USG Program Office.


 


3.6.5.1 [+] to US Government: At the end of CLIN0004 [+] by the FDA will
be shipped to the USG Program Office.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable:  [+] configuration approved by the FDA will be
shipped to the USG Program Office.


 


3.6.5.2 Project Management, Operations and Oversight: Oversight of
inventory and distribution will be managed by AVI personnel through site
visits, audits, and records review.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.6.6 Prepare and Deliver [+] to US Government: AVI proposed to
subcontract all manufacturing and testing of the drug substance and drug
product. The company will submit full details of manufacturing packaging and
testing of the drug substance and drug product without divesting intellectual
property rights, and it will not be necessary to submit a [+] to FDA. The US
GOVERNMENT will have the right of access to the full documentation for the [+]
as agreed in the contract.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: AVI will send an electronic
and a paper copy of the approved [+] to the USG Program Office.


 


3.6.6.1 Ensure completion of [+] at CMO: The CMOs and manufacturers of
some of the components of the final drug product configuration [+]. A copy of
the CMO’s Letter of Authorization permitting the FDA to access their
confidential information in connection with the [+] will have been submitted in
the [+]. AVI will endeavor to ensure that the CMO updates and maintains the
conditions of the [+].


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: A copy of the Letter of
Authorization for FDA to [access the DMF information] in connection with the
review of the [+].


 






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3.6.6.2 Submit Letter of Authorization for FDA review
of [+] to US Government: The
CMOs and manufacturers of some of the components of the final drug product configuration
[+] will [+] that will be referenced by the name and address of the supplier
and reference number in the [+]. A copy of the CMO’s Letter of Authorization
permitting the FDA to access their confidential information in connection with
the [+] will have been submitted in the [+]. AVI will endeavor to ensure that
the CMO updates and maintains the conditions of the [+].


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Deliver a copy of Letter of
Authorization (to FDA) to USG.


 


3.6.6.3 Program management, operations and oversight: Develop
timeline, manage vendors, anticipate and resolve problems, track project
compliance, report project progress. As part of the normal course of executing
project, regular team meetings will be held with each vendor and held
internally. This team is responsible for the project plan. Project progress and
any issues relative to the project plan will be documented and addressed with
the Product Development Team on at least a monthly basis. Regular conference
calls with the TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.6.7 Contract Program Management: AVI will track
progress on each element in the contract, including all financial and reporting
requirements; ensure compliance with contract and all government regulations.
AVI will manage all subcontracts and ensure that their timelines are met, and
the components contributed by each to the overall study are coordinated, on
budget, and that they are compliant with all contract and Government
regulations that are applicable.


 


Period of Work: Concurrent with all
CLIN0004 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide contract management
and financial oversight ensuring compliance.


 


3.6.7.1 Program Management: Track progress
and manage issues as they arise.


 


Period of Work: Concurrent with all
CLIN0004 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide project management
ensuring compliance.


 


3.6.7.2 Finance and [+]: Track financial work process and reporting.


 


Period of Work: Concurrent with all
CLIN0004 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide project financial
management ensuring compliance.


 


3.6.7.3 Contract and Subcontract Management: Manage our
compliance with contract and USG regulations; manage subcontractors and
relationship with them.


 


Period of Work: Concurrent with all
CLIN0004 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide contract and
subcontract management ensuring compliance.


 






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3.6.7.4 EDMS and QA: The EDMS will have been
fully implemented and routinely used to prepare, review and store documents for
the [+], and regulatory and quality compliance documents. AVI will continue to
store all documents in the validated EDMS and will make electronic document
submissions to the FDA, as needed. AVI will train all pertinent staff on the
EDMS, including Quality Assurance staff.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: EDMS system fully
operational. QA audits of all vendors will have been performed and any follow
up action items identified and tracked.


 


3.6.8 Drug Substance and Drug Product Ongoing
Stability Studies: Continue manufacturing assessment of stability [+]
prepared in CLIN0002.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Continue assessment of
stability study data (to include both drug substance and drug product).


 


3.6.8.1 Continue Drug Substance Stability Studies: Continue
stability study. 


 


Period of Work: Approximately [+] days (e.g.
[+]).


 


Deliverable: Continue assessment of drug
substance stability data.


 


3.6.8.2 Continue Drug Product Stability Studies: Continue
stability study.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Continue assessment of drug
product stability data.


 






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Appendix B:
Revised Statement of Work


 


3.0 CONTRACT


 


AVI BioPharma (AVI) Statement of Work for AVI-6003 as an effective
therapeutic for Marburgvirus:


 


3.2 CLIN0001 Technology
Development (Part 1): AVI will deliver the developmental
therapeutic end item that has completed [+] clinical trials, with all the
associated preclinical and regulatory requirements sufficient and in place to
support its delivery. This will comprise all those activities necessary for our
candidate drug product to complete the US GOVERNMENT (USG) Statement of
Objectives for CLIN0001. We will complete the planning (including assessment
and mitigation of risks) for manufacturing the drug supply, and execute process
development to enable scale up from the current [+] batch GLP material, through
a [+] batch cGMP engineering development scale, in anticipation of an ultimate
[+] modular manufacturing scale; includes analytical methods development and
validation ([+], drug substance) and method qualification (drug product), and
development of specifications for lot release.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Drug product with which [+]
clinical trials have been completed.


 


3.2.2 [+] Process Development and Qualification: AVI will prepare drug
substance for use in subsequent [+] studies (includes the use of previously
manufactured components outside this RFP to prepare drug substance). The [+]
development program will improve process reproducibility and prepare for
manufacturing at larger scales. AVI will investigate several steps that have
shown variability [+], and examine steps that have challenges in scale-up [+].
The overall goal of drug substance development is to design a [+] process that
is highly reproducible and that can be demonstrated at [+] scale, and usable in
the final manufacturing [+] scale. [+]. A stable, [+] form of the drug
substance will be produced.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Design scalable processes
for [+] and drug substance.


 


3.2.2.1 [+] Process Development and Qualification: The [+] development
program is aimed at improving reproducibility and scalability and ensuring the
quality of the product. The overall goal is to design [+] process that is
highly reproducible and easily scalable.


 


Period of Work: Approximately [+] day from
time of award (e.g. [+]).


 


Deliverable: Finalization of a highly
reproducible and easily scalable [+] process in preparation for manufacturing
at larger scales.


 


3.2.2.1.1 Synthesis and Characterization of
Authentics: This project will help ensure a consistent quality
of product. [+]. These authentics will be used as markers in the analytical
method validation to check the resolution of the methods.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Preparation of authentic
impurity markers


 


3.2.2.1.2 [+] Process Development: The [+] development program is aimed at
improving reproducibility and scalability. It will investigate several steps
that have shown [+]. The overall goal is to design a [+] process that is highly
reproducible and easily scalable.


 


	
   

  	
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  or disclosure of data contained on this sheet is subject to the

  	
   

  
	
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  restriction
  on the title page of this proposal.

  	
   

  



 






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Period of Work: Approximately [+] months
from time of award (e.g.[+]).


 


Deliverable: Improvement of specific
steps and finalization of a highly reproducible and easily scalable [+]
process.


 


3.2.2.1.3 Project Management, Operations and
Oversight: Project management will oversee the CROs that are
working [+] process development and will also manage the in-house development
effort.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.2.2.2 Drug Substance [+] Process Development: The drug
substance [+] process development program will involve optimization of the [+]
components of the manufacturing process. The overall goal is to design a highly
reproducible and scalable [+] drug substance manufacturing process that can be
demonstrated at an [+] and is usable at the final manufacturing [+] scale.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Demonstration of a
reproducible and scalable manufacturing process for drug substance.


 


3.2.2.2.1 Drug Substance [+] Process Development: Development
activities are to include optimization of [+] to produce a scalable synthesis
process as well as optimization of current [+] process to increase efficiency
of [+]. Investigation of alternative [+] methods [+] will also be conducted.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Optimization of the
synthesis and [+] components of the manufacturing process.


 


3.2.2.2.2 Project Management, Operations and
Oversight: This element entails oversight and guidance of the
development activities, as well as management of technical personnel.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.2.3 Manufacturing for Nonclinical Studies**: [+] production
will occur at [+], and they will supply all the [+] needed for CLIN0001 drug
substance manufacture, plus a contingency plan for any drug substance batch
needing to be repeated (this is essential to ensure concordance with the
timeline). Any excess [+] will be used during the scale up in CLIN0002. The
current [+] drug substance process will be transferred to a contract
manufacturing organization (CMO) accomplished in the [+] manufacture of
oligomeric therapeutic drugs. The CMO will perform scaling of process to [+],
plus process development and Reduction to Practice (RtP) run(s). Material for
toxicology studies will be made.


 






**Drug Product for the [+] clinical trial has
already been manufactured and is currently stored awaiting final preparations
for the start of the study.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Produce drug substance for
[+] studies using [+] scale drug substance process.


 


3.2.3.1 Manufacturing [+]: This production
is planned to occur at [+]. It will produce all the [+] needed for CLIN0001
drug substance manufacture plus a contingency if a drug substance batch needs
to be repeated. 


 






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Any excess [+] will be used during the scale up in CLIN0002.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Timely supply of [+] to
support CLIN0001 drug substance development and manufacture.


 


3.2.3.1.1 Contract Negotiation, Material Acquisition: Finalize and
sign contracts for production. Order long lead time and custom reagents to
support upcoming campaign.


 


Period of Work: Approximately [+] month
from time of award (e.g. [+]).


 


Deliverable: Contract and materials in
place for [+] manufacture.


 


3.2.3.1.2 Manufacture [+]: Produce all the
[+] needed for CLIN0001 drug substance development and manufacture.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Timely supply of [+] to
support CLIN0001 drug substance development and manufacture.


 


3.2.3.1.3 Quality Audits and Review: Quality audits
are managed by the Director of QA and scheduled in accordance with the Audit
Master Schedule. Automatic audit reminders are issued by the EDMS. Auditors
schedule travel to and from audits, write audit reports and provide lists of
findings and make recommendations. The Director of QA oversees all operational
aspects of audits and procedures connected with audits and audit reports. Audit
findings, recommendations and responses are reviewed by the Director of QA, the
VP of Regulatory Affairs and QA and non-compliance issues are brought to the
attention of the Chief Executive Officer (CEO), personally, by the Director of
QA on a biweekly basis. In addition, a QA Unit and Compliance Report is written
monthly by the Director of QA and presented to the CEO in a 1:1 meeting.
Functional management and staffing of the QA Unit is the responsibility of and
managed by the VP of Regulatory Affairs and QA.


 


Quality Audits, depending on the process step may include audits of
non-regulated facilities (non-cGMP and non-GLP facilities) or audits of
facilities that are required to comply with cGMP or GLP. These are Direct
Impact audits of Contract Manufacturing Organizations (CMOs), quality control
testing, storage and distribution facilities connected with the manufacture of
[+] and activated tails. Audit documentation includes a list of questions
directly suited to the service provided by the CMO and an ICH Q7-compliant
audit checklist. All CMOs must be audited and approved by QA and, when
applicable, readiness for Pre-Approval Inspection (PAI) by the FDA or other
regulatory agency is evaluated during an audit. Audit records have limited,
controlled review access for authorized departmental and senior management
staff and are reviewed through and archived using the EDMS.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: QA approved CMO (vendor)
and release of manufactured [+] for AVI-6003 program. Audit report completed
and satisfactory resolution of responses to findings for CMO providing [+]. Lot
release of [+] for drug substance manufacturing program in accordance with
QA-approved specifications using analytical methods.


 


3.2.3.1.4 Project Management, Operations and
Oversight: Project management will oversee the CMO that is
doing the CLIN001 production.


 






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Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.2.3.2 Manufacture Drug Substance: Select CMO experienced
in [+] synthesis of [+] drugs. Tech transfer of [+] scale process for drug
substance; scale-up of process to [+], process development and RtP run(s);
determine stable [+] form for drug substance.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Achieve [+] scale drug
substance process and produce material for [+] studies.


 


3.2.3.2.1 Select and Contract CMO: CMOs capable of
performing [+] synthesis have been reviewed for suitability for the API
manufacture, [+], and isolation. Site visits will be performed, followed by
quality audits, contract negotiations, technical transfer, and Quality
agreement execution.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Selection and completion of
contracts with a suitable CMO for API manufacture.


 


3.2.3.2.2 Manufacturing Tech Transfer at 8L: Production will
be introduced at the current [+] scale to allow comparability of previous lots
and to transfer knowledge to the new CMO. Each API will be made and purified at
this scale with the objective being to produce material suitable for
toxicological studies.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Demonstration of successful
tech transfer of current [+] sale and production of material suitable for [+]
studies.


 


3.2.3.2.3 Process Development, Reduction to Practice
at [+]: After the [+] tech transfer campaigns, the process
size will be adapted to a [+] size as part of normal development in order to
produce more material suitable for [+] studies. At this point process changes
may be introduced to make the process more efficient as long as the impurity
profiles remain unchanged.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Demonstration of
scalability of manufacturing process to [+] scale by successful completion of
RtP run(s).


 


3.2.3.2.4 Project Management, Operations and
Oversight: As part of the normal course of outsourcing
production, regular team meetings will be held and updates provided. Production
oversight from site visits and data review will be shared and discussed.
Regular conference calls with the CMO will be established to review progress
and results.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.2.4 Develop and Validate Analytical Assays and Lot
Release Specifications: Existing analytical methods will be refined
and validated for each [+]. Methods for drug substance will be developed and
validated to meet characterization criteria set with the FDA for release. For
the drug product assays, development will utilize synergies with drug substance
methods to reduce time and cost of method qualification. For both drug
substance and drug product, AVI will qualify vendors, facilities and conduct 


 






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audits.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Validated assays for [+]
and drug substance, qualification of the drug product assays, and development
of lot release specifications for [+], drug substance and drug product.


 


3.2.4.1 [+] Analytical Method Development and
Validation: Existing analytical methods will be refined and
validated for each [+].


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Audited report for
validated analytical methods for each [+].


 


3.2.4.1.1 Method Development and Validation: Methods
confirming process consistency will be developed by a qualified subcontractor.
Methods for assay and impurity profile will be validated to established
criteria for cGMP starting materials.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Audited report for
validated analytical methods for each [+].


 


3.2.4.1.2 Identify Impurities above ID Threshold: Process-critical
impurities will be synthesized and included in the validation process. Markers
for known impurities will be synthesized as part of the impurity profile.
Chromatograms of historic lots will be generated using the refined analytical
methods. A team of chemists will work on identifying and synthesizing all
impurities that occur [+]


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Identification and preparation
of markers for all impurities that occur above the [+].


 


3.2.4.1.3 Develop (Assess and Refine) Lot Release
Specifications: To ensure consistent quality, a team will assess and
refine all the [+] lot release specifications.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: Preparation of a lot
release specification for each [+].


 


3.2.4.1.4 cGMP Audits: See section 3.2.3.1.3
Quality Audits and Review for general description of Quality Audits. cGMP
audits are performed by experienced auditors for the Contract Manufacturing
Organizations (CMOs), quality control testing and storage and distribution
facilities. Audits employ a checklist approach, based on regulatory
requirements and ICH Q7 guidelines, which are customized to comply with requirements
for each subcontractor site and circumstance. When applicable, the readiness
for a Pre-Approval Inspection by the FDA or other regulatory agency (PAI) of
cGMP and GLP subcontractors is also evaluated. Under the Quality System, batch
release specifications, test methods and quality control test results,
protocols for stability studies and analytical methods and study reports or
data are reviewed for compliance with regulations and guidelines and approved
by the Director of QA.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Audit report completed and
satisfactory resolution of responses to findings by subcontract laboratories
testing [+] for drug substance for subsequent clinical use.


 






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3.2.4.1.5 Project Management, Operations and
Oversight: Track progress and manage issues as they arise.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.2.4.2 Drug Substance (DS) Analytical Method
Development and Validation: Drug substance analytical
methods will be developed and validated to meet characterization criteria set
forth by regulatory agency for release. Impurities will be isolated and
identified. Subcontractors will be qualified, and audits performed, by AVI QA
Unit.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Audited report for
validated analytical methods for drug substance release.


 


3.2.4.2.1 Method Development and Validation: Methods,
compliant with regulatory expectations, will be developed for impurity profile,
assay, identity and description. Method validation will be performed by
qualified vendor.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Methods for impurity
profile, assay, identity and description, validated and audited report as
appropriate.


