Document:

Exhibit 10.1

 

DATED   5 FEBRUARY 2019

 

(1) GRIFOLS WORLDWIDE OPERATIONS LIMITED

 

(2) GRIFOLS S.A.

 

(3) BIOTEST PHARMACEUTICALS CORPORATION

 

and

 

(4) HAEMA AG

 

 

AMENDMENT AND RESTATEMENT AGREEMENT

relating to

an agreement for the purchase and sale of source plasma originally dated

28 December 2018

 

 

 

THIS AGREEMENT dated 5 February 2019

 

BETWEEN:

 

(1)                                 GRIFOLS WORLDWIDE OPERATIONS LIMITED, a company duly organized and existing under the laws of the Republic of Ireland, having its registered office at Grange Castle Business Park, Grange Castle, Clondalkin, Dublin 22, Ireland (“GWWO”);

 

(2)                                 GRIFOLS S.A., a company validly incorporated and existing under the laws of Spain, with its principal place of business at Avinguda de la Generalitat, 152, Parc empresarial Can Sant Joan, 08174 Sant Cugat del Vallès, Barcelona (the “Guarantor”);

 

(3)                                 BIOTEST PHARMACEUTICALS CORPORATION, a corporation existing and incorporated under the laws of the State of Delaware (USA) with its principal place of business at 901 Yamato Road, Suite 101 Boca Raton, FL 33431-4409, USA (“Biotest”); and

 

(4)                                 HAEMA AG, a corporation existing and incorporated under the laws of Germany with its principal place of business at Landsteinerstrasse 1, 04103 Leipzig, Germany (“Haema” and, together with Biotest, the “Supplier”).

 

1.                                      BACKGROUND

 

(a)                                 This Agreement is supplemental to an agreement for the purchase and sale of source plasma originally dated 28 December 2018 and made between (1) GWWO, (2) the Guarantor, (3) Biotest and (4) Haema (the “Original PSA”).

 

(b)                                 The Parties have agreed, subject to the terms of this Agreement, to make certain amendments to the Original PSA and for such amendments to take retrospective effect on and from 28 December 2018.

 

(c)                                  With effect from the Effective Date, the Original PSA will be amended and restated so that it reads as if it were the Amended PSA and such amendment and restatement will be deemed to take retrospective effect from 28 December 2018.

 

2.                                      DEFINITIONS AND INTERPRETATION

 

2.1                               Definitions

 

In this Agreement:

 

“Amended PSA” means the agreement for the purchase and sale of source plasma in the form set out in schedule 3 (Amended PSA);

 

“Effective Date” means the date on which each Party to this Agreement has duly executed this Agreement; and

 

“Party” means a party to this Agreement.

 

2.2                               Clauses

 

(a)                                 In this Agreement any reference to a “clause” or “schedule” is, unless the context otherwise requires, a reference to a clause or schedule of this Agreement.

 

(b)                                 Clause and schedule headings are for ease of reference only.

 

 

2.3                               Continuing Obligations

 

Subject to the provisions of this Agreement:

 

(a)                                 the Original PSA shall remain in full force and effect; and

 

(b)                                 from the Effective Date, the Original PSA shall be read and construed as one document with this Agreement.

 

3.                                      RESTATEMENT

 

3.1                               Restatement

 

With effect from the Effective Date, the Original PSA shall be amended and restated so that it shall be read and be construed for all purposes as set out in schedule 3 (Amended PSA) and such amendment and restatement shall be deemed to take retrospective effect from 28 December 2018.

 

4.                                      MISCELLANEOUS

 

4.1                               Incorporation of Terms

 

The provisions of clauses 5.1 (Relationship of the Parties), 5.2 (Indemnification), 5.5 (Notices), 5.13 (Third Party Rights), 5.14 (Arbitration) and 5.16 (Confidentiality) of the Original PSA shall apply to this Agreement as if set out in full in this Agreement and as if references in those clauses to “this Agreement” are references to this Agreement.

 

4.2                               Counterparts

 

This Agreement may be executed in any number of counterparts, and this has the same effect as if the signatures on the counterparts were on a single copy of this Agreement.

 

5.                                      GOVERNING LAW AND ENFORCEMENT

 

This Agreement and any issues, disputes or claims arising out of or in connection with it (whether contractual or non-contractual in nature such as claims in tort, from breach of statute or regulation or otherwise) shall be governed by, and construed in accordance with, the laws of Ireland.

 

This Agreement has been entered into on the date stated at the beginning of this Agreement.

 

 

SCHEDULE 1:  AMENDED PSA

 

 

EXECUTION PAGES

 

	
GRIFOLS WORLDWIDE OPERATIONS   LIMITED
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
Name: 
    	
/s/ Alfredo Arroyo
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
Title: CFO
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
BIOTEST PHARMACEUTICALS   CORPORATION
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
Name: 
    	
/s/ Eduardo Herrero
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
Title: Authorized Signatory
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
HAEMA AG
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
Name: 
    	
/s/ Eduardo Herrero
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
Title: Authorized Signatory
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
GRIFOLS S.A.
    	
 
    	
GRIFOLS S.A.
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
Name: 
    	
/s/ Raimon Grifols
    	
 
    	
Name: 
    	
/s/ Víctor Grifols Deu
    
	
 
    	
 
    	
 
    
	
Title: Co-CEO
    	
 
    	
Title: Co-CEO
    

 

 

AGREEMENT FOR THE PURCHASE AND SALE

OF SOURCE PLASMA

 

This Agreement for the Purchase and Sale of Plasma (the “Agreement”) is made and entered into on 28 December 2018 as amended and restated on 5 February 2019 with effects as of 1 January 2019 (the “Effective Date”), by and between:

 

(i)                                    GRIFOLS WORLDWIDE OPERATIONS LIMITED, a company duly organized and existing under the laws of the Republic of Ireland, having its registered office at Grange Castle Business Park, Grange Castle, Clondalkin, Dublin 22, Ireland (“GWWO”),

 

(ii)                                GRIFOLS, S.A a company validly incorporated and existing under the laws of Spain, with with its principal place of business at Avinguda de la Generalitat, 152. Parc empresarial Can Sant Joan 08174 Sant Cugat del Vallès, Barcelona (“Guarantor”); and

 

(iii)                            BIOTEST PHARMACEUTICALS CORPORATION, a corporation existing and incorporated under the Laws of the State of Delaware (USA), with its principal place of business at 901 Yamato Road, Suite 101 Boca Raton, FL 33431-4409, USA (“BIOTEST”).

 

(iv)                             HAEMA AG, a corporation existing and incorporated under the Laws of Germany, with its principal place of business at Landsteinerstrasse 1, 04103 Leipzig, Germany (“HAEMA”, and collectively with BIOTEST, “SUPPLIER”).

 

This Agreement is governed by the following terms and conditions:

 

ARTICLE 1.  DEFINITIONS

 

1.1                               Left blank

 

1.1                               Definition of Plasma.  The term “Plasma” as used in this Agreement shall refer to the production of normal source plasma to be derived from automated plasmapheresis procedures conducted at the US Food and Drug Administration (“FDA”) and at European Authorities approved and IQPP-certified Plasma (when applicable) donor centers identified on Exhibit A attached hereto (the “Centers”), which Centers shall be operated by SUPPLIER and/or third parties and shall be subject to GWWO’s approval, all of which Plasma, collected or purchased and released by SUPPLIER shall comply with the specifications set forth herein, specifically those specifications set forth in the quality agreement attached hereto as Exhibit B (hereafter, the “Quality Agreement”).  The Parties shall enter into the Quality Agreement as soon as possible and in any event within 20 days of the Effective Date.  As used herein, the term “European Authorities” refers to and includes the European Medicines Agency, the MHRA, GHA and other constituent organizations with and through which the European Medicines Agency regulates plasma and plasma donor centers. Plasma shall further include various types of specialty plasma collected by SUPPLIER, including tetanus plasma, anti-D plasma, anti-HBs plasma, and rabies plasma.(1)

 

1.2          Definition of Plasma.  The term “Plasma” as used in this Agreement shall refer to the production of normal source plasma to be derived from automated plasmapheresis procedures conducted at the US Food and Drug Administration (“FDA”) and at European Authorities approved and IQPP-certified Plasma (when applicable) donor centers identified on Exhibit A attached hereto (the “Centers”), which Centers shall be operated by SUPPLIER and/or third parties and shall be subject to GWWO's approval, all of which Plasma, collected or purchased and released by SUPPLIER shall comply with the specifications set forth herein, specifically those specifications set forth in the quality agreement attached hereto as Exhibit B (hereafter, the “Quality Agreement”).  The Parties shall enter into the Quality Agreement as soon as possible and in any event within 20 days of the Effective Date.  As used herein, the term “European Authorities” refers to and includes the European Medicines Agency, the MHRA, GHA and other constituent organizations with and through which the European Medicines Agency regulates plasma and plasma donor centers. Plasma shall further include various types of specialty plasma collected by SUPPLIER, including tetanus plasma, anti-D plasma, anti-HBs plasma, and rabies plasma.

 

1.3                               Definition of Business Plan means the business plan in the form agreed between the parties prior to the original date of this Agreement.

 

(1) all redacted material in this Exhibit has been omitted pursuant to a request for confidential treatment and the material has been filed separately with the Security and Exchange Commission.

 

 

1.4                               Supplier’s Group means Scranton Plasma BV and its subsidiaries (including the Suppliers) and any entity (other than Scranton Enterprises) which is a holding company of Scranton Plasma BV

 

ARTICLE 2.  TERMS OF SALE

 

2.1                               Agreement to Purchase and Sell.  Pursuant to and subject to the terms and conditions of this Agreement: (a) SUPPLIER agrees to supply fully tested Plasma in accordance with this Agreement; and (b) GWWO agrees to take delivery of all the Plasma collected and/or purchased by SUPPLIER from the Centers, subject to the terms and conditions set forth in the Quality Agreement.

 

2.2                               Delivery Plan. Unless otherwise agreed to by the parties, each calendar year prior to November 15, GWWO and SUPPLIER’s management will discuss the upcoming year’s delivery schedule of Plasma (the “Delivery Plan”). GWWO shall provide SUPPLIER with a Delivery Plan for each calendar year no later than November 15 of the prior year.  The Delivery Plan shall provide an estimated delivery schedule for the production of each Center’s during each month of the following year. During the Term (as defined below), SUPPLIER will have the right to add additional center(s) to the approved listing of Centers, but such additional center(s) must meet the Quality Agreement and will be subject to GWWO’s approval (acting reasonably).  In this event, GWWO agrees to inspect any additional center(s) within ten (10) working days of notification, or within such reasonable time period as agreed in writing by the parties.

 

	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
				

 

2.3                               Price and Payment.

 

	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
				

 

2.3.2 Payment Terms.  Except for any invoice sums that are the subject of a good faith dispute between the parties, payment for Plasma received by GWWO shall be made to SUPPLIER within thirty (30) days from the date of issuance of the invoice from SUPPLIER, as such issuance date is referenced on the invoice.  A late fee of twelve percent (12%) per annum will be applied to all late invoice payments.

 

2.3.3                     Shipment Costs.  GWWO agrees to bear all costs of shipment, freight, insurance and all governmental taxes and duties incurred during shipping of the Plasma sold hereunder from the Centers to facilities designated by GWWO.  It is agreed that the shipments from the Centers will be bi-weekly or weekly depending on the volume at each of the Centers, or as otherwise agreed to in writing between the parties.

 

2.4                               Delivery and Risk of Loss.  Title and risk of loss with respect to Plasma collected by SUPPLIER hereunder shall transfer to GWWO when the Plasma is loaded by SUPPLIER at its Centers for transportation by GWWO.  With respect to Plasma purchased by SUPPLIER from a third-party, title and risk of loss shall transfer to GWWO when the Plasma reaches GWWO facilities. Upon request, SUPPLIER will provide GWWO with any reasonably requested production documentation related to any delivered Product.

 

	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
	
 
    	
 
    	
 
    
				

 

Notwithstanding the foregoing, this Agreement may be terminated by either party as set forth under Section 5.3.1 herein.

 

ARTICLE 3.  GENERAL PROVISIONS

 

3.1                               Specifications.  SUPPLIER warrants and agrees that all Plasma sold to GWWO hereunder will meet the terms and conditions of the Quality Agreement, as well as the following requirements and conditions:

 

The Centers must be approved plasma centers and licensed by the FDA and/or the European Authorities utilizing an approved system of procedures. SUPPLIER agrees that each Center shall follow the procedures as written in the Quality Agreement and any revisions to those procedures or the terms of the Quality Agreement as they may be issued or adopted by GWWO from time to time, as approved, when applicable, by the FDA or European Authorities, if such approval is required. SUPPLIER acknowledges that it has received full, complete and accurate copy of the

 

 

specifications of the Plasma as in effect as of the Effective Date. SUPPLIER also agrees to have all of its Centers QPP certified (quality plasma program as defined by PPTA) and to maintain that certification for the Term. Any Center that is not QPP certified during any portion of this Agreement can be excluded from supplying Plasma, but the lost Plasma volume may be replaced from one or more other Centers that are FDA and European Authorities approved and QPP certified plasma centers and that meet the Quality Agreement.

 

SUPPLIER represents and warrants that all Plasma sold to GWWO under this Agreement will be collected, processed, tested, stored, packaged, labeled and shipped in strict accordance with the Quality Agreement and all applicable FDA and European Authorities regulations, will meet all requirements of cGMPs, and will be fit for the purpose and use intended by GWWO.

 

If any of the Centers are closed as a result of regulatory sanctions placed on such Centers by the FDA or European Authorities, or if any Center is found by GWWO to be clearly deficient, SUPPLIER will have thirty (30) working days to provide, in writing, a corrective action plan acceptable to GWWO.  If the action plan is unacceptable, or if a Center cannot provide Plasma within sixty (60) days of a closure, this Agreement, at SUPPLIER’s option, can be modified to eliminate such Center and replace it with one or more other approved and QPP certified plasma Centers that meet GWWO’s approval and the terms of the Quality Agreement within sixty (60) days of any such modification of this Agreement. If SUPPLIER requests an additional Center to be added to this Agreement, GWWO agrees to inspect and approve, if the Center meets the terms of the Quality Agreement, any such additional Center within ten (10) working days. GWWO and SUPPLIER agree to give best efforts to complete all documentation necessary to effect the addition of such Center within the ten (10) day period. This provision for replacement Centers does not apply in the event of systemic deficiencies or problems that affect all or the majority of the Centers, and which event may be grounds for termination of this Agreement by GWWO with no further liability owing to SUPPLIER.

 

SUPPLIER or the relevant third parties shall operate each Center in accordance with its FDA and/or European Authorities approved Standard Operating Procedure (“SOP”).  In the event SUPPLIER wishes to modify or deviate from any of the practices of the instructions for the collection and handling of Plasma as set forth in its SOP, relevant changes or significant deviations must be approved in writing by GWWO.

 

SUPPLIER shall collect, process, store, package and ship the Plasma in strict accordance with the Quality Agreement given to SUPPLIER by GWWO during the Term. These may be amended from time to time by GWWO or by an appropriate governmental agency during the Term.  Any amendments by GWWO must be reasonable and meet industry standards.

 

SUPPLIER agrees to permit or cause to permit GWWO and any authorized representative of GWWO, the FDA, the European Authorities and any State or local governmental agency to conduct inspections of the Centers, testing facilities, and Corporate Offices at any time for the purposes of ensuring compliance with this Agreement or with all regulatory requirements, and will permit them to review all records kept by SUPPLIER regarding the Center’s quality systems and the collection, storage, processing and shipment of Plasma.  GWWO, at its sole option and expense, shall have the right to make and retain copies of all such records kept by SUPPLIER. As used herein, the term “Corporate Offices” means and includes offices housing any quality assurance, quality control, and compliance functions with respect to the Centers.

 

SUPPLIER agrees to comply with the mandatory disclosure obligations set forth in the Quality Agreement.

 

In the event that the costs incurred by SUPPLIER in the collection, packaging, sampling, labeling, testing, processing or storage of Plasma are increased or decreased to any extent above or below the cost in effect as of the Effective Date as a result of a modification by GWWO of the Quality Agreement, then the purchase price per liter shall be increased or decreased to the extent properly allocable to the Plasma sold to GWWO under this Agreement, using generally accepted cost accounting principles.  In the event a government mandated program significantly affects SUPPLIER’s costs, then the parties will negotiate how the costs or savings will be shared.  All cost allocations are independent of Section 2.2 of this Agreement.

 

3.2                               Testing.  SUPPLIER shall bear all costs of testing, including EIA and PCR (NAT) testing.  SUPPLIER agrees that samples for PCR (NAT) testing from any applicant donors will not be sent before first receiving negative

 

 

serological test results.  PCR samples from qualified donors can be sent on the day of donation.  PCR results, with the exception of re-tests, are expected to be received within twenty-one (21) days of sample submission.

 

Any plasma, which is not produced in accordance with the Quality Agreement, or other FDA regulations or is otherwise not as warranted can be rejected by GWWO notwithstanding prior payment by GWWO and returned to SUPPLIER. In such event, SUPPLIER shall then reimburse GWWO for any payments made to SUPPLIER for such rejected Plasma, as well as any testing costs. At GWWO’s option, such reimbursement shall be reflected as an offset and deduction against any outstanding invoices, a credit towards a future invoice, or as a separate payment to GWWO. SUPPLIER shall bear any and all costs and expenses of returning or disposing of any such rejected Plasma.  SUPPLIER shall have the right to instruct GWWO to destroy such rejected Plasma, at SUPPLIER’s cost and expense, in lieu of returning it to SUPPLIER.

 

GWWO shall not be obligated to buy or pay for any Plasma pursuant to this Agreement or any option under this Agreement, which does not, in all respects, comply with the Quality Agreement and the FDA or European Authorities regulations.

 

3.3                               Shipping of Plasma.  Plasma shall be packed by SUPPLIER in such a manner as to prevent damage to the Plasma or Plasma containers during shipping and shall be shipped by a transportation company designated by GWWO, subject to such other conditions set forth in the Quality Agreement and any other written instructions provided by GWWO.  No Plasma shall be released for sale pursuant to this Agreement unless and until such Plasma fully complies with the Quality Agreement, and SUPPLIER shall be responsible for ensuring compliance with the terms of the Quality Agreement such and release protocols.

 

3.4                               Donor Testing Results.  Subject to the confidentiality obligations set forth in Section 5.16 of this Agreement, SUPPLIER agrees to arrange testing for each donor of Plasma as required by Title 21 of the Code of Federal Regulations and any other applicable law and make available test results of all such tests to GWWO.  The method by which SUPPLIER will provide such test results, should GWWO require them, will be mutually agreed to between the SUPPLIER and GWWO.

 

3.5                               Licenses, Permits and Approvals.  SUPPLIER represents and warrants that it has obtained and shall continue to possess during the Term, a current, valid and unrevoked license from the United States Food and Drug Administration’s Center for Biologic Evaluation and Research (CBER) and/or European Authorities (depending on the Plasma origin) authorizing and qualifying SUPPLIER to conduct automated plasmapheresis, as well as any special programs to be pursued by SUPPLIER at any or all of the Centers identified herein, as well as a license permitting SUPPLIER to produce and ship Plasma related products derived from the automated operations conducted at the Centers.  In addition, SUPPLIER represents and warrants that it shall maintain for the Term, all other local, state and federal licenses, permits and approvals required to operate the Center and, as a condition precedent to the commencement of GWWO’s performance of its obligations hereunder, SUPPLIER agrees to furnish a copy of all such licenses, permits, and approvals to GWWO.

 

ARTICLE 4.  PERSONNEL, MATERIAL AND ADDITIONAL RELATED SERVICES TO BE FURNISHED

 

4.1                               SUPPLIER agrees to furnish all managerial, administrative, medical and professional personnel (including persons qualified to conduct plasmapheresis operation) required to produce the annual quantities of Plasma set forth in Section 2.1 hereof.  In addition, SUPPLIER agrees to provide, at its own cost and expense, all facilities, equipment, materials and softgoods needed to produce Plasma at each Center.  All personnel and equipment provided by SUPPLIER shall be under the management, supervision and control of SUPPLIER and not GWWO, at all times.

 

4.2                               Further, Haema undertakes to assume and perform, on behalf of GWWO, all necessary services, tasks and dealings related or derived from the supply of its Plasma to any third party designated by GWWO, such as, without limitation, quality, regulatory and/or technical requirements, all in accordance with the instructions provided by GWWO from time to time and in compliance with law.

 

 

ARTICLE 5.  MISCELLANEOUS PROVISIONS

 

5.1                               Relationship of the Parties.  The relationship between GWWO and SUPPLIER is, and during the Term shall be, that of buyer and seller. SUPPLIER is in no way the partner, legal representative or agent of GWWO for any purpose whatsoever and has no right or authority to incur, assume, or create, in writing or otherwise, any warranty, liability or obligation of any kind, expressed or implied, in the name of, or on behalf of GWWO. The terms of this Agreement shall not be construed as creating a dependent agency relationship for U.S. federal income tax purposes.

 

5.2                               Indemnification.  SUPPLIER and GWWO hereby indemnify and agree to hold harmless each other and its respective affiliates, agents, employees, officers and directors, from and against any and all claims, losses, liabilities, damages, attorney’s fees, costs and expenses which may be sustained by and/or claimed against the other party by virtue of the negligent performance of services rendered by the other party, the willful misconduct by the other party or its officers, employees or agents, or any representation or warranty contained in this Agreement being breached, untrue or materially misleading, by omission or otherwise.  It being understood, however, that, save for GWWO’s obligation under Section 2.1 b), the financial liability under this section shall be limited to the extent of each party’s insurance coverage that shall be in force and maintained during the Term (which in the case of GWWO shall be the standard insurance cover of GRIFOLS and its Affiliates from time to time procured and maintained on a prudent basis and at least consistent with current and past practice as at the original date of this agreement.  GWWO shall provide the SUPPLIER with confirmation of such insurance on an annual basis)

 

5.3                               Default.

 

5.3.1                     Rights and Remedies

 

In the event

 

	
(a)
    	
SUPPLIER or GWWO is in breach of any provision, or is in default   of any obligation under this Agreement, or in the event of any representation   or warranty contained in this Agreement is breached, untrue or materially   misleading, by omission or otherwise, and such breach is not subject to   remedy or curable, or
    
	
 
    	
 
    
	
 
    	
 
    
	
 
    	
 
    	
 
    

 

then the non-breaching party (which in the case of 5.3.1 (b) shall only be SUPPLIER not GWWO) will be entitled to forthwith terminate the Agreement, by serving a written notice thereof to the breaching party.  For the avoidance of doubt if GRIFOLS is in default of                                                                   and as a result SUPPLIER cannot perform any of its obligations under this Agreement, GWWO shall not be able to claim that SUPPLIER is in breach of this Agreement.

 

For any other type of breach, and upon written notice from the non-breaching party to the breaching party on the occurrence of the breach, the parties shall meet and discuss in good faith the remedies to apply in order to rectify the breach and the term in which such breach should be remedied (the “Remedial Plan”). Should the parties not reach an agreement on the Remedial Plan within a reasonable timeframe thereafter not to exceed thirty (90) days from the initial notice’s date issued by the non-breaching party, the breach shall be submitted to each party’s executives, who, within a term not to exceed ninety (90) days thereafter (or such longer term as the parties’ executives may agree to at that time), shall decide upon the Remedial Plan.  In the event that each party’s executives do not reach a consensus on the Remedial Plan, the non-breaching party shall be entitled to terminate the Agreement.

 

Notwithstanding any of the above, the SUPPLIER may terminate this Agreement forthwith by written notice on Change of Control of the SUPPLIER.

 

5.3.2                     Remedies Cumulative; No Waiver

 

The rights and remedies available to GWWO and SUPPLIER under this Agreement (including, without limitation, the remedies set forth in Sections 3.1, 3.2, 5.2, 5.3 and 5.4.1) or any other agreement among the parties are cumulative, and the exercise of any right or remedy shall not preclude or dismiss GWWO’s or SUPPLIER’s right to pursue any other or additional right or remedy, including, without limitation, specific performance, injunctive relief, termination, cancellation or rescission as permitted at law or in equity, and any claim for damages. The failure to exercise any right or remedy in the event of any breach or default shall not constitute a waiver or adversely affect GWWO’s or SUPPLER’s right to exercise any right or remedy for the same or any other breach or default.

 

 

5.3.3 Guarantee

 

The Guarantor hereby irrevocably and unconditionally guarantees to the SUPPLIER the prompt and full discharge by GWWO (and its Affiliates, where relevant)  of all of GWWO’s (or, where relevant, its Affiliate) covenants, agreements, obligations and liabilities under this Agreement, including the due and punctual payment of all amounts which are or may become due and payable by GWWO hereunder, when and as the same shall become due and payable (collectively, the “GWWO Obligations”), in accordance with the terms hereof or thereof.  The Guarantor acknowledges and agrees that, with respect to all GWWO Obligations to pay money, such guaranty shall be a guaranty of payment and performance and not of collection and shall not be conditioned or contingent upon the pursuit of any remedies against GWWO.  If GWWO shall default in the due and punctual performance of any GWWO Obligation, including the full and timely payment of any amount due and payable pursuant to any GWWO Obligation, the Guarantor will forthwith perform or cause to be performed such GWWO Obligation and will forthwith make full payment of any amount due with respect thereto at its sole cost and expense.

 

The liabilities and obligations of the Guarantor pursuant to this Agreement are unconditional and absolute and, without limiting the generality of the foregoing, shall not be released, discharged or otherwise affected by:

 

(a)                                 any acceleration, extension, renewal, settlement, compromise, waiver or release in respect of any GWWO Obligation by operation of law or otherwise;

 

(b)                                 the invalidity or unenforceability, in whole or in part, of this Agreement;

 

(c)                                  any modification or amendment of or supplement to this Agreement;

 

(d)                                 any change in the corporate existence, structure or ownership of GWWO or the Guarantor or any insolvency, bankruptcy, reorganization or other similar proceeding affecting any of them or their assets; or

 

(e)                                  any other act, omission to act, delay of any kind by any party hereto or any other person, or any other circumstance whatsoever that might, but for the provisions of this Section, constitute a legal or equitable discharge of the obligations of the Guarantor hereunder.

 

The Guarantor irrevocably and unconditionally agrees with the SUPPLIER that, if any obligation guaranteed by it is or becomes unenforceable, invalid or illegal, it will, as an independent and primary obligation, indemnify the SUPPLIER immediately on demand against any cost, loss or liability it incurs as a result of GWWO or the Guarantor not paying any amount which would, but for such unenforceability, invalidity or illegality, have been payable by it under this Agreement on the date which it would have been due.

 

The Guarantor hereby waives any right, whether legal or equitable, statutory or non-statutory, to require the SUPPLIER to proceed against or take any action against or pursue any remedy with respect to GWWO or any other person or make presentment or demand for performance or give any notice of non-performance before the SUPPLIER may enforce its rights hereunder against the Guarantor.

 

This guarantee is to be a continuing guarantee and accordingly the Guarantor’s obligations hereunder shall remain in full force and effect until the GWWO Obligations shall have been performed in full.  If at any time any performance by any person of any GWWO Obligation is rescinded or must be otherwise restored or returned, whether upon the insolvency, bankruptcy or reorganization of GWWO or otherwise, the Guarantor’s obligations hereunder with respect to such GWWO Obligation shall be reinstated at such time as though such GWWO Obligation had become due and had not been performed.

 

5.4                               Force Majeure.  The performance of GWWO and SUPPLIER hereunder is subject to all contingencies except those beyond the direct control of GWWO and SUPPLIER including, without being limited to, the following:

 

5.4.1                     Strikes, or other labor disputes or labor troubles of any kind;

 

5.4.2                     Hurricanes, floods, earthquakes, droughts, or accidents;

 

5.4.3                     Commotions, insurrections, riots, wars, or consequences of war;

 

 

5.4.4                     Acts of God or perils of the sea;

 

5.4.5                     Rules, laws, orders, actions, quotas, embargoes, seizures, regulations, restrictions, or actions of any governmental agency or divisions thereof, or rejections by inspectors or retentions of goods by customs authorities;

 

5.4.6                     Breakdowns in manufacturing machinery, casualties, fires, loss of goods in public or private warehouses, provided, however, that such breakdowns, casualties, fires or losses are not the result of GWWO’s or SUPPLIER’s intentional acts;

 

5.4.7                     In any such event, GWWO and SUPPLIER shall have the right, at its good faith and election and without incurring any liability for such occurrence or event to:

 

a.                                      Notify other party of its intention and mutually agree between the parties to perform a modified or restricted agreement and perform the Agreement as so restricted or modified because of any of the foregoing contingencies.  In the event the parties hereto mutually agree to perform a modified or restricted Agreement, the restricted or modified performance shall operate as a complete discharge of any obligations hereunder which are inconsistent with such modification or restriction; or

 

b.                                      Perform the Agreement within a reasonable time after the causes of nonperformance or delay have terminated.

 

5.4.8                     Notwithstanding any other provision of this Agreement, in the event of the occurrence of any of the events described in Section 5.4.6, GWWO shall be obligated to continue to perform each of its obligations under this Agreement, including the obligation to purchase the amounts of Plasma specified herein at the then prevailing price thereof (as determined pursuant to this Agreement), and all risk of economic loss relating thereto shall be for the account of GWWO.

 

5.5                               Notices.  All notices or other communications required or permitted to be given or made under this Agreement may be effected by personal delivery in writing, which shall then be deemed communicated the same day as the personal delivery thereof, or by registered or certified mail, postage prepaid, return receipt requested, which shall then be deemed communicated five (5) days from the mailing thereof (each a “Notice”). Notices shall be addressed to the parties at the address given below or at such address as the respective parties may hereafter designate to the other in writing:

 

If addressed to GWWO:

 

Grifols Worldwide Operations, Ltd.

Grange Castle Business Park

Grange Castle

Clondalkin

Dublin 22

Ireland

 

If addressed to Guarantor:

 

Grifols SA

Avinguda de la Generalitat, 152

Parc empresarial Can Sant Joan

08174 Sant Cugat del Vallès,

Barcelona

 

 

Spain

 

If addressed to BIOTEST:

 

Biotest Pharmaceuticals Corporation

901 Yamato Road, Suite 101

Boca Raton

FL 33431-4409

USA

 

If addressed to HAEMA:

 

Haema AG

Landsteinerstrasse 1, 04103

Leipzig

Germany

 

5.6                               Applicable Law.  This Agreement and any issues, disputes or claims arising out of or in connection with it (whether contractual or non-contractual in nature such as claims in tort, from breach of statute or regulation or otherwise) shall be governed by, and construed in accordance with, the laws of Ireland.

 

5.7                               Effectiveness of Agreement.  This Agreement shall become effective only upon execution and acceptance by GWWO and SUPPLIER.

 

5.8                               Multiple Originals.  This Agreement may be executed simultaneously or in one or more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument.