 


3.2.4.2.2 Identify Impurities above [+]: Impurities will
be identified and the identity verified by synthesis of authentic compounds.
Detection level of impurities will be established.


 


Period of Work: Approximately [+] months
from analytical method development and validation (e.g. [+]).


 


Deliverable: Establish identity and
detection levels of impurities.


 


3.2.4.2.3 Develop (Assess and Refine) Lot Release
Specifications: Release specifications will be established that
ensure consistency between production lots. RTP batches will be used to refine
release specifications and assess the analytical method capability to meet the
specification threshold according to ICH Q6A recommendations. Director of QA
participates in review and approval of specifications that are compliant with
cGMP and compendial requirements.


 


Period of Work: Approximately [+] month (e.g.
[+]).


 


Deliverable: cGMP-compliant lot release
specifications are approved for drug substance for subsequent clinical use.


 


3.2.4.2.4 Quality Audits and review: Documentation
for drug substance (DS) analytical method development and validation will be reviewed
by QA for compliance with regulatory requirements. See section 3.2.3.1.3
Quality Audits and Review and section 3.2.4.1.4 cGMP Audits. Audits occur,
reports are completed and satisfactory responses are received to audit
findings. Director of QA reviews and approves validation protocols and
validation reports for the analytical methods.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Audits occur, audit reports
are completed audit findings are resolved and validated analytical tests and
methods are approved for drug substance.


 






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3.2.4.2.5 Project Management, Operations and
Oversight: Track progress and manage issues as they arise.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.2.4.3 Drug Product (DP) Analytical Method
Development and Qualification: Drug product analytical
method development and qualification will characterize phosphate buffered
saline filled drug product. Method development will utilize synergies with drug
substance methods to reduce time and cost of method qualification. Includes
subcontractor qualification and audits by AVI QA Unit.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Qualified analytical test
methods (validated assay method) that comply with the FDA’s quality and regulatory requirements for release of
drug product.


 


3.2.4.3.1 Method Development and Qualification:      Methods, compliant with
regulatory expectations, will be developed for impurity profile, assay,
identity, and description. Method qualification will be performed by qualified
vendor. A contract analytical development laboratory will be chosen and methods
for drug product analysis and release will be developed that comply with the
FDA’s quality and regulatory
requirements.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Audited reports for
qualified methods for impurity profile, identity, and description and validated
method for assay.


 


3.2.4.3.2 Identify Impurities above ID Threshold: Impurities will
be identified and the identity verified by synthesis of authentic compounds.
Detection level of impurities will be established.


 


Period of Work: Approximately [+] months
from analytical method development and validation (e.g. [+]).


 


Deliverable: Establish identity and
detection levels of impurities.


 


3.2.4.3.3 Develop (Assess and Refine) Lot Release
Specifications: Release specifications will be established that
ensure consistency between production lots. RTP batches will be used to refine
release specifications and assess the analytical method capability to meet the
specification threshold according to ICH Q6A recommendations.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: Lot release specification
in compliance with the FDA’s quality and
regulatory requirements for drug product for subsequent clinical use.


 


3.2.4.3.4 cGMP Audits: Documentation for drug
product (DP) analytical method development and validation will be reviewed by
QA for compliance with regulatory requirements. See section 3.2.4.1.4 above.
Audit occurs, report completed and satisfactory resolution of responses to
findings by subcontract testing laboratories developing analytical methods and
testing drug product for subsequent clinical use. Lot release of will occur
using QA-approved validated analytical methods and specifications compliant
with compendia and other regulatory requirement.


 






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Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Completed and QA reviewed
validation reports. Audit report completed and satisfactory resolution of
responses to findings by subcontract testing laboratories. Lot release tests
and specifications that comply with the FDA’s quality and
regulatory requirements are approved by the Director of QA.


 


3.2.4.3.5 Project Management, Operations and
Oversight: Track progress and manage issues as they arise.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.2.5 Nonclinical Toxicology: AVI will
conduct [+] studies [+]. A new assay will be used for the determination of drug
levels in biological matrices, and each component of the study drug will be
assayed independently. The method will be validated (GLP) in plasma as is
required for study protocols for pharmacokinetic analysis. An existing [+] will
be transferred and validated (GLP) for the analysis of dosing solutions, over a
[+]. The single dose [+] will evaluate the effect of a single dose on target
organs observed. Quality Audits will be conducted on the contract research
organization (CRO) and the audit records maintained by the AVI EDMS.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Completed GLP-compliant
non-clinical toxicology study reports for studies in [+], including [+]
reports.


 


3.2.5.1 [+] Method Validation: Feasibility
studies have proven a [+] method acceptable for the determination of drug
levels in biological matrices. Each component of the study drug is assayed
independently. The method will be validated (GLP) in matrices corresponding to
samples specified by study protocols for pharmacokinetic analysis [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audited final report on
validated [+] method for detection of drug levels in biological matrices.


 


3.2.5.2 Analytical Method Validation for Determination
of Dose Solution Concentration: An existing [+] method will
be transferred and validated (GLP) for the analysis of dosing solutions. The
method will be validated over a concentration range suitable for determination
of concentration, homogeneity, and stability of the dose formulations for the
non-clinical toxicology studies.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: Audited final report on
validated method for concentration of drug levels.


 


3.2.5.3 [+]: The single dose [+] study
will evaluate the effect of a [+]. The results will have an impact on the
dosages and escalation in the [+] trial. This study requires validation of the
analytical method.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audited final report for
[+] study.


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
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3.2.5.4 [+]: This study provides
supportive data for the repeat dose study [+] that has been completed. Allow
correlation of observed effects with exposure.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audited final report for
[+] study.


 


3.2.5.5 [+]: In vitro study to assess the
effects of the test article on [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audited final report for
[+] study.


 


3.2.5.6 [+]: To investigate the actions
of the test article/vehicle on action potential [+] methods. This study will
identify potential risk of [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audited final report for
[+] study.


 


3.2.5.7 [+] with Long Recovery: [+] - this study
will determine [+] in multidose
clinical trial.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audited final report for [+] Study with Long Recovery.


 


3.2.5.8 cGLP Audits: Quality Audits conducted in
this arena are Direct Impact audits of our Contract Research Organizations
(CRO). Audits include a list of questions directly suited to the CRO and a
GLP/cGMP [+] checklist. All CROs (through audits) are approved (or rejected) by
QA and audit records are maintained by the AVI EDMS. See section 3.2.3.1.3 for
general description of Quality Audits. Audits of [+] facilities, [+]
laboratories, and related study data will be conducted by experienced auditors
from the Quality Unit. Audits employ a checklist approach, based on regulatory
requirements (21 CFR Part 58 for GLP compliance) and ICH guidelines; the
checklists are customized to comply with requirements applicable for each
subcontractor facility and type of testing. When applicable, the readiness for a
Pre-Approval Inspection by the FDA or other regulatory agency (PAI) of GLP
subcontractors is also evaluated.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Audit and audit report
completed and acceptable responses to findings are received from subcontract
[+] facilities and [+] laboratories testing AVI-6003 for [+]. GLP studies will
occur using QA-approved protocols that meet regulatory and IUCAC and USG
requirements and validated [+] methods are used.


 


3.2.5.9 Project Management, Operations and Oversight: Track progress
and manage issues as they arise.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.2.6 Pilot [+] Studies (Complete).


 


3.2.7 Contract Program Management**: AVI will track
progress on each element in the contract, including all financial and reporting
requirements; ensure compliance with contract and all government


 






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regulations. AVI will manage all subcontracts and ensure that their
timelines are met, and the components contributed by each to the overall study
are coordinated, on budget, and that they are compliant with all contract and
Government regulations that are applicable.


 






**Work will continue during period [+] on this
program — namely [+] and regulatory to prepare for [+] clinical study. Program
management will be required to oversee those tasks.


 


Period of Work: Concurrent with all
CLIN0001 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide contract management
and financial oversight ensuring compliance.


 


3.2.7.1 Program Management: Track progress
and manage issues as they arise.


 


Period of Work: Concurrent with all
CLIN0001 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide project management
ensuring compliance.


 


3.2.7.2 Finance and [+]: Track financial
work process and reporting.


 


Period of Work: Concurrent with all
CLIN0001 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide project financial
management ensuring compliance.


 


3.2.7.3 Contract and Subcontract Management: Manage our
compliance with contract and USG regulations; manage subcontractors and
relationship with them.


 


Period of Work: Concurrent with all
CLIN0001 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide contract and
subcontract management ensuring compliance.


 


3.2.7.4 EDMS Installation, Validation, Implementation,
Training and QA: AVI will implement enhancements to the Quality
Systems Approach already in place, including installation of a secure 21CFR
Part 11 compliant EDMS and preparation for electronic document submission to
the FDA. AVI will train all pertinent staff on EDMS and Quality Assurance.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: EDMS system will have been
selected, installed and fully operational. QA audits of all vendors will have
been performed and any follow up action items identified and tracked.


 


3.3 CLIN0001 Technology Development — [+] Clinical
Study (Part 2): Using the currently filed IND, and [+] data obtained
subsequently, AVI will establish agreement with the FDA for the acceptable
protocol** [+], such as [+] review and approval. AVI will conduct and report
the [+] clinical study in healthy [+].


 






**Discussions with the FDA are planned for [+] which
will cover the [+] and additional input to the proposed [+] study may be
requested.


 


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Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Final study report for [+]
clinical study agreed upon by the government.


 


3.3.1 Support [+] Submission: An [+] cannot
be granted until the appropriate legislative order has been given by Congress,
however, AVI will submit a Request for Consideration for an [+] and briefing
document (per Section 564(c) of the FD&C Act), amendments under Project
Bioshield Act of 2004, and draft FDA Guideline of June 2005. The Request for
Consideration will contain data from all available research and nonclinical
studies together with draft protocol synopses for the [+] studies and the first
clinical study. The FDA will be asked to provide advice on the additional
requirements to achieve an [+].


 


As requested by the FDA in the meeting, AVI will continue to submit
additional scientific, [+] and [+] study data in final study reports as [+]
when the final reports are available with the intention of fulfilling all
requirements for an [+] before such use is required.


 


Period of Work: Approximately [+] days from
start of preparation of the Request for Consideration and Briefing Document to
final receipt of FDA“s Minutes of the Meeting (e.g. [+]).


 


Deliverable: Letter to the FDA requesting
a meeting to discuss the Request for Consideration as an [+] and Briefing
Document submitted as an [+]. In addition, after the meeting with the FDA the
company’s notes of the meeting with the FDA will be submitted as an [+].


 


3.3.1.1 Support [+] Submission, Meeting with FDA and
USG: AVI’s regulatory affairs, staff will prepare the Meeting Request Letter
and Briefing Document for the Request for Consideration as an [+] Meeting with
the FDA and submit them as [+]. After the Meeting with the FDA, AVI’s
regulatory affairs staff will prepare notes of the meeting and submit them as
an [+]. The Request for Consideration as an [+] submissions will be planned,
prepared and managed by AVI’s regulatory affairs staff, using FDA compliant
electronic templates, e-publishing techniques and the EDMS. Meeting
arrangements and follow-up Meeting Minutes will also be prepared and managed by
RA. Oversight will be provided by AVI’s senior management.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: Letter to the FDA requesting
a meeting to discuss a Request for Consideration as an [+] and Briefing
Document submitted as an [+]. After the meeting with the FDA the Company’s
notes of the [+] with the FDA will be submitted as an [+].


 


3.3.1.2 Project Management, Operations and Oversight: Consideration
as an [+] request managed by AVI regulatory affairs, using FDA compliant
electronic templates, electronic document management and e-submission. Meeting
arrangements and follow-up meeting minutes also managed by RA. Oversight is
provided by AVI’s senior management.


 


Period of Work: Approximately [+] month
from meeting date being offered with FDA (e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones to timeline and budget.


 


3.3.2 [+] Clinical Study: The [+] will be
conducted with [+] to this award. The timeline will not allow AVI to wait for
full manufacturing scale [+] cGMP drug product material, however the drug
product used will be comparable and the assay method validated. The study and
discussions with the FDA will be based on the IND already opened for drug
product. Dosing will start at the [+]. Based on the pharmacokinetics, safety
and general tolerability, [+].


 






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Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: [+] clinical study report;
study conducted with research scale cGMP drug product.


 


3.3.2.1 Clinical Site and Local Laboratory Activities:
The study will be planned and executed at an audited, selected [+]
Clinical Research Facility with support from a fully CLIA accredited
laboratory. From initiation onward the site(s) will be monitored through to
study completion and site close out.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Plan, conduct and complete
[+] clinical study. Provide all required data to the CRO for final study
report.


 


Final report describing [+] clinical study conducted with research
scale cGMP drug product manufactured at a cGMP-compliant facility.


 


3.3.2.1.1 Contracts and Budget: Contract and
budget will be negotiated and agreed with the [+] CRO and supporting
laboratories.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: All contracts (site and
laboratories) to permit study to be executed are agreed and signed.


 


3.3.2.1.2 Final Protocol to FDA; [+] submissions: Final [+]
protocol submitted to FDA, [+]; feedback received and incorporated 


prior to study initiation.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: All approvals received
before initiation of clinical study.


 


3.3.2.1.3 Site Activities: First Subject In to Last
Subject Out: The study will be planned and executed at an
audited, selected [+] Clinical Research Facility. Site will be involved with
review of study specific documentation and trained prior to first subject first
visit. All interactions with site will be documented. Regular site monitoring
will be planned and documented to ensure data has been verified and entered in
a timely fashion, while ensuring subject safety. Any compliance issues will be
raised to the clinical team for response.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: [+] clinical study
conducted under cGCP and completed on schedule, within budget.


 


3.3.2.1.4 Site Close Out: After
completion of the last subject last visit, all data queries will be completed
by the site and/or laboratory, previously validated database locked, analyses
run, and draft study report prepared. In parallel formal close out of the
clinical site, with disposal of unused drug supplies and completion of all
outstanding documentation will occur.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: All open queries and action
items associated with clinical study execution are completed and documented in
a site close out visit report.


 


3.3.2.2 Outsource Services: Identify,
select and qualify subcontractors needed to execute clinical study. 


 






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Assigned vendor personnel will participate in a kick off meeting in
which study expectations and needs, including timelines, will be discussed.
Protocol and procedure training will occur. A communication plan and reports
will be developed prior to first subject enrolled.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Training records, meeting
minutes confirming that subcontractors are trained to the study and ready to
perform services.


 


3.3.2.2.1 [+] Method Validation: Feasibility
studies have proven a [+] method acceptable for the determination of drug
levels in [+] matrices. Each component of the study drug is assayed
independently. The method will be validated (GLP) in matrices corresponding to
samples specified by the clinical study protocol for pharmacokinetic analysis
[+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Validated [+] assay for
drug levels in [+] matrices.


 


3.3.2.2.2 Clinical Research Organization and Data
Management: The CRO is key to study success. Their team along
with AVI personnel are responsible for site start up activities, site training,
and study execution, including data collection and management. The statistical
support is part of the CRO. This group and Data Management will develop the
plans necessary for data collection, query management, data analysis and
quality checks. They will prepare reports for the [+] reviews. The final
clinical study report will be written by CRO personnel.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Executed contract between
AVI and CRO.


 


3.3.2.2.3 Central Laboratory Services and Data
Transfer: Exploratory [+] accessioning and analyses will each
be conducted at a central lab facility. Data from each will be sent to data
management vendor for inclusion in final study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Laboratory data report.


 


3.3.2.2.4 [+]: An independent [+] will be
appointed to oversee and confirm dose escalation decisions. A [+] charter will
be prepared and agreed with [+] members, a contract developed and a kickoff
meeting and then dose escalation meetings with open and closed sessions.
Members of the [+] will be available to review safety data and confirm or
reject dose escalation to the next higher dose.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Decision to dose escalate;
continue or stop study as documented in meeting minutes.


 


3.3.2.2.5 Provide Electronic Data Management with
Access to US Government: Enable [+] web portal with secure access to
assigned study, company, vendor, and USG personnel.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Functional secure EDC
portal access.


 






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3.3.2.2.6 Drug Warehousing and Distribution: Store clinical
trial material at refrigerated conditions in secure, temperature controlled and
monitored unit. Implement traceable distribution system with chain of custody
documentation.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Provide clinical trial
material on time to site(s) and keep adequate records.


 


3.3.2.3 Study Documents for Clinical Sites and Final
Study Report: The Clinical Research Organization (CRO) is
responsible for preparing and providing to AVI for review all appropriate study
specific documents, except the clinical protocol. Upon AVI authorization the
CRO will send these documents to the sites in preparation for study start.
Additionally, should any unexpected or serious safety events be reported, the
CRO will document, discuss with AVI medical monitor, and complete the appropriate
forms. At the study end, the CRO will prepare the tables, listings and figures
and draft the final study report which will then be finalized with AVI input.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Shipping receipts showing
what was sent to whom and when.


 


3.3.2.3.1 Prepare and Distribute Study Documents: CRO, lab
vendors and drug warehouse provide complete set of documents and forms to
effectively and efficiently conduct study, including but not limited to: study
specific data collection forms (electronic case report forms), the study
operations manual, training on the protocol, clinical trial material storage,
inventory and administration, use of [+], safety reporting, and Good Clinical
Practice regulations.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: All study related documents
including but not limited to: study plan and timeline, eCRF completion
guidelines, monitoring reports, protocol compliance tracking, communication
plan, meeting minutes, training materials and logs, drug accountability logs
and final study report.


 


3.3.2.3.2 Final Study Report: Prepare
compliant and complete final clinical study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Submission ready final clinical
study report.


 


3.3.2.4 Regulatory Submissions and Templates: The near final
draft clinical protocol, FDA Form 1571, FDA Form 3674, FDA Form 1572,
information on the investigators (including a copy of the cv of the Principal
Investigator), study facility, and [+] will be submitted as an [+] for review
by the FDA. An electronic template that is compliant with electronic submission
requirements will be used for the protocol. Other “Essential Documents”
specified by the ICH guideline on Good Clinical Practice and 21 CFR will be collected
and reviewed for compliance. The clinical study will be registered on
www.Clinicaltrials.gov or an equivalent public access database.


 


Period of Work: Approximately [+] months
from start of collection of “Essential Documents” to notification from the FDA
that it is “Safe to Proceed” (not including [+] reviews and approvals). (e.g.
[+]).


 


Deliverable: FDA Letter confirming that
it is “Safe to Proceed” with the clinical study.


 


3.3.2.5 GCP Audits: Clinical data and document
quality checks are carried out by clinical monitors 


 






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during routine monitoring of each clinical study, as required under
GCP. See section 3.2.1.3 for general description of quality Audits and Review.
Quality Audits performed by experienced auditors from the QA Unit at clinical
investigational sites (hospitals, etc.) are Direct Impact audits that will be
specifically designed to verify compliance with GCP requirements and local and
international regulatory regulations and guidelines. Audits will include,
contractor site selection audit, study audits during the study and an end of
study audit. Audit documentation will be managed and archived in the EDMS.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audit and audit report are
completed and satisfactory responses to audit findings are received from CRO“s
clinical facilities and [+] laboratories testing drug product in clinical
studies. GCP-compliant clinical studies will occur using QA-approved protocols
that meet regulatory and Institutional Review Board, HIPAA and USG
requirements. Validated [+] methods are used for testing clinical samples.


 


3.3.2.6 Project Management, Operations and Oversight: Develop
timeline, manage vendors, anticipate and resolve problems, track protocol
compliance, report progress As part of the normal course of conducting clinical
trials, regular team meetings will be held with each vendor and held
internally. This team is responsible for the study plan. Study progress and any
issues relative to the study plan will be documented and addressed with the
Product Development Team on at least a monthly basis. Regular conference calls
with the TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] months (e.g.
[+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.3.3 Store Drug Product from Clinical Lot for 2 Years
Past End of Study: Samples from the drug product batches used in the
[+] clinical study will be stored under specified controlled storage conditions
for 2 years past the completion of the study.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Store samples of drug
product used in [+] clinical study.


 


3.3.3.1 Initiate Drug Product Storage at Drug
Distributor Warehouse: Drug product from the clinical trial will be
retained for at least 2 years past the end of the clinical study end. These
samples will be held at the recommended storage temperature in a secured
refrigerated unit that is calibrated and monitored.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Store samples of drug
product used in [+] clinical study.


 


3.3.3.2 cGMP Audits: See section 3.2.3.1.3
Quality Audits and Review for general description of quality audits and section
3.2.4.1.4 for description of cGMP audits. Audits occur, audit reports are completed
and satisfactory responses to audit findings are received from the subcontract
facility storing and distributing AVI-6003 drug product for subsequent clinical
use. Release and shipping of clinical supplies to clinical facilities will
occur using QA-approved procedures that are compliant with GCP and local and
international regulatory requirements.


 






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Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Audit and audit report are
completed and satisfactory responses to audit findings are received from the
CMO drug product storage facility and conditions are acceptable for drug
product lots for subsequent distribution for clinical use.


 


3.3.3.3 Project Management, Operations and Oversight: Oversight of
warehouse storage of drug product will be managed by AVI personnel through site
visits, audits, and records review.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.3.4. Stability Studies: Samples from
the [+] (drug substance and drug product) and [+] scale (drug substance), will
be placed on a stability study at recommended storage temperature and an elevated
temperature as per ICH guidelines for a minimum of [+] consistent with the RFP.
A final stability report will be written by the Contract organization that
performs the stability studies.


 


Period of Work: Approximately [+] days from
time of award (e.g. [+]).


 


Deliverable: Samples of drug substance
and drug product set up for [+] stability studies.


 


3.3.4.1 Contract Analytical Lab, Method Transfer,
Short Term Stability of Drug Product at Dilutions for Clinical Study: Identify
infusion sets, short term stability for at least [+].


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Report on short term
stability of drug product under conditions of clinical study.


 


3.3.4.2 Contract and Initiate [+]: These studies will confirm the stability
of the regular [+]. These studies are expected to confirm result from previous
stability studies.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Ongoing stability studies
of [+].


 


3.3.4.3 Refine Stability Indicating Analytical Methods
for Drug Substance and Drug Product: Forced degradation studies
will identify degradants using HPLC/mass spectrometry. Once peak retention
times are matched to degradant/impurity ID, stability program will utilize
validated HPLC methods.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Completion of analytical
method development for Drug Substance and Drug Product.


 


3.3.4.4 24 Months Stability Studies Drug Product: Drug substance
and the resultant drug product will be placed on a stability study at
recommended storage temperature and an elevated temperature as per ICH
guidelines for a minimum of [+] consistent with the RFP. This is applicable to
cGMP materials made at both the [+] scales. A final stability report will be
written by the Contract organization that performs the stability studies.


 


Period of Work: Approximately [+] months
from time of award (e.g. [+]).


 


Deliverable: Ongoing [+] study with drug
product prepared for [+] clinical study in CLIN0001.


 






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3.3.4.5 Ongoing Quality Audits and Review including [+] Stability Programs: Drug substance and
the resultant drug product will be placed on a stability study at recommended
storage temperature and an elevated temperature as per ICH guidelines for a
minimum of [+] consistent with the RFP. This is applicable to cGMP materials
made at both the [+] scales. A final stability report will be written by the
Contract organization that performs the stability studies See section 3.2.3.1.3
Quality Audits and Review for a general description of quality audits and
section 3.2.4.1.4 for a description of cGMP audits. cGMP audits occur, reports
are completed and satisfactory responses to audit findings are received from
subcontract laboratories conducting stability studies. Analytical testing
occurs using QA-approved validated analytical methods and stability
specifications compliant with compendia and other regulatory requirements.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: Audit report completed and
satisfactory responses to audit findings received. Stability data are reported
at regular intervals and reviewed by AVI.


 


3.3.4.6 Ongoing Program Management, Operations and
Oversight including [+] Stability Programs: Develop timeline, manage
vendors, anticipate and resolve problems, track protocol compliance, report
progress As part of the normal course of conducting clinical trials, regular
team meetings will be held with each vendor and held internally. Study progress
and any issues relative to the study plan will be documented and addressed with
the Product Development Team on at least a [+] basis. Regular conference calls
with the TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.3.5 End of [+] FDA Meeting: AVI will
request an End of [+] Meeting to discuss the future development plan including
design of the [+] and the application of the [+] as soon as the data from the
first clinical study is available, and appropriate questions of the agency can
be formulated to enable the further clinical development. Agreement will be
sought on fixed dose combination drug products, toxicology, toxicokinetics,
clinical and pharmaceutical development of the drug substance and drug product,
[+] development and review, with advanced notification of USG Program Office.
The scheduling will depend on FDA, but the meeting should occur within 75 days
of the formal request, and the briefing book will be sent to the FDA, at least
4 weeks ahead of the meeting. FDA feedback will be incorporated into the
subsequent development plans. AVI’s regulatory affairs staff will plan, prepare
and compile the submission documents using electronic templates and
e-publishing techniques; documents will be managed and stored electronically
using the EDMS.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: AVI submits an End of [+]
Meeting Request Letter and Briefing Document to the FDA, participates in the
meeting with FDA and prepares meeting notes. AVI reviews the FDA“s official
Meeting Minutes to assure that key elements of the discussions and agreements
reached are documented. The FDA“s requirements and expectations for the
appropriate regulatory procedural enhancements leading to a potential [+] are
clear.


 


3.3.5.1 [+] FDA Meeting Request [+], Preparation of
Briefing Documents: Just before the completion of [+], AVI’s regulatory
affairs staff will manage, prepare and compile the [+] Meeting Request Letter
and Briefing Document, with key components being provided by the research and
development staff and


 






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subcontractors. The submission will be prepared using electronic
templates, published using e-publishing techniques and all documents will be
managed and controlled in the EDMS. The [+] Meeting will be planned and held,
then AVI will prepare Meeting Notes that will be submitted to the FDA. The FDA’s
official Meeting Minutes will be reviewed for clarity and agreement with AVI’s
understanding of the outcomes. As necessary, AVI will continue proactive
dialogue with the FDA by mutually convenient means.


 


Period of Work: Approximately [+] weeks
(e.g. [+]).


 


Deliverable: [+] Meeting Request Letter
and Briefing Document submitted to the FDA. A meeting date is agreed and the
meeting (with participation of appropriate USG representatives) is planned.


 


3.3.5.2 FDA Meeting, Minutes, Follow-up: AVI and USG
representatives will attend the End of [+] Meeting. Agreement will be sought on
a variety of development and regulatory procedural topics including for example
applicability of fixed dose combination drug product requirements, toxicology,
toxicokinetics, clinical and pharmaceutical development of the drug substance
and drug product, [+] development and review FDA feedback will be incorporated
into the subsequent development plans.


 


Period of Work: Approximately [+] weeks
(e.g. [+]).


 


Deliverable: The [+] Meeting with the
FDA occurs. AVI“s Meeting Notes and the FDA“s Meeting Minutes are prepared and
reflect mutual agreements and understandings of the requirements for further
development and the applicable regulatory procedures.


 


3.3.6 Complete [+] Clinical Trial and [+]: AVI will complete
a [+] study to assess safety, tolerability and pharmacokinetics in [+] (RFP
3.3.2). The results from this first clinical study will be submitted to FDA as
a supplement to the IND as soon as the data is available and the appropriate
study reports are prepared.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Conduct and complete [+]
clinical trial Submission of an [+] containing the Final Study Report of the
[+] Clinical Trial and other [+] as needed to support continuing nonclinical,
pharmaceutical and clinical research and development.


 


3.3.6.1 Prepare for and Meet with FDA to Discuss [+]: Due to the
complexity and uncertainty about the FDA’s expectations and requirements for
[+] approval using the [+], AVI’s regulatory affairs group will plan, request
and manage a specific, [+] Meeting with the FDA and other interested USG
agencies to discuss the application of the [+]. A Meeting Request Letter and
Briefing Document will be prepared and submitted at least 4 weeks ahead of the
meeting. AVI will prepare Meeting Notes and will review the FDA’s official
Meeting Minutes to assure agreement on the issues discussed. If necessary,
further clarifications may be requested in writing. AVI will continue an open
dialogue with the FDA and USG agencies involved and document those discussions.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Meeting Request and
Briefing Document, attendance at the [+] Meeting, AVI’s Meeting Notes and FDA’s
official Meeting Minutes. Agreement with the FDA and USG agencies regarding the
applicability and requirements for developing oligomeric drug products under
the [+], and for [+] approval.


 






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3.3.6.2 Prepare and Submit [+] and [+]: AVI will submit
[+] containing appropriate research and development data to the FDA and provide
notifications to USG Program Office The agreement of the FDA will be sought to
submit the protocols for the [+]
studies as well as the [+] safety
study for [+] and the relevant
protocols will be submitted. AVI’s regulatory affairs staff will plan, prepare
and manage all submissions as electronic documents using electronic templates,
e-publishing techniques and the EDMS.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: [+] will be submitted as
[+] and the FDA“s review comments will be incorporated before finalizing study
protocols. [+] will be submitted as research and development data reports are
available in order to keep the IND as current as possible. Copies of major
submissions and correspondence will be forwarded to USG, as required.


 


3.3.6.3 Project Management, Operations and Oversight: Develop
timeline, manage vendors, anticipate and resolve problems, track protocol
compliance, report progress. As part of the normal course of conducting
clinical trials, regular team meetings will be held with each vendor and held internally.
This team is responsible for the study plan. Study progress and any issues
relative to the study plan will be documented and addressed with the Product
Development Team on at least a monthly basis. Regular conference calls with the
TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.3.7 Deliver [+] of Clinical Material to US
Government: A sample of the drug product used in the [+] clinical study will be provided to the
USG.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Deliver sample drug product
used in [+] clinical safety study to USG.


 


3.3.7.1 Ship [+] to US Government: At the end of
CLIN0001 at least [+] of the drug product(s) will be delivered to the recipient
specified by the USG.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Deliver sample of drug
product used in [+] clinical safety study to USG.


 


3.3.7.2 Project Management, Operations and Oversight: Oversight of
inventory and distribution will be managed by AVI personnel through site
visits, audits, and records review.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4 CLIN0002: AVI will
deliver the developmental therapeutic end item that has achieved [+] clinical
trials, based upon CLIN0001, additional prior studies and all the associated
regulatory requirements sufficient and in place to support this. This will
comprise all those activities necessary for our candidate product to complete
the USG Statement of Objectives in CLIN0002.


 






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Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Drug product on which [+]
clinical trials have been completed.


 


3.4.1 Refine [+]: The critical goal of these
studies is to obtain concurrence with FDA on the [+] study to be conducted
under the [+]. Critical viral parameters will be addressed in PK/PD studies of
[+], and in monitoring [+], both conducted at USAMRIID. The correlation of the
[+] from natural infections, will guide the format and goals of the [+] study.
The [+] study will be discussed and refined with the FDA. AVI will submit the
protocols for the [+] prior to subcontracting the studies to USAMRIID (the
proposed vendor to be pre-qualified as acceptable for GLP-compliant studies).
The final protocols and final study reports will be submitted to FDA as [+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Establish model for [+]
Studies with FDA.


 


3.4.1.1 Delayed Time to Treatment in [+]: Critical
efficacy parameters will be addressed in a study with various preplanned delays
between exposure of [+] and initiation of treatment. The work will be conducted
at USAMRIID. The final protocols and final study reports will be submitted to
FDA as [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Complete Delayed Time to
Treatment Efficacy Study.


 


3.4.1.2 [+]: Critical viral parameters
will be addressed in [+], conducted at USAMRIID. The final protocols and final
study reports will be submitted to FDA as [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Complete [+].


 


3.4.1.3 Viral Time Course in [+]: Critical viral
parameters will be addressed in this study conducted at USAMRIID. The final
protocols and final study reports will be submitted to FDA as [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Complete viral timecourse
study in [+].


 


3.4.1.4 [+]: Critical viral parameters
will be addressed in [+], conducted at USAMRIID. The final protocols and final
study reports will be submitted to FDA as [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Complete [+].


 


3.4.1.5 Quality Audits: See section 3.2.3.1.3 for a
general description of Quality Audits. Audits of [+] facilities, [+]
laboratories, and related study data will be conducted by experienced auditors
from the Quality Unit. Audits employ a checklist approach, based on regulatory
requirements (21 CFR Part 58 for GLP compliance) and ICH guidelines; the
checklists are customized to address the quality and regulatory requirements
for each subcontractor facility and type of testing. When applicable, the
readiness for a Pre-Approval Inspection by the FDA or other regulatory agency
(PAI) of GLP subcontractors is also 


 






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evaluated.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audit and audit reports are
completed and satisfactory responses to audit findings are received from
subcontract [+] laboratories testing drug product for nonclinical studies. GLP
studies will occur using QA-approved protocols that meet regulatory and IUCAC
and USG requirements and validated [+] methods are used for analysis of test
articles.