 

5.9                               Partial Invalidation.  In the event any provision of this Agreement shall for any reason be or become void or unenforceable, the remaining provisions shall continue in full force and effect, and under no circumstances shall an unenforceable provision have any effect upon any provision which is otherwise enforceable.

 

5.10                        Paragraph Headings.  The subject headings of the paragraphs and subparagraphs of this Agreement are included for the purposes of convenience only, and shall not affect the construction or interpretation of any of its provisions.

 

5.11        Assignability.  Except as otherwise set forth herein, this Agreement shall not be assignable by either party hereto, either voluntarily or by operation of law or otherwise, without the prior written consent of the other party.  Such prohibition on the assignment of rights under this Agreement shall be operable to the extent permitted by law.  Any assignment without prior written consent is void.  Consent shall not be unreasonably withheld.  Notwithstanding the above, the Supplier may assign its rights under this Agreement (by way of security only) to any bank(s) and/or financial institution(s) lending money or making other banking facilities available to its parent corporation (or to its affiliate or subsidiary under common ownership or control) for the acquisition of the Supplier (“Lender”). On the enforcement of any security of a kind referred to in this Clause 5.11 any person having the benefit of such security (including any administrative receiver) may assign any or all of the relevant rights to any person, but the continuing party's liability to any assignee in respect of those rights shall not be greater than if no assignment had taken place.

 

 

5.12                        Successors and Assigns.  This Agreement shall be binding upon and inure to the benefit of the parties hereto, their successors and assigns, subject to the provisions of Section 5.11 above.

 

5.13                        Third Party Rights.  Except for such corporation(s), firm(s), partnership(s) or other legal entity(ies) affiliated with and under common ownership and control of GWWO or SUPPLIER, nothing in this Agreement, whether expressed or implied, is intended to confer any rights or remedies under or by reason of this Agreement on any persons other than the parties to it and their respective successors and assigns, nor is this Agreement intended to relieve or discharge the obligation or liability of any third persons to any party to this Agreement, nor shall any provision give any third persons any right of subrogation or action over or against any party to this Agreement.

 

5.14                        Arbitration.  Any dispute under, or in connection with, or arising out of this Agreement, including any dispute as to the existence or validity of this Agreement, shall be referred, by written notice from either party, (the “Referral”), to the decision of a single arbitrator selected by agreement of the parties, or failing agreement within ten (10) days of the date of the Referral, as may be nominated by the President of the Law Society of Ireland.  Any such reference to arbitration will be a submission to arbitration within the meaning of the Arbitration Act 2010 or any Act amending or repealing same and shall be arbitration conducted in the city of Dublin (Ireland) in the English language and shall be governed by the Arbitration Act 2010 subject to the following provisions. The award rendered by the arbitrator shall be final and binding upon the parties hereto.

 

The parties agree that the courts of Ireland shall have power to make any order for third party discovery of documents and exclusive power to make any order relating to security for costs of the arbitration.

 

If an arbitrator declines the appointment or after appointment is removed by order of a competent court or is incapable of acting or dies and the parties do not, within twenty-eight (28) days of the vacancy arising, fill the vacancy, then the vacancy will be filled on the nomination of President of the Law Society of Ireland.

 

The existence, content and results of the arbitration and any rulings or awards shall be confidential to the parties and, without the prior written consent of the other party, neither party may disclose the existence, content, or results of any such arbitration, save as required by law, or for the purpose of presenting or preparing its case in the arbitration or for the purpose any legal proceedings regarding the arbitration or any rulings or awards.

 

5.15                        Authority to Execute.  SUPPLIER is not a party to, nor is it bound by any agreement which precludes or otherwise restricts the performance of its obligations hereunder. SUPPLIER represents and warrants that it has the right, legal capacity and authority to enter into this Agreement and that the execution of this Agreement has been duly authorized.

 

5.16                        Confidentiality.  GWWO and SUPPLIER and its employees and agents shall hold in confidence any and all documents, materials and information provided to SUPPLIER by GWWO, including but not limited to the terms and conditions of this Agreement include permission to disclose agreement and all related information to lenders].  SUPPLIER agrees that it will not disclose, except to their employees and agents on a need-to-know basis, any such information or documents described herein at any time during, or after termination of this Agreement, without the prior written consent of GWWO.  The requirements of this Paragraph shall not apply to information which is publicly disclosed by GWWO.  In addition to the above, both SUPPLIER and GWWO shall fully comply with the U.S. Department of Health and Human Services’ regulation on “Privacy Standards for Individually Identifiable Health Information” which comprises 45 C.F.R. §§ 160.101 through 164.534, promulgated pursuant to the Health Insurance Portability and Accountability Act of 1996.

 

5.17                       Entire Agreement.  This Agreement constitutes the entire agreement of the parties hereto with respect to the subject matter hereof and supersedes all prior agreements or understandings, both written and oral, with respect to such subject matter.  No party hereto has made any representation or warranty or given any covenant to another party hereto except as set forth in this Agreement.

 

 

5.18                       Order of Precedence

 

In the event of any conflict or inconsistency between the terms of any of the sections of this Agreement and any Exhibit (including the Quality Agreement) the terms of the section of the Agreement shall prevail and shall be the binding obligation of the Parties.

 

 

EXHIBIT A DONOR   CENTERS 16 

    

 

BIOTEST centers   IL · I c ·: I 233 West Hancock Avenue,"m"""   ""'.ouov1 Athens Augusta GEORGIA 2704 Peach Orchard Road,Augusta GA   30906 1616 East Wooster StreeBowling Green,OH 43402 718 22nd Av.S, Brookings   SO 57006 500 Old Greenville Hwy Ste 500-2,ClemsonSC 29631 2235 Dave Ward   Drive, #205, Conway AR 72034 1027 Commerce Boulevard, Dickson City PA 18519   4391 Colonial Boulevard,Fort Myers Fl33966 2315 NW 13th Street, Gainesville   F3l2609 6837 Taft Street, Hollywood F3l3024 408 S. Gilbert St,Iowa City lA   52240 1213 Country Club Road, Jacksonville NC 285414111 113 Yopp Rd.,   Jacksonville-2 NC 28540 5915 1st Avenue, Keamey NE 68847 300 S. 17th Street,   Lincoln NE 68508 3110 Lake Washington Road, Melbourne,Fl32934 2501Discovery   Drive Suite 400,Orlando,FL 32826 100 Business Pari< Way, Royal Palm,F3l   3411 618 NW loop 410 Suite 101,San Antonio TX 78216 2860 Cerrillos Road,   Santa Fe NM 87507 311N.Patterson StreeValdosta, GA 31601 1012 Princeton St,   Vennillion SO 57069 GEORGIA OHIO SOUTH DAKOTA SOUTH CAROLINA ARKANSAS PENNSYLVANIA   FLORIDA FLORIDA FLORIDA IOWA NORTH CAROLINA NORTH CAROLINA NEBRASKA NEBRASKA   FLORIDA FLORIDA FLORIDA TEXAS NEW MEXICO GEORGIA SOUTH DAKOTA OHIO Bowling   Green Brookings Clemson Conway DicksonCity Fort Myers Gainesville Hollywood   Iowa City Jacksonville Jacksonville Keamey lincoln Melboume Orlando Royal   Palm San Antonio Santa Fe Valdosta Vermillion Youngstown 6000 Mahoning   Avenue,Youngstown OH 44515 27/1212018 

    

 

HaemaAG centres   I I Center Center Location Post Code GERMANY 1 RaemaAG, BERLIN-GHARLOTTENBURG   Wilmersdorfer StraBe 54 10627 - 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19   20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 Haema AG, BERLIN-HELLESDORF   Haema AG, BERLIN-MARZAHN Haema AG, BERLIN-PRENZLAUER BERG Haema AG,   BERLIN-TEGEL Haema AG, BERLIN-WEDDING Haema AG, BONN Haema AG,   BRANDENBURG/HAVEL Haema AG, CHEMNITZ Haema AG, DORTMUND Haema AG,   DRESDEN-FETSCHERPLATZ Haema AG, DRESDEN-WORL TRADE CENTER Haema AG, ERFURT   Haema AG, ESSEN Haema AG,FRANKFURT/DOER Haema AG,FREIBERG Haema AG,GERA Haema   AG, GORLITZ Haema AG, GOTHA Haema AG, GRIMMA Haema AG, HALLE Haema AG, HAMM   Haema AG,JENA Haema AG, LEIPZIG-GONNEWITZ Haema AG, LEIPZIG-GOHLIS ARKADEN   Haema AG, LEIPZIG-MARKT Haema AG, LOBECK Haema AG, MUNCHEN Haema AG, PLAUEN   Haema AG, POTSDAM HaemaAG,REGENSBURG Haema AG, ROSTOCK Haema AG, SCHWERIN   Haema AG, WEIMAR Haema AG, ZWICKAU Peter-Weiss-Gasse 1 HavemannstraBe 12b   Landsberger Allee 117 12627 12689 10407 - - ----< Berliner StraBe 25   BadstraBe 4a PoststraBe 19, KirchhofstraBe 1-2 Markt 5, 13507 13357 53111   14776 09111 44135 D-01307 D-01067 ---- Ostenhellweg 50-52, Fetscherplatz 2   --Rosenstrase 30 - -··· Lachsgasse 3, Kettwiger Str. 64, Kari-Marx-StraBe 2   BahnhofstraBe 40, Breitscheidstra&e 1-5, An der Frauenkirche12   Oststra&e 51, Kathe-Kollwitz-StraRe 6, Neustadter Passage 17A, Westring2,   Goethestra&e 3 A, 99084 45127 15230 09599 7545 02826 r--t I I I 99887   04668 06122 59065 07743 04277 D-04155 D-04109 23552 80335 8523 14480 93053   18057 19055 I I I --1-- ----Kari-Liebknecht-Stra&e 155, Lutzowstrase 11   Markt9 Sandstr,1-15 Dachauer Str. 70, Klostermarkt-Oberer Steinweg 10,   NuthestraBe 1 ----1--------+----Hildegard-von-Bingen-StraBe 1, Deutsche MED   Platz_2 -----r--- I Friedrichstr.18 SteubenstraBe 15, MarienstraBe 3, 99423   8056 27/1212018 

    

 

EXHIBIT B   QUALITY AGREEMENT 17 

    

 

QUALITY   AGREEMENT SOURCE PLASMA INTENDED FOR THE MANUFACTURE OF MEDICINAL PRODUCTS   FOR HUMAN USE This Quality Agreement is part of the Services Agreement dated   28-December-2018 by and between Grifols Worldwide Operations, Ltd.   ("MANUFACTURER") with its principal place of business at Grange   Castle Business Park, Grange Castle, Clondalkin, Dublin 22, Ireland and Haema   AG with its principal place of business at landsteinerstrasse 1, 04103   leipzig, Germany ("HAEMA", and "PLASMA SUPPLIER"). The   term of this Quality Agreement ("Agreement") commenced on the date   set forth above (the "Effective Date") of signature of the Services   Agreement. This Agreement document will be updated due to the continuous   evolution of standards of quality and safety for the collection, testing,   processing, storage and distribution of human plasma. Appendices to this   Agreement may be revised without revision to this Agreement as long as   appropriate approvals and proper signatures according controlled   documentation systems for both parties are in place. 1. GENERAL PROVISIONS 1)   MANUFACTURER is a company that manufactures medicinal products or   intermediate fractions for further processing derived from human plasma and   uses Source Plasma as starting material/raw material. 2) In connection with   its medicinal products business, MANUFACTURER desires to obtain, and PLASMA   SUPPLIER desires to provide, Source Plasma (including hyperimmune plasma)   solely in accordance with the terms and conditions set forth in this   Agreement covering the technical and quality requirements of Source Plasma as   a raw material for further manufacturing at MANUFACTURER. Source Plasma is   obtained and manufactured by PLASMA SUPPLIER from Health Authority licensed   Plasma (Human) collection centers PLASMA SUPPLIER may also supply   MANUFACTURER with Source Plasma obtained from other approved suppliers   (contract and third party). PLASMA SUPPLIER is responsible for the assurance   that the Source Plasma obtained from these suppliers (including cent§.rs,   laboratory test, storage facilities or transport/transit companies) meets all   of the requirements stipulated in this agreement and MANUFACTURER   Specifications. A detailed list of centers, laboratories, storage facilities   and transport/transit companies is enclosed in ATTACHMENT 1. PLASMA SUPPLIER   will also provide additional services to the MANUFACTURER. PLASMA SUPPLIER   will be responsible for the handling, storage, and transport of intermediate   pastes and for the handling, storage, transport and release of plasma that is   contracted to the MANUFACTURER for further processing. Such services must   meet all of the applicable requirements for the materials in accordance with   the terms and conditions set forth in this Agreement, the applicable   regulations, and the MANUFACTURERS Specifications. 3) to PLASMA SUPPLIER   agrees that all Source Plasma ("Plasma") supplied to MANUFACTURER   as starting material produce medicinal products for human use hereunder will   meet the following requirements, specifications and conditions. 

    

 

2. QUALITY AND   TECHNICAL REQUIREMENTS General 1) All Plasma supplied by PLASMA SUPPLIER   under this Agreement must be derived from Source Plasma collected at plasma   collection centers approved by competent authorities that have all necessary   and regulatory approvals and permits,. All Plasma supplied by PLASMA SUPPLIER   under this Agreement must be collected, processed, tested, stored, packaged,   labeled, released and shipped in compliance with all applicable sections of   the origin Country Regulation, including without limitation current Good   Manufacturing Practices ("cGMP") A list of relevant regulations is   enclosed in ATTACHMENT 2. 2) PLASMA SUPPLIER shall collect, process, test,   store, package, label, release and ship the Plasma in accordance with MANUFACTURER   Plasma Specifications ("MANUFACTURER Specifications"). A copy of   the MANUFACTURER Specifications is enclosed as ATTACHMENT 3. PLASMA SUPPLIER   hereby acknowledges receipt of a copy of MANUFACTURER Specifications and   Shipping instructions, which are incorporated herein by reference as though   fully set forth herein. These may be amended from time to time by   MANUFACTURER or by updates due to new Quality or Regulatory requirements made   by an appropriate governmental agency during the term of this Agreement, and   upon receipt thereof, PLASMA SUPPLIER shall jointly review with MANUFACTURER,   be in agreement and approve any such amendments and not unreasonably withheld   or delay. 3) Plasma collection centers will screen all donors to ensure that   each of them is under good health conditions and that plasma is not collected   from a high risk population for blood-borne infections. Therefore, plasma   centers with an active High Risk Donor collection program (donors known to be   positive for HIV, HCV or HBV at the time of collection) will not be accepted   by Grifols. 4) Plasma is for further manufacture use only and is not to be   represented as suitable for use as a finished human drug. 5) The MANUFACTURER   Specifications may be changed and/or modified by MANUFACTURER requirement in   order to comply with any new legislation in force and/or new controls or test   methods which are available in order to obtain the safest Plasma as possible.   6) PLASMA SUPPLIER, agrees to maintain regular plasma configuration and do   not to alter the configuration of the normal donor panel population as   starting material for all plasma-derived products without MANUFACTURER   approval. Units from donors that have participated in a hyperimmune program   cannot be used as Source Plasma without prior knowledge of the MANUFACTURER   to avoid cluster of units going to same plasma pool. Plasma is for further   manufacture use only and is not to be represented as suitable for use as a   finished human drug. Quality Control 7) PLASMA SUPPLIER agrees to arrange   testing for each donor of plasma in accordance with MANUFACTURER   Specifications, as well as National Regulations, applicable European   Directive, as well as any other applicable federal, state, and local or   foreign competent authorities, governmental agencies regulations concerning   donor testing, and agrees to furnish test results of all such tests to   MANUFACTURER in agreed certificate format when required. Both parties shall   ensure that all laboratories used are in compliance with cGMP and are   qualified in all of the methodologies associated with plasma testing. All   testing laboratories used to test Plasma supplied must be on the approved   laboratory list as per Attachment 1. All testing methods must be validated   and fulfil adequate levels of sensitivity and specificity according to their   intended use, fulfilling all regulation in force. All validations, including   protocols, reports and documentation shall be approved by the quality   assurance function of the laboratory. 

    

 

Tests and   analysis of the Plasma shall be done in a laboratory approved by PLASMA   SUPPLIER using licensed kits. AITACHMENT 4 includes a list of approved test   kits and validated NAT platfonns. Plasma testing shall be perfonned according   test kit manufacturer instructions. Submission of plasma samples to testing   laboratories for any testing will be compliant with written procedures for   submission of such samples. This includes, but is not limited to: use of   approved containers and shippers, procedures for handling and shipping of   samples, and the preparation and submission of appropriate documentation with   samples. The laboratories shall be responsible to notify the centers of any   paperwork or samples received that does not confonn to the requirements for   sample paperwork, sample labeling and sample shipping. 8)Each unit of Plasma   must meet the quality control specifications and the claimed and approved   shelf-life for the Plasma at the maximum approved storage temperature as   stated in the labeling specified in the MANUFACTURER Specifications. Subcontracted   Operations 9) PLASMA SUPPLIER and MANUFACTURER shall jointly agree in writing   on any contracted service (i.e., donor center collection, plasma storage,   shipping, testing) to be completed by any third party per the MANUFACTURER   Specifications. MANUFACTURER will have the right to audit any such facility   and may jointly audit with the PLASMA SUPPLIER auditors. PLASMA SUPPLIER will   provide a written report to MANUFACTURER confinning that the Plasma units   have been collected, tested, shipped and stored properly and meet the   requirements of the MANUFACTURER Specifications. Both parties shall ensure   that all sites or services used are in compliance with cGMP and are qualified   in all of the methodologies associated with plasma handling and its premises.   All contract sites used for the collection, transport, testing or storage of   the Plasma supplied must be on MANUFACTURER approved suppliers list. The   contracted sites must show that methods are validated fulfilling regulation   in force. All validations, including protocols, reports and documentation   shall be approved by the quality assurance function of the third party   organization. Any contracted organization must be approved and listed in   ATIACHMENT 1 and testing must comply with ATIACHMENT 4. Traceability and   look-Back Communication (Post-Collection Information) 10) PLASMA SUPPLIER   shall communicate to MANUFACTURER in writing within (5) five calendar days   all infonnation on a donor after a donation that fulfilled all MANUFACTURER   Specifications is rejected for seroconversion, CJD/nvCJD or post donation   infonnation that may become an infectious disease. Notification instructions   and required notification information are detailed in MANUFACTURER   Specifications (traceability requirements and look back). PLASMA SUPPLIER   will notify MANUFACTURER as soon as practicable and in no case later than (5)   five calendar days of discovery of significant deviations that may impact   batch(s) or Plasma previously released and/or shipped to MANUFACTURER. 11)   PLASMA SUPPLIER shall supply to the MANUFACTURER a report prior to product   release on all post donation notifications received after pooling so that the   MANUFACTURER can perfonn a viral risk assessment on the product. Change   Control 12) All changes shall undergo a technical and cGMP impact assessment.   PLASMA SUPPLIER will notify MANUFACTURER in advance of any planned changes   reasonably foreseeable to affect the regulatory submissions to the Health   Autorities involved (. PLASMA SUPPLIER will have responsibility for providing   justification for the changes and validating (when appropriate) any such   changes to cGMP standards. Change control procedures will include a 

    

 

requirement for   PLASMA SUPPLIER to obtain written approval from MANUFACTURER prior to the   implementation of any change reasonably foreseeable to affect any regulatory   submission, and any other change to parameters that are covered by the change   control scope that could have an effect on the safety, purity, etc. of the   Plasma collected. The scope of the change management process includes   collecting, testing, labeling, storage and shipping processes of Plasma, as   well as intermediate fractions, storage and shipping. The associated changes   may relate to: the master batch records, bill of materials, analytical   standards, test methods and Specifications; and any changes to validated   facilities, utilities, computer systems, equipment or processes used in the   cleaning, manufacturing, testing, storage or shipment with respect to Plasma   or intermediate fractions. Grifols Source Plasma Specifications may be   changed and/or modified by Grifols as required in order to comply with   current European requirements. Grifols shall submit all proposed revisions to   the Specifications to PLASMA SUPPLIER for review and approval, which cannot   be unreasonably withheld. Grifols shall advise PLASMA SUPPLIER of all   proposed revisions to the Specifications as promptly as practicable so as to   provide PLASMA SUPPLIER with as much notice as possible. PLASMA SUPPLIER   shall have thirty (30) business days to agree to implement or otherwise   respond to Grifols proposed revisions to the Specifications;. PLASMA SUPPLIER   response shall, if applicable, state PLASMA SUPPLIER reasons (which shall be   commercially reasonable) for refusing to implement such revisions. PLASMA   SUPPLIER and Grifols shall attempt in good faith to resolve any disputes as   to the implementation of any requested revisions. Timeline for implementation   of the change will be agreed by both companies. Quality Assurance 13) PLASMA   SUPPLIER shall have a quality management system that ensures all critical   processes involved in collection, processing, packaging, labelling, testing,   storage, release and transportation are conducted in adequate facilities and   according to current GMP principles as well as current legislation. PLASMA   SUPPLIER shall maintain an active quality management system which at least   shall review deviations and trends, ensure appropriate training of personnel,   conduct internal audits on a periodic basis, with a follow up of deviations   with a CAPA program and a change control system in force. The quality system   shall apply to all operations which may impact on quality and safety of   Plasma, from donor selection to Plasma delivery to the MANUFACTURER. 14)   PLASMA SUPPLIER shall be responsible for creating the manufacturing and   testing master documentation specific to Plasma collection. It shall be   responsible for creating and maintaining at the Premises all SOPs ad other   documentation required to support cGMP operations. 15) Any deviation from the   process and SOPs during Plasma collection, storage or testing must be   appropriately explained, investigated, documented and approved in the batch   records or analytical records. The deviation documentation must identify the   cause and the corrective action, where appropriate, and must assess the   impact to the Plasma donor's safety, and Plasma's quality. PLASMA SUPPLIER   shall develop appropriate procedures for deviation investigations. PLASMA   SUPPLIER will notify MANUFACTURER as soon as practicable before shipment or   in no case later than (5) five calendar days of discovery that may impact   batch(s) or Plasma previously released and/or shipped. 16) PLASMA SUPPLIER   shall ensure that adequate trained and qualified staff is conducting the activities   with a clear description of employee responsibilities. Training must be   conducted according to an approved training program. Initial and continuous   training shall be performed as well as proper staff competency follow-up.   Training records shall be retained and available for review. 17) Materials to   be used in the collection of Plasma shall be approved in accordance with   applicable legal requirements for Plasma collection. Upon receipt of such   materials, PLASMA SUPPLIER shall confirm the proper condition of packaging,   sterility certification, locks and seals and check that labels correspond   with the shipping documents. PLASMA SUPPLIER shall implement an appropriate   system to maintain certification of materials and chemicals used in the   collection and testing of Plasma. For those specified materials of animal   origin, if any, PLASMA 

    

 

SUPPLIER shall   assure each lot is in full compliance with licensed requirements, with   National regulations and final approved by Grifols). 18) PLASMA SUPPLIER   shall approve all vendors and suppliers of critical raw materials, reagents   and components used in the collection and testing of Plasma and shall   maintain an approved supplier list. PLASMA SUPPLIER shall ensure that all   materials are received, stored, segregated and used correctly, and all   materials are appropriate for their intended use. It also shall ensure   appropriate separation and/or segregation of any materials that may present a   potential hazard to the materials used in the production of Plasma units.   PLASMA SUPPLIER shall be responsible for maintaining the relevant certificate   of analysis, certificate of compliance and/or certification of origin (as   appropriate) for the materials. Storage and Shipping 19) Storage and shipment   of Plasma supplied by PLASMA SUPPLIER under this Agreement must be conducted   in approved facilities that have all necessary and regulatory approvals.   Storage facilities and shipping process must be properly validated. 20)   Plasma must be frozen within twenty-four (24) hours of collection by cooling   rapidly in conditions validated to ensure that a temperature of -25°C or below   is attained at the core of each Plasma unit within twelve (12) hours of   placing in the freezer apparatus. Plasma must be stored at -20°C or lower.   Freezing, storage and shipping must be done according to WHO recommendations.   21) PLASMA SUPPLIER shall provide sufficient and suitable storage facilities   that meet the storage specifications for Plasma units, as documented and   agreed upon in the MANUFACTURER Specification, SOPs, applicable regulations   related to Plasma storage, National Regulations for-Human Plasma for   Fractionation. Any off-site Plasma storage facilities used must be approved   by PLASMA SUPPLIER quality assurance and meet the same requirements. Mobile   storage facilities shall only be used short tenn for emergency situations and   must be appropriately validated to maintain correct temperatures. It shall be   ensured that during storage of Plasma before shipping the plasma has been   properly packaged and protected to avoid deterioration, interference, theft,   product contamination or mixture with any other materials. PLASMA SUPPLIER   will maintain proper segregation of the Plasma units. Details of any labeling   requirements and shipping container sealing and integrity will be documented.   The Plasma units shall be suitably packaged for transit, with each outer   container being labeled as per written procedures. 22) Unreleased Plasma that   is shipped to a PLASMA SUPPLIER quarantine location at the authorized plasma   warehouse will be stored in a physically segregated area in a controlled,   validated warehouse. Oversight of that area and the Plasma contained therein   is the responsibility of PLASMA SUPPLIER quality assurance organization. Such   unreleased Plasma must be controlled by standard operating procedures,   including appropriate labeling and electronic material status. Such   procedures will govern post unit donation removal, temperature deviation   reporting requirements, unit and lot traceability, employee access and   training, release of Plasma and final transfer to MANUFACTURER, regulatory   filings and other such notifications and regulatory requirements not   specifically covered by this Agreement whenever applicable. 23) Rejected   Plasma must be properly segregated, identified and dispositioned under   quality assurance control. Biological Product Devi ations and Recalls 24)   PLASMA SUPPLIER shall be responsible for monitoring the manufacturing and   release data of the Plasma and if detects a potentially reportable deviation,   as applicable to Plasma sent to MANUFACTURER, this should be reported and   discussed with MANUFACTURER within five (5 business day of confirmation.   PLASMA SUPPLIER is responsible for Plasma unit deviation reporting to the   appropriate regulatory authorities. Page 5 of 32 

    

 

25)   MANUFACTURER, as the medicinal product license holder, shall be responsible   for reporting deviations pertaining to biological products to the regulatory   authorities. PLASMA SUPPLIER will work collaboratively with MANUFACTURER on   filing any such report thought to be due to the collection of Plasma. PLASMA   SUPPLIER will promptly perfonn investigations for any issues that are thought   to be Plasma unit based. Both parties shall collaborate in the development of   the global reporting regulatory strategy for the event. PLASMA SUPPLIER shall   provide necessary infonnation to MANUFACTURER if receives a warning letter,   significant regulatory observation or BPDR follow up question(s). 26) PLASMA   SUPPLIER is responsible for Plasma unit recall or withdrawal per the   applicable regulations. MANUFACTURER shall be notified of any recall and of   any problems thought to be due to Plasma quality within five(S) business day   of confinnation. When requested by MANUFACTURER, PLASMA SUPPLIER will perform   investigations for these problems. Investigation reports regarding the defect   or cause of recall will be forwarded to MANUFACTURER within a mutually   agreeable timeframe. MANUFACTURER is responsible for any final product or   intennediate product recall or withdrawal for those products that are   manufactured. Equipment, Computer and Facility Validation and/or   Qualification Process 27) PLASMA SUPPLIER shall ensure that all process,   equipment, systems and facilities are qualified and validated if applicable   prior its use and after any significant change to ensure that processes are   capable of consistently achieving the Plasma specifications. Documentation   must be reviewed and approved. Calibration and preventive maintenance   programs shall be established for equipment. It will maintain cGMP validation   status of process procedures, computers and associated equipment with respect   to the manufacturing, storage and shipping procedures that are used in   connection with Plasma. PLASMA SUPPLIER shall be responsible for all   equipment, computer and facility qualification activities associated with the   Plasma collection, storage and shipment. Validations must meet National   Regulations and further approved by Grifols, as applicable and will promptly,   upon request by MANUFACTURER, make validation reports available for review.   PLASMA SUPPLIER shall develop procedures and implementation plans to assure   that all computer systems and software are compliant with required   Regulations 28) PLASMA SUPPLIER will approve all process qualifications   applicable to the Plasma collection, including, but not limited to, the   freezer validation and shipping validation for test samples and Plasma.   PLASMA SUPPLIER will provide copies of validation reports upon request.   Validation reports may also be requested as part of an audit or an event   review. Plasma Release 29) PLASMA SUPPLIER collection centers and third party   suppliers shall all have at least one Qualified Person on the Premises to   oversee the quality aspects of the Plasma collection, testing, shipment,   evaluate deviations, etc., in order to assure compliance with cGMPs. 30) PLASMA   SUPPLIER has designated a person for plasma release for further manufacturing   of medicinal products in accordance with applicable regulations. PLASMA   SUPPLIER and its suppliers shall release units by means of a corporate   Qualified Person who will document and certify that each unit of Plasma has   been collected and tested in approved facilities according to GMP and that   the units fulfil quality and safety requirements of the MANUFACTURER   Specifications. The Responsible Person and designee are named in this   Agreement as the individuals authorised to release Plasma units. 3. LICENSES,   PERMITS AND APPROVALS 

    

 