 


3.4.1.6 Project Management, Operations and Oversight: Develop
timeline, manage vendors, anticipate and resolve problems, track protocol
compliance, report progress As part of the normal course of conducting clinical
trials, regular team meetings will be held with each vendor and held
internally. This team is responsible for the study plan. Study progress and any
issues relative to the study plan will be documented and addressed with the
Product Development Team on at least a monthly basis. Regular conference calls
with the TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.2 Develop and Validate Analytical Assays for Drug
Product: AVI will complete analytical methods development and
validation for drug product and finalization of specifications for lot release
of drug product. The development and validation of formulated product
analytical test methods utilize the analytical test methods developed and validated
for therapeutic drug substance, where applicable. The addition of compendial
tests and limits for sterility,, to those for appearance, identification, assay
and impurities will meet the regulatory requirements for lot release and for
the product lots in ICHcompliant stability testing programs. The Director of QA
will participate in the review and approval of analytical test methods,
analytical validation protocols and reports, and drug product specifications
that comply with compendia and other regulatory requirements.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Complete development of
analytical methods, validation and specifications for drug product.


 


3.4.2.1 Drug Product Analytical Method Development and
Validation: Drug product analytical development will exploit
similarities between the drug substance and the drug product to accelerate
development and minimize validation time. As with drug substance, multiple HPLC
methods are required for purity identification. Includes vendor qualification,
facilities and API process audits of batch records by AVI QA Unit. AVI will
complete analytical methods development and validation for drug product and
finalization of specifications for lot release of drug product. The addition of
methods for sterility, to those for appearance, identification, assay and
impurities will meet the regulatory scrutiny required for cGMP release and ICH
stability.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Complete development of
analytical methods for drug product, and audited validation report.


 


3.4.2.2 Refine Drug Product Lot Release Specification:
Based upon the results from the CLIN0001 manufacturing experience
product specifications for each of the drug substances and the drug product will
be developed. For the individual drug substances these will be similar to those
developed in 


 






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CLIN0001 since [+] studies will have been based upon these
specifications that were used in the IND. Refinement of the specifications will
be made based upon new assay development and analysis of lots used in the [+]
studies and clinical trials.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Develop specifications for
each drug substance and drug product.


 


3.4.2.3 Quality Audits: Documentation
for analytical assay method development and validation will be reviewed by QA
for compliance with regulatory requirements. See section 3.2.3.1.3 Quality
Audits and Review and section 3.2.4.1.4 cGMP Audits. Audits occur, audit
reports are completed and satisfactory responses to audit findings are received
from subcontract analytical testing laboratories developing and validating
analytical methods for drug product for subsequent clinical use. The Director
of QA participates in the review and approval of validation protocols and
validation reports.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audits occur, audit reports
are completed and satisfactory responses to audit findings are received from
the test facilities. Validated analytical methods are developed and approved.


 


3.4.2.4 Project Management, Operations and Oversight: Develop
timeline, manage vendors, anticipate and resolve problems, track protocol
compliance, report progress As part of the normal course of conducting clinical
trials, regular team meetings will be held with each vendor and held
internally. This team is responsible for the study plan. Study progress and any
issues relative to the study plan will be documented and addressed with the
Product Development Team on at least a monthly basis. Regular conference calls
with the TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.3 Scale-up Manufacturing, Qualification and
Validation of cGMP Manufacturing Process: Manufacturing goals will
include scale-up of the raw material supply [+], as well as that of drug
substance. Further suppliers will be qualified. AVI will manufacture the drug
substance and drug product supply at [+] batch scale for the [+] clinical
studies (. AVI will also initiate the development of the full manufacturing
scale of [+] manufacturing, and initiate validation of [+], including for
stability at this full [+] scale. The manufacturing facilities will be audited
for compliance with cGMP and other quality and regulatory requirements by
experienced auditors. The Director of QA will participate in the review and
approval of process validation protocols and reports.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Drug product for [+]
clinical trials and validated drug substance for [+] clinical trials will be
prepared. Release drug product lots for [+] clinical trials manufactured using
a validated process at a cGMP-compliant facility. Lots meet the AVI-approved
drug product specification and have been tested using validated analytical
methods.


 


3.4.3.1 [+] Manufacturing Scale-Up: As part of the
scale up process the [+] manufacturing supply chain needs to be established to
produce [+] on the scale required to support the intended manufacturing
scale-up. The current production capacity [+] multiple manufacturers will be
utilized. However, even this effort will 


 






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require expansion of [+] facilities for [+] of the activated [+]. [+]
are needed to be made at the [+] to support scale up activities.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Assured supply for [+] and
other raw materials.


 


3.4.3.1.1 Contract Additional [+] Manufacturing and
[+] Sites: Negotiate and sign contracts with the additional [+]
manufacturing and [+] CMOs.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Selection and contract
finalization of additional [+] CMOs.


 


3.4.3.1.2 Manufacture of [+]: Complete tech
transfer with all new CMOs. Scale-up the [+] production process and manufacture
the required [+] to support the drug substance manufacture.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Timely supply of [+] to
support drug substance manufacture.


 


3.4.3.1.3 [+] Development and Validation: Evaluate the
feasibility of [+]

recovery. The Director of QA participates in the review and approval of process
protocols and reports.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Report on feasibility and
impact on cost of [+].


 


3.4.3.1.4 Quality Audits and Review: See section
3.2.3.1.3 Quality Audits and Review and section 3.2.4.1.4 cGMP Audits. Audits occur,
audit reports are completed and satisfactory responses to audit findings are
received from the CMO.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Completed audit reports.
Audits occur, audit reports are completed and satisfactory responses to audit
findings are received from the CMO. Approved master batch records are developed
for manufacturing [+] at the approved scale.


 


3.4.3.1.5 Project Management, Operations and
Oversight: Develop timeline, manage vendors, anticipate and resolve
problems, track project plan compliance, report progress. Progress and any
issues will be documented and addressed with the Product Development Team on at
least a monthly basis. Regular conference calls with the TMTI will be
established to review progress and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.3.2 Manufacturing Scale-Up, Large Scale
Manufacturing and Validation: GMP drug product for [+] clinical
trial will be manufactured from cGMP drug substance prepared at [+] scale
previously demonstrated in CLIN0001. The process will be scaled from the [+].
The drug substance process will undergo process validation in which [+] lots of
drug substance are made at the [+] commercial scale 


 






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and placed on stability. Material from the first validation lot will be
used to manufacture drug product for [+] clinical trial. Quality Audits
conducted in this arena are Direct Impact audits of our Contract Manufacturing
Organization (CMOs) first cGMP run. It will include observation of the
manufacturing process per cGMP/Q7 guidelines and will be documented with a
report that will be added to the initial CMO audit and filed within EDMS. The
Director of QA participates in the review and approval of process validation
protocols and reports.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Audited validation report
for large scale manufacturing at a suitably qualified CMO.


 


3.4.3.2.1 Manufacture and release cGMP drug substance
and drug product: Based on experience from CLIN001, the APIs will be
produced under cGMP conditions at the [+] scale at this stage and drug product
will be manufactured for [+] clinical trial. Production and QA oversight will
be given and data generated carefully reviewed. The Director of QA participates
in the review and approval of batch records and in the review of analytical
testing of drug substance prior to approving lot release.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Drug product for [+]
clinical trial.


 


3.4.3.2.2 Drug Substance Manufacturing Scale Up to
[+]: From the [+] scale, the process will be increased to a [+]. The purpose
of using a smaller reaction size in a larger capacity reactor is to control
costs during clinical development, but enable future scale increases in already
qualified equipment. This allows minimization of costs during the program and
later enables production of RFP threshold quantities for commercial production.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Demonstration of [+] scale
manufacturing process by successful completion of RtP run(s).


 


3.4.3.2.3 Validation of cGMP Drug Substance
Manufacturing Process: Once the [+] scale is established, a process
validation protocol will be written and executed under the guidance of the CMO
with direct input from AVI. Results of this validation will be reviewed and, if
acceptable, approved. The protocol will contain acceptance criteria in order to
evaluate the success. The Director of QA participates in the review and
approval of validation protocols, validation reports, and master batch records.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Audited validation report
for drug substance manufacturing process at [+] scale.


 


3.4.4 Refine and Select Drug Product Formulation: AVI will work
with a formulation contract CRO, and a drug product CMO to formulate a [+] drug
product that will show enhanced stability without cold storage conditions.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Decision on final
formulation for drug product formulation.


 






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3.4.4.1 [+] Product Screening Studies: Determine
important physicochemical parameters leading to design of solution [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Data to support decision on
final [+] formulation.


 


3.4.4.2 Accelerated Stability Studies Leading to
Selection of [+] Drug Product Formulation: [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Data to support decision on
final [+] formulation.


 


3.4.4.3 Determine Extractables and Leachables: Determine if
any chemical components are extracted or leached from containers, closures, or
materials used in administration of the drug.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Data to support decision on
final [+] formulation.


 


3.4.4.4 Quality Audits: Perform
audit/review of all documentation See section 3.2.3.1.3 Quality Audits and
Review for a general description of quality audits. The CMO developing the drug
product formulation is audited to qualify the contractor as acceptable. An
audit report is completed and satisfactory responses to audit findings are
received. The formulation study protocols, draft batch records and data
obtained during manufacture of the new formulation, and the results of
analytical testing are reviewed by the Director of QA. The Director of QA
participates in the review and approval of a master batch record, analytical
test methods and their validation and proposed specifications derived from the
development of a new formulation.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Completed Audit reports.
Master batch record, analytical test methods and their validation protocols and
reports and revised specifications for the new formulation reviewed and
approved by the Director of QA.


 


3.4.4.5 Project Management, Operations and Oversight: Track progress
and manage issues as they arise.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.5 Manufacture cGMP Material at Scale for
Nonclinical and Clinical Studies and Consistency Lots: AVI will
prepare cGMP drug product for the [+] clinical safety studies from the first
validation batch of [+] scale drug substance. Three drug product batches will
be validated, and all will provide material for stability studies.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: [+] scale cGMP drug product
manufactured for [+].


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
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3.4.5.1 Drug Product Engineering Runs: Drug product
configuration and process will be transferred to CMO; engineering runs will be
performed to confirm successful transfer.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Process suitable for GMP
drug manufacture.


 


3.4.5.1.1 Drug Product Engineering Run 1: An engineering
run is planned with the first drug substance of the combination product
manufactured in CLIN0002 for the purposes of testing all fill finish
capabilities including [+], formulation testing, and product testing for
adherence to product specifications.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Successful tech transfer
and final process suitable for GMP drug manufacture.


 


3.4.5.1.2 Drug Product Engineering Run 2: An engineering
run is planned with the first drug substance of the combination product
manufactured in CLIN0002 for the purposes of testing all fill finish
capabilities including [+], formulation testing, and product testing for
adherence to product specifications.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Successful tech transfer
and final process suitable for GMP drug manufacture.


 


3.4.5.2 Manufacture, Release, Label 3 Consistency Lots
of Drug Product: Material produced at scale will be filled for the
clinical lots and for the consistency lots at a size commensurate with the
production scale of the contract manufacturing organization.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Released, labeled drug
product for clinical trials.


 


3.4.5.3 cGMP Audits: All manufacturing sites for
which a scale up is required has been previously audited and approved by QA.
The actual scale up of drug product manufacturing includes a review of all
relevant documentation for any pertinent quality issues, content uniformity,
completion and an onsite QA “for cause” visit if required. See section
3.2.3.1.3 Quality Audits and Review for general description of quality audits
and section 3.2.4.1.4 for description of cGMP audits. Full cGMP audits occur,
audit reports are completed and satisfactory responses to audit findings are
received from the CMO. Batch records and analytical test data for lot release
are reviewed by the Director of QA. Release and shipping procedures for
clinical supplies to clinical facilities are reviewed.


 


The Director of QA reviews and approves batch records, batch production
data and results of analytical testing for lot release.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Completed audit reports.
Audits occur, audit reports completed, satisfactory responses are received for
any audit findings, master batch records and other documents are reviewed and
approved for manufacturing and release of drug product.


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
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3.4.5.4 Project Management, Operations and Oversight: The program
will be managed by AVI personnel and consist of initial technology transfer and
reduction to practice lots prior to cGMP production. Hands on training may be
provided initially but after establishment of the process and successful
manufacturing the program will be managed through conference calls, sites
visits, audits, data and document review including specifications and
comparison of release data with those specifications.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.6 Stability Studies: Drug product
will be evaluated according to ICH stability requirements. The duration of the
stability program is [+], and it will exceed the minimum requirement in the
statement of objectives and Target Product Profile (TPP) threshold. The stability
program includes full term aging studies at [+] will not be performed on the
drug substance, but will be performed on the [+] drug product.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Stability studies of [+]
and validated drug substance have been initiated. Stability studies set up for
[+] scale cGMP drug product material manufactured for [+] safety studies.


 


3.4.6.1 Stability on [+] and Drug Substance ([+]
Stability Program Starts): Follow ICH guideline Q1A to
acquire data to justify retest date at defined storage condition.


 


Period of Work: Approximately [+] Days
(e.g. [+]).


 


Deliverable: Completion of stability
studies from CLIN0001 and initiation of studies on [+] and validated drug
substance.


 


3.4.6.1.1 Ongoing Stability on [+]: This is the
completion of the [+] stability program started in CLIN0001.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Completion of stability
studies of [+].


 


3.4.6.1.2 Stability Studies Drug Substance ([+]
Stability Program Starts): Each drug substance
manufactured will be placed on a [+] stability program in order to demonstrate
the long term product characteristics of the material. Since these drug
substances are at a new scale of production stability needs to be performed
until a suitable quantity of lots have been made to demonstrate shelf life. All
lots made in CLIN0002 will be placed on stability.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Initiation of stability
program for drug substance.


 


3.4.6.2 Stability on Drug Product ([+] Stability
Program Starts): Follow ICH guideline Q1A to acquire data to justify
expiration date at defined storage condition.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
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Deliverable: Initiation of stability
program for drug product.


 


3.4.6.2.1 Ongoing Drug Product Stability Studies: Continue ICH
guideline Q1A to acquire data to justify expiration date at defined storage
conditions. Drug product manufactured prior to the start of CLIN0002 will
continue on stability and final reports will be issued at the end of the study.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Ongoing stability data for
drug product.


 


3.4.6.2.2 Stability Studies Drug Product ([+]
Stability Program): New drug product stability studies will be set up
for [+]. Multiple temperature storage conditions will be examine to provide the
storage conditions for optimal use.


 


Period of Work: Approximately [+] week
(e.g. [+]).


 


Deliverable: Initiation of stability
program for drug product.


 


3.4.6.3 cGMP Audit: Stability Study Audits are
Direct Impact audits. Audits include a list of questions directly suited to the
supplier and a cGMP, GLP (Analytical) checklist (again dependent on supplier).
All suppliers (through audits) are approved (or rejected) by QA and audit
records are maintained by the AVI EDMS. See section 3.2.3.1.3 Quality Audits
and Review for general description of quality audits and section 3.2.4.1.4 for
description of cGMP audits. Full cGMP audits occur, audit reports are completed
and satisfactory responses to audit findings are received from the CMO
conducting stability studies for AVI. The Director of QA reviews and approves
stability study protocols as well as reports on stability data.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Audited final report on
stability and shelf life of drug product. Full cGMP audits occur, audit reports
are completed and satisfactory responses to audit findings are received in
order to qualify the CMO. Stability study protocols are reviewed and approved.


 


3.4.6.4 Project Management, Operations and Oversight: Track progress
and manage issues as they arise.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.7 Stability Testing to Define Operational Storage
(Time Temperature Indicator): Each drug product is [+],
which makes room temperature storage feasible and reduces cold chain
requirements, exceeding minimum requirement in the statement of objectives and
TPP threshold. The scope of the stability studies will establish the Time
Temperature Indicator (TTI), since it includes full term accelerated
conditions. Based upon the results, a TTI can be established to support the
product shipments. As part of the operational storage and distribution
criteria, product shipments will be monitored for excursions during shipment
using temperature monitoring devices.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
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Deliverable: Stability studies set up
for [+] scale cGMP product material to establish TTI.