1. All Plasma   supplied by PLASMA SUPPLIER under this Agreement must be derived from Plasma   collected at an approved plasma collection center located in XXXXXX that has   all necessary and regulatory approvals and permits,. The plasma collection   center(s) under this Agreement are set forth in ATTACHMENT 1. 2. PLASMA   SUPPLIER represents and warrants that all their plasmapheresis donor centers   in operation are certified under the Plasma Protein Therapeutics   Association's International Quality Plasma Program ("PPTA IQPP").   PLASMA SUPPLIER must preserve these certifications without interruption for   the remaining term of this Agreement. If PLASMA SUPPLIER fails to maintain   such plasmapheresis donor centers certifications, then MANUFACTURER has to be   immediately notified within one (1) business day to evaluate actions to be   taken. 3. PLASMA SUPPLIER agrees to follow the mutually agreed upon MANUFACTURER   Specifications and all other requirements or specifications issued in writing   by MANUFACTURER, and any versions to those procedures, requirements or   specifications as they may be issued or adopted by MANUFACTURER and agreed   upon by PLASMA SUPPLIER, as approved by appropriate governmental regulatory   agency or competent authority, if such approval is mandated by law or   required by MANUFACTURER. 4. In the event of a suspension, revocation, or   other administrative action adversely affecting or limiting any such license,   permit or approval, MANUFACTURER shall be immediately notified within one (1)   business day to take necessary actions. 5. PLASMA SUPPLIER may not relocate,   open or close any plasmapheresis collection centers, testing laboratories or   plasma storage facilities without prior written notification to the   MANUFACTURER. Written approval by MANUFACTURER is required for inclusion of   new centers, testing laboratories, plasma warehouses and transportation   companies, which shall not be unreasonably withheld. 4. INSPECTIONS 1.   Collection and storage of the Plasma shall be conducted in a suitable   controlled environment and such Premises shall be regularly inspected and   monitored to ensure compliance with cGMP, and other applicable manufacturing   authorizations. 2. PLASMA SUPPLIER will be responsible for qualification and   auditing of all vendors of supplies used in the collection and shipment of   Plasma. All suppliers must appear on the PLASMA SUPPLIER approved supplier   list. PLASMA SUPPLIER is responsible for handling complaints to the vendor   for supplies and the interaction with the vendor to resolve those complaints.   3. MANUFACTURER shall have the right to conduct periodic audits of the   approved plasmapheresis donor collection centres, testing laboratories, Corporate   Quality Management Systems, plasma warehouse storage facilities and/or   transport/transit and shipping companies and to review all procedures and   records kept by such facilities related the collection, processing, testing,   storage, packaging, labeling, release and shipping of plasma as well as all   operations conducted in conformance with generally accepted industry   practice. These audits may be done as joint audits with PLASMA SUPPLIER, at   the discretion of the MANUFACTURER. MANUFACTURER will provide PLASMA SUPPLIER   with not less than thirty (30) day notice prior to any of its audits, unless   agreed otherwise by the Parties, and such audits shall be during normal   business hours, shall be limited to matters reasonably related to this   Quality Agreement, and shall be conducted in conformance with generally   accepted cGMP. No audit shall continue in duration for more than three (3)   business days unless such an extension is reasonably necessary. A maximum of   three (3) auditors shall participate in any inspection unless otherwise   agreed between PLASMA SUPPLIER and MANUFACTURER. Such audits shall occur   periodically (at least, every two years) for facilities having an acceptable   inspection I audit history unless otherwise necessary to inspect or audit as   a result of requirements by regulatory authorities or a serious failure or   material concern that either impacts or threatens to :fiJ% p,,, 7 of" 

    

 

impact quality,   safety, potency, or compliance with this Quality Agreement. In the event of   such additional audit(s), MANUFACTURER shall provide PLASMA SUPPLIER   reasonable written notice of its intent to conduct such additional audit(s).   MANUFACTURER maintains the right to event reviews (directed audit), in   addition to periodic audits, to address significant quality, performance or   safety problems associated with the products.These events should be   requested, scheduled and conducted at the first available date. 4. PLASMA   SUPPLIER shall be entitled to perform at least one (1) standard cGMP   compliance audit every year of the above facilities to encompass all cGMP   operations (testing laboratories, plasma warehouses, transport companies,   corporate offices). 5. PLASMA SUPPLIER Compliance Audit Team will provide a   written report to MANUFACTURER of all observations. Within thirty (30) days   of the audit date, PLASMA SUPPLIER will coordinate to provide a written   response to all findings that details corrective action to be implemented.   PLASMA SUPPLIER will ensure that all corrective actions are implemented and provide   a report to MANUFACTURER upon implementation. In those instances where   corrective action will require an extended period to implement, PLASMA   SUPPLIER shall provide reports to MANUFACTURER on the progress of such   corrective action at such intervals as mutually agreed upon by the parties.   6. MANUFACTURER shall have also the right to cause any authorized   representative of the Public Health Service, any state, local, foreign   competent regulatory authorities and governmental agencies, and any   authorized third party as deemed necessary or desirable to carry out its   business worldwide, to conduct periodic inspections of the approved   plasmapheresis donor collection centers, testing laboratories, plasma   warehouse storage facilities and/or transport/transit and shipping companies   and to review all procedures and all records kept by such donor centers or   such testing laboratories regarding the collection, processing, testing,   storage, packaging, labeling, release and shipping of Plasma, and all   operations conducted in conformance with generally accepted industry   practices. MANUFACTURER shall have the right to make and retain copies of all   such procedures and records kept by donor centers, as well as copies of all   correspondence between donor centers and any governmental regulatory agencies   regarding any such inspections. 7. MANUFACTURER will be responsible for   ultimate approval of all Plasma centers and their status as approved or not   approved to ship plasma to the MANUFACTURER. The information will be   contained in the MANUFACTURER list of approved Plasma suppliers and the types   of Plasma the center is approved to collect. 8. PLASMA SUPPLIER agrees to   send MANUFACTURER written notice of any federal, state or local government   for cause audit or relevant investigation of the donor centers, testing   laboratories, storage, release and shipping facilities/companies with no more   than ten (10) business day of the investigation's commencement. 9. PLASMA   SUPPLIER agrees to communicate to MANUFACTURER within ten (10) business days   of discovery of critical event (failure of a plasma collection center,   storage facility, testing laboratory and/or transportation which may impact   quality or safety of the Plasma supplied 10. PLASMA SUPPLIER will notify   MANUFACTURER in a timely manner of any meetings or substantive discussions   with r any other regulatory authority that directly relate to the   manufacture, supply and/or control of Plasma supplied. 11. PLASMA SUPPLIER   shall provide to MANUFACTURER within ten (10) business days an information of   the following: (i) Update of critical findings related to the inspection   performed, (ii) Notice of Intent to Revoke License Letter, (iii) License   Suspension Letter, (iv) Seizure action regarding Corporate Offices, plasma   collection centers, storage facilities, or testing laboratories. 12. In a   quarterly basis, PLASMA SUPPLIER shall provide Grifols a summary of   regulatory National authority inspection of any plasma collection centers,   testing laboratories, storage facilities, and corporate offices, included in 

    

 

Attachment 1 of   the this Quality Agreement. This summary shall include information concerning   inspections of National health authority. This summary will also include a   list of critical observations and an overall evaluation of the regulatory   inspections outcome including: • Identification of the facility •   Identification of inspection date • Category (# of Minor, Major, Critical) •   Result: pass/not pass • - Kind of Deficiencies (for example: Documentation,   Storage, etc.). 13. In the event that during an inspection by MANUFACTURER   (or PLASMA SUPPLIER as designee), self notification to PLASMA SUPPLIER by the   donor center, test lab, warehouse or transportation company or by any   authorized representative of the Public Health Service, or any state or local   or foreign competent authorities and governmental agencies to corporate,   donor centers, test labs, plasma warehouses or transportation company,   critical or serious observations are found that may impact quality or safety   of the plasma supplied PLASMA SUPPLIER shall give MANUFACTURER notice within   five(5) business days and establish a timeframe to pass the inspection and   resolve issues. In the event that PLASMA SUPPLIER has not corrected the   failure, MANUFACTURER shall be immediately informed in order to take   necessary actions, including termination of this Quality Agreement and the   Supply Agreement in the event such breach remains uncured for a period of   sixty (60) business days. 5. DOCUMENTATION AND RECORD RETENTION 1) PLASMA   SUPPLIER shall make available upon request documents such as Site Master   Files (Donor Centers, Testing Laboratories, Storage Facilities, Corporate   Offices related to Quality Management Systems), floor plans, equipment   validation, and other production information in order to ensure safety,   purity, and potency of the product. MANUFACTURER, as the Plasma-derived   product license holder, is responsible to prepare and submit any regulatory   submission linked to in process and final product as required by applicable   regulations,. PLASMA SUPPLIER shall provide all documentation requested by   MANUFACTURER to support regulatory submissions. PLASMA SUPPLIER commits to   provide to MANUFACTURER on a regular basis the relevant information and   regulatory documentation that is necessary for Regulatory Submissions   according to final product applicable regulations . Such documentation shall   include at minimum, certificates of approval by competent health authorities   for facilities, laboratories, plasma warehouses and transportation companies,   inspection status information, donor suitability criteria, approved technical   specifications for soft goods, main equipment validation protocol, methods   and validations of testing platforms, proficiency studies and epidemiological   data. 2) 3) 4) Epidemiology data and viral marker data must be supplied by   PLASMA SUPPLIER in accordance with the current regulatory requirements. Data   must be submitted using the standard forms found in the Source Plasma   Specification. Should a PLASMA SUPPLIER donor center exceed (on an annual   basis, Jan-December.) the Grifols and/or its affiliated or parent company   established VM Alert Limits (Attachment 3): •PLASMA SUPPLIER will provide   Grifols an investigation and corrective/preventive actions (when   appropriate); and •Plasma will not be accepted from a donor center that has   exceeded the Grifols established Viral Marker Alert Limits for three (3)   consecutive years.. 5) PLASMA SUPPLIER shall keep complete and accurate   records of equipment usage, cleaning, testing, temperature holds, and any   maintenance/calibration performed and other parameters in accordance with the   most stringent applicable legal requirements. 6) PLASMA SUPPLIER agrees to   retain donor records according to all applicable sections and regulations   issued or promulgated by Competent Authorities applicable federal, state, and   local or foreign competent authorities and governmental agencies regulations.   Page 9 of32 

    

 

7) The   following items will have to be recorded and stored appropriately by PLASMA   SUPPLIER in order to secure the quality and safety of the partially processed   biological materials to comply with the current regulation identified in this   Quality Agreement in order to comply with applicable period as may be   required by any law or regulation governing the distribution of biological   products manufactured from such Plasma o o o traceability records donorcard   health record of each donor (including health history and physical   examination of each donor, which are maintained in the donor management   system) donor questionnaires (i.e., AIDS,...) donor number whose plasma was   used for production pooling. NAT and serological test results, which are kept   in the donor management system. o o o 6. CONSEQUENCES OF TERMINATION Upon   termination of the supply contract: PLASMA SUPPLIER shall continue to comply   with its obligation under this Agreement if and to the extent it continues to   have the responsibility for post donation information and look back   information after the expiry or termination of the Supply Agreement. All   obligation srelating to compliance with cGMP in respect of the plasma shall   continue in force according to the requirements of cGMP, including but not   limited to: Record Retention and availability . Regulatory inspections and   data requested Post donation information and look back information.   Epidemiological Data for the year after the termination of the supply   agreement. 7. CONTACT PERSONS In the event of serious failure, regulatory   issues, update or change in specifications: PLASMA SUPPLIER If addressed to   HAEMA: HaemaAG Landsteinerstrasse 1, 04103 Leipzig Germany MANUFACTURER   Grifols Worldwide Operations, Ltd. Grange Castle Business Park Grange Castle   Clondalkin Dublin 22 Ireland Page 10 of 32 

    

 

1) Each party   shall notify the other party in writing of any significant change in   reporting relationships involving the quality department or quality functions   within five (5) business days of such change and proceed according the Change   Control requirement process outlined in this agreement. 2) Each party shall   provide written notice to the other party of any change in the management of   a critical operation that is applicable to plasma (e.g., production, quality,   new center set up and validation) wHhin five (3) business days of such change   and proceed according the Change Control requirement process outlined in this   agreement.. ACCEPTANCE SIGNATURES: PLASMA SUPPLIER MANUFACTURER HaemaAG   Approved by: h.t{_ ! . /'\ Approved by:--\:::. '---­ 0 f . U /i. L0 ) 1 7·   <;_'-'"'-- l :J Date: Date: Ut (...e.-k "CS -\"-'.e._(   Haema o Name: Name: """' Dr. med. Barbara Baumann-Baretti   HaemaAG Title: Title: Medizinischer Vorstand Page 11 of 29 

    

 

ATTACHMENT 1   LIST OF CENTRES, TEST LABORATORIES, PLASMA WAREHOUSES, TRANSPORTATION   COMPANIES HAEMA centers Hoem:AG ccntrns Po tCodc wumersdorter Stra!lt Sli   Peter-\Velss·Gasse 1 H vcrn nnstra5e l2b Landsberger Allee 117 82rliner   StraBe 25 Bnd tr.rlle 4• Portstr.rBc 19, KirchhofstraBc1-2 11.1crkl5,   OsiQnhe!lwos SD-52, Fetscherplatl ZD ltosenstr..se 30 t.ach ; $Se3, Kettwiger   Str.64, !!:arl-1\larx-strcBe 2 11a hnhofstrafl. Sreits:heid51ra(l,ct 1-5,   Ader Frauenkirche 12 Osllitro8eSl, Kathe-Kollwitt·StraSe 5, Neustadter   Passage 17A. Wcstring 2, G cth<:$tr Be 3 A, !t31l-liebknecllt·Sirne 155,   Lutiow.>trase ll Markt9 Scndstr, l-15 1 2 3 Ha AG, BERLIN-CHAROITENBURG   Hcema AG, BERLIN·HELLI:SDORF Haema AG, BERLIN·MARZAHN Hne!rm AG,   BERLIN-PRENZLAUER BERG Haama AG, BERLIN-TEGEL li 'na IIG, BERLIN-V.JCDOING   Hoe.Tru AG, BONN H uAG,BRANDENBURG VE H.oa.'llA; G, CHEMNilZ Haem:a AG,   DORTMUND Haeme AG, ORESDEN-FETSCHERPLATZ Hl!!!ma AG, DRESDEN-WORL TRADE   CENTER HoomAG, ERFURT H<!"..ma AG, ESSEN Haema AG, FRANKFURT/DOER   Haome AG, FREIBERG Haamo AG, GERA H ma AG, GORUTZ H&"..ma AG,   GOTHrll Haa:na AG, GRIMMA HH1no AG, HALLE Hseme AG, 1-'.AMM Ha m.a AG, JENA   Haama AG, LElPZIG·CONNEWITZ Haem:; AG, LEIPZIG-GOHLIS ARi<AOEN H.,om:1 AG,   LEIPZIC-l.lARKT HaemA; G, LOBECK Hsemoe AG, MUNCHEN Haem:e AG, PLAUEN H;,eme   AG, POTSDAM 1-'.aemc AG, REGENSBURG Hoem::; AG, ROSTOCK Haemf;l..G,   SCH\1\'ERIN H:leme AG, WEIMAR Haem<! AG, ZWICKAU 105Z7 12627 12689 i0407   13507 13357 53111 14776 09111 44135 D-0130i 0·01057 55034 45127 15230 Ge593   75 02826 5EE67 041!89 06122 5!0055 0774:3 C-4277 D-4155 0.()4109 23552 eons   6523 14480 3 18057 19055 23 BOSS "' 5 e 7 e 9 10 11 12 13 14 15 16 17 1e   19 20 21 22 23 24 25 2o 27 :ze 23 3 31 32 33 34 35 DacheuerStr.70,   Kltctrmorllt-c-berer Steinweg 10, NuthestraSe 1 Hlldegiird-\·on Bir.genStraBe   1. DeutsChe MEO Platz 2 Friedrichstr.18 S ubensll'oBc 15, M ricn trn3e 3,   Haema Central Donor Laboratory, Wolfener STraBe 36, 12681 Berlin Ord r Center   Center Location GERJIIANY 

    

 

ATTACHMENT 2   RELEVANT REGULATIONS o EU Good Manufacturing Practices for Medicinal Products   for Human use, all as amended from time to time o Council of Europe: Guide to   the preparation use and quality assurance of blood components (current   version). o European Pharmacopeia monographs ('EP') requirements particularly   in respect of blood or blood components as starting material for the   manufacture of proprietary medicinal products. o Recommendations of the World   Health Organization (WHO). o Comission Directive 2005/61/EC of 30 September ·2005   implementing Directive 2002/98/EC as regards traceability requirements and   notification of serious adverse reactions and events. o Comission Directive   2004/33/EC of 22 March 2004 implementing Directive 2002/98/EC, regarding   donor suitability requirements. o Directive 2001/83/EC, GMP Annex 14 and   certain recommendations of the Council of Europe, as well as any other   applicable international, federal, state and local regulations concerning the   collection, processing, testing, packaging, labeling, release and shipping of   Plasma. storage, o Guideline on plasma-derived medicinal products   (EMA/CPMP/BWP, current version). Page 13 of29 

    

 

ATTACHMENT 3   SPECIFICATIONS 1.-PURPOSE To provide and describe the conditions required for   Source Plasma to be accepted by Grifols for the procurement of Source Plasma   intended for manufacture of hemoderivate products. This specification is   intended to assure that incoming plasma meets all Grifols requirements, in   addition to establish domestic and international regulations, 2.-SCOPE These   specifications cover all source plasma intended for fractionation, defined as   the fluid portion ofhwnan blood collected by plasmapheresis. Grifols can only   use plasma for fractionation that fulfils all the Grifols requirements for   all of the components that are part of Plasma Supply Chain, i.e.: Plasma   collection centers Plasma testing facilities and Plasma testing methods   Plasma storage facilities Plasma transportation companies. Every one of them   has to be approved by Grifols and previously authorized by competent Health   Authorities. 3.-RELATED DOCUMENTS o o o o o PPTA Viral Marker Standard PPTA   Qualified Donor Standard PPTA NAT Testing Standard EUEU Pharmacopeia   monograph for Hwnan Plasma for Fractionation Revision to Annex 14 to EU Guide   to GMP: Manufacture of products derived from hwnan blood or plasma   EUEMEA/CHMP/BWP/3794/03 Guideline on the Scientific Data Requirements for a   Plasma Master File EUEMEA/CHMP/BWP/125/04 Guideline on Epidemiological Data   on Blood Transmissible Infections eucouncil of Europe: Guide to the   preparation use and quality assurance ofblood components EUOirective   2002/98/CE EUOirective 2004/33/CE o o o o o EUfor plasma intented to be used   as raw material for Hemoderivates Products for European Market SPfor   plasmatic raw material intented to be processed in Spanish Manufacturing   Plant facilities :ff#t-""'"of29 

    

 

4.-PROCEDURE   All plasma units shall be collected by approved suppliers and collection   facilities, and tested by approved laboratories using approved kits, and   stored and transported using approved establishments in compliance with   Plasma types will be defined according to plasma center involved,   laboratories involved, testing methods involved, specific test for final   product destination requirement, warehouse involved and plasma carrier   involved in which is transported. The Supplier will keep updated a quality   assurance system that will include, at least, review and investigation of   deviations and detection of possible trending, performance of internal   compliance audits with corresponding follow-up of corrective and preventive   actions and implementation of an internal Change Control procedure. The   quality assurance system will be applied along the collection, processing,   testing, storage, and control procedures. All activities, functions and/or   documentation practices will be performed according to cGMP (current Good   Manufacturing Practices). 4.1. PLASMA COLLECTION Plasmapheresis Centers   Plasmapheresis centers shall be approved by the Health Authorities of plasma   origin and be in compliance with Epidemiological data established by   Manufacturing company.(IQPP certified). Plasma collection centers will screen   all donors to ensure that each of them is under good health conditions and   that plasma is not collected from a high risk population. Management and   control of donors should be done using an IT system. In addition for plasma intended   for use as raw material in hemoderivate products for European market, plasma   centers have to be approved by European Health Authorities. Plasma Supplier   will supply Grifols for corresponding evaluation and for each center   Epidemiological Data of viral markers (HBV, HCV & HIV), annually in EMA   format and half­ yearly in PPTA format. All alert notifications and their   correspondinginvestigations aswell as their corrective/preventive actions (if   applicable) should be included in the continuous revision of epidemiological   data. Centers participating in specific programs of collecting plasma from   donors tested reactive/positive in viral markers cannot be Grifols'   suppliers. Donor selection Donor selection procedures shall fulfill with   competent authorities Regulations. In addition for plasma intended for use as   raw material in hemoderivate products for European market, Donor selection   process has to be in compliance with those established by European Health   Authorities. All plasma donations shall be from qualified donors. Page 15 of   29 

    

 

Sterility   Plasma is separated from cells by an aseptic method using a sterile system   designed to prevent micro-organism contamination. Furthermore, the plasma   containers are closed, with the aim to prevent the possibility of   contamination. 4.2 PLASMA TESTING The laboratory shall be approved by   competent authorities. The laboratory will keep approved and updated SOPs,   containing the necessary working instructions. All analytical methods shall   be validated and shall have an optimum level of sensitivity and specificity   and shall fulfill with current legislation. All the validations, including   protocols, reports and related documentation will be approved by Quality   Assurance area. The laboratory will join in certification programs   (proficiency testing) to ensure suitability of methods and techniques in use.   Plasma shall be tested by facilities approved by competent authorities   (additionally approved by a competent Health Authority Likewise, all   analytical methods used shall be approved by competent authorities   (additionally approved by a competent Health Authority and shall be included   as part of the approved specifications. For plasma intended to be used as raw   material for hemoderivate products for European Market, testing facilities   and analytical methods used have to be approved by European Health   Authorities. Plasma testing requirements Prior to use, the test kit   manufacturer, test kit methodology and testing facility must be approved by   Grifols. • All donors shall be screened for all the biochemical parameters   required by national authorities as control of the donor and for indirect   coombs reactivity in the first donation and every 90 days, and the obtained   result must be non-reactive. • All donors shall be screened for excluding   Syphilis presence as required by national regulations. Donor test is   performed every 4 months. • All plasma units must be tested and found   non-reactive for Hepatitis B surface antigen (HBsAg) by a validated test   method approved by competent authorities. • All plasma units must be tested   and found non-reactive for HIV-1 and HIV-2 antibodies by a validated test   method approved by competent authorities. • All plasma units must be tested   and found non-reactive for Hepatitis C antibodies by a validated test method   approved by competent authorities. • Additionally, all plasma units must be   tested and found non-reactive by means of pools consisting of not more than   512 individual units for HBV-DNA, HCV-RNA and HIV-RNA 

    

 

 

by a validated   test method approved by competent authorities and for HAY-RNA and Parvovirus   B19-DNA by a validated test method. The cut-off of Parvovirus B19-DNA   determination must be such to ensure that plasma manufacturing pools do not   exceed a titer of lx104 IU/ml. • All plasma units must be tested for all   viral or non-viral markers as required by the plasma Supplier's Health   Authorities. • For plasma intended to be used as raw material for   hemoderivate products for European Market, analytical methods used have to be   approved by European Health Authorities. Hyperimmune plasma For hyperimmune   plasma all donors shall be immunized using Competent authorities approved   immunizing program and shall contain at least the titers agreed with the   Supplier. These are described in corresponding registers (IG_REG-000683 and   IG_REG-000686). Traceability and look Back Requirements While fully   respecting confidentiality, there is a system in place which enables the path   taken by each donation to be traced, both forward from the donor and back   from the finished medicinal product, including but not limited to plasma   center, plasma donor number, analytical testing and results, plasma   manufacturing pool testing, Data of Manufacturing process and final product   identification. It's a system by which we can identify and remove look back   and PDI units. A look-back unit is a unit of plasma that complies with all   the established requirements but collected from a donor, from whom a   subsequent donation has been rejected for any reason, related with an   infection or with behavior that may involve belonging to a risk group (Post­   Donation Information), Creutzfeldt-Jakob disease (CJD) or new variant   Creutzfeldt-Jakob disease (nvCJD). HEY-NAT testing will be performed   exclusively for donors of medicinal products. In case of an HEY positive   result, the corresponding blood components will be discarded and a look back   report will include all donations (including plasma for fractionation) within   6 months before the reactive one. In case of reasons related to infection or   belonging to risk group behaviour (PDI), Plasma Suppliers shall communicate   to Grifols manufacturing companies all the plasma units drawn from a donor   within twelve months prior to the date of the last negative tested donation   for anti­ HCY and HCY-RNA, for HBsAg and HBY-DNA and for anti-HIY 1/2 and   HIY-RNA. In case of CJD and nvCJD risk factors and/or diagnosis,   communications shall include all the units sent to any Grifols manufacturing   company from that donor. Look-back units shall be notified to any Grifols   manufacturing company in written form as quickly as possible and not more   than three (5) calendar days from the event that caused the procedure. Page   17 of 29 

    

 

4.3. PLASMA   PROCESSING Physical conditions of plasma units and samples Each plasma unit   shall be collected from a single donor. All plasma units must be placed in   the freezer within one hour of collection and maintained at - 20° C or   colder. In case of plasma intended for used as raw material in hemoderivate   products for European Market, it has to be in compliance with European   Pharmacopeia requirements: Plasma intended for the recovery of labile   proteins in plasma is frozen within 24h after collection by cooling rapidly   in conditions validated to ensure that a temperature of - 25°C or below is   attained at the core of each plasma unit within 12h after placing in the   freezing apparatus, ensuring the preservation from activity oflabile   coagulation factors. Plasma intended for the recovery of not labile proteins   in plasma is frozen by cooling at - 20°C or colder as soon as possible and at   the latest within 24h after collection. All plasma units shall be accompanied   by a plasma sample of not less than 2 ml and both shall be identified with   the bleed number and bar code. Both unit and sample of plasma shall exhibit   neither hemolytic nor lipemia signs when visually inspected, nor both plasma   bottle and sample tube shall not have any fissure or be broken. Storage The   warehouse shall be approved by Grifols and by competent authorities. All   plasma units and their corresponding samples shall be kept at -20 oc or   colder, unless more restrictive conditions are required by the competent   Health Authorities. Temperature of all shipments will be monitored using   validated temperature recorders in order to ensure that plasma units and   their corresponding samples have been kept at temperatures according to   specification (S-20°C). Any deviation shall be investigated and approved. In   case of plasma intended for used as raw material in hemoderivate products for   European Market, the warehouse has to be also approved by European Health   Authorities. Quarantine Plasma pool will be ready for fractionation once   completed mtrumum volume needed for processing a production lot and prior   minimum quarantine of 2 or 3 months from collection date for all units   included on it. The quarantine period (2 or 3 months) will be determined   depending on fractionation product destination and it will be controlled by   computer management system. 

    

 

Shelf-life   Source plasma has a shelf-life of 36 months in all manufacturing plants in   which plasma is processed. Plasma must not be older than 30 months when   shipped to Grifols Manufacturing company. For units older than 30 months, it must   be necessary a previous authorization by Qualified person of Grifols   Manufacturing company. 4.4. PLASMA SHIPPING Shipment All carriers used to   transport Source Plasma must be approved by Grifols. The temperature of the   transport trailer must be -25°C or colder prior to loading the plasma   shipment. The shipping procedure has to be designed to keep all plasma units   and samples at -20 oc or colder during the whole transportation process   according to Regulationos of Plasma Origin Country. In addition for plasma   intended for use in hemoderivate products for European market the shipping   procedure has to be in compliance with Ph. Eur. Monography, 'Human Plasma for   Fractionation' Temperature of all shipments will be monitored using validated   temperature recorders, in order to ensure that plasma units and their   corresponding samples have been kept at temperatures according to   specification ( -20°C). Any deviation shall be investigated to analyze cause   and potential impact before to accept and approved plasma involved in it. All   documents and plasma pool samples (if required) shall be sent in advance to   any Grifols manufacturing company for shipment confirmation. For plasma   intended as raw material for use in hemoderivate products for European   market, all carriers used as raw material for used to transport Source Plasma   must be approved by competent European Health Authorities. Identification of   the shipping boxes The plasma Supplier shall identify boxes as following:   -Supplier name. -Shipment number. -Total boxes by shipment. -Box/boxes   (number of order regarding total number of boxes). Label All plasma units   have to be labeled with at least the following information: 1-Supplier name.   2-Product name. 3-Bleed number (code bar). iff·"'' 

    

 

4-Volume or   weight of the unit. 5-Date of collection. 6-Storage temperature. 7-Type and   volume of anticoagulant. 8-Results of viral testing. Bleed Documentation   Bleed documentation must contain the data displayed below: 1-Supplier name.   2-Product name. 3-Bleed number. 4-Donor number. 5-Shipment number or date of   shipment. 6-Date of collection. 7-Test result for each one of the viral   markers tested. The bleed number must be the same, as per numbers, prefixes   and suffixes, in: -The list of donations. -The plasma unit label. -The plasma   unit bar code reading. -The plasma sample label. -The plasma sample bar code   reading. -The Alert notification of the look-back units. 4.5 QUA LITY   ASSURANCE Inspections All plasma Suppliers, as well as laboratories,   warehouses and transport companies, shall inform Grifols of the result of the   inspections of the competent Health Authorities (Europe, other). All plasma   Suppliers laboratories, warehouses and transport companies, may be audited   periodically by Grifols staff or personnel authorized by Grifols. During   these audits all procedures and reports of plasma suppliers, laboratories,   warehouses and transport companies related to collection, processing,   testing, storage, packaging, labelling and shipment of plasma may be   reviewed. Serious incidences Plasma Supplier shall inform within 5 working   days, any serious incidence produced at center, laboratory, and warehouse   facilities and/or during transport process, which may affect the quality and   safety of the provided plasma. Changes Control Plasma Supplier shall inform   any Grifols Manufacturing company of any planned changes that may have an   impact in the quality and safety of plasma during collection, processing,   testing, 

    

 

storage,   packaging, labeling and shipment. Those changes requiring license amendment   from Health Authorities (variations to the approved registry) need prior   written approval of Grifols manufacturing company before their   implementation. Documentation and Records An approved system of documentation   and proper control systems of review and authorization will be established.   Documentation shall be updated annually if necessary. All donor .records   shall be retained by the Supplier for at least 30 years from the date of   collection of the last donation for each donor. If necessary, Grifols and   plasma Supplier will agree on additional donor records, health information,   donor questionnaires, donor number and testing if requested by competent   Health Authorities. All donor testing records shall be retained by the   supplier for at least 30 years from the date of the shipment of each unit to   Grifols. Plasma Supplier will provide upon request by Grifols copies of   documents related to collection, receipt, storage, handling and distribution   of products (i.e. recorder temperatures, maintenance records, etc...) Plasma   Supplier will keep updated and available upon request by Grifols, documents   such as SMF (Site Master File), map and flows, chart, equipment and process   validation and any other production documents that ensure the quality and   safety of plasma. Plasma Supplier will provide annually -or upon request by   Grifols-the necessary documentation to keep updated the Plasma Master File.   Training and qualified personnel There should be a sufficient number of   qualified personnel and Center shall provide training in accordance with an   approved program. Initial and continuing training will be performed and   effectiveness assessed. Training records shall be kept for all personnel. Premises   and Equipment (qualification and maintenance). Materials Equipment, systems,   premises and instruments shall be qualified or validated before use or after   any relevant change. Related qualification and validation documentation shall   be reviewed and approved. A calibration program and preventive maintenance   program for equipment and instruments shall be established. Critical   materials shall come from approved Suppliers that meet the documented   requirements and specifications. 4.6.PLASMA RELEASE Plasma units release:   Certificate of Compliance The Supplier shall only release plasma units to its   delivery to any Grifols manufacturing company as long as the Responsible   Person states in a Certificate of Compliance that: Page 21 of 29 

    

 

• All source   plasma units fulfill the requirements and Source Plasma Specifications in   accordance with the Quality Agreement in force. • All plasma units of the   shipment have been tested and found non-reactive for viral markers,   specifying the test kits and/or reagents used in each case for: o HBsAg,   anti-HIV 1/2, anti-HCV, tested in individual units o Luetic serology,   initially tested and every 4 months o Indirect Coombs, initially tested and   at least every 3 months o HAV-RNA, HBV-DNA, HCV-RNA, HIV-RNA and Parvovirus   B19-DNA, tested by means of pools consisting of not more than 512 individual   units. • All collection, processing, testing, quality control records review,   storage, packing and labeling operations have been performed under current   Good Manufacturing Practices, The certificate must be issued by the   Responsible Person of the Plasma Supplier. The Supplier will provide Grifols   with a list of names of the Responsible Persons and authorized designees and   their corresponding signatures and responsibilities. 