 


3.4.7.1 Conduct Stability Studies under [+]: These studies
will be conducted at [+] temperature than the recommended storage condition to
determine additional time that the material may exposed to harsher conditions
without risk.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Stability studies completed
to establish TTI.


 


3.4.7.2 Conduct Shipping and Transport Stability
Studies: These studies will show that the drug product is
stable under the actual conditions of shipping.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Stability studies completed
to establish TTI.


 


3.4.7.3 Quality Audits: Stability Study
Audits are Direct Impact audits. Audits include a list of questions directly
suited to the supplier and a cGMP, GLP (Analytical) checklist (again dependent
on supplier). All suppliers (through audits) are approved (or rejected) by QA
and audit records are maintained by the AVI EDMS. The Director of QA reviews
and approves stability study protocols as well as reports on stability data.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Documented audit findings
Approved stability study protocol and approved study data and reports.


 


3.4.7.4 Project Management, Operations and Oversight: Track progress
and manage issues as they arise.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.8 Conduct Nonclinical Studies: In addition
to the multiple studies completed to date and forming the basis for the open
IND, the studies since then and prior to this award that will supplement that
IND, AVI will also complete further [+] studies, for example [+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Conduct [+] scale cGMP
product material.


 


3.4.8.1 [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Final Report on [+].


 


3.4.8.2 [+] to provide data necessary
for registration.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
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Deliverable: Sufficient [+].


 


3.4.8.3 [+] Mass Balance: Mass balance
study required to show fate of drug in [+]; required data for registration.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Final report from CRO on
mass balance in the [+].


 


3.4.8.4 [+] in vivo Metabolism: Provide data
on metabolism of drug in [+] model. Required for registration and determination
if any metabolites are present that need to be monitored in preclinical and
clinical trials.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
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Deliverable: Final report from CRO on in
vivo metabolism in the [+].


 


3.4.8.5 [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Final report from CRO on
protein binding.


 


3.4.8.6 [+] Dose Range Finding Study: To determine
the effect of treatment on the [+]
development, with determination of appropriate dose levels for the definitive
[+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Audited final report on [+]
study.


 


3.4.8.7 [+] Study: The definitive study to
determine the effect of treatment on the [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audited final report on [+]
study.


 


3.4.8.8 Quality Audits: All preclinical
studies will be monitored by AVI during critical in-life phases to assure
adherence to GLPs and protocol; monitoring will also be done by CRO QA unit.
Study reports reviewed by CRO QA unit and by AVI to assure accuracy See section
3.2.3.1.3 Quality Audits and Review for a general description of quality
audits. GLP audits occur, reports are completed and satisfactory responses to
audit findings are required from CROs conducting AVI-6003 nonclinical studies
and [+] testing facilities. Analytical testing occurs using AVI“s QA-approved
validated analytical methods. The Director of QA participates in the review and
approval of [+] method validation protocols and validation reports. All nonclinical
studies will be monitored by AVI during critical in-life phases to assure
adherence to GLP requirements. Study monitoring will also be done by the CRO“s
QA unit. Study reports and data listings will be reviewed by the CRO“s QA unit
and by AVI “s monitor and QA Unit to assure accuracy.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audits will occur, audit
reports completed and satisfactory responses to audit findings will be required
from nonclinical CROs and [+] testing facilities. Study reports and data
listings will be reviewed and approved by the CRO“s QA unit and by AVI“s
monitor and QA Unit.


 


3.4.8.9 Project Management, Operations and Oversight: Track progress
and manage issues as they arise.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.9 [+] Efficacy Studies in [+]: The [+] studies
will confirm therapeutic efficacy at specific dose levels and expected
exposures that will be mimicked in [+]. Using the currently filed IND, clinical
safety and any [+] obtained during CLIN0001, any additional preclinical data,
and based on the protocol developed with FDA as to the studies necessary under
the [+], AVI will conduct the [+] studies, necessary to show protection against
an [+] challenge by injection.


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
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Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Conduct NHP [+] studies
using [+] scale cGMP product material.


 


3.4.9.1 [+] Efficacy Studies in [+] #1: The [+] studies
will confirm therapeutic efficacy at specific dose levels and expected
exposures that will be mimicked in [+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Conduct NHP [+] studies
using [+] scale AVI-6003 cGMP product material


 


3.4.9.1.1 [+] Acquisition and Acclimatization: Prior to [+]
protocols are reviewed by [+]. Once protocols are approved, [+]. [+] are held
in quarantine to ensure acclimation to the laboratory setting and receive a
final health evaluation. Finally, randomization and cage arrangements are
finalized.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Sufficient [+] acclimated
and released for first pivotal study to begin.


 


3.4.9.1.2 Conduct Study, Laboratory Analyses, Viral
Sequencing: This is the [+] of the study involving [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Completion of the [+]
portion of the first [+] study.


 


3.4.9.1.3 Data Analyses, Final Study Report: Compile
observations and unblind data. Statistical analysis and preparation of a final
study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Presentation of final study
report.


 


3.4.9.2 [+] Studies in [+]: The [+] studies
will confirm therapeutic efficacy at specific dose levels and expected
exposures that will be mimicked in [+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Conduct NHP [+] studies
using [+] scale AVI-6003 cGMP product material.


 


3.4.9.2.1 [+] Acquisition and Acclimation: Prior to [+]
protocols are reviewed by [+]. Once protocols are approved, [+] acquisition can
take place. [+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Sufficient [+] acclimated
and released for second pivotal study to begin.


 


3.4.9.2.2 Conduct Study, Laboratory Analyses, [+]: This is the [+], treatment with the [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Completion of the [+]
portion of the [+] study.


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
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3.4.9.2.3 Data Analyses, Final Study Report: Compile
observations and unblind data. Statistical analysis and preparation of a final
study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Presentation of final study
report.


 


3.4.9.3 Data Management: Full data
management and statistical analysis plans will be developed by a qualified
Contract Research Organization, and shared with the FDA (and USG) before
studies completed. The CRO will monitor source documents (to the extent
possible in [+] environment), collect data, ensure all data queries are
clarified, lock database, analyze and then reveal treatment allocation.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Conduct analyses of pivotal
efficacy studies for study reports.


 


3.4.9.4 GLP Audits: See section 3.2.3.1.3
Quality Audits and Review for a general description of quality audits. GLP
audits occur, reports are completed and satisfactory responses to audit
findings are required from CROs conducting nonclinical studies and [+] testing
facilities. Analytical testing occurs using AVI“s QA-approved validated
analytical methods. The Director of QA participates in the review and approval
of [+] method validation protocols and validation reports. All nonclinical
studies will be monitored by AVI during critical in-life phases to assure
adherence to GLP requirements. Study monitoring will also be done by the CRO“s
QA unit. Study reports and data listings will be reviewed by the CRO“s QA unit
and by AVI“s monitor and QA Unit to assure accuracy.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audits will occur, audit
reports completed and satisfactory responses to audit findings will be required
from nonclinical CROs and [+] testing facilities. Study reports and data
listings will be reviewed and approved by the CRO“s QA unit and by AVI“s
monitor and QA Unit.


 


3.4.9.5 Project Management, Operations and Oversight: Develop
timeline, manage vendors, anticipate and resolve problems, track project plan
compliance, report progress. Progress and any issues will be documented and
addressed with the Product Development Team on at least a monthly basis.
Regular conference calls with the TMTI will be established to review progress
and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.10 Activities to Achieve Pivotal Efficacy Studies:
AVI will prepare and submit [+]. The Final Protocols for the [+]
studies will also be submitted after the FDA responses are received from the
[+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: [+] submitted to the FDA.


 


3.4.10.1 [+] (Clinical, Nonclinical): [+] will be
submitted as soon as study reports are available to keep the [+]. The Final Protocols
for the [+] studies will also be submitted as [+] after the FDA responses are
received from the [+].


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
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Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: [+] submitted to the FDA.


 


3.4.10.2 [+] (Drug Substance, Drug Product): [+] will be
submitted as soon as data are available on the lots of drug substance and drug
product that will be used in the [+] Studies are available. Additional [+] will
be submitted as reports and data are available to keep the [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Prepare and submit [+].


 


3.4.10.3 Project Management, Operations and Oversight:
Develop timeline, manage vendors, anticipate and resolve problems,
track project compliance, report progress. As part of the normal course of
executing project, regular team meetings will be held with each vendor and held
internally. This team is responsible for the project plan. Project progress and
any issues relative to the project plan will be documented and addressed with
the Product Development Team on at least a monthly basis. Regular conference
calls with the TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.11 Request and Conduct [+] Meeting with the FDA: AVI will
request an [+] to provide a summary of results of the [+] clinical studies and
to discuss the [+] clinical development plan. The topic of designation as a
[+]. A Meeting Request Letter and Briefing Document will be submitted to the
FDA. Advanced notification of the meeting, plus copies of all meeting-related
documents will be provided to the USG Program Office in a timely manner. After
the meeting AVI“s regulatory affairs staff will prepare and submit notes of the
meeting as an [+]. The FDA“s official Meeting Minutes will be reviewed to
ensure that they reflect the same meeting outcomes and agreements as those
documented by AVI.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: [+] Request and Briefing
Document submitted to the FDA. Participate in [+] with FDA. Prepare notes of
the meeting and review the FDA“s official Meeting Minutes to assure that both
the FDA and AVI agree on the outcomes of the discussion and agreements.


 


3.4.11.1 Prepare Meeting Request and Briefing
Document: The Meeting Request Letter and Briefing Document
will be prepared as soon as is feasible and submitted to the FDA at least one
month in advance of the requested meeting date. . Advanced notification of the
meeting, plus copies of all meeting-related documents will be provided to the
USG Program Office in a timely manner.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: [+] Request Letter and Briefing
Document submitted to the FDA.


 


3.4.11.2 [+].


 


Period of Work: Approximately [+] month
(e.g. [+]).


 






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Deliverable: Submit request for [+] to
the FDA.


 


3.4.11.3 FDA Meeting, Minutes and Follow Up: AVI will attend
the [+] with the FDA. AVI will submit notes of the meeting to the FDA and
ensure that the company is in agreement with the outcomes and agreements
recorded in the FDA“s official Meeting Minutes. Clarifications will be
requested, as necessary. AVI will continue an open dialogue with the FDA as
development continues.


 


Period of Work: Approximately [+] week
(e.g. [+]).


 


Deliverable: AVI will provide copies of
the company“s notes and the FDA“s official Meeting Minutes to the USG Program
office.


 


3.4.11.4 Project Management, Operations and Oversight:
Develop timeline, manage vendors, anticipate and resolve problems,
track compliance, report progress. Project progress and any issues relative to
the development plan will be documented and addressed with the Product Development
Team on at least a monthly basis. Regular conference calls with the TMTI will
be established to review progress and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.12 [+].


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Deliver sample of drug
product used in [+] clinical safety study to USG.


 


3.4.12.1 Ship [+] to US Government: At the end of
CLIN0002 at least [+] of the drug product(s) will be delivered to the
recipient specified by the US Government.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Deliver sample of drug
product used in [+] clinical safety study to USG.


 


3.4.12.2 Project Management, Operations and Oversight:
Track progress and manage issues as they arise.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.13 [+] Clinical Study: A [+]
Volunteers. A goal for this study is to establish a [+], the intended
therapeutic schedule. [+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Complete [+] clinical study
and issue final clinical study report.


 


3.4.13.1 Clinical Site and Local Laboratory
Activities: The study will be planned and executed at audited,
selected [+] Clinical Research site(s) with support from selected, fully
[+] accredited laboratory. Site and laboratory will have had satisfactory
GCP/GLP audits and then site will be initiated,


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
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monitored through to study completion and
close out.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Plan, conduct and complete
[+] clinical study. Provide all required data to the CRO for final study
report.


 


3.4.13.1.1 Contracts and Budgets: Contracts will
be negotiated with vendors for the execution of this study.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Signed contracts in place
with all vendors before initiation of [+] clinical study.


 


3.4.13.1.2 Protocol [+] Approval: Full [+] in
parallel; AVI will answer any questions and amend protocol if necessary. The
Amended protocol will be submitted to the [+] for approval prior to and
notification of site(s) start study. All required information about the
investigator, site, testing laboratories and CRO responsibilities will be
submitted to the FDA prior to study start at any site.


 


Period of Work: Approximately [+] months
(e.g [+]).


 


Deliverable: FDA, Ethics Committee and
[+] approvals received before study start.


 


3.4.13.1.3 Site Activities First Patient First Visit
to Last Patient Last Visit: The study will be planned
and executed at an audited, selected [+] Clinical Research Facility. Site will
be involved with review of study specific documentation and trained prior to
first subject first visit. All interactions with the site will be documented.
Regular site monitoring will be planned and documented to ensure data has been
verified and entered in a timely fashion, while ensuring subject safety. Any
compliance issues will be raised to the clinical team for response.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Complete [+] study and
complete electronic case report forms on schedule and within budget.


 


3.4.13.1.4 Site(s) Close Out: After
completion of the last subject last visit, all data queries will be completed
by the site and/or laboratory, previously validated database locked, analyses
run, and draft study report prepared. In parallel formal close out of the
clinical site, with disposal of unused drug supplies and completion of all
outstanding documentation will occur.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: All open queries and action
items associated with clinical study execution are completed and documented in
a site close out visit report.


 


3.4.13.2 Outsource Services: Identify,
select and qualify subcontractors needed to execute clinical study. Assigned
vendor personnel will participate in a kick off meeting in which study
expectations and needs, including timelines, will be discussed. Protocol and
procedure training will occur. A communication plan and reports needed will be
developed prior to first subject enrolled.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
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Deliverable: Training records, meeting
minutes confirm that subcontractors are trained to the study and ready to
perform services.


 


3.4.13.2.1 Clinical Research Organization and Data
Management: The CRO is key to study success. Their team along
with AVI personnel are responsible for site start up activities, site training,
and study execution, including data collection and management. The statistical
support is part of the CRO. This group and Data Management will develop the
plans necessary for data collection, query management, data analysis and
quality checks. They will prepare reports for the [+] reviews. The final
clinical study report will be written by CRO personnel.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Executed contract between
AVI and CRO.


 


3.4.13.2.2 Central Laboratory Services and Data
Transfer: [+] and analyses will each be conducted at a central
lab facility. Data from each will be sent to data management vendor for
inclusion in final study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Laboratory data reports
provided to data management vendor.


 


3.4.13.2.3 [+]: An independent [+] will be appointed to oversee and confirm
dose escalation decisions. A [+] will be prepared and agreed with [+] members,
a contract developed and a kickoff meeting and then [+] meetings with open and
closed session. Members of the [+] will be available to [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Decisions to [+] as
documented in meeting minutes.


 


3.4.13.2.4 Provide Electronic Data Management with
Access to US Government: Enable [+] web portal with secure access to
assigned study, company, vendor, and USG personnel.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Functional secure EDC
portal access.


 


3.4.13.2.5 Drug Warehousing and Distribution: Store clinical
trial material at [+] in secure, temperature controlled and monitored unit.
Implement traceable distribution system with chain of custody documentation.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Provide clinical trial
material on time to site(s) and keep adequate records.


 


3.4.13.3 Provide Documents to Clinical Sites and
Complete Study Reports: CRO, lab vendors and drug warehouse provide
complete set of documents and forms to effectively and efficiently conduct
study, including but not limited to: study specific data collection forms
(electronic case report forms), the study operations manual, training on the
protocol, clinical trial material storage, inventory and administration, use of
[+], and Good Clinical Practice regulations.


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Shipping receipts showing
what was sent to whom and when.


 


3.4.13.3.1 Prepare and Distribute Study Documents: CRO, lab
vendors and drug warehouse provide complete set of documents and forms to
effectively and efficiently conduct study.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: All study related documents
including but not limited to: study plan and timeline, [+] completion
guidelines, monitoring reports, protocol compliance tracking, communication
plan, meeting minutes, training materials and logs, drug accountability logs
and final study report.


 


3.4.13.3.2 Final Study Reports: Prepare
submission ready final clinical study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Submit compliant and
complete [+] will be submitted to the FDA as an [+].