    

 

ATTACHMENT 4   TEST KITS FOR EIA/NAT TEST KITS FOR EIAINAT Viral Marker Test Kits of   Individual Donors Re1dstration Number 00011 00021 00079 NAT: Name of test   Analytical Technique . - NAT-HCV N T-HIV NAT-HE!_V NAT-HAV NAT-PVB19 TaqMan   Real-Time Multiplex RT­ PCR Cobas MPX-Test for cobas 6800/8800 TaqMan   Real-Time Duplex RT-PCR Cobas DPX-Test for cobas 6800/8800 Test kit   Manufacturer Roche Diagnostics GmbH EC-Mark: yes 23of29 Parameter Test   Method/ Name of the Test Kit Manufacturer License I Establishment Anti-HCV   ChLWABBOTI PRISM HCV) Abbott Laboratories 0088/0964174/00012 HIV-p24-Antigen,   Anti-HIV-I+ Anti-HIV-2 ChLWABBOTI Prism HlV A'i/ Ab Combo Abbott Laboratories   0088/0964174/ 00074 HBsAg ChLWABBOTI PRISM HBsAg Abbott Laboratories 0088/0964   I 74/ Anti-HCV ChLWARCHITEcr Anti-HCV Reagent Ki Abbott Laboratories   0088/0964174/ H!V-p24-Antigen, Anti-H!V-1 +Anti-HIV-2 ChLWARCHITEcr HIV   A'i/Ab Combo ReagentKit Abbott Laboratories 0088/0964174/ HBsAg ChLWARCHITEcr   HBsAg Qualitative II Abbott Laboratories CE0843 

    

 

ATTACHMENT 5   TABLE OF RESPONSIBILITIES Summary Table and Division of Quality   Responsibilities of PLASMA SUPLIERIMANUFACTURER 1.1. The responsible Party is   denoted by X DESCRIPTION PLASMA SUPPLIER MANUFACTURER 1 GENERAL PROVISIONS   Negotiate the Quality Agreement X X Notification of change in reporting   relationship involving Contact Persons X X Assure that Plasma obtained from   Source Plasma (Human) collection centers from Haema meet all the requirements   stipulated in this Agreement and the MANUFACTURER Specifications X   Responsible for the handling, storage, and transport of intennediates pastes   and plasma that is contracted to the MANUFACTURER in accordance with the   tenns and conditions set forth in this Agreement, the applicable   regulationsand the MANUFACTURER Specifications X Approve any new contract or   third party Suppliers of Plasma X X 2 QUALITY AND TECHNICAL REQUIREMENTS   Collect, process, test, store, package, label, release Plasma in accordance   with MANUFACTURER Specifications X ship Plasma in accordance with   MANUFACTURER Specifications X QUALITY CONTROL Arrange testing lor each donor   of plasma in accordance with MANUFACTURER Specifications, as well as   applicable regulations X Ensure all laboratories are in compliance wilh cGMP   and are qualified in all the methodologies associated with Plasma and the   Premises X Perform testing and analysis of the Plasma in approved   laboratories using licensed kits included in the EU Plasma Master File if   plasma is intended for EU X 

    

 

age 25 of29   DESCRIPTION PLASMA SUPPLIER MANUFACTURER SUBCONTRACTING OPERATIONS Agree in   writing on any contracted service (i.e., storage, testing) to be completed by   third party per the MANUFACTURER Specifications X X Perform audits of third   party contractors X X Provide a written report to MANUFACTURER confirming   that the Plasma units have been collected, tested, shipped and stored   properly and meet the requirements of the MANUFACTURER Specifications X   Ensure all sites or services used are in compliance with cGMP and are   qualified in all of the methodologies associated with Plasma and the   Premises. X X TRACEABILITY AND LOOK BACK COMMUNICATION (POST-DONATION   COLLECTION INFORMATION Communicate to MANUFACTURER in writing within 5   calendar days all information per this Agreement on a donor after a donation   that fulfilled all MANUFACTURER Specifications is rejected for seroconversion   or post donation information that may become an infectious disease   (Notifications per the MANUFACTURER Specifications) X Notify the MANUFACTURER   no later than 5 calendar days of discovery of significant deviations that may   impact batches or Plasma previously released and/or shipped to the   MANUFACTURER. X Supply a report prior to product release on all post donation   notifications received after pooling so that the MANUFACTURER can perform a   viral risk assessment on the product X CHANGE CONTROL Notify MANUFACTURER in   advance of any planned changes reasonably foreseeable to affect the   regulatory submissions to regulatory authorities including EU Plasma Master   File variations and/or available supply of the Plasma-Obtain written approval   from MANUFACTURER prior to the implementation of such changes and any other   change that are covered by the change control scope of this Agreement that   could have any effect on the safety, purity, etc. of the Plasma collected X   Provide justification for the changes and validate any changes to cGMP   standards X Provide written approval for change controls per this Agreement X   

    

 

DESCRIPTION PLASMA   SUPPLIER MANUFACTURER QUALITY ASSURANCE Maintain an active quality management   system, which shall apply to all operations which may impact on the quality   and safety of the Plasma X Document and investigate deviations from the   processes and procedures per this Agreement and notify MANUFACTURER as soon   as possible before shipment or in no case later than 5 calendar days of   discovery that a deviation may impact a batch or Plasma previously released   and/or shipped X Approve the use of materials for the collection of Plasma;   confirm the proper condition of the packaging, sterility certification,   locks/seals, shipping documentation; ensure that each lot is in full   compliance with licensed requirements and with applicable regulations X   Approve all vendors and Suppliers of critical raw materials, reagents and   components used in the collection and testing of Plasma; Ensure materials are   received, stored, segregated and used correctly and all materials are   appropriate for their intended use;Maintain relevant certificates of   analysis, certificates of compliance, certificates of origin for such   materials, as appropriate; Maintain an approved vendor list X STORAGE AND   SHIPPING Provide storage conditions for the Plasma that meets the agreed upon   MANUFACTURER Specifications, SOPs, applicable regulations related to Plasma   storage and the EP monograph-Human Plasma to Fractionation X Maintain proper   segregation of the Plasma units X Provide quality assurance oversight of   unreleased Plasma received into quarantine and stored in a controlled,   validated warehouse X Provide quality assurance oversight to segregate,   identify and disposition rejected plasma X BIOLOGICAL PRODUCT DEVIATIONS AND   RECALLS Monitor the manufacturing and release data of the Plasma to detect   potentially reportable deviations within 5 business day of confirmation X   Plasma unit deviation reporting to the appropriate regulatory authorities X   Biological product deviation reporting to the appropriate regulatory   authorities X X 

    

 

Page 27of29   DESCRIPTION PLASMA SUPPLIER MANUFACTURER Perform investigations for any   issues thought to be Plasma unit based and provide information to   MANUFACTURER X Responsible for Plasma unit recall or withdrawal; Provide   notification to MANUFACTURER within 5 business day of confinmation and   perfonm investigations for these problems and forward investigation report to   MANUFACTURER within mutually agreeable timeframe X Responsible for final   product or intermediate product recall or withdrawal X EQUIPMENT, COMPUTER AND   FACILITY VALIDATION AND/OR QUALIFICATION PROCESS Ensure all processes,   equipment, systems and facilities are qualified and validated, as applicable,   per this Agreement X Approve all process qualifications appUcabte to the   Plasma collection, including but not limited to, the freezer validation and   Haema-shipping validation for test samples and Plasma X Approve all process   qualiffcaUons applicable to the Plasma shipping validation for test samples   and Plasma X PLASMA RELEASE Have at least one Qualified Person on the   Premises to oversee the quality aspects of the Plasma collection, testing,   shipment and evaluate deviations, In order to ensure compliance with cGMP;   the Responsible Person will certify that .each unit of Plasma has been   collected and tested In approved facilities according to GMP and fulfil   quality and safety requirements according to the MANUFACTURER Specifications   X 3 LICENSES, PERMITS AND APPROVALS Represents and warrants that all their   plasmapheresis donor centers in operation are currently certified under the   PPTA IQPP; such certification must be preserved without interruption during   the tenm of this Agreement; if plasmapheresis donor center fails to remain   certified, notification to MANUFACTURER immediately, or within five business   dav X Follow al requirements and specifications for exporting products to   Europe X Notify MANUFACTURER within five business day in the event of a   suspension, revocation or other administrative action adversely affecting or   limiting license, permit or approval X Provide prior writlen notification to   MANUFACTURER prior to relocating, opening or closing a plasmapheresis center;   Obtain wrillen approval from MANUFACTURER for indusion of new centers,   testing laboratories,plasma warehouses and transportation companies X 

    

 

DESCRIPTION   PLASMA SUPPLIER MANUFACTURER 4 INSPECTIONS Audit and qualify all vendors of   supplies used in the collection and shipment of Plasma X Handle complaints to   the vendor of supplies X Allow the MANUFACTURER to conduct annual inspections   of the approved plasmapheresis donor collection centers, testing   laboratories, plasma warehouse storage facilities X Responsible for the   ultimate approval of all Plasma centers and their status as approved or not   approved to ship Plasma to the MANUFACTURER X Provide written report to   MANUFACTURER within 30 days of the audit date X Ensure that all the   corrective actions are implemented and provide a report to the MANUFACTURER X   Provide written notice to MANUFACTURER of any investigations of the donor   centers, testing laboratorieS, storage, release and shipping   facilities/companies with no more than 10 business days of the   investiaation's commencement X Communicate to MANUFACTURER within 5 business   day any event or serious failure of a center, testing laboratory, storage   and/or transportation which may impact quality or safety of the Plasma   supplied X Notify MANUFACTURER of any meetings/substantive discussions with   regulatory authorities that directly relate to the manufacture, supply and/or   control of the Plasma supplied X 

    

 

DESCRIPTION   PLASMA SUPPLIER MANUFACTURER 5DOCUMENTATION AND RECORD RETENTION Responsible   for preparing and submitting regulatory submissions linked to the process and   final product as required by applicable regulations X Provide all the   documentation requested to support regulatory submissions, annual update for   the EU Plasma Master File, epidemiology date/viral marker data X Keep   complete and accurate records of equipment usage, cleaning, testing,   temperature holds, and any maintenance/calibration performed, per this   Agreeement X Retain donor records per applicable regulations and per this   Agreement X 

    

 

QUALITY   AGREEMENT SOURCE PLASMA INTENDED FOR THE MANUFACTURE OF MEDICINAL PRODUCTS   FOR HUMAN USE This Quality Agreement ("Agreement") is part of the   Services Agreement dated 28-December-2018 by and between Grifols Worldwide   Operations, Ltd. ("MANUFACTURER"} with its principal place of   business at Grange Castle Business Park, Grange Castle, Clondalkin, Dublin   22, Ireland, and Biotest Pharmaceuticals Corporation with its principal place   of business at 901 Yamato Road, Suite 101 Boca Raton, FL 33431-4409, USA ("PLASMA   SUPPLIER"} and collectively "parties or Parties"}. The term of   this Agreement commenced on the date set forth above (the "Effective   Date") of signature of the Services Agreement. This Agreement document   will be updated due to the continuous evolution of standards of quality and   safety for the collection, testing, processing, storage and distribution of   human plasma. Appendices to this Agreement may be revised without revision to   this Agreement as long as appropriate approvals and proper signatures according   controlled documentation systems for both parties are in place. 1. GENERAL   PROVISIONS 1} MANUFACTURER is a company that manufactures medicinalproducts   or intermediate fractions for further processing derived from human plasma   and uses as starting material/raw material (hereinafter "Source   Plasma"). 2) In connection with its medicinal products business,   MANUFACTURER desires to obtain, and PLASMA SUPPLIER desires to provide,   Source Plasma (including hyperimmune plasma) solely in accordance with the terms   and conditions set forth in this Agreement covering the technical and quality   requirements of Source Plasma as a raw material for further manufacturing at   MANUFACTURER. Source Plasma is obtained and manufactured by PLASMA SUPPLIER   from Health Authority Licensed Plasma (Human) collection centers PLASMA   SUPPLIER may also supply MANUFACTURER with Source Plasma obtained from other   approved suppliers (contract and third party). PLASMA SUPPLIER is responsible   for the assurance that the Source Plasma obtained from these suppliers   (including centers, laboratory test, storage facilities or transport/transit   companies) meets all of the requirements stipulated in this Agreement and   MANUFACTURER Specifications. A detailed Jist of centers, laboratories,   storage facilities and transport/transit companies can be found on ATTACHMENT   1. 3) PLASMA SUPPLIER agrees that all plasma ("Plasma") derived   from Source Plasma supplied to MANUFACTURER as starting material to produce   medicinal products for human use hereunder meet the following requirements,   specifications and conditions. 

    

 

2. QUALITY AND   TECHNICAL REQUIREMENTS 1) All Plasma supplied by PLASMA SUPPLIER under this   Agreement must be derived from Source Plasma collected at plasma collection   centers approved by competent authorities that have all necessary and   regulatory approvals and permits. All Plasma supplied by PLASMA SUPPLIER   under this Agreement must be collected, processed, tested, stored, packaged,   labeled, released and shipped in compliance with all applicable sections of   the origin Country Regulation, including without limitation current Good   Manufacturing Practices ("cGMP"). A list of relevant regulations   can be found on ATTACHMENT 2. 2) PLASMA SUPPLIER shall collect, process, test,   store, package, label, release and ship the Plasma in accordance with   MANUFACTURER Plasma Specifications ("MANUFACTURER Specifications").   A copy of the MANUFACTURER Specifications can be found on ATTACHMENT 3.   PLASMA SUPPLIER hereby acknowledges receipt of a copy of MANUFACTURER   Specifications and Shipping instructions, which are incorporated herein by   reference as though fully set forth herein. These may be amended from time to   time by MANUFACTURER or by updates due to new Quality or Regulatory   requirements made by an appropriate governmental agency during the term of   this Agreement, and upon receipt thereof, PLASMA SUPPLIER shall jointly   review with MANUFACTURER, be in agreement and approve any such amendments   with regard to updated Quality or Regulatory Requirements and such approval   of the amendments shall not be unreasonably withheld or delayed. 3) Plasma   collection centers will screen all donors to ensure that each of them is   under good health conditions and that plasma is not collected from a high   risk population for blood-borne infections. Therefore, plasma centers with an   active High Risk Donor collection program (donors known to be positive for   HIV, HCV or HBV at the time of collection) will not be accepted by   MANUFACTURER. 4) Plasma is for further manufacture use only and is not to be   represented as suitable for use as a finished human drug. 5) The MANUFACTURER   Specifications may be changed and/or modified by MANUFACTURER requirements in   order to comply with any new legislation in force and/or new controls or test   methods which are available in order to obtain the safest Plasma as possible.   6) PLASMA SUPPLIER, agrees to maintain regular plasma configuration to not   alter the configuration of the normal donor panelpopulation as starting   materialfor all plasma-derived products without MANUFACTURER approval. Units   from donors that have participated in a hyperimmune program cannot be used as   Source Plasma without prior kno,wledge of the MANUFACTURER to avoid cluster   c1f units going to same plasma pool. Plasma is for further manufacture use   only and is not to be represented as suitable for use as a finished human   drug. Quality Control 7) PLASMA SUPPLIER agrees to arrange testing for each   donor of plasma in accordance with MANUFACTURER Specifications, as well as NationalRegulations,   applicable European Directive, as well as any other applicable federal,   state, and local or foreign competent authorities, governmental agencies   regulations concerning donor tesling, and agrees to furnish test results of   all such tests to MANUFACTURER in an agreed certificate format when required.   Both parties shall ensure that all laboratories used are in compliance with   cGMP and are qualified in all of the methodologies associated with plasma   testing. All testing laboratories used to test Plasma supplied must be on the   approved laboratory list as per Attachment 1. All testing methods must be   validated and fulfil adequate levels of sensitivity and specificity according   to their intended use, fulfilling all regulations in force. All validations,   including protocols, reports and documentation shall be approved by the   quality assurance function of the laboratory. 

    

 

Tests and   analysis of the Plasma shall be done in a laboratory approved by PLASMA   SUPPLIER using licensed kits. ATTACHMENT 4 includes a list of approved test   kits and validated NAT platforms. Plasma testing shall be performed according   to test kit manufacturer instructions. Submission of plasma samples to   testing laboratories for any testing will be compliant with written   procedures for submission of such samples. This includes, but is not limited   to: use of approved containers and shippers, procedures for handling and   shipping of samples, and the preparation and submission of appropriate   documentation with samples. The laboratories shall be responsible to notify   the centers of any paperwork or samples received that do not conform to the   requirements for sample paperwork, sample labeling and sample shipping. 8)   Each unit of Plasma must meet the quality control specifications and the   claimed and approved shelf-life for the Plasma at the maximum approved   storage temperature as stated in the labeling specified in the MANUFACTURER   Specifications. Subcontracted Operations 9) PLASMA SUPPLIER and MANUFACTURER   shall jointly agree in writing on any contracted service (i.e., donor center   collection, plasma storage, shipping, testing) to be completed by any third   party per the MANUFACTURER Specifications. MANUFACTURER will have the right   to audit any such facility and may jointly audit with the PLASMA SUPPLIER's   auditors. PLASMA SUPPLIER will provide a written report to MANUFACTURER   confirming that the Plasma units have been collected, tested, shipped and   stored properly and meet the requirements of the MANUFACTURER Specifications.   Both parties shall ensure that all sites or services used are in compliance   with cGMP and are qualified in all of the methodologies associated with   plasma handling and its premises. All contract sites used for the collection,   transport, testing or storage of the Plasma supplied must be on   MANUFACTURER's approved suppliers list. The contracted sites must show that   methods are validated fulfilling regulations in force. All validations,   including protocols, reports and documentation shall be approved by the   quality assurance function of the third party organization. Any contracted   organization must be approved and listed on ATTACHMENT 1 and testing must   comply with ATTACHMENT 4. Traceability and Look-Back Communication   {Post-Collection Information) 10) PLASMA SUPPLIER shall communicate to   MANUFACTURER in writing within three (3) calendar days all information on a   donor after a donation that fulfilled all MANUFACTURER Specifications is   rejected for seroconversion, CJD/nvCJD or post donation information that may   become an infectious disease. Notification instructions and required   notification information are detailed in MANUFACTURER Specifications   (traceability requirements and look back). Pl.ASMA SUPPLIER will notify   MANUFACTURER as soon as practicable and in no case later than three (3)   calendar days of discovery of significant deviations that may impact batch(s)   or Plasma previously released and/or shipped to MANUFACTURER. 11) PLASMA   SUPPLIER shall supply to the MANUFACTURER a report prior to product release on   all post donation notifications received after pooling so that the   MANUFACTURER can perform a viral risk assessment on the product. Change   Control 12) All changes shall undergo a technical and cGMP impact assessment.   PLASMA SUPPLIER will notify MANUFACTURER in advance of any planned changes   reasonably foreseeable to affect the regulatory submissions to the Health   Authorities involved. PLASMA SUPPLIER will have responsibility for providing   justification for the changes and validating (when appropriate) any such   changes to cGMP standards. Change control procedures will include a   requirement for PLASMA SUPPLIER to obtain written approval from MANUFACTURER   prior to the implementation of any change reasonably foreseeable to affect   any regulatory submission, and any other change to 

    

 

parameters that   are covered by the change control scope that could have an effect on the   safety, purity, etc. of the Plasma collected. The scope of the change   management process includes collecting, testing, labeling, storage and   shipping processes of Plasma, as well as intermediate fractions, storage and   shipping. The associated changes may relate to: the master batch records,   bill of materials, analytical standards, test methods and Specifications; and   any changes to validated facilities, utilities, computer systems, equipment   or processes used in the cleaning, manufacturing, testing, storage or   shipment with respect to Plasma. MANUFACTURER Source Plasma Specifications   may be changed and/or modified by MANUFACTURER as required in order to comply   with current European requirements. MANUFACTURER shall submit all proposed   revisions to the Specifications to PLASMA SUPPLIER for review and approval,   which cannot be unreasonably withheld. MANUFACTURER shall advise PLASMA   SUPPLIER of all proposed revisions to the Specifications as promptly as   practicable so as to provide PLASMA SUPPLIER with as much notice as possible.   PLASMA SUPPLIER shall have thirty (30) business days to agree to implement or   otherwise respond to MANUFACTURER proposed revisions to the Specifications.   PLASMA SUPPLIER response shall, if applicable, state PLASMA SUPPLIER reasons   (which shall be commercially reasonable) for refusing to implement such   revisions. PLASMA SUPPLIER and MANUFACTURER shall attempt in good faith to   resolve any disputes as to the implementation of any requested revisions.   Timeline for implementation of the change will be agreed by both companies.   Quality Assurance 13) PLASMA SUPPLIER shall have a quality management system   that ensures all critical processes involved in collection, processing,   packaging, labelling, testing, storage, release and transportation are   conducted in adequate facilities and according to current GMP principles as   well as current legislation. PLASMA SUPPLIER shall maintain an active quality   management system which at least shall review deviations and trends, ensure   appropriate training of personnel, conduct internal audits on a periodic   basis, with a follow up of deviations with a CAPA program and a change control   system in force. The quality system shall apply to all operations which may   impact on quality and safety of Plasma, from donor selection to Plasma   delivery to the MANUFACTURER. 14) PLASMA SUPPLIER shall be responsible for   creating the manufacturing and testing master documentation specific to   Plasma collection. It shall be responsible for creating and maintaining at   the Premises all standard operating procedures ("SOPs") and other   documentation required to support cGMP operations. 15) Any deviation from the   process and SOPs during Plasma collection, storage or testing must be   appropriately explained, investigated, documented and approved in the batch   records or analytical records. The deviation documentation must identify the   cause and the corrective action, where appropriate, and must assess the   impact to the Plasma donor's safety, and Plasma's quality. PLASMA SUPPLIER   shall develop appropriate procedures for deviation investigations. PLASMA   SUPPLIER will notify MANUFACTURER as soon as practicable before shipment or   in no case later than three (3) calendar days of discovery that may impact   batch(s) or Plasma previously released and/or shipped. 16) PLASMA SUPPLIER   shall ensure that adequate trained and qualified staff is conducting the   activities with a clear description of staff responsibilities. Training must   be conducted according to an approved training program. Initial and   continuous training shall be pertormed as well as proper staff competency   follow-up. Training records shall be retained and available for review. 17)   Materials to be used in the collection of Plasma shall be approved in   accordance with applicable legal requirements for Plasma collection. Upon   receipt of such materials, PLASMA SUPPLIER shall confirm the proper condition   of packaging, sterility certification, locks and seals and check that labels   correspond with the shipping documents. PLASMA SUPPLIER shall implement an   appropriate system to maintain certification of materials and chemicals used   in the collection and testing of Plasma. For those specified materials of   animal origin, if any, PLASMA SUPPLIER 

    

 

shall assure   each lot is in full compliance with licensed requirements, with National   regulations and final approved by MANUFACTURER. 18) PLA.SMA SUPPLIER shall   approve all vendors and suppliers of critical raw materials, reagents and   components used in the collection and testing of Plasma and shall maintain an   approved supplier list. PLASMA SUPPLIER shall ensure that all materials are   received, stored, segregated and used correctly, and all materials are   appropriate for their intended use. It also shall ensure appropriate   separation and/or segregation of any materials that may present a potential   hazard to the materials used in the production of Plasma units. PLASMA   SUPPLIER shall be responsible for maintaining the relevant certificate of   analysis, certificate of compliance and/or certification of origin (as   appropriate) for the materials. Storage and Shipping 19) Storage and shipment   of Plasma supplied by PLASMA SUPPLIER under this Agreement must be conducted   in approved facilities that have all necessary and regulatory approvals.   Storage facilities and shipping process must be properly validated. 20)   Plasma must be frozen within twenty-four (24) hours of collection by cooling   rapidly in conditions validated to ensure that a temperature of -25°C or   below is attained at the core of each Plasma unit within twelve (12) hours of   placing in the freezer apparatus. Plasma must be stored at -20°C or lower.   Freezing, storage and shipping must be done according to WHO recommendations.   21) PLASMA SUPPLIER shall provide sufficient and suitable storage facilities   that meet the storage specifications for Plasma units, as documented and   agreed upon in the MANUFACTURER Specification, SOPs, applicable regulations   related to Plasma storage, National Regulations for-Human Plasma for   Fractionation. Any off-site Plasma storage facilities used must be approved   by PLASMA SUPPLIER quality assurance and meet the same requirements. Mobile   storage facilities shall only be used short term for emergency situations and   must be appropriately validated to maintain correct temperatures. It shall be   ensured that during storage of Plasma before shipping the plasma has been   properly packaged and protected to avoid deterioration, interference, theft,   product contamination or mixture with any other materials. PLA.SMA SUPPLIER   will maintain proper segregation of the Plasma units. Details of any labeling   requirements and shipping container sealing and integrity will be documented.   The Plasma units shall be suitably packaged for transit, with each outer   container being labeled as per written procedures. 22) Unreleased Plasma that   is shipped to a PLASMA SUPPLIER quarantine location at the authorized plasma   warehouse will be stored in a physically segregated area in a controlled,   validated warehouse. Oversight of that area and the Plasma contained therein   is the responsibility of PLASMA SUPPLIER quality assurance organization. Such   unreleasedPlasma must be controlled by standard operating procedures,   including appropriate labeling and electronic material status. Such   procedures will govern post unit donation removal, temperature deviation   reporting requirements, unit and lot traceability, employee access and   training, release of Plasma and final transfer to MANUFACTURER, regulatory   filings and other such notifications and regulatory requirements not   specifically covered by this Agreement whenever applicable. 23) Rejected   Plasma must be properly segregated, identified and dispositioned under   quality assurance control. Biol ogical Product Deviations and Recalls 24)   PLASMA SUPPLIER shall be responsible for monitoring the manufacturing and   release data of the Plasma and if detects a potentially reportable deviation,   as applicable to Plasma sent to MANUFACTURER, this should be reported and   discussed with MANUFACTURER within one (1) business day of confirmation.   PLASMA SUPPLIER is responsible for Plasma unit deviation reporting to the   appropriate regulatory authorities. Page 5 of29 -----·--- 

    

 

25)   MANUFACTURER, as the medicinal product license holder, shall be responsible   for reporting deviations pertaining to biological products to the regulatory   authorities. PLASMA SUPPLIER will work collaboratively with MANUFACTURER on   filing any such report thought to be due to the collection of Plasma. PLASMA   SUPPLIER will promptly perform investigations for any issues that are thought   to be Plasma unit based. Both parties shall collaborate in the development of   the global reporting regulatory strategy for the event. PLASMA SUPPLIER shall   provide necessary information to MANUFACTURER if it receives a warning   letter, significant regulatory observation or BPDR follow up question(s). 26)   PLASMA SUPPLIER is responsible for Plasma unit recall or withdrawal per the   applicable regulations. MANUFACTURER shall be notified of any recall and of   any problems thought to be due to Plasma quality within one (1) business day   of confirmation. When requested by MANUFACTURER, PLASMA SUPPLIER will perform   investigations for these problems. Investigation reports regarding the defect   or cause of recall will be forwarded to MANUFACTURER within a mutually   agreeable timeframe. MANUFACTURER is responsible for any final product or   intermediate product recall or withdrawal for those products that are   manufactured. Equipment. Computer and Facility Validation and/or   Qualification Process 27) PLASMA SUPPLIER shall ensure that all process,   equipment, systems and facilities are qualified and validated if applicable   prior its use and after any significant change to ensure that processes are   capable of consistently achieving the Plasma specifications. Documentation   must be reviewed and approved. Calibration and preventive maintenance   programs shall be established for equipment. It will maintain cGMP validation   status of process procedures, computers and associated equipment with respect   to the manufacturing, storage and shipping procedures that are used in   connection with Plasma. PLASMA SUPPLIER shall be responsible for all   equipment, computer and facility qualification activities associated with the   Plasma collection, storage and shipment. Validations must meet National   Regulations and further approved by MANUFACTURER, as applicable and will   promptly, upon request by MANUFACTURER, make validation reports available for   review. PLASMA SUPPLIER shall develop procedures and implementation plans to   assure that all computer systems and software are compliant with required   Regulations. 28) PLASMA SUPPLIER will approve all process qualifications   applicable to the Plasma collection, including, but not limited to, the   freezer validation and shipping validation for test samples and Plasma.   PLASMA SUPPLIER will provide copies of validation reports upon request.   Validation reports may also be requested as part of an audit or an event   review. Plasma Release 29) PLASMA SUPPLIER collection centers and third party   suppliers shall all have at least one quality Responsible person on the   Premises to oversee the quality aspects of the Plasma collection, testing,   shipment, evaluate deviations, etc., in order to assure compliance with   cGMPs. 30) PLASMA SUPPLIER has designated a person for plasma release for   further manufacturing of medicinal products in accordance with applicable   regulations PLASMA SUPPLIER and its suppliers shall release units by means of   a corporate Responsible Person who will document and certify that each unit   of Plasma has been collected and tested in approved facilities according to   GMP and that the units fulfil quality and safety requirements of the   MANUFACTURER Specifications. The Responsible Person and designee are named in   this Agreement as the individuals authorised to release Plasma units. 3.   LICENSES. PERMITS AND APPROVALS 1. All Plasma supplied by PLASMA SUPPLIER   under this Agreement must be derived from Plasma collected at an approved   plasma collection center located in XXXXXX that has all necessary and   regulatory approvals and permits.,. The plasma collection center(s) under   this Agreement are set forth on AITACHMENT 1. ag' e 6 of 29 

    

 

2. PlASMA   SUPPLIER represents and warrants that all their plasmapheresis donor centers   in operation are certified under the Plasma Protein Therapeutics   Association's International Quality Plasma Program ("PPTA IQPP").   PlASMA SUPPLIER must preserve these certifications without interruption for   the remaining term of this Agreement. If PlASMA SUPPLIER fails to maintain   such plasmapheresis donor centers certifications, then MANUFACTURER has to be   immediately notified within one (1) business day to evaluate actions to be   taken. 3. PlASMA SUPPLIER agrees to follow the mutually agreed upon   MANUFACTURER Specifications and all other requirements or specifications   issued in writing by MANUFACTURER, and any versions to those procedures,   requirements or specifications as they may be issued or adopted by MANUFACTURER   and agreed upon by PlASMA SUPPLIER, as approved by appropriate governmental   regulatory agency or competent authority, if such approval is mandated by law   or required by MANUFACTURER. 4. In the event of a suspension, revocation, or   other administrative action adversely affecting or limiting any such license,   permit or approval, MANUFACTURER shall be immediately notified within one (1)   business day to take necessary actions. 5. PlASMA SUPPLIER may not relocate,   open or close any plasmapheresis collection centers, testing laboratories or   plasma storage facilities without prior written notification to the   MANUFACTURER. Written approval by MANUFACTURER is required for inclusion of   new centers, testing laboratories, plasma warehouses and transportation companies,   which shall not be unreasonably withheld. 4. INSPECTIONS 1. Collection and   storage of the Plasma shall be conducted in a suitable controlled environment   and such Premises shall be regularly inspected and monitored to ensure   compliance with cGMP, and other applicable manufacturing authorizations. 2.   PlASMA SUPPLIER will be responsible for qualification and auditing of all   vendors of supplies used in the collection and shipment of Plasma. All   suppliers must appear on the PlASMA SUPPLIER approved supplier list. PlASMA   SUPPLIER is responsible for handling complaints to the vendor for supplies   and the interaction with the vendor to resolve those complaints. 3.   MANUFACTURER shall have the right to conduct periodic audits of the approved   plasmapheresis donor collection centers, testing laboratories,   Corporate.Quality Management Systems, plasma warehouse storage facilities   and/or transport/transit and shipping companies and to review all procedures   and records kept by such facilities related the collection, processing,   testing, storage, packaging, labeling, release and shipping of plasma as well   as all operations conducted in conformance with generally accepted industry   practice. These audits may be done as joint audits with PlASMA SUPPLIER, at   the discretion of the MANUFACTURER. MANUFACTURER will provide PlASMA SUPPLIER   with not less than thirty (30) days' notice prior to any of its audits,   unless agreed otherwise by the Parties, and such audits shall be during   normal business hours, shall be limited to matters reasonably related to this   Quality Agreement, and shall be conducted in conformance with generally   accepted cGMP. No audit shall continue in duration for more than three (3)   business days unless such an extension is reasonably necessary. A maximum of   three (3) auditors shall participate in any inspection unless otherwise   agreed between PlASMA SUPPLIER and MANUFACTURER. Such audits shall occur   periodically (at least, every two years) for facilities having an acceptable   inspection I audit history unless otherwise necessary to inspect or audit as   a result of requirements by regulatory authorities or a serious failure or   material concern that either impacts or threatens to impact quality, safety,   potency, or compliance with this Quality Agreement. In the event of such   additional audit(s), MANUFACTURER shall provide PLASMA SUPPLIER reasonable   written notice of its intent to conduct such additional audit(s). Page 7 of   29 

    

 

 

MANUFACTURER   maintains the right to event reviews (directed audit), in addition to   periodic audits, to address significant quality, performance or safety   problems associated with the products. These events should be requested,   scheduled and conducted at the first available date. 4. PLASMA SUPPLIER shall   be entitled to perform at least one (1) standard cGMP compliance audit every   year of the above facilities to encompass all cGMP operations (testing   laboratories, plasma warehouses, transport companies, corporate offices). 5.   PLASMA SUPPLIER Compliance Audit Team will provide a written report to   MANUFACTURER of all observations. Within thirty (30) days of the audit date,   PLASMA SUPPLIER will coordinate to provide a written response to all findings   that details corrective action to be implemented. PLASMA SUPPLIER will ensure   that all corrective actions are implemented and provide a report to   MANUFACTURER upon implementation. In those instances,. where corrective   action will require an extended period to implement, PLASMA SUPPLIER shall   provide reports to MANUFACTURER on the progress of such corrective action at   such intervals as mutually agreed upon by the parties. 6. MANUFACTURER shall   have also the right to cause any authorized representative of the Public Health   Service, any state, local, foreign competent regulatory authorities and   governmental agencies, and any authorized third party as deemed necessary or   desirable to carry out its business worldwide, to conduct periodic   inspections of the approved plasmapheresis donor collection centers, testing   laboratories, plasma warehouse storage facilities andfor transportftransit   and shipping companies and to review all procedures and all records kept by   such donor centers or such testing laboratories regarding the collection,   processing, testing, storage, packaging, labeling, release and shipping of   Plasma, and all operations conducted in conformance with generally accepted   industry practices. MANUFACTURER shall have the right to make and retain   copies of all such procedures and records kept by donor centers, as well as   copies of all correspondence between donor centers and any governmental   regulatory agencies regarding any such inspections. 7. MANUFACTURER will be   responsible for ultimate approval of all Plasma centers and their status as   approved or not approved to ship plasma to the MANUFACTURER. The information   will be contained in the MANUFACTURER's list of approved plasma suppliers and   the types of Plasma the center is approved to collect. 8. PLASMA SUPPLIER   agrees to send MANUFACTURER written notice of any federal, state or local   government for cause audit or relevant investigation of the donor centers,   testing laboratories, storage, releae and shipping facilitiesfcompanies with   no more than three (3) business day of the investigation's commencement. 9.   PLASMA SUPPLIER agrees to communicate to MANUFACTURER within ten (10)   business days of discovery of critical event (failure of a plasma collection   center, storage facility, testing laboratory andfor transportation which may   impact quality or safety of the Plasma supplied 10. PLASMA SUPPLIER will   notify MANUFACTURER in a timely manner of any meetings or substantive   discussions with r any other regulatory authority that directly relate to the   manufacture, supply and/or control of Plasma supplied. 11. PLASMA SUPPLIER   shall provide to MANUFACTURER within ten (10) business days any information   of the following: (i) Update of critical findings related to the inspection   performed, (ii) Notice of Intent to Revoke License Letter, (iii) License   Suspension Letter, (iv) Seizure action regarding Corporate Offices, plasma   collection centers, storage facilities, or testing laboratories. 12. On a   quarterly basis, PLASMA SUPPLIER shall provide MANUFACTURER, a summary of   regulatory national authority inspections of any plasma collection centers,   testing laboratories, storage facilities, and corporate offices, included on   Attachment 1 of this Quality Agreement. This summary shall include   information concerning inspections of National health authority. This summary   will also include a list of critical observations and an overall evaluation   of the regulatory inspections outcome including: 

    

 

•   Identification of the facility • Identification of inspection date • Category   (#of Minor, Major, Critical) • Result: pass/not pass • Kind of Deficiencies   (for example: Documentation, Storage, etc.). 13. In the event that during an   inspection by MANUFACTURER (or PLASMA SUPPLIER as designee),   self-notification to PLASMA SUPPLIER by the donor center, test lab, warehouse   or transportation company or by any authorized representative of the Public   Health Service, or any state or local or foreign competent authorities and   governmental agencies to corporate, donor centers, test labs, plasma warehouses   or transportation company, critical or serious observations are found that   may impact quality or safety of the plasma supplied, PLASMA SUPPLIER shall   give MANUFACTURER notice within one (1) business days and establish a   timeframe to pass the inspection and resolve issues. In the event that PLASMA   SUPPLIER has not corrected the failure, MANUFACTURER shall be immediately   informed in order to take necessary actions, including termination of this   Quality Agreement and the Supply Agreement in the event such breach remains   uncured for a period of sixty (60) business days. 5. DOCUMENTATION AND RECORD   RETENTION 1) PLASMA SUPPLIER shall make available upon request documents such   as Site Master Files (Donor Centers, Testing Laboratories, Storage   Facilities, Corporate Offices related to Quality Management Systems), floor   plans, equipment validation, and other production information in order to   ensure safety, purity, and potency of the product. 2) MANUFACTURER, as the   Plasma-derived product license holder, is responsible to prepare and submit   any regulatory submission linked to in process and final product as required   by applicable regulations. PLASMA SUPPLIER shall provide all documentation   requested by MANUFACTURER to support regulatory submissions. 3) PLASMA SUPPLIER   commits to provide to MANUFACTURER on a regular basis, the relevant   information and regulatory documentation that is necessary for Regulatory   Submissions according to final product applicable regulations. Such   documentation shall include at minimum, certificates of approval by competent   health authorities for facilities, laboratories, plasma warehouses and   transportation companies, inspection status information, donor suitability   criteria, approved technical specifications for soft goods, main equipment   validation protocol, methods and validations of testing platforms,   proficiency studies and epidemiological data. 4) Epidemiology data and viral   marker data must be supplied by PLASMA SUPPLIER in accordance with the   current regulatory requirements. Data must be submitted using the standard   forms found in the Source Plasma Specification. Should a PLASMA SUPPLIER   donor center exceed (on an annual basis, Jan-December.) the MANUFACTURER   and/or its affiliated or parent company established VM Alert Limits (Attachment   3): •PLASMA SUPPLIER will provide MANUFACTURER an investigation and   corrective/preventive actions (when appropriate); and •Plasma will not be   accepted from a donor center that has exceeded the MANUFACTURER established   Viral Marker Alert Limits for three (3) consecutive years. 5) PLASMA SUPPLIER   shall keep complete and accurate records of equipment usage, cleaning,   testing, temperature holds, and any maintenance/calibration performed and   other parameters in accordance with the most stringent applicable legal   requirements. 6) PLASMA SUPPLIER agrees to retain donor records according to   all applicable sections and regulations issued or promulgated by Competent   Authorities applicable federal, state, and local or foreign competent   authorities and governmental agencies regulations. 7) The following items   will have to be recorded and stored appropriately by PLASMA SUPPLIER in order   to secure the quality and safety of the partially processed biological   materials to comply with the current regulation identified in this Page 9   of29 

    

 

Quality   Agreement in order to comply with applicable pertod as may be required by any   law or regulation governing the distrtbution of biological products   manufactured from such Plasma: o o o traceability records donor card health   record of each donor (including health history and physical examination of   each donor, which are maintained in the donor management system) donor   questionnaires (i.e., AIDS,) donor number whose plasma was used for   production pooling. NAT and serological test results, which are kept in the   donor management system. o o o 6. CONSEQUENCES OF TERMINATION Upon   termination of the supply contract: PlASMA SUPPLIER shall continue to comply   with its obligation under this Agreement if and to the extent it continues to   have the responsibility for post donation information and look back   information after the expiry or termination of the Supply Agreement. All   obligations relating to compliance with cGMP in respect of the plasma shall   continue in force according to the requirements of cGMP, including but not   limited to: Record Retention and availability Regulatory inspections and data   requested Post donation information and look back information.   Epidemiological Data for the year after the termination of the supply   agreement. 7. CONTACT PERSONS In the event of serious failure, regulatory   issues, update or change in specifications: PLASMA SUPPLIER If addressed to   BIOTEST: Biotest Pharmaceuticals Corporation 901 Yamato Road, Suite 101 Boca   Raton FL 33431-4409 USA MANUFACTURER Grifols Worldwide Operations, Ltd.   Grange Castle Business Park Grange Castle Clondalkin Dublin 22 Ireland 1)   Each party shall notify the other party in wrtting of any significant change   in reporting relationships involving the quality department or quality   functions within five (5) business days of such change and proceed according   the Change Control requirement process oullined In this agreement. age 10 of   29 - --- -------- 

    

 

2) Each party   shall provide written notice to the other party of any change in the   management of a critical operation that is applicable to plasma (e.g.,   production, quality, new center set up and validation) within five (3)   business days of such change and proceed according the Change Control requirement   process outlined in this agreement. 3) PLASMA SUPPLIER shall communicate to   MANUFACTURER within one (1) business day of notification or discovery,   whichever is first, of debarment, under Section 306(a) or 306(b) of the   Federal Food, Drug and Cosmetic Act [21 USC 335a] of any of PLASMA SUPPLIER   employees or agents involved in the collection or control of the Plasma.   ACCEPTANCE SIGNATURES: PLASMA SUPPLIER MANUFACTURER Biotest Phann ceu 'cals   CorP?ration Approved by: -'--:7.>::::..::;4/-­ Approved b•'.f::;:;;:;:   ======--- Date: 6>/kftr 1· '-Llt.. Cj Date: I ' Name: Ileana Ca isle   lS\.---\" <i/11--/ Name: \}c._e._e. Title: Title: CEO/President Page   11 of 29 

    

 

ATTACHMENT 1   LIST OF CENTERS, TEST LABORATORIES, PLASMA WAREHOUSES, TRANSPORTATION   COMPANIES 

    

 

BIOTEST   PHARMACEUTICALS PLASMA CENTERS 210<1 PoarAI Orclul<dRoad. oAuguStl GA   30l10il 1616 Ea•t Wacster Stroll!. 8ci'Niing Green, OHG102 718 22nd AI S.   Broaid!lga Stl S7COG .AI.igmla Bw.ing Qrec Brocki1195 Clenlaon Co WQY   OiQu;QnCily Fort Myers Gllil'll.lMiille HOII]'WOOd lc\o.'!i City   Jadls!:lnvllla Jacl<sllnv le Kl!'limay t...ncoln Molbeumc 01lando Royal   PCIItl Antonio SanlsFt: Val:lo$:a Vmmll an 'I'CIWlg$lcwn GEO GIA 01-110 souru   DAJ<OTA 5:lO Old Gnserwlb! Hny Sle SOC*'-n $C 2!1631 2235 Dave wero ort   e,mfi,COIIYI'By AR 7'2034 1027 Coomen:e Baul• ani, Di ksm ClPA tSSI 9 391   CpiQn8et.S van;l, Fl>lt Mfl3S9Ge :2315 NW 13111 Slr<l*Gainesville FL32&'J!I   6837 TSfHt Ollywood Flll3024 SOUlli CAROUNA. ARKANSAS PENNSYLVANIA FLORIDA   FLORillA FLOIUOA IOWA I«>RTH CARO INA NORTH CAROUNA NEBRASKA NEBRASKA   FLORIDA FLORIDA FLO IDA TI5)(A.S NEWr.tE>QCO GEORGIA SOUTH DAKOTA OHIO   ..r.oe S. Glb:ut St•• IIIWil City tA 522.W 1'21$ Counlly tl\lb Road. nviHt NC   ::18541-'1411 113 Y pp.JK caonYUieNC :285110 59151dA\'E!<'tllB, Kellmty NE   58$47 3CO S.17111S1reet t.mciiiJ!liiE6BS08 3110 Lake 'fo'Wlingilln Road,   Melbourne,FL 32<134 2501 Dit o;o el}' Drive Sui! co.Or'.amlo, Ft. 32e2D   1110Buslncs:;P, r!<Wfi'!, Royal Pelm, 1'1.33411 616 1('1/l.a>p 410 Suc   101,a;m MIOilko TX 71!216 2/leQ Cerrii':J& Road,Sana! Fe NM 87607 311 N.   Pa .!fSQnSireet, V.,DStl!l, GA31M1 1012 Prin::o!Dn St., VNI'II'illiOn SD   57C69 6000 falla'ling A.....,ue. YDUng IDwn Oli+IS15 Illoint Ccmimo City   5altl> \1\' an;.ocK A\IOl'IVO, A!I'IMIS GA 305U1A_\lla<n;GEOI(GIA 

    

 

ATTACHMENT 2   RELEVANT REGULATIONS o 21 CFR Parts 210, 211, 600. o EU Good Manufacturing   Practices for MedicinalProducts for Human use, all as amended from time to   time o Council of Europe: Guide to the preparation use and quality assurance   of blood components (current version). o European Pharmacopeia monographs   ('EP') requirements particularly in respect of blood or blood components as   starting material for the manufacture of proprietary medicinal products. o   Recommendations of the World Health Organization (WHO). o Commission   Directive 2005/61/EC of 30 September 2005 implementing Directive 2002/98/EC   as regards traceability requirements and notification of serious adverse   reactions and events. o Commission Directive 2004/33/EC of 22 March 2004   implementing Directive 2002198/EC, regarding donor suitability requirements.   o Directive 2001/83/EC, GMP Annex 14 and certain recommendations of the   Council of Europe, as well as any other applicable international, federal,   state and local regulations concerning the collection, processing, testing,   storage, packaging, labeling, release and shipping of Plasma. o Guideline on   plasma-derived medicinal products (EMA/CPMP/BWP, current version). 

    

 

ATIACHMENT3   SPECIFICATIONS 1.-PURPOSE To provide and describe the conditions required for   Source Plasma to be accepted by MANUFACTURER for the procurement of Source   Plasma intended for manufacture of hemoderivate products. This specification   is intended to assure that incoming plasma meets all MANUFACTURER   requirements, in addition to establish domestic and international   regulations, 2.-.SCOPE These specifications cover all source plasma intended   for fractionation, defined as the fluid portion of human blood collected by   plasmapheresis. MANUFACTURER can only use plasma for fractionation that   fulfils all the MANUFACTURER requirements for all of the components that are   part of Plasma Supply Chain, i.e.: Plasma collection centers Plasma testing   facilities and Plasma testing methods Plasma storage facilities Plasma   transportation companies. Every one of them has t9 be approved by   MANUFACTURER and previously authorized by competent Health Authorities.   3.-RELATED DOCUMENTS FDA:21 Code Federal Regulation all applicable sections o   21 CFR 210-Current Good Manufacturing Practice in Manufacturing, Processing,   Packing or Holding of Drugs; General. 21 CFR 211 - Good Manufacturing   Practice for Finished Pharmaceuticals. 21 CFR 600 - Biological Products   General 21 CFR 606 - Current Good Manufacturing Practices for Blood and Blood   Components 21 CFR 610-General Biological Products Standards 21 CFR   640-Additional Standards for Human Blood and Blood Products, Plasma and   Source Plasma 42 CFR 493 - CLIA regulations FDA approved Standard Operating   Procedures Manuals All current FDA guidance documents related to collecting,   testing, processing, storing or transporting Source Plasma PPTA Viral Marker   Standard PPTA Qualified Donor Standard PPTA NAT Testing Standard EUEU   Pharmacopeia monograph for Human Plasma for Fractionation Revision to Annex   14 to EU Guide to GMP: Manufacture of products derived from human blood or   plasma EUEMEA/CHMP/BWP/3794/03 Guideline on the Scientific Data Requirements   for a Plasma Master File o o o o o o o o o o o o o o 

    

 

o   EUEMEA/CHMP/BWP/125/04 Guideline on Epidemiological Data on Blood   Transmissible Infections EUCouncil of Europe: Guide to the preparation use   and quality assurance of blood components EUDirective 2002/98/CE EUDirective   2004/33/CE sPReal Decreta 1088/2005 o o o o EUFor plasma intended to be used   as raw material for Hemoderivates Products for European Market sPFor   plasmatic raw material intended to be processed in Spanish Manufacturing   Plant facilities 4.-PROCEDURE All plasma units shall be collected by approved   suppliers and collection facilities, and tested by approved laboratories   using approved kits, and stored and transported using approved establishments   in compliance with all applicable sections of US Code of Federal Regulations   (US CFR Tille 21) and all applicable requirements related to final product   destination (i.e.: European Regulations) if it's the intended for use in.   Plasma types will be defined according to plasma center involved,   laboratories involved, testing methods involved, specific test for final   product destination requirement, warehouse involved and plasma carrier   involved in which is transported. The PLASMA SUPPLIER will keep updated a   quality assurance system that will include, at least, review and   investigation of deviations and detection of possible trending, performance   of internal compliance audits with corresponding follow-up of corrective and   preventive actions and implementation of an internal Change Control   procedure. The quality assurance system will be applied along the collection,   processing, testing, storage, and control procedures. All activities,   functions and/or documentation practices will be performed according to cGMP   (current Good Manufacturing Practices). 4.1. PLASMA COLLECTION Plasmapheresis   Centers Plasmapheresis centers shall be approved by the Health Authorities of   plasma origin and be in compliance with Epidemiological data established by   Manufacturing company (IQPP certified). Plasma collection centers will screen   all donors to ensure that each of them is under good health conditions and   that plasma is not collected from a high risk population. Management and   control of donors should be done using an IT system. In addition, for plasma   intended for use as raw material in hemoderivate products for European   market, plasma centers have to be approved by European Health Authorities.   PLASMA SUPLIER will supply MANUFACTURER for corresponding evaluation and for   each center Epidemiological Data of viral markers (HBV, HCV & HIV),   annually in EMA format and half-yearly in PPTA format. All alert   notifications and their corresponding investigations as well as their   corrective/preventive actions (if applicable) should be included in the   continuous revision of epidemiological data. Centers participating in   specific programs of collecting plasma from donors tested reactive/positive   in viral markers cannot be MANUFACTURER's suppliers. 

    

 

Donor selection   Donor selection procedures shall fulfill with competent authorities   Regulations. In addition, for plasma intended for use as raw material in   hemoderivate products for European market, Donor selection process has to be   in compliance with those established by European Health Authorities. All   plasma donations shall be from qualified donors. Sterility Plasma is separated   from cells by an aseptic method using a sterile system designed to prevent   micro-organism contamination.Furthermore, the plasma containers are closed,   with the aim to prevent the possibility of contamination. 4.2 PLASMA TESTING   The laboratory shall be approved by competent authorities. The laboratory   will keep approved and updated SOPs, containing the necessary working   instructions. All analytical methods shall be validated and shall have an   optimum level of sensitivity and specificity and shall fulfill with current   legislation. All the validations, including protocols, reports and related   documentation will be approved by Quality Assurance area. The laboratory will   join in certification programs (proficiency testing) to ensure suitability of   methods and techniques in use. Plasma shall be tested by facilities approved   by competent authorities (additionally approved by a competent Health   Authority (i.e. EMA). Likewise, all analytical methods used shall be approved   by competent authorities (additionally approved by a competent Health   Authority (i.e. EMA) and shall be included as part of the approved   specifications. For plasma intended to be used as raw material for   hemoderivate products for European Market, testing facilities and analytical   methods used have to be approved by European Health Authorities. Plasma   testing requirements Prior to use,the test kit manufacturer, test kit   methodology and testing facility must be approved by MANUFACTURER. • All   donors shall be screened for all the biochemical parameters required by   national authorities as control of the donor and for indirect coombs   reactivity in the first donation and every 90 days, and the obtained result   must be non-reactive. • All donors shall be screened for excluding Syphilis   presence as required by national regulations. Donor test is performed every 4   months. • All plasma units must be tested and found non-reactive for   Hepatitis B surface antigen (HBsAg) by a validated test method approved by   competent authorities. • All plasma units must be tested and found   non-reactive for HIV-1 and HIV-2 antibodies by a validated test method   approved by competent authorities. • All plasma units must be tested and   found non-reactive for Hepatitis C antibodies by a validated test method   approved by competent authorities. • Additionally, all plasma units must be   tested and found non-reactive by means of pools consisting of not more than   512 individual units for HCV-DNA, HCV-RNA and HIV-RNA by a validated test   method approved by 

    

 

competent   authorities and for HAV-RNA and Parvovirus 819-DNA by a validated test   method. The cut-off of Parvovirus 819-DNA detennination must be such to   ensure that plasma manufacturing pools do not exceed a titer of 1x1()4 IU/ml.   • All plasma units must be tested for all viral or non-viral markers as   required by the plasma Supplies Health Authorities. • For plasma intended to   be used as raw material for hemoderivate products for European Market,   analytical methods used have to be approved by European Health Authorities. Hyperimmune   plasma For hyperimmune plasma all donors shall be immunized using Competent   authorities approved immunizing program and shall contain at least the titers   agreed with the Supplier. These are described in corresponding registers   (IG_REG-000683 and IG_REG-000686). Traceability and look Back Requirements   While fully respecting confidentiamy, there is a system in place which   enables the path taken by each donation to be traced, both forward from the   donor and back from the finished medicinal product, including but not limited   to plasma center, plasma donor number, analytical testing and results, plasma   manufacturing pool testing, Data of Manufacturing process and final product   identification. lfs a system by which we can identify and remove look back and   POl units. A look-back unit is a unit of plasma that complies with all the   established requirements but collected from a donor, from whom a subsequent   donation has been rejected for any reason, related with an infection or with   behavior that may involve belonging to a risk group (Post-Donation   Information), Creutzfeldt-Jakob disease (CJD) or new variant   Creutzfeldt-Jakob disease (nvCJD). In case of reasons related to infection or   belonging to risk group behavior (POl), Plasma Suppliers shall communicate to   MANUFACTURER's manufacturing companies all the plasma units drawn from a   donor within twelve months prior to the date of the last negative tested   donation for anti-HCV and HCV-RNA, for HBsAg and HBV-DNA and for anti-HIV 1/2   and HIV-RNA. In case of CJD and nvCJD risk factors and/or diagnosis,   communications shall include all the units sent to any MANUFACTURER's   manufacturing company from that donor. Look-back units shall be notified to   any MANUFACTURER's manufacturing company in written form as quickly as possible   and not more than three (3) calendar days from the event that caused the   procedure. 4.3. PLASMA PROCESSING Physical conditions of plasma units and   samples Each plasma unit shall be collected from a single donor. All plasma   units must be placed in the freezer within one hour of collection and   maintained at -20° C or colder. In case of plasma intended for used as raw   material in hemoderivate products for European Market, it has to be in   compliance with European Phannacopeia requirements: Plasma intended for the   recovery of labile proteins in plasma is frozen within 24h after collection   by cooling rapidly in conditions validated to ensure that a temperature of   -25°C or below is attained at the core of each plasma unit within 12h after   placing in the freezing apparatus, ensuring the preservation from activity of   labile coagulation factors. 

    

 

Plasma intended   for the recovery of not labile proteins in plasma is frozen by cooling at   -20°C or colder as soon as possible and at the latest within 24h after   collection. All plasma units shall be accompanied by a plasma sample of not   less than 2 ml and both shall be identified with the bleed number and bar   code. Both unit and sample of plasma shall exhibit neither hemolytic nor   lipemia signs when visually inspected, nor both plasma bottle and sample tube   shall not have any fissure or be broken. Storage The warehouse shall be   approved by MANUFACTURER and by competent authorities. All plasma units and   their corresponding samples shall be kept at -20 oc or colder, unless more   restrictive conditions are required by the competent Health Authorities.   Temperature of all shipments will be monitored using validated temperature   recorders in order to ensure that plasma units and their corresponding samples   have been kept at temperatures according to specification ( -20°C). Any   deviation shall be investigated and approved. In case of plasma intended for   used as raw material in hemoderivate products for European Market, the   warehouse has to be also approved by European Health Authorities. Quarantine   Plasma pool will be ready for fractionation once completed minimum volume   needed for processing a production lot and prior minimum quarantine of 2 or 3   months from collection date for all units included on it. The quarantine   period (2 or 3 months) will be determined depending on fractionation product   destination and it will be controlled by computer management system.   Shelf-life Source plasma has a shelf-life of 36 months in all manufacturing   plants in which plasma is processed. Plasma must not be older than 30 months   when shipped to MANUFACTURER's manufacturing company. For units older than 30   months, it must be necessary a previous authorization by Qualified person of   MANUFACTURER 'S manufacturing company. 4.4. PLASMA SHIPPING Shipment All   carriers used to transport Source Plasma must be approved by MANUFACTURER.   The temperature of the transport trailer must be -25°C or colder prior to   loading the plasma shipment. The shipping procedure has to be designed to   keep all plasma units and samples at -20 °C or colder during the whole   transportation process according to Regulations of Plasma Origin Country. In   addition, for plasma intended for use in hemoderivate products for European   market the shipping procedure has to be in compliance with Ph. Eur.   Monography, 'Human Plasma for Fractionation' Page 19 of 29 

    

 

Temperature of   all shipments will be monitored using validated temperature recorders, in   order to ensure that plasma units and their corresponding samples have been   kept at temperatures according to specification (:S-20°C). Any deviation   shall be investigated to analyze cause and potential impact before to accept   and approved plasma involved in it. All documents and plasma pool samples (if   required) shall be sent in advance to any MANUFACTURER's manufacturing   company for shipment confirmation. For plasma intended as raw material for   use in hemoderivate products for European market, all carriers used as raw   material for used to transport Source Plasma must be approved by competent   European Health Authorities. Identification of the shipping boxes The plasma   Supplier shall identify boxes as following: -Supplier name. -Shipment number.   -Total boxes by shipment. -Box/boxes (number of order regarding total number   of boxes). Label All plasma units have to be labeled with at least the   following information: 1-Supplier name. 2-Product name. 3-Bleed number (code   bar). 4-Volume or weight of the unit. 5-Date of collection. 6-Storage   temperature. 7-Type and volume of anticoagulant. 8-Results of viral testing.   Bleed Documentation Bleed documentation must contain the data displayed   below: 1-Supplier name. 2-Product name. 3-Bleed number. 4-Donor number.   5-Shipment number or date of shipment. 6-Date of collection. 7-Test result   for each one of the viral markers tested. The bleed number must be the same,   as per numbers, prefixes and suffixes, in: -The list of donations. -The   plasma unit label. -The plasma unit bar code reading. -The plasma sample   label. -The plasma sample barcode reading. -The Alert notification of the   look-back units 

    

 

4.5 QUALITY   ASSURANCE Inspections All plasma Suppliers, as well as laboratories,   warehouses and transport companies, shall inform MANUFACTURER of the result   of the inspections of the competent Health Authorities (US FDA, Europe,   other). All plasma Suppliers laboratories, warehouses and transport   companies, may be audited periodically by MANUFACTURER's staff or personnel   authorized by MANUFACTURER. During these audits all procedures and reports of   plasma suppliers, laboratories, warehouses and transport companies related to   collection, processing, testing, storage, packaging, labelling and shipment   of plasma may be reviewed. Serious incidences PLASMA SUPPLIER shall inform   within three ("3") working days, any serious incidence produced at   center, laboratory, and warehouse facilities and/or during transport process,   which may affect the quality and safety of the provided plasma. Changes   Control PLASMA SUPPLIER shall inform any MANUFACTURER manufacturing company   of any planned changes that may have an impact in the quality and safety of   plasma during collection, processing, testing, storage, packaging, labeling   and shipment. Those changes requiring license amendment from Health   Authorities (variations to the approved registry) need prior written approval   of MANUFACTURER's manufacturing company before their implementation.   Documentation and Records An approved system of documentation and proper   control systems of review and authorization will be established.   Documentation shall be updated annually if necessary. All donor records shall   be retained by the Supplier for at least 40 years from the date of collection   of the last donation for each donor. If necessary, MANUFACTURER and PLASMA   SUPPLIER will agree on additional donor records, health information, donor   questionnaires, donor number and testing if requested by competent Health   Authorities. All donor testing records shall be retained by the supplier for   at least 40 years from the date of the shipment of each unit to MANUFACTURER.   PLASMA SUPPLLIER will provide upon request by MANUFACTURER'S copies of   documents related to collection, receipt, storage, handling and distribution   of products (i.e. recorder temperatures, maintenance records, etc...) PLASMA   SUPPLIER will keep updated and available upon request by MANUFACTURER's,   documents such as SMF (Site Master File), map and flows, chart, equipment and   process validation and any other production documents that ensure the quality   and safety of plasma. PLASMA SUPPLIER will provide annually -or upon request   by MANUFACTURER-the necessary documentation to keep updated the Plasma Master   File. Training and qualified personnel There should be a sufficient number of   qualified personnel and Center shall provide training in accordance with an   approved program. Initial and continuing training will be performed and   effectiveness assessed. Training records shall be kept for all personnel. 