 


3.4.13.4 GCP Audits: Audits will be performed of
Clinical Study Sites.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audits will occur, audit
reports completed and satisfactory responses to audit findings will be required
from clinical sites. Study reports and data listings will be reviewed and
approved by the CRO“s QA unit and by AVI“s monitor and QA Unit.


 


3.4.13.5 Project Management, Operations and Oversight:
Develop timeline, manage vendors, anticipate and resolve problems,
track protocol compliance, report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.14 [+] Clinical Study: AVI will
conduct a [+]. A specialized [+], is expected to support efficient enrollment
and evaluation. Subject accrual and treatment is scheduled for less than [+]
months. The results will be available for the planning of the expanded [+] trial.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Conduct [+] clinical study using [+] scale cGMP drug
product material and issue final clinical study report.


 


3.4.14.1 Clinical Site and Local Laboratory Activities: Clinical
sites and laboratories will be audited for compliance with GCP, selected and
then initiated, monitored through to study completion and close out. The study
will be planned and executed at audited, selected [+] Clinical Research site(s) with
support from a fully [+] accredited laboratory. From initiation forward the
site(s) will be monitored through to study completion and site close out.


 


Period of Work: Approximately [+] Days
(e.g. [+]).


 


Deliverable: Plan, conduct and complete
[+] clinical study. Provide all required data to the CRO for final study
report.


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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3.4.14.1.1 Contracts and Budgets: Contracts will
be negotiated with vendors for the execution of this study.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Signed contracts in place
with all vendors before initiation of [+] clinical study.


 


3.4.14.1.2 [+] Approval: Full protocol
will be submitted to [+] in parallel; AVI with CRO will answer any questions
and amend protocol if necessary to ensure final ethics approval, and
notification of site(s) prior to study start.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: All approvals received
before initiation of clinical study.


 


3.4.14.1.3 Site Activities First Patient in to Last
Patient Out: The study will be planned and executed at an
audited, selected [+] Clinical Research Facility. Site will be involved with
review of study specific documentation and trained prior to first subject first
visit. All interactions with the site will be documented. Regular site
monitoring will be planned and documented to AVI (or Contract Research
Organization staff) will monitor conduct of the [+] study to ensure data has been verified and entered in a
timely fashion, while ensuring subject safety. Any compliance issues will be
raised to the clinical team for response.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Complete in life portion of
[+] study and complete electronic
case report forms on schedule and within budget.


 


3.4.14.1.4 Site(s) Close Out: After
completion of the last subject last visit, all data queries will be completed
by the site and/or laboratory, previously validated database locked, analyses
run, and draft study report prepared. In parallel formal close out of the
clinical site, with disposal of unused drug supplies and completion of all
outstanding documentation will occur.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: All open queries and action
items associated with clinical study execution are completed and documented in
a site close out visit report.


 


3.4.14.2 Outsource Services: Identify, select
and qualify subcontractors needed to execute clinical study. Assigned vendor
personnel will participate in a kick off meeting in which study expectations
and needs, including timelines, will be discussed. Protocol and procedure
training will occur. A communication plan and reports needed will be developed
prior to first subject enrolled.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Training records, meeting
minutes confirm that subcontractors are trained to the study and ready to perform
services.


 


3.4.14.2.1 Clinical Research Organization and Data
Management: The CRO is key to study success. Their team along
with AVI personnel are responsible for site start up activities, site training,
and study execution, including data collection and management. The statistical
support is part of the CRO. This group and Data Management will develop the
plans necessary for data collection, query management,


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
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data analysis and quality checks. They will prepare reports for the [+]
reviews. The final clinical study report will be written by CRO personnel.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Executed contract between
AVI and CRO.


 


3.4.14.2.2 Central Laboratory Services and Data
Transfer: [+] and analyses will each be conducted at a central
lab run at one facility. Data from each will be sent to data management vendor
for inclusion in final study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Laboratory data reports
provided to data management vendor.


 


3.4.14.2.3 [+]: An independent [+] will be
appointed to oversee and confirm dose escalation decisions. A [+] charter will
be prepared and agreed with [+] members, a contract developed and a kickoff
meeting and then dose escalation meetings with open and closed session. Members
of the [+] will be available to review safety data and confirm or reject
escalation to the next higher dose.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Decisions to dose escalate,
continue or stop study as documented in meeting minutes.


 


3.4.14.2.4 Provide Electronic Data Management with
Access to US Government: Enable [+]
with secure access to assigned study, company, vendor, and USG personnel.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Functional secure [+] access.


 


3.4.14.2.5 Drug Warehousing and Distribution: Store clinical
trial material at refrigerated conditions in secure, temperature controlled and
monitored unit. Implement traceable distribution system with chain of custody
documentation.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Provide clinical trial
material on time to site(s) and keep adequate records.


 


3.4.14.3 Provide Documents to Clinical Sites and
Complete Study Reports: CRO, lab vendors and drug warehouse provide
complete set of documents and forms to effectively and efficiently conduct
study, including but not limited to: study specific data collection forms
(electronic case report forms), the study operations manual, training on the
protocol, clinical trial material storage, inventory and administration, use of
[+], and Good Clinical Practice
regulations.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Shipping receipts showing
what was sent to whom and when.


 


3.4.14.3.1 Prepare and Distribute Study Documents: CRO, lab
vendors and drug warehouse provide complete set of documents and forms to
effectively and efficiently conduct study.


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: All study related documents
including but not limited to: study plan and timeline, [+] guidelines, monitoring reports, protocol
compliance tracking, communication plan, meeting minutes, training materials
and logs, drug accountability logs and final study report.


 


3.4.14.3.2 Final Study Report: Prepare
Submission ready final clinical study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: The Final Study Report will
be submitted to the FDA as an [+].
Submit compliant and complete final clinical study report.


 


3.4.14.4 GCP Audits: Audits will be performed of
Clinical Study Sites.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audits will occur, audit
reports completed and satisfactory responses to audit findings will be required
from clinical sites. Study reports and data listings will be reviewed and
approved by the CRO“s QA unit and by AVI“s monitor and QA Unit.


 


3.4.14.5 Project Management, Operations and Oversight:
Track progress and manage issues as they arise.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.4.15 Contract Program Management: AVI will track
progress on each element in the contract, including all financial and reporting
requirements; ensure compliance with contract and all government regulations.
AVI will manage all subcontracts and ensure that their timelines are met, and
the components contributed by each to the overall program are coordinated, on
budget, and that they are compliant with all contract and Government regulations
that are applicable. In addition AVI will continue to implement enhancements to
the Quality Systems Approach already in place, including installation of a
secure 21 CFR Part 11 compliant EDMS and preparation for electronic submission
of documents to the FDA. The EDMS will be utilized for document management and
control, including collaborative authoring of study reports and eCTD text for
the [+], revision and versioning control with metadata for audit trails, and
secure document repository. The EDMS will provide authorized representatives of
USG electronic access to program status information. The use of eCTD compliant
document templates and completed reports for electronic submissions to the FDA
will be managed, controlled, archived and regulated under the Quality System in
the EDMS.


 


Period of Work: Concurrent with all
CLIN0002 activities. Approximately [+] days (e.g. [+]).


 


Deliverable: Provide contract management
and financial oversight ensuring compliance. 


 


3.4.15.1 Program Management: Track progress
and manage issues as they arise.


 


Period of Work: Concurrent with all
CLIN0002 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide project management
ensuring compliance.


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
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3.4.15.2 Finance and [+]: Track financial
work process and reporting.


 


Period of Work: Concurrent with all
CLIN0002 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide project financial
management ensuring compliance.


 


3.4.15.3 Contract and Subcontract Management: Manage our
compliance with contract and USG regulations; manage subcontractors and
relationship with them.


 


Period of Work: Concurrent with all
CLIN0002 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide contract and
subcontract management ensuring compliance.


 


3.4.15.4 EDMS and QA: AVI will continue to store
all documents on the validated EDMS and preparation for electronic document
submission to the FDA. AVI will train all pertinent staff on EDMS and Quality
Assurance.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: EDMS system fully
operational. QA audits of all vendors will have been performed and any follow
up action items identified and tracked.


 


3.5 CLIN0003: AVI will
deliver the developmental therapeutic end item that has achieved [+] Clinical
Study, based upon CLIN0001 and CLIN0002 (recognizing that some activities will
be concurrent), additional prior studies and all the associated regulatory
requirements sufficient and in place to support this. This will comprise all
those activities necessary for our candidate drug product to complete the USG
Statement of Objectives in CLIN0003.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Drug product on which [+]
Clinical Study has been completed.


 


3.5.1 Complete Pivotal Efficacy Studies: This has been
moved to CLIN0002 3.4.9.1 and 3.4.9.2.


 


3.5.2 [+]: Continue to implement
enhancements to the Quality Systems Approach already in place, including
installation of a secure 21CFR Part 11 compliant EDMS and preparation for
electronic submission of documents to the FDA.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Submit the quality
amendment to FDA as a supplement to the AVI-6003 [+].


 


3.5.2.1 Write and Submit [+]: Update
information stored on EDMS and preparation for electronic submission of
documents to the FDA.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Submit the quality
amendment to FDA as an [+].


 


3.5.2.2 Respond to FDA Questions: Develop and
provide response to any questions or recommendations from FDA following filing
of [+].


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
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Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Submit to FDA as an [+].


 


3.5.2.3 Project Management, Operations and Oversight: Develop
timeline, manage vendors, anticipate and resolve problems, track protocol
compliance, report project progress. As part of the normal course of conducting
clinical trials, regular team meetings will be held with each vendor and held
internally. This team is responsible for the project plan. Project progress and
any issues relative to the project plan will be documented and addressed with
the Product Development Team on at least a monthly basis. Regular conference
calls with the TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget


 


3.5.3 [+] Study: Using the currently filed
AVI-6003 [+], clinical safety and any [+] data obtained during CLIN0001 and
CLIN0002, AVI will initiate the [+]
Study in [+] using the protocols
agreed with FDA, while ensuring all necessary [+] study requirements such as
[+] review and approval. AVI will conduct this [+]. FDA concurrence that this will be sufficient for the
safety database to [+] will be
sought.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Conduct and audit [+] study and issue final study report.


 


3.5.3.1 Clinical Site and Local Laboratory Activities:
The study will be planned and executed at audited, selected [+]
Clinical Research site(s) with support from a fully [+] accredited laboratory.
From initiation forward the site(s) will be monitored through to study
completion and site close out.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Plan, conduct and complete
[+] clinical study. Provide all
required data to the CRO for final study report.


 


3.5.3.1.1 Contracts and Budgets: Contracts will
be negotiated with vendors for the execution of this study.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Signed contracts in place
with all vendors before initiation of [+] clinical study.


 


3.5.3.1.2 [+] Approval: Full protocol
will be submitted to [+] in parallel; AVI with the CRO will answer any
questions and amend protocol if necessary to ensure final ethics approval and
notification of site(s) prior to study start.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: FDA, Ethics Committee and
[+] approvals received before initiation of the [+] study.


 


3.5.3.1.3 Site Activities First Patient in to Last
Patient Our: The study will be planned and executed at an
audited, selected clinical sites. Sites will be involved with review of study
specific documentation and trained prior to first subject first visit. All
interactions with the sites will be documented. Regular site


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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monitoring will be planned and documented to AVI (or Contract Research
Organization staff) will monitor conduct of the [+] study to ensure data have been verified and entered in a
timely fashion, while ensuring subject safety. Any compliance issues will be
raised to the clinical team for response.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Complete in life portion of
pivotal safety study and complete electronic case report forms on schedule and
within budget.


 


3.5.3.1.4 Site(s) Close Out: After
completion of the last subject last visit, all data queries will be completed
by the site and/or laboratory, previously validated database locked, analyses
run, and draft study report prepared. In parallel formal close out of the
clinical site, with disposal of unused drug supplies and completion of all
outstanding documentation will occur.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: All open queries and action
items associated with clinical study execution are completed and documented in
a site close out visit report.


 


3.5.3.2 Outsource Services: Identify,
select and qualify subcontractors needed to execute clinical study. Assigned
vendor personnel will participate in a kick off meeting in which study
expectations and needs, including timelines, will be discussed. Protocol and
procedure training will occur. A communication plan and reports needed will be
developed prior to first subject enrolled.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Training records, meeting
minutes confirm that subcontractors are trained to the study and ready to
perform services.


 


3.5.3.2.1 Clinical Research Organization and Data
Management: The CRO is key to study success. Their team along
with AVI personnel are responsible for site start up activities, site training,
and study execution, including data collection and management. The statistical
support is part of the CRO. This group and Data Management will develop the
plans necessary for data collection, query management, data analysis and
quality checks. They will prepare reports for the [+] reviews. The final
clinical study report will be written by CRO personnel.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Executed contract between
AVI and CRO.


 


3.5.3.2.2 Central Laboratory Services and Data
Transfer: [+] and analyses will each be conducted at a central
lab facility. Data from each will be sent to data management vendor for
inclusion in final study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Laboratory data reports
provided to data management vendor.


 


3.5.3.2.3 [+]: An independent [+] will be
appointed to oversee and confirm dose escalation decisions. A [+] will be prepared and agreed with [+]
members, a contract developed and a kickoff meeting and then dose escalation
meetings with open and closed session. Members of the [+] will be available to
review


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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safety data and confirm or reject escalation to the next higher dose.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Provide safety oversight
for pivotal safety study. Decisions to dose escalate, continue or stop study as
documented in meeting minutes.


 


3.5.3.2.4 Provide Electronic Data Management with
Access to US Government: Enable [+] with secure access to assigned
study, company, vendor, and USG personnel.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Functional, secure [+]
access.


 


3.5.3.2.5 Drug Warehousing and Distribution: Store clinical
trial material at refrigerated conditions in secure, temperature controlled and
monitored unit. Implement traceable distribution system with chain of custody
documentation.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Provide clinical trial
material on time to site(s) and keep adequate records.


 


3.5.3.3 Provide Documents to Clinical Sites and
Complete Study Reports: CRO, lab vendors and drug warehouse provide
complete set of documents and forms to effectively and efficiently conduct
study, including but not limited to: study specific data collection forms
(electronic case report forms), the study operations manual, training on the
protocol, clinical trial material storage, inventory and administration, use of
[+], and Good Clinical Practice regulations.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Shipping receipts showing
what was sent to whom and when.


 


3.5.3.3.1 Prepare and Distribute Study Documents: CRO, lab
vendors and drug warehouse provide complete set of documents and forms to
effectively and efficiently conduct study.


 


Period of Work: Approximately [+] months (e.g.
[+]).


 


Deliverable: All study related documents
including but not limited to: study plan and timeline, eCRF completion
guidelines, monitoring reports, protocol compliance tracking, communication
plan, meeting minutes, training materials and logs, drug accountability logs
and final study report.


 


3.5.3.3.2 Final Study Report: Prepare
submission ready final clinical study report.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Submit submission and
complete final clinical study report.


 


3.5.3.4 GCP Audits: Audits will be performed of
Clinical Study Sites.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Audits will occur, audit
reports completed and satisfactory responses to audit findings will be required
from clinical sites. Study reports and data listings will be reviewed and
approved by the


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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CRO“s QA unit and by AVI“s monitor and QA Unit.


 


3.5.3.5 Project Management, Operations and Oversight: Track progress
and manage issues as they arise.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.5.4 Refine and Select Formulation and Delivery
System: AVI will continue the assessment of stability for
the validation lots prepared in CLIN0002. The drug kit per treatment will
comprise [+]. The storage of the kit will be [+]. This drug product kit meets
the [+].


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Finalize the drug kit
components for drug product.


 


3.5.4.1 Determine Configuration for Market: All details of
the commercial formulation are finalized ([+]).


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Finalize the drug kit
components for AVI-6003 product.


 


3.5.4.2 Identify Manufacturer for Packaging Final
Product: Establish contract for assembling final marketing
packages.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Finalize the vendor for
manufacture, labeling and packaging of AVI-6003 product.


 


3.5.4.3 Continue Drug Substance and Drug Product
Stability Studies: Continue drug substance and drug product stability
studies.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Continue stability for drug
substance and drug product.


 


3.5.4.4 Project Management, Operations and Oversight: Track progress
and manage issues as they arise.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.5.5 Deliver [+] to US Government: Deliver at
least [+] of product, from the lot used for the [+] study.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Deliver sample of drug
product used in [+] study to USG.