    

 

Premises and   Equipment (qualification and maintenance). Materials Equipment. systems,   premises and instruments shall be qualified or validated before use or after   any relevant change. Related qualification and validation documentation shall   be reviewed and approved. A calibration program and preventive maintenance   program for equipment and instruments shall be established. Critical   materials shall come from approved suppliers that meet the documented   requirements and specifications. 4.6. PLASMA RELEASE Plasma units released:   Certificate of Compliance The PLASMA SUPPLIER shall only release plasma units   to its delivery to any MANUFACTURER's manufacturing company as long as the   Responsible Person states in a Certificate of Compliance that: • All source   plasma units fulfill the requirements and Source Plasma Specifications in   accordance with the Quality Agreement in force. • All plasma units of the   shipment have been tested and found non-reactive for viral markers,   specifying the test kits and/or reagents used in each case for: .o HBsAg,   anti-HIV 1/2, anti-HCV, tested in individual units o Luetic serology,   initially tested and every 4 months o Indirect Coombs, initially tested and   at least every 3 months o HAV-RNA, HCV-DNA, HCV-RNA, HIV-RNA and Parvovirus   819-DNA, tested by means of pools consisting of not more than 512 individual   units. • All collection, processing, testing, quality control records review,   storage, packing and labeling operations have been performed under current   Good Manufacturing Practices, The certificate must be issued by the   Re.sponsible Person of the Plasma Supplier. The PLASMA SUPPLIER will provide   MANUFACTURER with alist of names of the Responsible Persons and authorized   designees and their corresponding signatures and responsibililies. 

    

 

ATTACHMENT 4   TEST KITS FOR EIA/NAT TEST KITS FOR EIA/NAT Viral Marker Test Kits of   Individual Donors Ucenst I Establishment Page23of29 Parameter Test Method/   Name of tht Te;t Kit Manufacturer u.s. Ret!istration Number Anti-HCV ABBOTI   PRISM HCV Hepatitis C Virus Encoded Antigens (Recombinant cl 00-3. HCr43.   NS5) Abbott Laboratories U.S License 43 Anti-HIV-1/2 ABBOTI Prism HN 0 Plus   Virus Types I and 2 (E. coli, B, megalerum, Recombinant) Antigen and   Synthetic Peptide Abboll Laboratories U.S. License 43 HBsAg ABBOTI PRISM   HBsAg, Antibody to Hepatitis B Surface Antigen (Mouse MonoclonallgM) Abboll   Laboratories U.S. License 43 Anti-HCV Hepntitis C Virus Encoded Antigen ORTHO   HCV v3.0 ELISA TSystem (Recombinant c22-3. c200. NS5) Ortho-Ciinical   Diagnostics, Inc. U.S. License 43 Anti-HIV-1/2 GS HIV-1/HIV-2 Plus 0 EIA   Bio-Rad Laboratories U.S. License 43 HBsAg GS HBsAg EIA 3.0 Bio-Rad   Laboratories U.S. License 43 

    

 

ATIACHMENT 5   TABLE OF RESPONSIBILITIES Summary Table and Division of Quality   Responsibilities of PLASMA SUPLIERIMANUFACTURER 1.1.The responsible Party is   denoted by X Page 24 of29 DESCRIPTION PLASMA SUPPLIER MANUFACTURER GENERAL   PROVISIONS NegoUale the Quality Agreement X X Notification of change in   reporting relationship involving Contact Persons X X Assure that Plasma   obtained from US FDA licensed Source Plasma (Human) collection centers meet   all the requirements stipulated in this Agreement and the MANUFACTURER   Specifications X Responsible for the handling, storage, and transport of   intermediates pastes and plasma that is contracted to the MANUFACTURER in   accordance with the terms and conditions set forth in this Agreement, the   applicable regulations and the MANUFACTURER Specifications X Approve any new   contract or third party Suppliers of Plasma X X QUALITY AND TECHNICAL   REQUIREMENTS Collect, process, test, store, package, label, release and ship   Plasma in accordance with MANUFACTURER Specifications X QUALITY CONTROL   Arrange testing for each donor of plasma in accordance with MANUFACTURER   Specifications, as well as applicable regulations X Ensure all laboratories   are in compliance with cGMP and are qualified in all the methodologies   associated with Plasma and the Premises X Perform testing and analysis of the   Plasma in approved laboratories using licensed kits included in the EU Plasma   Master File if plasma is intended for EU X 

    

 

Page 25 of29   DESCRIPTION PLASMA SUPPLIER MANUFACTURER SUBCONTRACTING OPERATIONS Agree in   writing on any contracted service (i.e., storage, testing) to be completed by   third party per the MANUFACTURER Specifications X X Perform audits of third   party contractors X X Provide a written report to MANUFACTURER confirming   that the Piasa units have been collected, tested, shipped and stored property   and meet the requirements of the MANUFACTURER Specifications X Ensure all   sites or services used are in compliance with cGMP and are qualified in all   of the methodologies associated with Plasma and the Premises. X X   TRACEABILITY AND LOOK BACK COMMUNICATION (POST-DONATION COLLECTION   INFORMATION Communicate to MANUFACTURER in writing within 3 calendar days all   information per this Agreement on a donor after a donation that fulfilled all   MANUFACTURER Specifications is rejected for seroconversion or post donation   information that may become an infectious disease (Notifications per the   MANUFACTURER Specifications) X Notify the MANUFACTURER no later than 3   calendar days of discovery of significant deviations that may impact batches   or Plasma previously released and/or shipped to the MANUFACTURER. X Supply a   report prior to product release on all post donation notifications received   after pooling so that the MANUFACTURER can perform a viral risk assessment on   the product X CHANGE CONTROL Notify MANUFACTURER in advance of any planned   changes reasonably foreseeable to affect the regulatory submissions to regulatory   authorities including EU Plasma Master File variations and/or available   supply of the Plasma-Obtain written approval from MANUFACTURER prior to the   implementation of such changes and any other change that are covered by the   change control scope of this Agreement that could have any effect on the   safely, purity, etc. of the Plasma collected X Provide justification for the   changes and validate any changes to cGMP standards X Provide written approval   for change controls per this Agreement X 

    

 

DESCRIPTION   PLASMA SUPPLIER MANUFACTURER QUALITY ASSURANCE Maintain an active quality   management system, which shall apply to all operations which may impact on   the quality and safety of the Plasma X Document and investigate deviations   from the processes and procedures per this Agreement and notify MANUFACTURER   as soon as possible before shipment or in no case later than three ('3")   calendar days of discovery that a deviation may impact a batch or Plasma   previously released and/or shipped X Approve the use of materials for the   collection of Plasma; confirm the proper condition of the packaging,   sterility certification, locks/seals, shipping documentation; ensure that   each lot is in full compliance with licensed requirements and with applicable   regulations X Approve all vendors and Suppliers of critical raw materials,   reagents and components used in the collection and testing of Plasma;Ensure   materials are received, stored, segregated and used correctly and all   materials are appropriate for their intended use; Maintain relevant   certificates of analysis, certificates of compliance, certificates of origin   for such materials, as appropriate; Maintain an approved vendor list X   STORAGE AND SHIPPING Provide storage conditions for the Plasma that meets the   agreed upon MANUFACTURER Specifications,SOPs, applicable regulations related   to Plasma storage and the EP monograph-Human Plasma to Fractionation X   Maintain proper segregation of the Plasma units X Provide quality assurance   oversight of unreleased Plasma received into quarantine and stored in a   controlled, validated warehouse X Provide quality assurance oversight to   segregate, identify and disposition rejected plasma X BIOLOGICAL PRODUCT   DEVIATIONS AND RECALLS Monitor the manufacturing and releasetata af the   Plasma to detect potentially reportable deviations within one ("   1") business day of confirmation X Plasma unit deviation reporting to   the appropriate regulatory authorities X Biological product deviation   reporting to the appropriate regulatory authorities X X 

    

 

Page 27 of29   DESCRIPTION PLASMA SUPPLIER MANUFACTURER Perform investigations for any   issues thought to be Plasma unit based and provide information to   MANUFACTURER X Responsible for Plasma unit recall or withdrawal; Provide   notification to MANUFACTURER within one ('1') business day of confirmation   and perform investigations for these problems and forward investigation   report to MANUFACTURER within mutually a!jreeable timeframe X Responsible for   final product or intermediate product recall or withdrawal X EQUIPMENT,   COMPUTER AND FACILITY VALIDATION AND/OR QUALIFICATION PROCESS Ensure all   processes, equipment, systems and facilities are qualified and validated, as   applicable, per this Agreement X Approve all process qualifications   applicable to the Plasma collection, including but not limited to, the   freezer validation and shipping validation for test samples and Plasma X   PLASMA RELEASE Have at least one quality Responsible Person on the Premises   to oversee the quality aspects of the Plasma collection, testing, shipment   and evaluate deviations, in order to ensure compliance with cGMP; the   Responsible Person will certify that each unit of Plasma has been collected   and tested in approved facilities according to GMP and fulfil quality and   safety requirements according to the MANUFACTURER Specifications X 1   LICENSES, PERMITS AND APPROVALS Represents and warrants that all their   plasmapheresis donor centers in operation are currently certified under the   PPTA IQPP; such certification must be preserved without interruption during   the term of this Agreement; if plasmapheresis donor center fails to remain   certified, notification to MANUFACTURER immediately, or within one {"1')   business day X Follow al requirements and specifications for exporting   products to Europe X Notify MANUFACTURER within one business day in the event   of a suspension, revocation or other administrative action adversely   affecting or limiting license, permit or approval X Provide prior written   notification to MANUFACTURER prior to relocating, opening or closing a   plasmapheresis center; Obtain written approval from MANUFACTURER for   inclusion of new centers, testing laboratories, plasma warehouses and   transportation companies X 

    

 

 

DESCRIPTION   PLASMA SUPPLIER MANUFACTURER 2 INSPECTIONS Audit and qualify all vendors of   supplies used in the collection and shipment of Plasma X Handle complaints to   the vendor of supplies X Allow the MANUFACTURER to conduct annual inspections   of the approved plasmapheresis donor collection centers, testing   laboratories, plasma warehouse storage facilities and/or transport/transit   and shipping companies and the BIOMAT USA,Inc. quality systems per this   Agreement X Responsible for the ulllmale approval of all Plasma centers and   their status as approved or not approved to ship Plasma to the MANUFACTURER X   Provide written report to MANUFACTURER within thirty ('30') days of the audit   date X Ensure that all the corrective actions are implemented and provide a   report to the MANUFACTURER X Provide wrltlen notice to MANUFACTURER of any   investigations ofthe donor centers, testing laboratories, storage, release   and shipping facilities/companies with no more than three (' 3') business   days of the investiqallon·s commencement X Communicate to MANUFACTURER within   one ("1') business day any event or serious failure of a center, testing   laboratory, storage and/or transportation which may impact quafi(y or safely   of !he Plasma supplied X Notify MANUFACTURER of any meetings/substantive   discussions with regulatory authorities that direclly relate to the   manufacture, supply and/or control of !he Plasma supplied X Provide to   MANUFACTURER a copy of the following within one ('1")business day of   receipt: (i) List of Observations Form FDA 483, (ii) Information Letter,   (iii) Warning Letter, (iv) Notice of Intent to Revoke License Letter, (v)   Suspension Letter, Seizure Letter or the like issued by n qulatory authority   X 

    

 

DESCRIPTION   PLASMA SUPPLIER MANUFACTURER 3 DOCUMENTATION AND RECORD RETENTION Responsible   for preparing and submitting regulatory submissions linked to the process and   final product as required by applicable regulations X Provide alllhe   documentation requested to support regulatory submissions, annual update for   the EU Plasma Master File, epidemiology dale/viral marker data X Keep   complete and accurate records of equipment usage, cleaning, testing,   temperature holds, and any maintenance/calibration performed, per this   Agreement X Retain donor records per applicable regulations and per this   Agreement X 

    

 

EXHIBIT C   ANNUAL PLAN 18 

    

 

EXHIBIT C   ANNUAL PLANExhibit

Exhibit 4.4

SPECTRUM PHARMACEUTICALS, INC. 
 
SUBORDINATED DEBT SECURITIES 

 
INDENTURE 
 
Dated as of 
 
______________________________________________________________________________
Trustee 
 

TABLE OF CONTENTS

	
					
	 
	 
	 
	Page
	

	ARTICLE 1
	DEFINITIONS
	1
	

	 
	Section 1.01
	Definitions of Terms
	1
	

	ARTICLE 2
	ISSUE, DESCRIPTION, TERMS, EXECUTION, REGISTRATION AND EXCHANGE OF SECURITIES
	5
	

	 
	Section 2.01
	Designation and Terms of Securities
	5
	

	 
	Section 2.02
	Form of Securities and Trustee’s Certificate
	7
	

	 
	Section 2.03
	Denominations:  Provisions for Payment
	8
	

	 
	Section 2.04
	Execution and Authentications
	9
	

	 
	Section 2.05
	Registration of Transfer and Exchange
	10
	

	 
	Section 2.06
	Temporary Securities
	11
	

	 
	Section 2.07
	Mutilated, Destroyed, Lost or Stolen Securities
	11
	

	 
	Section 2.08
	Cancellation
	12
	

	 
	Section 2.09
	Benefits of Indenture
	12
	

	 
	Section 2.10
	Authenticating Agent
	13
	

	 
	Section 2.11
	Global Securities
	13
	

	ARTICLE 3
	REDEMPTION OF SECURITIES AND SINKING FUND PROVISIONS
	14
	

	 
	Section 3.01
	Redemption
	14
	

	 
	Section 3.02
	Notice of Redemption
	14
	

	 
	Section 3.03
	Payment Upon Redemption
	16
	

	 
	Section 3.04
	Sinking Fund
	16
	

	 
	Section 3.05
	Satisfaction of Sinking Fund Payments with Securities
	16
	

	 
	Section 3.06
	Redemption of Securities for Sinking Fund
	17
	

	ARTICLE 4
	COVENANTS
	17
	

	 
	Section 4.01
	Payment of Principal, Premium and Interest
	17
	

	 
	Section 4.02
	Maintenance of Office or Agency
	17
	

	 
	Section 4.03
	Paying Agents
	18
	

	ARTICLE 5
	SECURITYHOLDERS’ LISTS AND REPORTS BY THE COMPANY AND THE TRUSTEE
	19
	

	 
	Section 5.01
	Company to Furnish Trustee Names and Addresses of Securityholders
	19
	

	 
	Section 5.02
	Preservation Of Information; Communications With Securityholders
	19
	

	 
	Section 5.03
	Reports by the Company
	20
	

	 
	Section 5.04
	Reports by the Trustee
	20
	

	ARTICLE 6
	REMEDIES OF THE TRUSTEE AND SECURITYHOLDERS ON EVENT OF DEFAULT
	21
	

	 
	Section 6.01
	Events of Default
	21
	

	 
	Section 6.02
	Collection of Indebtedness and Suits for Enforcement by Trustee
	23
	

	 
	Section 6.03
	Application of Moneys Collected
	24
	

	 
	Section 6.04
	Limitation on Suits
	24
	

	 
	Section 6.05
	Rights and Remedies Cumulative; Delay or Omission Not Waiver
	25
	

	 
	Section 6.06
	Control by Securityholders
	26
	

	 
	Section 6.07
	Undertaking to Pay Costs
	26
	

i

TABLE OF CONTENTS 
(cont.)

	
					
	 
	 
	 
	Page
	

	ARTICLE 7
	CONCERNING THE TRUSTEE
	26
	

	 
	Section 7.01
	Certain Duties and Responsibilities of Trustee
	27
	

	 
	Section 7.02
	Certain Rights of Trustee
	28
	

	 
	Section 7.03
	Trustee Not Responsible for Recitals or Issuance or Securities
	29
	

	 
	Section 7.04
	May Hold Securities
	29
	

	 
	Section 7.05
	Moneys Held in Trust
	29
	

	 
	Section 7.06
	Compensation and Reimbursement
	29
	

	 
	Section 7.07
	Reliance on Officers’ Certificate
	30
	

	 
	Section 7.08
	Disqualification; Conflicting Interests
	30
	

	 
	Section 7.09
	Corporate Trustee Required; Eligibility
	31
	

	 
	Section 7.10
	Resignation and Removal; Appointment of Successor
	31
	

	 
	Section 7.11
	Acceptance of Appointment By Successor
	32
	

	 
	Section 7.12
	Merger, Conversion, Consolidation or Succession to Business
	33
	

	 
	Section 7.13
	Preferential Collection of Claims Against the Company
	34
	

	 
	Section 7.14
	Notice of Default
	34
	

	ARTICLE 8
	CONCERNING THE SECURITYHOLDERS
	34
	

	 
	Section 8.01
	Evidence of Action by Securityholders
	34
	

	 
	Section 8.02
	Proof of Execution by Securityholders
	35
	

	 
	Section 8.03
	Who May be Deemed Owners
	35
	

	 
	Section 8.04
	Certain Securities Owned by Company Disregarded
	35
	

	 
	Section 8.05
	Actions Binding on Future Securityholders
	36
	

	ARTICLE 9
	SUPPLEMENTAL INDENTURES
	36
	

	 
	Section 9.01
	Supplemental Indentures Without the Consent of Securityholders
	36
	

	 
	Section 9.02
	Supplemental Indentures With Consent of Securityholders
	37
	

	 
	Section 9.03
	Effect of Supplemental Indentures
	38
	

	 
	Section 9.04
	Securities Affected by Supplemental Indentures
	38
	

	 
	Section 9.05
	Execution of Supplemental Indentures
	38
	

	ARTICLE 10
	SUCCESSOR ENTITY
	38
	

	 
	Section 10.01
	Company May Consolidate, Etc
	39
	

	 
	Section 10.02
	Successor Entity Substituted
	39
	

	 
	Section 10.03
	Evidence of Consolidation, Etc. to Trustee
	40
	

	ARTICLE 11
	SATISFACTION AND DISCHARGE
	40
	

	 
	Section 11.01
	Satisfaction and Discharge of Indenture
	40
	

	 
	Section 11.02
	Discharge of Obligations
	40
	

	 
	Section 11.03
	Deposited Moneys to be Held in Trust
	41
	

	 
	Section 11.04
	Payment of Moneys Held by Paying Agents
	41
	

	 
	Section 11.05
	Repayment to Company
	41
	

	ARTICLE 12
	IMMUNITY OF INCORPORATORS, STOCKHOLDERS, OFFICERS AND DIRECTORS
	42
	

	 
	Section 12.01
	No Recourse
	42
	

	ARTICLE 13
	MISCELLANEOUS PROVISIONS
	42
	

	 
	Section 13.01
	Effect on Successors and Assigns
	42
	

ii

TABLE OF CONTENTS 
(cont.)

	
					
	 
	 
	 
	Page
	

	 
	Section 13.02
	Actions by Successor
	42
	

	 
	Section 13.03
	Surrender of Company Powers
	42
	

	 
	Section 13.04
	Notices
	43
	

	 
	Section 13.05
	Governing Law
	43
	

	 
	Section 13.06
	Treatment of Securities as Debt
	43
	

	 
	Section 13.07
	Certificates and Opinions as to Conditions Precedent
	43
	

	 
	Section 13.08
	Payments on Business Days
	44
	

	 
	Section 13.09
	Conflict with Trust Indenture Act
	44
	

	 
	Section 13.10
	Counterparts
	44
	

	 
	Section 13.11
	Separability
	44
	

	 
	Section 13.12
	Compliance Certificates
	44
	

	ARTICLE 14
	SUBORDINATION OF SECURITIES
	45
	

	 
	Section 14.01
	Subordination Terms
	45
	

iii

INDENTURE
INDENTURE, dated as of [              ], 201(  ), between SPECTRUM PHARMACEUTICALS, INC., a Delaware corporation (the “Company”), and [TRUSTEE], as trustee (the “Trustee”):
WHEREAS, for its lawful corporate purposes, the Company has duly authorized the execution and delivery of this Indenture to provide for the issuance of subordinated debt securities, in an unlimited aggregate principal amount to be issued from time to time in one or more series as in this Indenture provided, as registered Securities without coupons, to be authenticated by the certificate of the Trustee;
WHEREAS, to provide the terms and conditions upon which the Securities are to be authenticated, issued and delivered, the Company has duly authorized the execution of this Indenture; and
WHEREAS, all things necessary to make this Indenture a valid agreement of the Company, in accordance with its terms, have been done.
NOW, THEREFORE, in consideration of the premises and the purchase of the Securities by the holders thereof, it is mutually covenanted and agreed as follows for the equal and ratable benefit of the holders of Securities:

ARTICLE 1
DEFINITIONS
Section 1.01    Definitions of Terms.
The terms defined in this Section (except as in this Indenture or any indenture supplemental hereto otherwise expressly provided or unless the context otherwise requires) for all purposes of this Indenture and of any indenture supplemental hereto shall have the respective meanings specified in this Section and shall include the plural as well as the singular.  All other terms used in this Indenture that are defined in the Trust Indenture Act of 1939, as amended (the “Securities Act”), or that are by reference in such Act defined in the Securities Act of 1933, as amended (except as herein or any indenture supplemental hereto otherwise expressly provided or unless the context otherwise requires), shall have the meanings assigned to such terms in said Trust Indenture Act and in said Securities Act as in force at the date of the execution of this instrument.
“Authenticating Agent” means an authenticating agent with respect to all or any of the series of Securities appointed by the Trustee pursuant to Section 2.10.
“Bankruptcy Law” means Title 11, U.S. Code, or any similar federal or state law for the relief of debtors.
“Board of Directors” means the Board of Directors of the Company or any duly authorized committee of such Board.

1

“Board Resolution” means a copy of a resolution certified by the Secretary or an Assistant Secretary of the Company to have been duly adopted by the Board of Directors and to be in full force and effect on the date of such certification.
“Business Day” means, with respect to any series of Securities, any day other than a day on which federal or state banking institutions in the Borough of Manhattan, the City of New York, or in the city of the Corporate Trust Office of the Trustee, are authorized or obligated by law, executive order or regulation to close.
“Certificate” means a certificate signed by any Officer.  The Certificate need not comply with the provisions of Section 13.07.
“Company” means Spectrum Pharmaceuticals, Inc., a corporation duly organized and existing under the laws of the State of Delaware, and, subject to the provisions of Article Ten, shall also include its successors and assigns.
“Corporate Trust Office” means the office of the Trustee at which, at any particular time, its corporate trust business shall be principally administered, which office at the date hereof is located at [              ].
“Custodian” means any receiver, trustee, assignee, liquidator or similar official under any Bankruptcy Law.
“Default” means any event, act or condition that with notice or lapse of time, or both, would constitute an Event of Default.
“Defaulted Interest” has the meaning set forth in Section 2.03.
“Depositary” means, with respect to Securities of any series for which the Company shall determine that such Securities will be issued as a Global Security, The Depository Trust Company, New York, New York, another clearing agency, or any successor registered as a clearing agency under the Securities and Exchange Act of 1934, as amended (the “Exchange Act”), or other applicable statute or regulation, which, in each case, shall be designated by the Company pursuant to either Section 2.01 or 2.11.
“Event of Default” means, with respect to Securities of a particular series, any event specified in Section 6.01, continued for the period of time, if any, therein designated.
“Global Security” means, with respect to any series of Securities, a Security executed by the Company and delivered by the Trustee to the Depositary or pursuant to the Depositary’s instruction, all in accordance with the Indenture, which shall be registered in the name of the Depositary or its nominee.
“Governmental Obligations” means securities that are (a) direct obligations of the United States of America or the other government or governments which issued the foreign currency in which the principal of (or premium, if any) or interest on such Security in respect thereof shall be payable, in each case where 

2

the timely payment or payments thereunder are supported by the full faith and credit of such government or governments or (b) obligations of a Person controlled or supervised by and acting as an agency or instrumentality of the United States of America or the government or governments that issued the foreign currency in which the principal of (or premium, if any) or interest on such Security in respect thereof shall be payable, in each case where the timely payment or payments thereunder are unconditionally guaranteed as a full faith and credit obligation by the United States of America or such other government or governments, and which, in the case of (a) or (b), are not callable or redeemable at the option of the issuer thereof at any time prior to the stated maturity of the Securities, and shall also include a depositary receipt issued by a bank or trust company as custodian with respect to any such Governmental Obligation or a specific payment of principal of or interest on any such Governmental Obligation held by such custodian for the account of the holder of such depositary receipt; provided, however, that (except as required by law) such custodian is not authorized to make any deduction from the amount payable to the holder of such depositary receipt from any amount received by the custodian in respect of the Governmental Obligation or the specific payment of principal of or interest on the Governmental Obligation evidenced by such depositary receipt.
“herein”, “hereof” and “hereunder”, and other words of similar import, refer to this Indenture as a whole and not to any particular Article, Section or other subdivision.
“Indenture” means this instrument as originally executed or as it may from time to time be supplemented or amended by one or more indentures supplemental hereto entered into in accordance with the terms hereof.
“Interest Payment Date”, when used with respect to any installment of interest on a Security of a particular series, means the date specified in such Security or in a Board Resolution or in an indenture supplemental hereto with respect to such series as the fixed date on which an installment of interest with respect to Securities of that series is due and payable.
“Notice of Default” shall have the meaning as set forth in Section 6.01(a)(3).
“Officer” means, with respect to the Company, the chairman of the Board of Directors, a chief executive officer, a president, a chief financial officer, a chief operating officer, any executive vice president, any senior vice president, any vice president, the treasurer or any assistant treasurer, the controller or any assistant controller or the secretary or any assistant secretary.
“Officers’ Certificate” means a certificate signed by any two Officers.  Each such certificate shall include the statements provided for in Section 13.07, if and to the extent required by the provisions thereof.
“Opinion of Counsel” means an opinion in writing subject to customary exceptions of legal counsel, who may be an employee of or counsel for the Company, that is delivered to the Trustee in accordance with the terms hereof.  Each such opinion shall include the statements provided for in Section 13.07, if and to the extent required by the provisions thereof.

3

“Outstanding”, when used with reference to Securities of any series, means, subject to the provisions of Section 8.04, as of any particular time, all Securities of that series theretofore authenticated and delivered by the Trustee under this Indenture, except (a) Securities theretofore canceled by the Trustee or any paying agent, or delivered to the Trustee or any paying agent for cancellation or that have previously been canceled; (b) Securities or portions thereof for the payment or redemption of which moneys or Governmental Obligations in the necessary amount shall have been deposited in trust with the Trustee or with any paying agent (other than the Company) or shall have been set aside and segregated in trust by the Company (if the Company shall act as its own paying agent); provided, however, that if such Securities or portions of such Securities are to be redeemed prior to the maturity thereof, notice of such redemption shall have been given as in Article Three provided, or provision satisfactory to the Trustee shall have been made for giving such notice; and (c) Securities in lieu of or in substitution for which other Securities shall have been authenticated and delivered pursuant to the terms of Section 2.07.
“Person” means any individual, corporation, partnership, joint venture, joint-stock company, limited liability company, association, trust, unincorporated organization, any other entity or organization, including a government or political subdivision or an agency or instrumentality thereof.
“Predecessor Security” of any particular Security means every previous Security evidencing all or a portion of the same debt as that evidenced by such particular Security; and, for the purposes of this definition, any Security authenticated and delivered under Section 2.07 in lieu of a lost, destroyed or stolen Security shall be deemed to evidence the same debt as the lost, destroyed or stolen Security.
“Responsible Officer” when used with respect to the Trustee means the chairman of its board of directors, the chief executive officer, the president, any vice president, the secretary, the treasurer, any trust officer, any corporate trust officer or any other officer or assistant officer of the Trustee customarily performing functions similar to those performed by the Persons who at the time shall be such officers, respectively, or to whom any corporate trust matter is referred because of his or her knowledge of and familiarity with the particular subject.
“Securities” means the debt Securities authenticated and delivered under this Indenture.
“Security Register” and “Security Registrar” shall have the meanings as set forth in Section 2.05.
 “Securityholder”, “holder of Securities”, “registered holder”, or other similar term, means the Person or Persons in whose name or names a particular Security shall be registered on the books of the Company kept for that purpose in accordance with the terms of this Indenture.
“Subsidiary” means, with respect to any Person, (i) any corporation at least a majority of whose outstanding Voting Stock shall at the time be owned, directly or indirectly, by such Person or by one or more of its Subsidiaries or by such Person and one or more of its Subsidiaries, (ii) any general partnership, joint venture or similar entity, at least a majority of whose outstanding partnership or similar interests shall at the time be owned by such Person, or by one or more of its Subsidiaries, or by such Person and one or more of its Subsidiaries and (iii) any limited partnership of which such Person or any of its Subsidiaries is a general partner.

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“Trust Indenture Act” means the Trust Indenture Act of 1939, as amended.
 “Trustee” means [               ], and, subject to the provisions of Article Seven, shall also include its successors and assigns, and, if at any time there is more than one Person acting in such capacity hereunder, “Trustee” shall mean each such Person.  The term “Trustee” as used with respect to a particular series of the Securities shall mean the trustee with respect to that series.
 “Voting Stock”, as applied to stock of any Person, means shares, interests, participations or other equivalents in the equity interest (however designated) in such Person having ordinary voting power for the election of a majority of the directors (or the equivalent) of such Person, other than shares, interests, participations or other equivalents having such power only by reason of the occurrence of a contingency.
ARTICLE 2
ISSUE, DESCRIPTION, TERMS, EXECUTION, REGISTRATION AND EXCHANGE
OF SECURITIES
Section 2.01    Designation and Terms of Securities.
(a)    The aggregate principal amount of Securities that may be authenticated and delivered under this Indenture is unlimited.  The Securities may be issued in one or more series up to the aggregate principal amount of Securities of that series from time to time authorized by or pursuant to a Board Resolution or pursuant to one or more indentures supplemental hereto.  Prior to the initial issuance of Securities of any series, there shall be established in or pursuant to a Board Resolution, and set forth in an Officers’ Certificate, or established in one or more indentures supplemental hereto:
(1)    the title of the Securities of the series (which shall distinguish the Securities of that series from all other Securities);
(2)    any limit upon the aggregate principal amount of the Securities of that series that may be authenticated and delivered under this Indenture (except for Securities authenticated and delivered upon registration of transfer of, or in exchange for, or in lieu of, other Securities of that series);
(3)    the date or dates on which the principal of the Securities of the series is payable, any original issue discount that may apply to the Securities of that series upon their issuance, the principal amount due at maturity, and the place(s) of payment;
(4)    the rate or rates at which the Securities of the series shall bear interest or the manner of calculation of such rate or rates, if any;
(5)    the date or dates from which such interest shall accrue, the Interest Payment Dates on which such interest will be payable or the manner of determination of such Interest Payment Dates, the place(s) of payment, and the record date for the determination of holders to whom interest is payable on any such Interest Payment Dates or the manner of determination of such record dates;
(6)    the right, if any, to extend the interest payment periods and the duration of such extension;

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(7)    the period or periods within which, the price or prices at which and the terms and conditions upon which Securities of the series may be redeemed, in whole or in part, at the option of the Company;
(8)    the obligation, if any, of the Company to redeem or purchase Securities of the series pursuant to any sinking fund, mandatory redemption, or analogous provisions (including payments made in cash in satisfaction of future sinking fund obligations) or at the option of a holder thereof and the period or periods within which, the price or prices at which, and the terms and conditions upon which, Securities of the series shall be redeemed or purchased, in whole or in part, pursuant to such obligation;
(9)    the form of the Securities of the series including the form of the certificate of authentication for such series;
(10)    if other than denominations of one thousand U.S. dollars ($1,000) or any integral multiple thereof, the denominations in which the Securities of the series shall be issuable;
(11)    any and all other terms (including terms, to the extent applicable, relating to any auction or remarketing of the Securities of that series and any security for the obligations of the Company with respect to such Securities) with respect to such series (which terms shall not be inconsistent with the terms of this Indenture, as amended by any supplemental indenture) including any terms which may be required by or advisable under United States laws or regulations or advisable in connection with the marketing of Securities of that series;
(12)    whether the Securities are issuable as a Global Security and, in such case, the terms and the identity of the Depositary for such series;
(13)    whether the Securities will be convertible into or exchangeable for shares of common stock or other securities of the Company or any other Person and, if so, the terms and conditions upon which such Securities will be so convertible or exchangeable, including the conversion or exchange price, as applicable, or how it will be calculated and may be adjusted, any mandatory or optional (at the Company’s option or the holders’ option) conversion or exchange features, and the applicable conversion or exchange period;
(14)    if other than the principal amount thereof, the portion of the principal amount of Securities of the series which shall be payable upon declaration of acceleration of the maturity thereof pursuant to Section 6.01;
(15)    any additional or different Events of Default or restrictive covenants (which may include, among other restrictions, restrictions on the Company’s ability or the ability of the Company’s Subsidiaries to:  incur additional indebtedness; issue additional securities; create liens; pay dividends or make distributions in respect of their capital stock; redeem capital stock; place restrictions on such Subsidiaries placing restrictions on their ability to pay dividends, make distributions or transfer assets; make investments or other restricted payments; sell or otherwise dispose of assets; enter into sale-leaseback transactions; engage in transactions with stockholders or affiliates; issue or sell stock of their Subsidiaries; or effect a consolidation or merger) or financial covenants (which may include, among other 

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financial covenants, financial covenants that require the Company and its Subsidiaries to maintain specified interest coverage, fixed charge, cash flow-based or asset-based ratios) provided for with respect to the Securities of the series;
(16)    if other than U.S. dollars, the coin or currency in which the Securities of the series are denominated (including, but not limited to, foreign currency);
(17)    the terms and conditions, if any, upon which the Company shall pay amounts in addition to the stated interest, premium, if any, and principal amounts of the Securities of the series to any Securityholder that is not a “United States person” for federal tax purposes;
(18)    any restrictions on transfer, sale or assignment of the Securities of the series; and
(19)    the subordination terms of the Securities of the series.
All Securities of any one series shall be substantially identical except as to denomination and except as may otherwise be provided in or pursuant to any such Board Resolution or in any indentures supplemental hereto.
If any of the terms of the series are established by action taken pursuant to a Board Resolution of the Company, a copy of an appropriate record of such action shall be certified by the secretary or an assistant secretary of the Company and delivered to the Trustee at or prior to the delivery of the Officers’ Certificate of the Company setting forth the terms of the series.
Securities of any particular series may be issued at various times, with different dates on which the principal or any installment of principal is payable, with different rates of interest, if any, or different methods by which rates of interest may be determined, with different dates on which such interest may be payable and with different redemption dates.
Section 2.02    Form of Securities and Trustee’s Certificate.
The Securities of any series and the Trustee’s certificate of authentication to be borne by such Securities shall be substantially of the tenor and purport as set forth in one or more indentures supplemental hereto or as provided in a Board Resolution, and set forth in an Officers’ Certificate, and they may have such letters, numbers or other marks of identification or designation and such legends or endorsements printed, lithographed or engraved thereon as the Company may deem appropriate and as are not inconsistent with the provisions of this Indenture, or as may be required to comply with any law or with any rule or regulation made pursuant thereto or with any rule or regulation of any securities exchange on which Securities of that series may be listed, or to conform to usage.
Section 2.03    Denominations:  Provisions for Payment.
The Securities shall be issuable as registered Securities and in the denominations of one thousand U.S. dollars ($1,000) or any integral multiple thereof, subject to Section 2.01(a)(10).  The Securities of a particular series shall bear interest payable on the dates and at the rate specified with respect to that series.  Subject to Section 2.01(a)(16), the principal of and the interest on the Securities of any series, as well as 

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any premium thereon in case of redemption thereof prior to maturity, shall be payable in the coin or currency of the United States of America that at the time is legal tender for public and private debt, at the office or agency of the Company maintained for that purpose in the Borough of Manhattan, the City and State of New York.  Each Security shall be dated the date of its authentication.  Interest on the Securities shall be computed on the basis of a 360-day year composed of twelve 30-day months.
The interest installment on any Security that is payable, and is punctually paid or duly provided for, on any Interest Payment Date for Securities of that series shall be paid to the Person in whose name said Security (or one or more Predecessor Securities) is registered at the close of business on the regular record date for such interest installment.  In the event that any Security of a particular series or portion thereof is called for redemption and the redemption date is subsequent to a regular record date with respect to any Interest Payment Date and prior to such Interest Payment Date, interest on such Security will be paid upon presentation and surrender of such Security as provided in Section 3.03.
Any interest on any Security that is payable, but is not punctually paid or duly provided for, on any Interest Payment Date for Securities of the same series (herein called “Defaulted Interest”) shall forthwith cease to be payable to the registered holder on the relevant regular record date by virtue of having been such holder; and such Defaulted Interest shall be paid by the Company, at its election, as provided in clause (1) or clause (2) below:
(1)    The Company may make payment of any Defaulted Interest on Securities to the Persons in whose names such Securities (or their respective Predecessor Securities) are registered at the close of business on a special record date for the payment of such Defaulted Interest, which shall be fixed in the following manner:  the Company shall notify the Trustee in writing of the amount of Defaulted Interest proposed to be paid on each such Security and the date of the proposed payment, and at the same time the Company shall deposit with the Trustee an amount of money equal to the aggregate amount proposed to be paid in respect of such Defaulted Interest or shall make arrangements satisfactory to the Trustee for such deposit prior to the date of the proposed payment, such money when deposited to be held in trust for the benefit of the Persons entitled to such Defaulted Interest as in this clause provided.  Thereupon the Trustee shall fix a special record date for the payment of such Defaulted Interest which shall not be more than 15 nor less than 10 days prior to the date of the proposed payment and not less than 10 days after the receipt by the Trustee of the notice of the proposed payment.  The Trustee shall promptly notify the Company of such special record date and, in the name and at the expense of the Company, shall cause notice of the proposed payment of such Defaulted Interest and the special record date therefor to be mailed, first class postage prepaid, to each Securityholder at his or her address as it appears in the Security Register (as hereinafter defined), not less than 10 days prior to such special record date.  Notice of the proposed payment of such Defaulted Interest and the special record date therefor having been mailed as aforesaid, such Defaulted Interest shall be paid to the Persons in whose names such Securities (or their respective Predecessor Securities) are registered on such special record date and shall be no longer payable pursuant to the following clause (2).
(2)    The Company may make payment of any Defaulted Interest on any Securities in any other lawful manner not inconsistent with the requirements of any securities exchange on which such 

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Securities may be listed, and upon such notice as may be required by such exchange, if, after notice given by the Company to the Trustee of the proposed payment pursuant to this clause, such manner of payment shall be deemed practicable by the Trustee.
Unless otherwise set forth in a Board Resolution or one or more indentures supplemental hereto establishing the terms of any series of Securities pursuant to Section 2.01 hereof, the term “regular record date” as used in this Section with respect to a series of Securities and any Interest Payment Date for such series shall mean either the fifteenth day of the month immediately preceding the month in which an Interest Payment Date established for such series pursuant to Section 2.01 hereof shall occur, if such Interest Payment Date is the first day of a month, or the first day of the month in which an Interest Payment Date established for such series pursuant to Section 2.01 hereof shall occur, if such Interest Payment Date is the fifteenth day of a month, whether or not such date is a Business Day.
Subject to the foregoing provisions of this Section, each Security of a series delivered under this Indenture upon transfer of or in exchange for or in lieu of any other Security of such series shall carry the rights to interest accrued and unpaid, and to accrue, that were carried by such other Security.
Section 2.04    Execution and Authentications.
The Securities shall be signed on behalf of the Company by one of its Officers.  Signatures may be in the form of a manual or facsimile signature.
The Company may use the facsimile signature of any Person who shall have been an Officer, notwithstanding the fact that at the time the Securities shall be authenticated and delivered or disposed of such Person shall have ceased to be such an officer of the Company.  The seal of the Company may be in the form of a facsimile of such seal and may be impressed, affixed, imprinted or otherwise reproduced on the Securities.  The Securities may contain such notations, legends or endorsements required by law, stock exchange rule or usage.  Each Security shall be dated the date of its authentication by the Trustee.
A Security shall not be valid until authenticated manually by an authorized signatory of the Trustee, or by an Authenticating Agent.  Such signature shall be conclusive evidence that the Security so authenticated has been duly authenticated and delivered hereunder and that the holder is entitled to the benefits of this Indenture.  At any time and from time to time after the execution and delivery of this Indenture, the Company may deliver Securities of any series executed by the Company to the Trustee for authentication, together with a written order of the Company for the authentication and delivery of such Securities, signed by an Officer, and the Trustee in accordance with such written order shall authenticate and deliver such Securities.
In authenticating such Securities and accepting the additional responsibilities under this Indenture in relation to such Securities, the Trustee shall be entitled to receive, and (subject to Section 7.01) shall be fully protected in relying upon, an Opinion of Counsel stating that the form and terms thereof have been established in conformity with the provisions of this Indenture.

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The Trustee shall not be required to authenticate such Securities if the issue of such Securities pursuant to this Indenture will affect the Trustee’s own rights, duties or immunities under the Securities and this Indenture or otherwise in a manner that is not reasonably acceptable to the Trustee.
Section 2.05    Registration of Transfer and Exchange.
(a)    Securities of any series may be exchanged upon presentation thereof at the office or agency of the Company designated for such purpose in the Borough of Manhattan, the City and State of New York, for other Securities of such series of authorized denominations, and for a like aggregate principal amount, upon payment of a sum sufficient to cover any tax or other governmental charge in relation thereto, all as provided in this Section.  In respect of any Securities so surrendered for exchange, the Company shall execute, the Trustee shall authenticate and such office or agency shall deliver in exchange therefor the Security or Securities of the same series that the Securityholder making the exchange shall be entitled to receive, bearing numbers not contemporaneously outstanding.
(b)    The Company shall keep, or cause to be kept, at its office or agency designated for such purpose in the Borough of Manhattan, the City and State of New York, or such other location designated by the Company, a register or registers (herein referred to as the “Security Register”) in which, subject to such reasonable regulations as it may prescribe, the Company shall register the Securities and the transfers of Securities as in this Article provided and which at all reasonable times shall be open for inspection by the Trustee.  The registrar for the purpose of registering Securities and transfer of Securities as herein provided shall be appointed as authorized by Board Resolution (the “Security Registrar”).
Upon surrender for transfer of any Security at the office or agency of the Company designated for such purpose, the Company shall execute, the Trustee shall authenticate and such office or agency shall deliver in the name of the transferee or transferees a new Security or Securities of the same series as the Security presented for a like aggregate principal amount.
All Securities presented or surrendered for exchange or registration of transfer, as provided in this Section, shall be accompanied (if so required by the Company or the Security Registrar) by a written instrument or instruments of transfer, in form satisfactory to the Company or the Security Registrar, duly executed by the registered holder or by such holder’s duly authorized attorney in writing.
(c)    Except as provided pursuant to Section 2.01 pursuant to a Board Resolution, and set forth in an Officers’ Certificate, or established in one or more indentures supplemental to this Indenture, no service charge shall be made for any exchange or registration of transfer of Securities, or issue of new Securities in case of partial redemption of any series, but the Company may require payment of a sum sufficient to cover any tax or other governmental charge in relation thereto, other than exchanges pursuant to Section 2.06, Section 3.03(b) and Section 9.04 not involving any transfer.
(d)    The Company shall not be required (i) to issue, exchange or register the transfer of any Securities during a period beginning at the opening of business 15 days before the day of the mailing of a notice of redemption of less than all the Outstanding Securities of the same series and ending at the close of business on the day of such mailing, nor (ii) to register the transfer of or exchange any Securities of any 

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series or portions thereof called for redemption, other than the unredeemed portion of any such Securities being redeemed in part.  The provisions of this Section 2.05 are, with respect to any Global Security, subject to Section 2.11.
Section 2.06    Temporary Securities.
Pending the preparation of definitive Securities of any series, the Company may execute, and the Trustee shall authenticate and deliver, temporary Securities (printed, lithographed, typewritten or otherwise produced) of any authorized denomination.  Such temporary Securities shall be substantially in the form of the definitive Securities in lieu of which they are issued, but with such omissions, insertions and variations as may be appropriate for temporary Securities, all as may be determined by the Company.  Every temporary Security of any series shall be executed by the Company and be authenticated by the Trustee upon the same conditions and in substantially the same manner, and with like effect, as the definitive Securities of such series.  Without unnecessary delay the Company will execute and will furnish definitive Securities of such series and thereupon any or all temporary Securities of such series may be surrendered in exchange therefor (without charge to the holders), at the office or agency of the Company designated for the purpose in the Borough of Manhattan, the City and State of New York, and the Trustee shall authenticate and such office or agency shall deliver in exchange for such temporary Securities an equal aggregate principal amount of definitive Securities of such series, unless the Company advises the Trustee to the effect that definitive Securities need not be executed and furnished until further notice from the Company.  Until so exchanged, the temporary Securities of such series shall be entitled to the same benefits under this Indenture as definitive Securities of such series authenticated and delivered hereunder.
Section 2.07    Mutilated, Destroyed, Lost or Stolen Securities.
In case any temporary or definitive Security shall become mutilated or be destroyed, lost or stolen, the Company (subject to the next succeeding sentence) shall execute, and upon the Company’s request the Trustee (subject as aforesaid) shall authenticate and deliver, a new Security of the same series, bearing a number not contemporaneously outstanding, in exchange and substitution for the mutilated Security, or in lieu of and in substitution for the Security so destroyed, lost or stolen.  In every case the applicant for a substituted Security shall furnish to the Company and the Trustee such security or indemnity as may be required by them to save each of them harmless, and, in every case of destruction, loss or theft, the applicant shall also furnish to the Company and the Trustee evidence to their satisfaction of the destruction, loss or theft of the applicant’s Security and of the ownership thereof.  The Trustee may authenticate any such substituted Security and deliver the same upon the written request or authorization of any officer of the Company.  Upon the issuance of any substituted Security, the Company may require the payment of a sum sufficient to cover any tax or other governmental charge that may be imposed in relation thereto and any other expenses (including the fees and expenses of the Trustee) connected therewith.
In case any Security that has matured or is about to mature shall become mutilated or be destroyed, lost or stolen, the Company may, instead of issuing a substitute Security, pay or authorize the payment of the same (without surrender thereof except in the case of a mutilated Security) if the applicant for such 

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payment shall furnish to the Company and the Trustee such security or indemnity as they may require to save them harmless, and, in case of destruction, loss or theft, evidence to the satisfaction of the Company and the Trustee of the destruction, loss or theft of such Security and of the ownership thereof.
Every replacement Security issued pursuant to the provisions of this Section shall constitute an additional contractual obligation of the Company whether or not the mutilated, destroyed, lost or stolen Security shall be found at any time, or be enforceable by anyone, and shall be entitled to all the benefits of this Indenture equally and proportionately with any and all other Securities of the same series duly issued hereunder.  All Securities shall be held and owned upon the express condition that the foregoing provisions are exclusive with respect to the replacement or payment of mutilated, destroyed, lost or stolen Securities, and shall preclude (to the extent lawful) any and all other rights or remedies, notwithstanding any law or statute existing or hereafter enacted to the contrary with respect to the replacement or payment of negotiable instruments or other securities without their surrender.
Section 2.08    Cancellation.
All Securities surrendered for the purpose of payment, redemption, exchange or registration of transfer shall, if surrendered to the Company or any paying agent, be delivered to the Trustee for cancellation, or, if surrendered to the Trustee, shall be canceled by it, and no Securities shall be issued in lieu thereof except as expressly required or permitted by any of the provisions of this Indenture.  On request of the Company at the time of such surrender, the Trustee shall deliver to the Company canceled Securities held by the Trustee.  In the absence of such request the Trustee may dispose of canceled Securities in accordance with its standard procedures and deliver a certificate of disposition to the Company.  If the Company shall otherwise acquire any of the Securities, however, such acquisition shall not operate as a redemption or satisfaction of the indebtedness represented by such Securities unless and until the same are delivered to the Trustee for cancellation.
Section 2.09    Benefits of Indenture.
Nothing in this Indenture or in the Securities, express or implied, shall give or be construed to give to any Person, other than the parties hereto and the holders of the Securities (and, with respect to the provisions of Article Fourteen, the holders of any indebtedness of the Company to which the Securities of any series are subordinated) any legal or equitable right, remedy or claim under or in respect of this Indenture, or under any covenant, condition or provision herein contained; all such covenants, conditions and provisions being for the sole benefit of the parties hereto and of the holders of the Securities (and, with respect to the provisions of Article Fourteen, the holders of any indebtedness of the Company to which the Securities of any series are subordinated).
Section 2.10    Authenticating Agent.
So long as any of the Securities of any series remain Outstanding there may be an Authenticating Agent for any or all such series of Securities which the Trustee shall have the right to appoint.  Said Authenticating Agent shall be authorized to act on behalf of the Trustee to authenticate Securities of such series issued upon exchange, transfer or partial redemption thereof, and Securities so authenticated shall 

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be entitled to the benefits of this Indenture and shall be valid and obligatory for all purposes as if authenticated by the Trustee hereunder.  All references in this Indenture to the authentication of Securities by the Trustee shall be deemed to include authentication by an Authenticating Agent for such series.  Each Authenticating Agent shall be acceptable to the Company and shall be a corporation that has a combined capital and surplus, as most recently reported or determined by it, sufficient under the laws of any jurisdiction under which it is organized or in which it is doing business to conduct a trust business, and that is otherwise authorized under such laws to conduct such business and is subject to supervision or examination by federal or state authorities.  If at any time any Authenticating Agent shall cease to be eligible in accordance with these provisions, it shall resign immediately.
Any Authenticating Agent may at any time resign by giving written notice of resignation to the Trustee and to the Company.  The Trustee may at any time (and upon request by the Company shall) terminate the agency of any Authenticating Agent by giving written notice of termination to such Authenticating Agent and to the Company.  Upon resignation, termination or cessation of eligibility of any Authenticating Agent, the Trustee may appoint an eligible successor Authenticating Agent acceptable to the Company.  Any successor Authenticating Agent, upon acceptance of its appointment hereunder, shall become vested with all the rights, powers and duties of its predecessor hereunder as if originally named as an Authenticating Agent pursuant hereto.
Section 2.11    Global Securities.
(a)    If the Company shall establish pursuant to Section 2.01 that the Securities of a particular series are to be issued as a Global Security, then the Company shall execute and the Trustee shall, in accordance with Section 2.04, authenticate and deliver, a Global Security that (i) shall represent, and shall be denominated in an amount equal to the aggregate principal amount of, all of the Outstanding Securities of such series, (ii) shall be registered in the name of the Depositary or its nominee, (iii) shall be delivered by the Trustee to the Depositary or pursuant to the Depositary’s instruction and (iv) shall bear a legend substantially to the following effect:  “Except as otherwise provided in Section 2.11 of the Indenture, this Security may be transferred, in whole but not in part, only to another nominee of the Depositary or to a successor Depositary or to a nominee of such successor Depositary.”
(b)    Notwithstanding the provisions of Section 2.05, the Global Security of a series may be transferred, in whole but not in part and in the manner provided in Section 2.05, only to another nominee of the Depositary for such series, or to a successor Depositary for such series selected or approved by the Company or to a nominee of such successor Depositary.
(c)    If at any time the Depositary for a series of the Securities notifies the Company that it is unwilling or unable to continue as Depositary for such series or if at any time the Depositary for such series shall no longer be registered or in good standing under the Exchange Act, or other applicable statute or regulation, and a successor Depositary for such series is not appointed by the Company within 90 days after the Company receives such notice or becomes aware of such condition, as the case may be, or if an Event of Default has occurred and is continuing and the Company has received a request from the Depositary, this Section 2.11 shall no longer be applicable to the Securities of such series and the 

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Company will execute, and subject to Section 2.04, the Trustee will authenticate and deliver the Securities of such series in definitive registered form without coupons, in authorized denominations, and in an aggregate principal amount equal to the principal amount of the Global Security of such series in exchange for such Global Security.  In addition, the Company may at any time determine that the Securities of any series shall no longer be represented by a Global Security and that the provisions of this Section 2.11 shall no longer apply to the Securities of such series.  In such event the Company will execute and, subject to Section 2.04, the Trustee, upon receipt of an Officers’ Certificate evidencing such determination by the Company, will authenticate and deliver the Securities of such series in definitive registered form without coupons, in authorized denominations, and in an aggregate principal amount equal to the principal amount of the Global Security of such series in exchange for such Global Security.  Upon the exchange of the Global Security for such Securities in definitive registered form without coupons, in authorized denominations, the Global Security shall be canceled by the Trustee.  Such Securities in definitive registered form issued in exchange for the Global Security pursuant to this Section 2.11(c) shall be registered in such names and in such authorized denominations as the Depositary, pursuant to instructions from its direct or indirect participants or otherwise, shall instruct the Trustee.  The Trustee shall deliver such Securities to the Depositary for delivery to the Persons in whose names such Securities are so registered.
ARTICLE 3
REDEMPTION OF SECURITIES AND SINKING FUND PROVISIONS
Section 3.01    Redemption.
The Company may redeem the Securities of any series issued hereunder on and after the dates and in accordance with the terms established for such series pursuant to Section 2.01 hereof.
Section 3.02    Notice of Redemption.
(a)    In case the Company shall desire to exercise such right to redeem all or, as the case may be, a portion of the Securities of any series in accordance with any right the Company reserved for itself to do so pursuant to Section 2.01 hereof, the Company shall, or shall cause the Trustee to, give notice of such redemption to holders of the Securities of such series to be redeemed by mailing, first class postage prepaid, a notice of such redemption not less than 30 days and not more than 90 days before the date fixed for redemption of that series to such holders at their last addresses as they shall appear upon the Security Register, unless a shorter period is specified in the Securities to be redeemed.  Any notice that is mailed in the manner herein provided shall be conclusively presumed to have been duly given, whether or not the registered holder receives the notice.  In any case, failure duly to give such notice to the holder of any Security of any series designated for redemption in whole or in part, or any defect in the notice, shall not affect the validity of the proceedings for the redemption of any other Securities of such series or any other series.  In the case of any redemption of Securities prior to the expiration of any restriction on such redemption provided in the terms of such Securities or elsewhere in this Indenture, the Company shall furnish the Trustee with an Officers’ Certificate evidencing compliance with any such restriction.

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Each such notice of redemption shall specify the date fixed for redemption and the redemption price at which Securities of that series are to be redeemed, and shall state that payment of the redemption price of such Securities to be redeemed will be made at the office or agency of the Company in the Borough of Manhattan, the City and State of New York, upon presentation and surrender of such Securities, that interest accrued to the date fixed for redemption will be paid as specified in said notice, that from and after said date interest will cease to accrue and that the redemption is for a sinking fund, if such is the case.  If less than all the Securities of a series are to be redeemed, the notice to the holders of Securities of that series to be redeemed in part shall specify the particular Securities to be so redeemed.
In case any Security is to be redeemed in part only, the notice that relates to such Security shall state the portion of the principal amount thereof to be redeemed, and shall state that on and after the redemption date, upon surrender of such Security, a new Security or Securities of such series in principal amount equal to the unredeemed portion thereof will be issued.
(b)    If less than all the Securities of a series are to be redeemed, the Company shall give the Trustee at least 45 days’ notice (unless a shorter notice shall be satisfactory to the Trustee) in advance of the date fixed for redemption as to the aggregate principal amount of Securities of the series to be redeemed, and thereupon the Trustee shall select, by lot or in such other manner as it shall deem appropriate and fair in its discretion and that may provide for the selection of a portion or portions (equal to one thousand U.S. dollars ($1,000) or any integral multiple thereof) of the principal amount of such Securities of a denomination larger than $1,000, the Securities to be redeemed and shall thereafter promptly notify the Company in writing of the numbers of the Securities to be redeemed, in whole or in part.  The Company may, if and whenever it shall so elect, by delivery of instructions signed on its behalf by an Officer, instruct the Trustee or any paying agent to call all or any part of the Securities of a particular series for redemption and to give notice of redemption in the manner set forth in this Section, such notice to be in the name of the Company or its own name as the Trustee or such paying agent may deem advisable.  In any case in which notice of redemption is to be given by the Trustee or any such paying agent, the Company shall deliver or cause to be delivered to, or permit to remain with, the Trustee or such paying agent, as the case may be, such Security Register, transfer books or other records, or suitable copies or extracts therefrom, sufficient to enable the Trustee or such paying agent to give any notice by mail that may be required under the provisions of this Section.
Section 3.03    Payment Upon Redemption.
(a)    If the giving of notice of redemption shall have been completed as above provided, the Securities or portions of Securities of the series to be redeemed specified in such notice shall become due and payable on the date and at the place stated in such notice at the applicable redemption price, together with interest accrued to the date fixed for redemption and interest on such Securities or portions of Securities shall cease to accrue on and after the date fixed for redemption, unless the Company shall default in the payment of such redemption price and accrued interest with respect to any such Security or portion thereof.  On presentation and surrender of such Securities on or after the date fixed for redemption at the place of payment specified in the notice, said Securities shall be paid and redeemed at the applicable redemption price for such series, together with interest accrued thereon to the date fixed for redemption 

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(but if the date fixed for redemption is an interest payment date, the interest installment payable on such date shall be payable to the registered holder at the close of business on the applicable record date pursuant to Section 2.03).
(b)    Upon presentation of any Security of such series that is to be redeemed in part only, the Company shall execute and the Trustee shall authenticate and the office or agency where the Security is presented shall deliver to the holder thereof, at the expense of the Company, a new Security of the same series of authorized denominations in principal amount equal to the unredeemed portion of the Security so presented.
Section 3.04    Sinking Fund.
The provisions of Sections 3.04, 3.05 and 3.06 shall be applicable to any sinking fund for the retirement of Securities of a series, except as otherwise specified as contemplated by Section 2.01 for Securities of such series.
The minimum amount of any sinking fund payment provided for by the terms of Securities of any series is herein referred to as a “mandatory sinking fund payment,” and any payment in excess of such minimum amount provided for by the terms of Securities of any series is herein referred to as an “optional sinking fund payment”.  If provided for by the terms of Securities of any series, the cash amount of any sinking fund payment may be subject to reduction as provided in Section 3.05.  Each sinking fund payment shall be applied to the redemption of Securities of any series as provided for by the terms of Securities of such series.
Section 3.05    Satisfaction of Sinking Fund Payments with Securities.
The Company (i) may deliver Outstanding Securities of a series and (ii) may apply as a credit Securities of a series that have been redeemed either at the election of the Company pursuant to the terms of such Securities or through the application of permitted optional sinking fund payments pursuant to the terms of such Securities, in each case in satisfaction of all or any part of any sinking fund payment with respect to the Securities of such series required to be made pursuant to the terms of such Securities as provided for by the terms of such series, provided that such Securities have not been previously so credited.  Such Securities shall be received and credited for such purpose by the Trustee at the redemption price specified in such Securities for redemption through operation of the sinking fund and the amount of such sinking fund payment shall be reduced accordingly.
Section 3.06    Redemption of Securities for Sinking Fund.
Not less than 45 days prior to each sinking fund payment date for any series of Securities (unless a shorter period shall be satisfactory to the Trustee), the Company will deliver to the Trustee an Officers’ Certificate specifying the amount of the next ensuing sinking fund payment for that series pursuant to the terms of the series, the portion thereof, if any, that is to be satisfied by delivering and crediting Securities of that series pursuant to Section 3.05 and the basis for such credit and will, together with such Officers’ Certificate, deliver to the Trustee any Securities to be so delivered.  Not less than 30 days before each such sinking fund payment date the Trustee shall select the Securities to be redeemed upon such sinking fund 

16

payment date in the manner specified in Section 3.02 and cause notice of the redemption thereof to be given in the name of and at the expense of the Company in the manner provided in Section 3.02.  Such notice having been duly given, the redemption of such Securities shall be made upon the terms and in the manner stated in Section 3.03.
ARTICLE 4
COVENANTS
Section 4.01    Payment of Principal, Premium and Interest.
The Company will duly and punctually pay or cause to be paid the principal of (and premium, if any) and interest on the Securities of that series at the time and place and in the manner provided herein and established with respect to such Securities.  Payments of principal on the Securities may be made at the time provided herein and established with respect to such Securities by U.S. dollar check drawn on and mailed to the address of the Securityholder entitled thereto as such address shall appear in the Security Register, or U.S. dollar wire transfer to a U.S. dollar account (such wire transfer to be made only to a Securityholder of an aggregate principal amount of Securities of the applicable series in excess of U.S. $2,000,000 and only if such Securityholder shall have furnished wire instructions to the Trustee no later than 15 days prior to the relevant payment date).  Payments of interest on the Securities may be made at the time provided herein and established with respect to such Securities by U.S. dollar check mailed to the address of the Securityholder entitled thereto as such address shall appear in the Security Register, or U.S. dollar wire transfer to, a U.S. dollar account (such a wire transfer to be made only to a Securityholder of an aggregate principal amount of Securities of the applicable series in excess of U.S. $2,000,000 and only if such Securityholder shall have furnished wire instructions in writing to the Security Registrar and the Trustee no later than 15 days prior to the relevant payment date).
Section 4.02    Maintenance of Office or Agency.
So long as any series of the Securities remain Outstanding, the Company agrees to maintain an office or agency in the Borough of Manhattan, the City and State of New York, with respect to each such series and at such other location or locations as may be designated as provided in this Section 4.02, where (i) Securities of that series may be presented for payment, (ii) Securities of that series may be presented as herein above authorized for registration of transfer and exchange, and (iii) notices and demands to or upon the Company in respect of the Securities of that series and this Indenture may be given or served, such designation to continue with respect to such office or agency until the Company shall, by written notice signed by any officer authorized to sign an Officers’ Certificate and delivered to the Trustee, designate some other office or agency for such purposes or any of them.  If at any time the Company shall fail to maintain any such required office or agency or shall fail to furnish the Trustee with the address thereof, such presentations, notices and demands may be made or served at the Corporate Trust Office of the Trustee, and the Company hereby appoints the Trustee as its agent to receive all such presentations, notices and demands.  The Company initially appoints the Corporate Trust Office of the Trustee located in the Borough of Manhattan, the City of New York as its paying agent with respect to the Securities.
Section 4.03    Paying Agents.