 


3.5.5.1 Deliver [+] to US Government: At the end of
CLIN0003 at least [+] of the drug product(s) will be delivered to the recipient
specified by the USG.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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Deliverable: Deliver sample of drug
product used in [+] study to USG.


 


3.5.5.2 Project Management, Operations and Oversight: Oversight of
inventory and distribution will be managed by AVI personnel through site
visits, audits, and records review.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.5.6 Contract Program Management: AVI will track
progress on each element in the contract, including all financial and reporting
requirements; ensure compliance with contract and all government regulations.
AVI will manage all subcontracts and ensure that their timelines are met, and
the components contributed by each to the overall program are coordinated, on
budget, and that they are compliant with all contract and Government
regulations that are applicable.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Provide contract management
and financial oversight ensuring compliance.


 


3.5.6.1 Program Management: Track progress
and manage issues as they.


 


Period of Work: Concurrent with all
CLIN0003 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide project management
ensuring compliance.


 


3.5.6.2 Finance and [+]: Track financial
work process and reporting.


 


Period of Work: Concurrent with all
CLIN0002 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide project financial
management ensuring compliance.


 


3.5.6.3 Contract and Subcontract Management: Manage our
compliance with contract and USG regulations; manage subcontractors and
relationship with them.


 


Period of Work: Concurrent with all
CLIN0003 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide contract and
subcontract management ensuring compliance.


 


3.5.6.4 EDMS and QA: AVI will continue to store
all documents on the validated EDMS and preparation for electronic document
submission to the FDA. AVI will train all pertinent staff on EDMS and Quality
Assurance.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: EDMS system fully operational.
QA audits of all vendors will have been performed and any follow up action
items identified and tracked.


 


3.6 CLIN0004: AVI will
deliver the FDA approved therapeutic end item including all New Drug


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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Application and Approval activities resulting in the delivery of at
least [+], based upon CLIN0001, CLIN0002 and CLIN0003 (recognizing that some
activities will be concurrent), additional prior studies and all the associated
regulatory requirements sufficient and in place to support this. This will
comprise all those activities necessary for [+] drug product to complete the
USG Statement of Objectives in CLIN0004.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Drug product approved by
FDA.


 


3.6.1 [+] Meeting with the FDA: A [+] Meeting with the FDA will be
requested and a Briefing Document submitted approximately one month in advance
of the meeting. The FDA will schedule the meeting within 60 days of the
request. The purpose of the [+] Meeting is to reach agreement on the electronic
format and content of the [+]. The [+] will also be discussed at this meeting.
AVI will prepare notes of the meeting that will document the discussion and
agreements with the FDA; the notes will be submitted to the FDA. The FDA will
issue official Meeting Minutes. AVI will follow up to request clarifications,
as needed.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: AVI prepares and submits
Request Letter and Briefing Document, participates in the [+] meeting with the
FDA, prepares notes of the meeting that are submitted to the FDA.


 


3.6.1.1 Prepare Meeting Request and Briefing
Documents: The [+] Meeting Request Letter and Briefing document
will be prepared and submitted as soon as is feasible after the completion of
dosing in the clinical trials approximately [+] ahead of the meeting. Advanced
notification of the meeting, plus copies of all meeting-related documents will
be provided to the USG in a timely manner.


 


Period of Work: Approximately [+] month
(e.g. [+]).


 


Deliverable: AVI [+] Meeting Request
Letter and Briefing Document are submitted to the FDA.


 


3.6.1.2 [+] Meeting, Minutes and Follow Up: AVI will participate
in the [+] with FDA, take notes and obtain official minutes, following up on
any action items due. AVI will provide copies of the FDA’s Meeting Minutes to
USG.


 


Period of Work: Approximately [+] weeks
(e.g. [+]).


 


Deliverable: AVI’s [+] Meeting notes and
the FDA’s official Meeting Minutes.


 


3.6.1.3 Project Management, Operations and Oversight: Develop
timeline, manage vendors, anticipate and resolve problems, track project
compliance, report project progress. As part of the normal course of executing
project, regular team meetings will be held with each vendor and held
internally.


 


This team is responsible for the project plan. Project progress and any
issues relative to the project plan will be documented and addressed with the
Product Development Team on at least a monthly basis. Regular conference calls
with the TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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3.6.2 Prepare, Submit and FDA Review of [+]: AVI will
electronically submit an [+] that meets the “USG“s Target Product Profile. By
using eligibility as a small business enterprise, and employing regulatory
procedural relief benefits due [+], AVI is planning for the [+] to be prior to
the completion of the contractual period proposed. During the FDA“s review, AVI
will remain ready to respond promptly to any questions that arise by using
secure email correspondence. The USG will be kept fully informed of progress.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: AVI prepares and
electronically submits an [+] that meets the FDA’s requirements for review and
validation.


 


3.6.2.1 Complete and Submit [+] and Respond to FDA
Review Comments: AVI will complete and submit an [+] to the FDA; and
respond in a timely fashion to Information Requests and other comments from the
FDA reviewers.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: An [+] that has been
submitted electronically to the FDA and accepted for filing as an appropriately
structured electronic submission. Responses to Requests for Information and the
[+] from the FDA will be answered promptly.


 


3.6.2.2 Project Management and Oversight: Develop
timeline, manage vendors, anticipate and resolve problems, track project
compliance, report project progress. As part of the normal course of executing
project, regular team meetings will be held with each vendor and held
internally. This team is responsible for the project plan. Project progress and
any issues relative to the project plan will be documented and addressed with
the Product Development Team on at least a monthly basis. Regular conference
calls with the TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.6.3 [+] and Response to FDA [+]: Given the
issues faced by the FDA [+], it is likely that the FDA [+]. AVI will attend and
participate in an [+], and respond promptly to any questions in the [+]
approval occurs.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Responses to Requests for
Information from the FDA, will be submitted promptly. AVI will prepare a
Briefing Document and presentation materials for an [+]. Draft notes of the [+]
will be prepared.


 


3.6.3.1 [+]: AVI will plan and prepare
and, once confirmed, attend and participate at [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: AVI will prepare a
presentation and Briefing Document in advance of the [+].


 


3.6.3.2 Prepare and Submit Complete Response to [+]: At the
conclusion of their review the FDA will issue a [+].


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Complete Response will be
made to any questions asked by the FDA.


 


3.6.3.3 Project Management and Oversight: Develop
timeline, manage vendors, anticipate and resolve problems, track project
compliance, report project progress. As part of the normal course of executing
project, regular team meetings will be held with each vendor and held
internally. This team is responsible for the project plan. Project progress and
any issues relative to the project plan will be documented and addressed with
the Product Development Team on at least a monthly basis. Regular conference
calls with the TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.6.3.4 [+]: AVI will receive formal
confirmation [+]. AVI will submit [+] and participate in the final negotiations
of the [+].


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Receipt of the [+]. A copy
will be sent to the USG Program office.


 


3.6.4 [+] in Compliance with FDA Requirements: The [+]. The [+], or in
the electronic format required by the FDA at that time. The [+] will have been
submitted to the FDA in the [+] at that time.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Prepare [+].


 


3.6.4.1 Structured [+] Review and Responses: Preparation of the draft [+] (i.e. the
physician’s information and patient information leaflet) will be started before
[+] to facilitate discussion with the FDA and information will continue to be
added up [+]. Two versions are required to be submitted in the [+], one of
which is annotated with the source data for each statement. Both versions are
submitted electronically in the required XML format. During review by the FDA
Division and by [+], AVI will respond to comments promptly. At the conclusion
of the FDA review, AVI will resubmit [+]. [+] will be sent to the USG Program
Office at time of submission [+].


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Prepare draft labeling in
[+] and discussion with the FDA.


 


3.6.4.2 [+]: During the review of the [+] by the FDA Division and by
[+], AVI will respond promptly to comments. Recommendations of the FDA will be
discussed and incorporated and the finalized files will be resubmitted
immediately prior to [+].


 


Period of Work: Approximately [+] weeks
(e.g. [+]).


 


Deliverable: Final approved [+] to the
FDA immediately prior to [+]. Copy of the draft [+] is sent to USG Program
Office.


 


3.6.5 [+] by the FDA to US Government: Deliver [+] by
the FDA, to the USG office immediately after the [+].


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: [+] configuration approved
by the FDA will be delivered to the USG Program Office.


 


3.6.5.1 [+] to US Government: At the end of CLIN0004 [+] approved by the
FDA will be shipped to the USG Program Office.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: [+] approved by the FDA
will be shipped to the USG Program Office.


 


3.6.5.2 Project Management, Operations and Oversight: Oversight of
inventory and distribution will be managed by AVI personnel through site
visits, audits, and records review.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.6.6 Prepare and Deliver [+] to US Government: AVI proposed to
subcontract all manufacturing and testing of the drug substance and drug
product. The company will submit full details of manufacturing packaging and
testing of the drug substance and drug product without divesting intellectual
property rights, and it will not be necessary to submit a [+] to FDA. The US
GOVERNMENT will have the right of access to the full documentation for the [+]
as agreed in the contract.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: AVI will send an electronic
and a paper copy of the approved [+] to the USG Program Office.


 


3.6.6.1 Ensure completion of [+] at CMO: The CMOs and manufacturers of
some of the components of the final drug product configuration [+]. A copy of
the CMO’s Letter of Authorization permitting the FDA to access their
confidential information in connection with the [+] will have been submitted in
the [+]. AVI will endeavor to ensure that the CMO updates and maintains the
conditions [+].


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: A copy of the Letter of
Authorization for FDA to [+] in connection with the review of the [+].


 


3.6.6.2 Submit Letter of Authorization for FDA review
of [+] to US Government: The
CMOs and manufacturers of some of the components of the final drug product
configuration [+] will [+] that will be referenced by the name and address of
the supplier and reference number in the [+]. A copy of the CMO“s Letter of
Authorization permitting the FDA to access their confidential information in
connection with the [+] will have been submitted in the [+]. AVI will endeavor
to ensure that the CMO updates and maintains the conditions of the [+].


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Deliver a copy of Letter of
Authorization (to FDA) to USG.


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT TO
A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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3.6.6.3 Program management, operations and oversight: Develop
timeline, manage vendors, anticipate and resolve problems, track project
compliance, report project progress. As part of the normal course of executing
project, regular team meetings will be held with each vendor and held
internally. This team is responsible for the project plan. Project progress and
any issues relative to the project plan will be documented and addressed with
the Product Development Team on at least a monthly basis. Regular conference
calls with the TMTI will be established to review progress and results.


 


Period of Work: Approximately [+] day (e.g.
[+]).


 


Deliverable: Plan, monitor, and report
overall delivery of milestones and budget.


 


3.6.7 Contract Program Management: AVI will track
progress on each element in the contract, including all financial and reporting
requirements; ensure compliance with contract and all government regulations.
AVI will manage all subcontracts and ensure that their timelines are met, and
the components contributed by each to the overall study are coordinated, on
budget, and that they are compliant with all contract and Government
regulations that are applicable.


 


Period of Work: Concurrent with all
CLIN0004 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide contract management
and financial oversight ensuring compliance.


 


3.6.7.1 Program Management: Track progress
and manage issues as they arise.


 


Period of Work: Concurrent with all
CLIN0004 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide project management
ensuring compliance.


 


3.6.7.2 Finance and [+]: Track financial
work process and reporting.


 


Period of Work: Concurrent with all
CLIN0004 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide project financial
management ensuring compliance.


 


3.6.7.3 Contract and Subcontract Management: Manage our
compliance with contract and USG regulations; manage subcontractors and
relationship with them.


 


Period of Work: Concurrent with all
CLIN0004 activities, a period of approximately [+] days (e.g. [+]).


 


Deliverable: Provide contract and
subcontract management ensuring compliance.


 


3.6.7.4 EDMS and QA: The EDMS will have been
fully implemented and routinely used to prepare, review and store documents for
the [+], and regulatory and quality compliance documents. AVI will continue to
store all documents in the validated EDMS and will make electronic document
submissions to the FDA, as needed. AVI will train all pertinent staff on the
EDMS, including Quality Assurance staff.


 


Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: EDMS system fully
operational. QA audits of all vendors will have been performed and any follow
up action items identified and tracked.


 


3.6.8 Drug Substance and Drug Product Ongoing Stability
Studies: Continue manufacturing assessment of stability [+] prepared in
CLIN0002.


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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Period of Work: Approximately [+] days
(e.g. [+]).


 


Deliverable: Continue assessment of
stability study data (to include both drug substance and drug product).


 


3.6.8.1 Continue Drug Substance Stability Studies: Continue
stability study.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Continue assessment of drug
substance stability data.


 


3.6.8.2 Continue Drug Product Stability Studies: Continue
stability study.


 


Period of Work: Approximately [+] months
(e.g. [+]).


 


Deliverable: Continue assessment of drug
product stability data.


 






+DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN OMITTED PURSUANT
TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE COMMISSION.


 


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  CONTRACT
  DATA REQUIREMENTS LIST

  (2
  Data Items)

  	
  Form Approved

  OMB
  No. 0704-0188

  
	
   

  	
   

  
	
  The public reporting
  burden for this collection of information is estimated to average 110 hours
  per response, including the time for reviewing instructions, searching existing
  data sources, gathering and maintaining the data needed, and completing and
  reviewing the collection of information. Sand comments regarding this burden
  estimate or any other aspect of this collection of information, including
  suggestions for reducing the burden, to Department of Defense, Washington
  Headquarters Services, Directorate for Information Operations and Reports
  (0701-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA
  22202-4302, Respondents should be aware that notwithstanding any other
  provision of law, no person shall be subject to any penalty for failing to
  comp y with a collection of information if i does not display a currently
  valid OMB control number. Please DO NOT RETURN your form to the above
  address. Send completed form to the Government Issuing Contracting Officer
  for the Contract/PR No. Listed in Block E.

  
	
   

  
	
  A.
  CONTRACT LINE ITEM NO.

  	
  B.
  EXHIBIT

  	
  C.
  CATEGORY

  
	
  CLIN 0001

  	
  A

  	
  TDP

  	
   

  	
  TM

  	
   

  	
  OTHER

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  D.
  SYSTEM/ITEM

  	
  E.
  CONTRACT/PR NO.

  	
  F.
  CONTRACTOR

  
	
  HFV Develo mental
  Therapeutic

  	
   

  	
  TBD

  
	
   

  	
   

  	
   

  
	
  1.  DATA ITEM NO.

  	
  2. TITLE OF DATA ITEM

  	
  3. SUBTITLE

  
	
  A001

  	
  Contract Work
  Breakdown Structure (CWBS)

  	
   

  
	
   

  	
   

  	
   

  
	
  4. AUTHORITY (Data Acquisition Document No.)

  	
  5. CONTRACT REFERENCE

  	
  6. REQUIRING OFFICE

  
	
  DI-MGMT-81334C

  	
  NA

  	
  DTRAfTMTI

  
	
   

  	
   

  	
   

  
	
  7.  DO 250 REQ

  	
  9. DIST STATEMENT

  REQUIRED

  	
  10 FREQUENCY

  	
  12. DATE OF FIRST

  SUBMISSION

  	
   

  
	
  LT

  	
  NA

  	
  See BIR 16

  	
  See Blk 16

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  8. APP CODE

  	
   

  	
  11. AS OF DATE

  	
  13. DATE OF SUBSEQUENT

  	
   

  	
   

  	
   

  	
  b.
  COPIES

  	
   

  
	
   

  	
   

  	
   

  	
  SUBMISSION

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  Final

  	
   

  
	
  A

  	
   

  	
  See Blk 16

  	
  See Blk 16

  	
   

  	
   

  	
   

  	
  Draft

  	
   

  	
  Reg

  	
   

  	
  Repro

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  DTRA/TMTI

  	
   

  	
   

  	
   

  	
  1

  	
   

  	
  0

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  CBMS/KO

  	
   

  	
   

  	
   

  	
  1

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  15. TOTAL

  	
   

  	
   

  	
   

  	
  2

  	
   

  	
  0

  	
   

  
																						



 


16. REMARKS


 


The CWBS and CWBS
dictionary shall be updated semi-annually. The CWBS shall extend to elements to
completely define the entire proposed effort. The CWBS shall be to a depth and
breadth necessary to accurately describe the Offerors proposed effort, to a
minimum of a one level below the Control Account (Reference EVMS CDRL) level.
The initial CWBS shall be submitted in conjunction with the proposal. A revised
CWBS based on the awarded scope shall be submitted within 30 days of contract
award. Government will review initial and all subsequent CWBS and CWBS
dictionary. for organization, level of decomposition, and conformance with the
tasks in the statement of work. Contractor has 15 days to respond and resubmit
upon receipt of Government final comments.


 


	
  1.  DATA ITEM NO.

  	
  2. TITLE OF DATA ITEM

  	
  3. SUBTITLE

  
	
  A002

  	
  Contractor’s Progress,
  Status, & Management (PSM) Report

  	
  NA

  
	
   

  	
   

  	
   

  
	
  4. AUTHORITY (Data Acquisition
  Document No.)

  	
  5. CONTRACT REFERENCE

  	
  6. REQUIRING OFFICE

  
	
  DI-MGMT-80227

  	
  NA

  	
  DTRA/TMTI

  
	
   

  	
   

  	
   

  
	
  7.  ED 250 REQ

  	
  9. DIST STATEMENT

  REQUIRED

  	
  10 FREQUENCY ·

  	
  12, DATE OF FIRST

  SUBMISSION

  	
   

  
	
  LT

  	
  NA

  	
  Monthly

  	
  See Blk 16

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  8. APP CODE

  	
   

  	
  11. AS OF DATE

  	
  13. DATE OF SUBSEQUENT

  	
   

  	
   

  	
   

  	
  b.
  COPIES

  	
   

  
	
   

  	
   

  	
   

  	
  SUBMISSION

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  Final

  	
   

  
	
  A

  	
   

  	
  See Blk 16

  	
  See Blk 16

  	
   

  	
   

  	
   

  	
  Draft

  	
   

  	
  Reg

  	
   

  	
  Repro

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  DTRA/TMTI

  	
   

  	
  0

  	
   

  	
  1

  	
   

  	
  0

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  CBMS/KO

  	
   

  	
   

  	
   

  	
  1

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  15. TOTAL A

  	
   

  	
  0

  	
   

  	
  2

  	
   

  	
  0

  	
   

  
																



 


16.
REMARKS


 


The Contractor’s Progress, Status & Management report will indicate
the work progress and program status. The report will include performance,
schedule (CDRL A004) and cost (CDRL A005) updates. It shall also address
information related to risks, risk Mitigation activities, and issues. The
report is due the 15th of
each month after award until contract conclusion. Government will review
submissions for compliance with the Statement of Work and other contract
provisions. Provide final document within 10 days after approval of changes is
received. Contractor has 10 days to respond and resubmit upon receipt of
Government final comments.


 


	
  G.  PREPARED BY

  	
   

  	
  H. DATE

  	
   

  	
  I. APPROVED BY

  	
   

  	
  J. DATE

  
	
  /s/ Authorized Signatory

  	
   

  	
  21 Jun 10

  	
   

  	
  /s/ Authorized Signatory

  	
   

  	
  21 Jun 10

  



 


DD FORM
142 2, AUG 96 (EG)                                PREVIOUS EDITION MAY BE USED


 






	
  +

  	
  DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN
  OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY
  WITH THE COMMISSION

  



 
















 


	
  CONTRACT
  DATA REQUIREMENTS LIST

  (2
  Data Items)

  	
  Form Approved

  OMB
  No. 0704-0188

  
	
   

  	
   

  
	
  The public reporting
  burden for this collection of information is estimated to average 110 hours
  per response, including the time for reviewing instructions, searching existing
  data sources, gathering and maintaining the data needed, and completing and
  reviewing the collection of information. Send comments regarding this burden
  estimate or any other aspect of this collection of information, including
  suggestions for reducing the burden, to Department of Defense, Washington
  Headquarters Services, Directorate for Information Operations and Reports
  (0701-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA
  22202-4302. Respondents should be aware that notwithstanding any other
  provision of law, no person shall be subject to any penalty for failing to
  comply with a collection of information if i does not display a currently
  valid OMB control number. Please DO NOT RETURN your form to the above
  address. Send completed form to the Government Issuing Contracting Officer
  for the Contract/PR No. Listed in Block E.

  
	
   

  
	
  A.
  CONTRACT LINE ITEM NO,

  	
  B.
  EXHIBIT

  	
  C.
  CATEGORY

  
	
  CLIN 0001

  	
  ·  A

  	
  TDP

  	
   

  	
  TM

  	
   

  	
  OTHER

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  D.
  SYSTEM/ITEM

  	
  E.
  CONTRACT/PR NO.

  	
  F.
  CONTRACTOR

  
	
  1-lFV
  Developmental Therapeutic

  	
   

  	
  TBD

  
	
   

  	
   

  	
   

  
	
  1.  DATA ITEM NO.

  	
  2, TITLE OF DATA ITEM

  	
  3. SUBTITLE

  
	
  A003

  	
  Contract Funds
  Status Report, DD Form 1586

  	
   

  
	
   

  	
   

  	
   

  
	
  4, AUTHORITY (Data Acquisition Document
  No.)

  	
  5. CONTRACT REFERENCE

  	
  6. REQUIRING OFFICE

  
	
  DI-MGMT-81468

  	
  NA

  	
  DTRA/TMTI

  
	
   

  	
   

  	
   

  
	
  7.  DD 250 REQ

  	
  9. DIST STATEMENT

  REQUIRED

  	
  10 FREQUENCY

  	
  12. DATE OF FIRST

  SUBMISSION

  	
   

  
	
  LT

  	
  NA

  	
  Quarterly

  	
  See Blk 16

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  8. APP CODE

  	
   

  	
  11. AS OF DATE

  	
  13. DATE OF SUBSEQUENT

  	
   

  	
   

  	
   

  	
  b.
  COPIES

  	
   

  
	
   

  	
   

  	
   

  	
  SUBMISSION

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  Final

  	
   

  
	
  A

  	
   

  	
  See Blk 16

  	
  See Blk. 16

  	
   

  	
   

  	
   

  	
  Draft

  	
   

  	
  Reg

  	
   

  	
  Repro

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  DTRA/TMTI

  	
   

  	
   

  	
   

  	
  1

  	
   

  	
  0

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  CBMS/KO

  	
   

  	
   

  	
   

  	
  1

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  15. TOTAL

  	
   

  	
   

  	
   

  	
  2

  	
   

  	
  0

  	
   

  
																							



 


16. REMARKS


 


First report due
within 15 days after the end of the Contractor’s
first Fiscal Quarter (FQ) after award. Subsequent reports due within 15 days of
the end of each Contractors FQ. Government will review reports for accuracy,
completeness and compliance with contract provisions. Provide final document
within 10 days after receipt of Government comments.


 


	
  1.  DATA ITEM NO.

  	
  2. TITLE OF DATA ITEM

  	
  3. SUBTITLE

  
	
  A004

  	
  Integrated Master
  Schedule (IMS)

  	
  NA

  
	
   

  	
   

  	
   

  
	
  4. AUTHORITY (Data Acquisition
  Document No.)

  	
  5. CONTRACT REFERENCE

  	
  6. REQUIRING OFFICE

  
	
  DI-MGMT-81650

  	
  NA

  	
  DTRA/TMTI

  
	
   

  	
   

  	
   

  
	
  7.  DD 250 REQ

  	
  9. DIST STATEMENT

  REQUIRED

  	
  10 FREQUENCY

  	
  12. DATE OF FIRST

  SUBMISSION

  	
   

  
	
  LT

  	
  NA

  	
  See Blk 16

  	
  See Blk 16

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  8. APP CODE

  	
   

  	
  11. AS OF DATE

  	
  13. DATE OF SUBSEQUENT

  	
   

  	
   

  	
   

  	
  b.
  COPIES

  	
   

  
	
   

  	
   

  	
   

  	
  SUBMISSION ·

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  Final

  	
   

  
	
  A

  	
   

  	
  See Blk 16

  	
  See Blk 16

  	
   

  	
   

  	
   

  	
  Draft

  	
   

  	
  Reg

  	
   

  	
  Repro

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  DTRA/TMTI

  	
   

  	
   

  	
   

  	
  1

  	
   

  	
  0

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  CBMS/KO

  	
   

  	
   

  	
   

  	
  1

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  15. TOTAL 

  	
   

  	
   

  	
   

  	
  2

  	
   

  	
  0

  	
   

  
																



 


16.
REMARKS


 


The IMS shall include activities to completely address the SOW &
CWBS (CDRL A001). First report due 15 days prior to Kick-off. ·
Microsoft Project compatible file required. Subsequent updates due within 15
days of each Government Fiscal Quarter (Quarter (Q) 1 ends 31 Dec, Q2 ends 30
Mar, Q3 ends 30 Jun, Q4 ends 30 Sep). Government will review IMS submissions to
determine that it accurately documents the delivery date for each CLIN,
critical path, major milestones, tasks/activities, duration, lead/lag/slack
time, and schedule relationships, and is directly traceable to the SOW, Project
Management Plan and the CWBS. The Government will. evaluate whether the
tasks/activities in the IMS show predecessor/successor relationships and are sufficient
to account for the entire scope of work. Provide final document within 10 days
after receipt of Government comments


 


	
  G.  PREPARED BY

  	
   

  	
  H. DATE

  	
   

  	
  I. APPROVED BY

  	
   

  	
  J. DATE

  
	
  /s/ Authorized Signatory

  	
   

  	
  21 Jun 10

  	
   

  	
  /s/ Authorized Signatory

  	
   

  	
  21 Jun 10

  



 


DD FORM
14 2, AUG 96 (EG)                                PREVIOUS EDITION MAY BE USED


 






	
  +

  	
  DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN
  OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY
  WITH THE COMMISSION

  



 
















 


	
  CONTRACT
  DATA REQUIREMENTS LIST

  (2
  Data Items)

  	
  Form Approved

  OMB
  No. 0704-0188

  
	
   

  	
   

  
	
  The public reporting
  burden for this collection of information is estimated to average 110 hours
  per response, including the time for reviewing instructions, searching existing
  data sources, gathering and maintaining the data needed, and completing and
  reviewing the collection of information. Send comments regarding this burden
  estimate or any other aspect of this collection of information, Including
  suggestions for reducing the burden, to Department of Defense, Washington
  Headquarters Services, Directorate for Information Operations and Reports
  (0701-0188), 1216 Jefferson Davis Highway; Suite 1204, Arlington, VA
  22202-4302. Respondents should be aware that notwithstanding any other
  provision of law, no person shall be subject to any penalty for failing to
  comp y with a collection of Information if it does not display a currently
  valid OMB control number. Please DO NOT RETURN your form to the above
  address. Send completed form to the Government Issuing Contracting Officer
  for the Contract/PR No. Listed in Block E.

  
	
   

  
	
  A. CONTRACT LINE ITEM NO.

  	
  B. EXHIBIT

  	
  C. CATEGORY

  
	
  CLIN 0001

  	
  A

  	
  TDP

  	
   

  	
  TM

  	
   

  	
  OTHER

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  D. SYSTEM/ITEM

  	
  E. CONTRACT/PR NO.

  	
  F. CONTRACTOR

  
	
  HFV Developmental
  Therapeutic

  	
   

  	
  TBD

  
	
   

  	
   

  	
   

  
	
  1.  DATA ITEM NO,

  	
  2. TITLE OF DATA ITEM

  	
  3. SUBTITLE

  
	
  A005

  	
  Contract
  Performance Report

  	
   

  
	
   

  	
   

  	
   

  
	
  4. AUTHORITY (Data Acquisition Document
  No.)

  	
  5. CONTRACT REFERENCE

  	
  6. REQUIRING OFFICE

  
	
  DI-MGMT-81466A

  	
  N/A

  	
  DTRA/TMTI

  
	
   

  	
   

  	
   

  
	
  7.  DO 250 REQ

  	
  9. DIST STATEMENT

  REQUIRED

  	
  10 FREQUENCY

  	
  12. DATE OF FIRST

  SUBMISSION

  	
   

  
	
  LT

  	
  NA

  	
  monthly

  	
  See Blk 16

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  8. APP CODE

  	
   

  	
  11. AS OF DATE

  	
  13. DATE OF SUBSEQUENT

  	
   

  	
   

  	
   

  	
  b.
  COPIES

  	
   

  
	
   

  	
   

  	
   

  	
  SUBMISSION

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  Final

  	
   

  
	
  A

  	
   

  	
  See Blk 16

  	
  See Blk 16

  	
   

  	
   

  	
   

  	
  Draft

  	
   

  	
  Reg.

  	
   

  	
  Repro

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  DTRA/TMTI

  	
   

  	
   

  	
   

  	
  1

  	
   

  	
  0

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  CBMS/KO

  	
   

  	
   

  	
   

  	
  1

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  15. TOTAL

  	
   

  	
   

  	
   

  	
  2

  	
   

  	
  0

  	
   

  
																							



 


16. REMARKS


 


The CPR shall be submitted monthly. All
reports shall be submitted no later than 15 working days following the
Contractor’s accounting period cutoff date.


 


DD Forms are available and shall be used to
submit required formats as follows:


 


	
   

  	
   

  	
  DD Form Sample

  	
   

  
	
  CPR Format

  	
   

  	
  Number

  	
   

  	
  Format No.

  	
   

  
	
  Work Breakdown Structure

  	
   

  	
  2734/1

  	
   

  	
  1

  	
   

  
	
  Organizational Categories

  	
   

  	
  2734/2

  	
   

  	
  2

  	
   

  
	
  Baseline

  	
   

  	
  2734/3

  	
   

  	
  3

  	
   

  
	
  Staffing

  	
   

  	
  2734/4

  	
   

  	
  4

  	
   

  
	
  Explanations and Problem 

  Analyses

  	
   

  	
  2734/5

  	
   

  	
  5

  	
   

  



 


	
  1.  DATA ITEM NO.

  	
  2. TITLE OF DATA ITEM

  	
  3. SUBTITLE

  
	
  A006

  	
  In Process Review

  	
   

  
	
   

  	
   

  	
   

  
	
  4. AUTHORITY (Data Acquisition Document No.)

  	
  5. CONTRACT REFERENCE

  	
   

  
	
  DI-MGMT-80227 & DI-MGMT 80555A

  	
  NA

  	
   

  
	
   

  	
   

  	
   

  
	
  7.  DO 250 REQ

  	
  9. DIST STATEMENT

  REQUIRED

  	
  10. FREQUENCY

  	
  12. DATE OF FIRST

  SUBMISSION

  	
   

  
	
  LT

  	
  NA

  	
  Semi-monthly

  	
  See Blk 16

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  8, APP CODE

  	
   

  	
  11. AS OF DATE

  	
  13. DATE OF SUBSEQUENT

  	
   

  	
   

  	
   

  	
  5· COPIES

  	
   

  
	
   

  	
   

  	
   

  	
  SUBMISSION

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  Final

  	
   

  
	
  A

  	
   

  	
  See Blk 16

  	
  See Blk 16

  	
   

  	
   

  	
   

  	
  Draft

  	
   

  	
  Reg

  	
   

  	
  Repro

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  DTRA/TMTI

  	
   

  	
   

  	
   

  	
  1

  	
   

  	
  0

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  CBMS/KO

  	
   

  	
   

  	
   

  	
  1

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
  15. TOTAL

  	
   

  	
   

  	
   

  	
  2

  	
   

  	
  0

  	
   

  
																				



 


16.
REMARKS


 


Contractor shall present project status formally to the Government every
6 months in accordance with a Government provided agenda The information
contained in the In Process Review (IPR) is similar to that contained in the
Contractor PSM Report (CDRL A002). The Contractor shall provide a MS PowerPoint
read ahead 48 hours prior to the IPR.


 


	
  1. DATA ITEM NO.

  	
  2. TITLE OF DATA ITEM

  	
  3. SUBTITLE

  



 


	
  G.  PREPARED BY

  	
   

  	
  H. DATE

  	
   

  	
  I. APPROVED BY

  	
   

  	
  J. DATE

  
	
  /s/ Authorized Signatory

  	
   

  	
  21 Jun 10

  	
   

  	
  /s/ Authorized Signatory

  	
   

  	
  21 Jun 10

  



 


DD FORM
14 2, AUG 96 (EG)                                PREVIOUS EDITION MAY BE USED


 






	
  +

  	
  DESIGNATES PORTIONS OF THIS DOCUMENT THAT HAVE BEEN
  OMITTED PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY
  WITH THE COMMISSION