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(a)    If the Company shall appoint one or more paying agents for all or any series of the Securities, other than the Trustee, the Company will cause each such paying agent to execute and deliver to the Trustee an instrument in which such agent shall agree with the Trustee, subject to the provisions of this Section:
(1)    that it will hold all sums held by it as such agent for the payment of the principal of (and premium, if any) or interest on the Securities of that series (whether such sums have been paid to it by the Company or by any other obligor of such Securities) in trust for the benefit of the Persons entitled thereto;
(2)    that it will give the Trustee notice of any failure by the Company (or by any other obligor of such Securities) to make any payment of the principal of (and premium, if any) or interest on the Securities of that series when the same shall be due and payable;
(3)    that it will, at any time during the continuance of any failure referred to in the preceding paragraph (a)(2) above, upon the written request of the Trustee, forthwith pay to the Trustee all sums so held in trust by such paying agent; and
(4)    that it will perform all other duties of paying agent as set forth in this Indenture.
(b)    If the Company shall act as its own paying agent with respect to any series of the Securities, it will on or before each due date of the principal of (and premium, if any) or interest on Securities of that series, set aside, segregate and hold in trust for the benefit of the Persons entitled thereto a sum sufficient to pay such principal (and premium, if any) or interest so becoming due on Securities of that series until such sums shall be paid to such Persons or otherwise disposed of as herein provided and will promptly notify the Trustee of such action, or any failure (by it or any other obligor on such Securities) to take such action.  Whenever the Company shall have one or more paying agents for any series of Securities, it will, prior to each due date of the principal of (and premium, if any) or interest on any Securities of that series, deposit with the paying agent a sum sufficient to pay the principal (and premium, if any) or interest so becoming due, such sum to be held in trust for the benefit of the Persons entitled to such principal, premium or interest, and (unless such paying agent is the Trustee) the Company will promptly notify the Trustee of this action or failure so to act.
(c)    Notwithstanding anything in this Section to the contrary, (i) the agreement to hold sums in trust as provided in this Section is subject to the provisions of Section 11.05, and (ii) the Company may at any time, for the purpose of obtaining the satisfaction and discharge of this Indenture or for any other purpose, pay, or direct any paying agent to pay, to the Trustee all sums held in trust by the Company or such paying agent, such sums to be held by the Trustee upon the same terms and conditions as those upon which such sums were held by the Company or such paying agent; and, upon such payment by the Company or any paying agent to the Trustee, the Company or such paying agent shall be released from all further liability with respect to such money.

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ARTICLE 5
SECURITYHOLDERS’ LISTS AND REPORTS BY THE COMPANY AND THE 
TRUSTEE
Section 5.01    Company to Furnish Trustee Names and Addresses of Securityholders.
The Company will furnish or cause to be furnished to the Trustee (a) within 15 days after each regular record date (as defined in Section 2.03) a list, in such form as the Trustee may reasonably require, of the names and addresses of the holders of each series of Securities as of such regular record date, provided that the Company shall not be obligated to furnish or cause to furnish such list at any time that the list shall not differ in any respect from the most recent list furnished to the Trustee by the Company and (b) at such other times as the Trustee may request in writing within 30 days after the receipt by the Company of any such request, a list of similar form and content as of a date not more than 15 days prior to the time such list is furnished; provided, however, that, in either case, no such list need be furnished for any series for which the Trustee shall be the Security Registrar.
Section 5.02    Preservation Of Information; Communications With Securityholders.
(a)    The Trustee shall preserve, in as current a form as is reasonably practicable, all information as to the names and addresses of the holders of Securities contained in the most recent list furnished to it as provided in Section 5.01 and as to the names and addresses of holders of Securities received by the Trustee in its capacity as Security Registrar (if acting in such capacity).
(b)    The Trustee may destroy any list furnished to it as provided in Section 5.01 upon receipt of a new list so furnished.
(c)    Securityholders may communicate as provided in Section 312(b) of the Trust Indenture Act with other Securityholders with respect to their rights under this Indenture or under the Securities, and, in connection with any such communications, the Trustee shall satisfy its obligations under Section 312(b) of the Trust Indenture Act in accordance with the provisions of Section 312(b) of the Trust Indenture Act.
Section 5.03    Reports by the Company.
(a)    The Company covenants and agrees to provide to the Trustee (which delivery may be via electronic mail), after the Company files the same with the Securities and Exchange Commission, copies of the annual reports and of the information, documents and other reports (or copies of such portions of any of the foregoing as the Securities and Exchange Commission may from time to time by rules and regulations prescribe) that the Company files with the Securities and Exchange Commission pursuant to Section 13 or Section 15(d) of the Exchange Act; or, if the Company is not required to file information, documents or reports pursuant to either of such sections, then to file with the Trustee, in accordance with the rules and regulations prescribed from time to time by the Securities and Exchange Commission, such of the supplementary and periodic information, documents and reports that may be required pursuant to Section 13 of the Exchange Act, in respect of a security listed and registered on a national securities exchange as may be prescribed from time to time in such rules and regulations; provided, however, the Company shall not be required to deliver to the Trustee any materials for which the Company has sought 

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and received confidential treatment by the Securities and Exchange Commission; and provided further, so long as such filings are available on the Securities and Exchange Commission’s Electronic Data Gathering, Analysis and Retrieval System (EDGAR) or any successor system thereto, such filings shall be deemed to have been filed with the Trustee for purposes of this Section 5.03 without any further action required by the Company.
(b)    The Company covenants and agrees to file with the Trustee and the Securities and Exchange Commission, in accordance with the rules and regulations prescribed from to time by the Securities and Exchange Commission, such additional information, documents and reports with respect to compliance by the Company with the conditions and covenants provided for in this Indenture as may be required from time to time by such rules and regulations.
(c)    The Company covenants and agrees to transmit by mail, first class postage prepaid, or reputable over-night delivery service that provides for evidence of receipt, or in accordance with the applicable procedures of DTC, to the Securityholders, as their names and addresses appear upon the Security Register, within 30 days after the filing thereof with the Trustee, such summaries of any information, documents and reports required to be filed by the Company pursuant to subsections (a) and (b) of this Section as may be required by rules and regulations prescribed from time to time by the Securities and Exchange Commission.
Section 5.04    Reports by the Trustee.
(a)    If required by Section 313(a) of the Trust Indenture Act, the Trustee, within 60 days after each May 1, shall transmit by mail, first class postage prepaid, to the Securityholders, as their names and addresses appear upon the Security Register, a brief report dated as of such May 1, which complies with Section 313(a) of the Trust Indenture Act.
(b)    The Trustee shall comply with Section 313(b) and 313(c) of the Trust Indenture Act.
(c)    A copy of each such report shall, at the time of such transmission to Securityholders, be filed by the Trustee with the Company, with each securities exchange upon which any Securities are listed (if so listed) and also with the Securities and Exchange Commission.  The Company agrees to notify the Trustee when any Securities become listed on any securities exchange.
ARTICLE 6
REMEDIES OF THE TRUSTEE AND SECURITYHOLDERS ON EVENT OF 
DEFAULT
Section 6.01    Events of Default.
(a)    Whenever used herein with respect to Securities of a particular series, “Event of Default” means any one or more of the following events that has occurred and is continuing:
(1)    the Company defaults in the payment of any installment of interest upon any of the Securities of that series, as and when the same shall become due and payable, and such default continues for a period of 90 days; provided, however, that a valid extension of an interest payment period by the 

20

Company in accordance with the terms of any indenture supplemental hereto shall not constitute a default in the payment of interest for this purpose;
(2)    the Company defaults in the payment of the principal of (or premium, if any, on) any of the Securities of that series as and when the same shall become due and payable whether at maturity, upon redemption, by declaration or otherwise, or in any payment required by any sinking or analogous fund established with respect to that series; provided, however, that a valid extension of the maturity of such Securities in accordance with the terms of any indenture supplemental hereto shall not constitute a default in the payment of principal or premium, if any;
(3)    the Company fails to observe or perform any other of its covenants or agreements with respect to that series contained in this Indenture or otherwise established with respect to that series of Securities pursuant to Section 2.01 hereof (other than a covenant or agreement that has been expressly included in this Indenture solely for the benefit of one or more series of Securities other than such series) for a period of 90 days after the date on which written notice of such failure, requiring the same to be remedied and stating that such notice is a “Notice of Default” hereunder, shall have been given to the Company by the Trustee, by registered or certified mail, or to the Company and the Trustee by the holders of at least 25% in principal amount of the Securities of that series at the time Outstanding;
(4)    the Company pursuant to or within the meaning of any Bankruptcy Law (i) commences a voluntary case, (ii) consents to the entry of an order for relief against it in an involuntary case, (iii) consents to the appointment of a Custodian of it or for all or substantially all of its property or (iv) makes a general assignment for the benefit of its creditors; or
(5)    a court of competent jurisdiction enters an order under any Bankruptcy Law that (i) is for relief against the Company in an involuntary case, (ii) appoints a Custodian of the Company for all or substantially all of its property or (iii) orders the liquidation of the Company, and the order or decree remains unstayed and in effect for 90 days.
(b)    In each and every such case (other than an Event of Default specified in clause (4) or clause (5) above), unless the principal of all the Securities of that series shall have already become due and payable, either the Trustee or the holders of not less than 25% in aggregate principal amount of the Securities of that series then Outstanding hereunder, by notice in writing to the Company (and to the Trustee if given by such Securityholders), may declare the principal of (and premium, if any, on) and accrued and unpaid interest on all the Securities of that series to be due and payable immediately, and upon any such declaration the same shall become and shall be immediately due and payable.  If an Event of Default specified in clause (4) or clause (5) above occurs, the principal of and accrued and unpaid interest on all the Securities of that series shall automatically be immediately due and payable without any declaration or other act on the part of the Trustee or the holders of the Securities.
(c)    At any time after the principal of (and premium, if any, on) and accrued and unpaid interest on the Securities of that series shall have been so declared due and payable, and before any judgment or decree for the payment of the moneys due shall have been obtained or entered as hereinafter provided, the holders of a majority in aggregate principal amount of the Securities of that series then Outstanding 

21

hereunder, by written notice to the Company and the Trustee, may rescind and annul such declaration and its consequences if:  (i) the Company has paid or deposited with the Trustee a sum sufficient to pay all matured installments of interest upon all the Securities of that series and the principal of (and premium, if any, on) any and all Securities of that series that shall have become due otherwise than by acceleration (with interest upon such principal and premium, if any, and, to the extent that such payment is enforceable under applicable law, upon overdue installments of interest, at the rate per annum expressed in the Securities of that series to the date of such payment or deposit) and the amount payable to the Trustee under Section 7.06, and (ii) any and all Events of Default under the Indenture with respect to such series, other than the nonpayment of principal on (and premium, if any, on) and accrued and unpaid interest on Securities of that series that shall not have become due by their terms, shall have been remedied or waived as provided in Section 6.06.
No such rescission and annulment shall extend to or shall affect any subsequent default or impair any right consequent thereon.
(d)    In case the Trustee shall have proceeded to enforce any right with respect to Securities of that series under this Indenture and such proceedings shall have been discontinued or abandoned because of such rescission or annulment or for any other reason or shall have been determined adversely to the Trustee, then and in every such case, subject to any determination in such proceedings, the Company and the Trustee shall be restored respectively to their former positions and rights hereunder, and all rights, remedies and powers of the Company and the Trustee shall continue as though no such proceedings had been taken.
Section 6.02    Collection of Indebtedness and Suits for Enforcement by Trustee.
(a)    The Company covenants that (i) in case it shall default in the payment of any installment of interest on any of the Securities of a series, or in any payment required by any sinking or analogous fund established with respect to that series as and when the same shall have become due and payable, and such default shall have continued for a period of 90 days, or (ii) in case it shall default in the payment of the principal of (or premium, if any, on) any of the Securities of a series when the same shall have become due and payable, whether upon maturity of the Securities of a series or upon redemption or upon declaration or otherwise then, upon demand of the Trustee, the Company will pay to the Trustee, for the benefit of the holders of the Securities of that series, the whole amount that then shall have been become due and payable on all such Securities for principal (and premium, if any) or interest, or both, as the case may be, with interest upon the overdue principal (and premium, if any) and (to the extent that payment of such interest is enforceable under applicable law) upon overdue installments of interest at the rate per annum expressed in the Securities of that series; and, in addition thereto, such further amount as shall be sufficient to cover the costs and expenses of collection, and the amount payable to the Trustee under Section 7.06.
(b)    If the Company shall fail to pay such amounts forthwith upon such demand, the Trustee, in its own name and as trustee of an express trust, shall be entitled and empowered to institute any action or proceedings at law or in equity for the collection of the sums so due and unpaid, and may prosecute any such action or proceeding to judgment or final decree, and may enforce any such judgment or final decree 

22

against the Company or other obligor upon the Securities of that series and collect the moneys adjudged or decreed to be payable in the manner provided by law or equity out of the property of the Company or other obligor upon the Securities of that series, wherever situated.
(c)    In case of any receivership, insolvency, liquidation, bankruptcy, reorganization, readjustment, arrangement, composition or judicial proceedings affecting the Company, or its creditors or property, the Trustee shall have power to intervene in such proceedings and take any action therein that may be permitted by the court and shall (except as may be otherwise provided by law) be entitled to file such proofs of claim and other papers and documents as may be necessary or advisable in order to have the claims of the Trustee and of the holders of Securities of such series allowed for the entire amount due and payable by the Company under the Indenture at the date of institution of such proceedings and for any additional amount that may become due and payable by the Company after such date, and to collect and receive any moneys or other property payable or deliverable on any such claim, and to distribute the same after the deduction of the amount payable to the Trustee under Section 7.06; and any receiver, assignee or trustee in bankruptcy or reorganization is hereby authorized by each of the holders of Securities of such series to make such payments to the Trustee, and, in the event that the Trustee shall consent to the making of such payments directly to such Securityholders, to pay to the Trustee any amount due it under Section 7.06.
(d)    All rights of action and of asserting claims under this Indenture, or under any of the terms established with respect to Securities of that series, may be enforced by the Trustee without the possession of any of such Securities, or the production thereof at any trial or other proceeding relative thereto, and any such suit or proceeding instituted by the Trustee shall be brought in its own name as trustee of an express trust, and any recovery of judgment shall, after provision for payment to the Trustee of any amounts due under Section 7.06, be for the ratable benefit of the holders of the Securities of such series.
In case of an Event of Default hereunder, the Trustee may in its discretion proceed to protect and enforce the rights vested in it by this Indenture by such appropriate judicial proceedings as the Trustee shall deem most effectual to protect and enforce any of such rights, either at law or in equity or in bankruptcy or otherwise, whether for the specific enforcement of any covenant or agreement contained in the Indenture or in aid of the exercise of any power granted in this Indenture, or to enforce any other legal or equitable right vested in the Trustee by this Indenture or by law.
Nothing contained herein shall be deemed to authorize the Trustee to authorize or consent to or accept or adopt on behalf of any Securityholder any plan of reorganization, arrangement, adjustment or composition affecting the Securities of that series or the rights of any holder thereof or to authorize the Trustee to vote in respect of the claim of any Securityholder in any such proceeding.
Section 6.03    Application of Moneys Collected.
Any moneys collected by the Trustee pursuant to this Article with respect to a particular series of Securities shall be applied in the following order, at the date or dates fixed by the Trustee and, in case of the distribution of such moneys on account of principal (or premium, if any) or interest, upon presentation 

23

of the Securities of that series, and notation thereon of the payment, if only partially paid, and upon surrender thereof if fully paid:
FIRST:  To the payment of reasonable costs and expenses of collection and of all amounts payable to the Trustee under Section 7.06;
SECOND:  To the payment of all indebtedness of the Company to which such series of Securities is subordinated to the extent required by Section 7.06 and Article Fourteen;
THIRD:  To the payment of the amounts then due and unpaid upon Securities of such series for principal (and premium, if any) and interest, in respect of which or for the benefit of which such money has been collected, ratably, without preference or priority of any kind, according to the amounts due and payable on such Securities for principal (and premium, if any) and interest, respectively; and
FOURTH:  To the payment of the remainder, if any, to the Company, its successors or assigns, or any other Person lawfully entitled thereto.
Section 6.04    Limitation on Suits.
No holder of any Security of any series shall have any right by virtue or by availing of any provision of this Indenture to institute any suit, action or proceeding in equity or at law upon or under or with respect to this Indenture or for the appointment of a receiver or trustee, or for any other remedy hereunder, unless (i) such holder previously shall have given to the Trustee written notice of an Event of Default and of the continuance thereof with respect to the Securities of such series specifying such Event of Default, as hereinbefore provided; (ii) the holders of not less than 25% in aggregate principal amount of the Securities of such series then Outstanding shall have made written request upon the Trustee to institute such action, suit or proceeding in its own name as Trustee hereunder; (iii) such holder or holders shall have offered to the Trustee such reasonable indemnity as it may require against the costs, expenses and liabilities to be incurred therein or thereby; (iv) the Trustee for 60 days after its receipt of such notice, request and offer of indemnity, shall have failed to institute any such action, suit or proceeding; and (v) during such 60 day period, the holders of a majority in principal amount of the Securities of that series do not give the Trustee a direction inconsistent with the request.
Notwithstanding anything contained herein to the contrary or any other provisions of this Indenture, the right of any holder of any Security to receive payment of the principal of (and premium, if any) and interest on such Security, as therein provided, on or after the respective due dates expressed in such Security (or in the case of redemption, on the redemption date), or to institute suit for the enforcement of any such payment on or after such respective dates or redemption date, shall not be impaired or affected without the consent of such holder and by accepting a Security hereunder it is expressly understood, intended and covenanted by the taker and holder of every Security of such series with every other such taker and holder and the Trustee, that no one or more holders of Securities of such series shall have any right in any manner whatsoever by virtue or by availing of any provision of this Indenture to affect, disturb or prejudice the rights of the holders of any other of such Securities, or to obtain or seek to obtain priority over or preference to any other such holder, or to enforce any right under 

24

this Indenture, except in the manner herein provided and for the equal, ratable and common benefit of all holders of Securities of such series.  For the protection and enforcement of the provisions of this Section, each and every Securityholder and the Trustee shall be entitled to such relief as can be given either at law or in equity.
Section 6.05    Rights and Remedies Cumulative; Delay or Omission Not Waiver.
(a)    Except as otherwise provided in Section 2.07, all powers and remedies given by this Article to the Trustee or to the Securityholders shall, to the extent permitted by law, be deemed cumulative and not exclusive of any other powers and remedies available to the Trustee or the holders of the Securities, by judicial proceedings or otherwise, to enforce the performance or observance of the covenants and agreements contained in this Indenture or otherwise established with respect to such Securities.
(b)    No delay or omission of the Trustee or of any holder of any of the Securities to exercise any right or power accruing upon any Event of Default occurring and continuing as aforesaid shall impair any such right or power, or shall be construed to be a waiver of any such default or an acquiescence therein; and, subject to the provisions of Section 6.04, every power and remedy given by this Article or by law to the Trustee or the Securityholders may be exercised from time to time, and as often as shall be deemed expedient, by the Trustee or by the Securityholders.
Section 6.06    Control by Securityholders.
The holders of a majority in aggregate principal amount of the Securities of any series at the time Outstanding, determined in accordance with Section 8.04, shall have the right to direct the time, method and place of conducting any proceeding for any remedy available to the Trustee, or exercising any trust or power conferred on the Trustee with respect to such series; provided, however, that such direction shall not be in conflict with any rule of law or with this Indenture.  Subject to the provisions of Section 7.01, the Trustee shall have the right to decline to follow any such direction if the Trustee in good faith shall, by a Responsible Officer or officers of the Trustee, determine that the proceeding so directed, subject to the Trustee’s duties under the Trust Indenture Act, would involve the Trustee in personal liability or might be unduly prejudicial to the Securityholders not involved in the proceeding.  The holders of a majority in aggregate principal amount of the Securities of any series at the time Outstanding affected thereby, determined in accordance with Section 8.04, may on behalf of the holders of all of the Securities of such series waive any past default in the performance of any of the covenants contained herein or established pursuant to Section 2.01 with respect to such series and its consequences, except a default in the payment of the principal of, or premium, if any, or interest on, any of the Securities of that series as and when the same shall become due by the terms of such Securities otherwise than by acceleration (unless such default has been cured and a sum sufficient to pay all matured installments of interest and principal and any premium has been deposited with the Trustee (in accordance with Section 6.01(c))).  Upon any such waiver, the default covered thereby shall be deemed to be cured for all purposes of this Indenture and the Company, the Trustee and the holders of the Securities of such series shall be restored to their former positions and rights hereunder, respectively; but no such waiver shall extend to any subsequent or other default or impair any right consequent thereon.

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Section 6.07    Undertaking to Pay Costs.
All parties to this Indenture agree, and each holder of any Securities by such holder’s acceptance thereof shall be deemed to have agreed, that any court may in its discretion require, in any suit for the enforcement of any right or remedy under this Indenture, or in any suit against the Trustee for any action taken or omitted by it as Trustee, the filing by any party litigant in such suit of an undertaking to pay the costs of such suit, and that such court may in its discretion assess reasonable costs, including reasonable attorneys’ fees, against any party litigant in such suit, having due regard to the merits and good faith of the claims or defenses made by such party litigant; but the provisions of this Section shall not apply to any suit instituted by the Trustee, to any suit instituted by any Securityholder, or group of Securityholders, holding more than 10% in aggregate principal amount of the Outstanding Securities of any series, or to any suit instituted by any Securityholder for the enforcement of the payment of the principal of (or premium, if any) or interest on any Security of such series, on or after the respective due dates expressed in such Security or established pursuant to this Indenture.
ARTICLE 7
CONCERNING THE TRUSTEE
Section 7.01    Certain Duties and Responsibilities of Trustee.
(a)    The Trustee, prior to the occurrence of an Event of Default with respect to the Securities of a series and after the curing of all Events of Default with respect to the Securities of that series that may have occurred, shall undertake to perform with respect to the Securities of such series such duties and only such duties as are specifically set forth in this Indenture, and no implied covenants shall be read into this Indenture against the Trustee.  In case an Event of Default with respect to the Securities of a series has occurred (that has not been cured or waived), the Trustee shall exercise with respect to Securities of that series such of the rights and powers vested in it by this Indenture, and use the same degree of care and skill in their exercise, as a prudent man would exercise or use under the circumstances in the conduct of his own affairs.
(b)    No provision of this Indenture shall be construed to relieve the Trustee from liability for its own negligent action, its own negligent failure to act, or its own willful misconduct, except that:
(i)    prior to the occurrence of an Event of Default with respect to the Securities of a series and after the curing or waiving of all such Events of Default with respect to that series that may have occurred:
(A)    the duties and obligations of the Trustee shall with respect to the Securities of such series be determined solely by the express provisions of this Indenture, and the Trustee shall not be liable with respect to the Securities of such series except for the performance of such duties and obligations as are specifically set forth in this Indenture, and no implied covenants or obligations shall be read into this Indenture against the Trustee; and
(B)    in the absence of bad faith on the part of the Trustee, the Trustee may with respect to the Securities of such series conclusively rely, as to the truth of the statements and the 

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correctness of the opinions expressed therein, upon any certificates or opinions furnished to the Trustee and conforming to the requirements of this Indenture; but in the case of any such certificates or opinions that by any provision hereof are specifically required to be furnished to the Trustee, the Trustee shall be under a duty to examine the same to determine whether or not they conform to the requirements of this Indenture;
(ii)    the Trustee shall not be liable for any error of judgment made in good faith by a Responsible Officer or Responsible Officers of the Trustee, unless it shall be proved that the Trustee was negligent in ascertaining the pertinent facts;
(iii)    the Trustee shall not be liable with respect to any action taken or omitted to be taken by it in good faith in accordance with the direction of the holders of not less than a majority in principal amount of the Securities of any series at the time Outstanding relating to the time, method and place of conducting any proceeding for any remedy available to the Trustee, or exercising any trust or power conferred upon the Trustee under this Indenture with respect to the Securities of that series; and
(iv)    None of the provisions contained in this Indenture shall require the Trustee to expend or risk its own funds or otherwise incur personal financial liability in the performance of any of its duties or in the exercise of any of its rights or powers if there is reasonable ground for believing that the repayment of such funds or liability is not reasonably assured to it under the terms of this Indenture or adequate indemnity against such risk is not reasonably assured to it.
Section 7.02    Certain Rights of Trustee.
Except as otherwise provided in Section 7.01:
(a)    The Trustee may rely and shall be protected in acting or refraining from acting upon any resolution, certificate, statement, instrument, opinion, report, notice, request, consent, order, approval, bond, security or other paper or document believed by it to be genuine and to have been signed or presented by the proper party or parties;
(b)    Any request, direction, order or demand of the Company mentioned herein shall be sufficiently evidenced by a Board Resolution or an instrument signed in the name of the Company by any authorized officer of the Company (unless other evidence in respect thereof is specifically prescribed herein);
(c)    The Trustee may consult with counsel and the written advice of such counsel or any Opinion of Counsel shall be full and complete authorization and protection in respect of any action taken or suffered or omitted hereunder in good faith and in reliance thereon;
(d)    The Trustee shall be under no obligation to exercise any of the rights or powers vested in it by this Indenture at the request, order or direction of any of the Securityholders pursuant to the provisions of this Indenture, unless such Securityholders shall have offered to the Trustee reasonable security or indemnity against the costs, expenses and liabilities that may be incurred therein or thereby; nothing contained herein shall, however, relieve the Trustee of the obligation, upon the occurrence of an Event of 

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Default with respect to a series of the Securities (that has not been cured or waived), to exercise with respect to Securities of that series such of the rights and powers vested in it by this Indenture, and to use the same degree of care and skill in their exercise, as a prudent man would exercise or use under the circumstances in the conduct of his own affairs;
(e)    The Trustee shall not be liable for any action taken or omitted to be taken by it in good faith and believed by it to be authorized or within the discretion or rights or powers conferred upon it by this Indenture;
(f)    The Trustee shall not be bound to make any investigation into the facts or matters stated in any resolution, certificate, statement, instrument, opinion, report, notice, request, consent, order, approval, bond, security, or other papers or documents, unless requested in writing so to do by the holders of not less than a majority in principal amount of the Outstanding Securities of the particular series affected thereby (determined as provided in Section 8.04); provided, however, that if the payment within a reasonable time to the Trustee of the costs, expenses or liabilities likely to be incurred by it in the making of such investigation is, in the opinion of the Trustee, not reasonably assured to the Trustee by the security afforded to it by the terms of this Indenture, the Trustee may require reasonable indemnity against such costs, expenses or liabilities as a condition to so proceeding.  The reasonable expense of every such examination shall be paid by the Company or, if paid by the Trustee, shall be repaid by the Company upon demand; and
(g)    The Trustee may execute any of the trusts or powers hereunder or perform any duties hereunder either directly or by or through agents or attorneys and the Trustee shall not be responsible for any misconduct or negligence on the part of any agent or attorney appointed with due care by it hereunder.
In addition, the Trustee shall not be deemed to have knowledge of any Default or Event of Default except (1) any Event of Default occurring pursuant to Sections 6.01(a)(1) and 6.01(a)(2) or (2) any Default or Event of Default of which the Trustee shall have received written notification in the manner set forth in this Indenture or a Responsible Officer of the Trustee shall have obtained actual knowledge.  Delivery of reports, information and documents to the Trustee under Section 5.03 is for informational purposes only and the information and the Trustee’s receipt of the foregoing shall not constitute constructive notice of any information contained therein, or determinable from information contained therein including the Company’s compliance with any of their covenants thereunder (as to which the Trustee is entitled to rely exclusively on an Officers’ Certificate).
Section 7.03    Trustee Not Responsible for Recitals or Issuance or Securities.
(a)    The recitals contained herein and in the Securities shall be taken as the statements of the Company, and the Trustee assumes no responsibility for the correctness of the same.
(b)    The Trustee makes no representations as to the validity or sufficiency of this Indenture or of the Securities.
(c)    The Trustee shall not be accountable for the use or application by the Company of any of the Securities or of the proceeds of such Securities, or for the use or application of any moneys paid over 

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by the Trustee in accordance with any provision of this Indenture or established pursuant to Section 2.01, or for the use or application of any moneys received by any paying agent other than the Trustee.
Section 7.04    May Hold Securities.
The Trustee or any paying agent or Security Registrar, in its individual or any other capacity, may become the owner or pledgee of Securities with the same rights it would have if it were not Trustee, paying agent or Security Registrar.
Section 7.05    Moneys Held in Trust.
Subject to the provisions of Section 11.05, all moneys received by the Trustee shall, until used or applied as herein provided, be held in trust for the purposes for which they were received, but need not be segregated from other funds except to the extent required by law.  The Trustee shall be under no liability for interest on any moneys received by it hereunder except such as it may agree with the Company to pay thereon.
Section 7.06    Compensation and Reimbursement.
(a)    The Company covenants and agrees to pay to the Trustee, and the Trustee shall be entitled to, such reasonable compensation (which shall not be limited by any provision of law in regard to the compensation of a trustee of an express trust) as the Company and the Trustee may from time to time agree in writing, for all services rendered by it in the execution of the trusts hereby created and in the exercise and performance of any of the powers and duties hereunder of the Trustee, and, except as otherwise expressly provided herein, the Company will pay or reimburse the Trustee upon its request for all reasonable expenses, disbursements and advances incurred or made by the Trustee in accordance with any of the provisions of this Indenture (including the reasonable compensation and the expenses and disbursements of its counsel and of all Persons not regularly in its employ), except any such expense, disbursement or advance as may arise from its negligence or bad faith and except as the Company and Trustee may from time to time agree in writing.  The Company also covenants to indemnify the Trustee (and its officers, agents, directors and employees) for, and to hold it harmless against, any loss, liability or expense incurred without negligence or bad faith on the part of the Trustee and arising out of or in connection with the acceptance or administration of this trust, including the reasonable costs and expenses of defending itself against any claim of liability in the premises.
(b)    The obligations of the Company under this Section to compensate and indemnify the Trustee and to pay or reimburse the Trustee for reasonable expenses, disbursements and advances shall constitute additional indebtedness of the Company to which the Securities are subordinated.  Such additional indebtedness shall be secured by a lien prior to that of the Securities upon all property and funds held or collected by the Trustee as such, except funds held in trust for the benefit of the holders of particular Securities.
Section 7.07    Reliance on Officers’ Certificate.

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Except as otherwise provided in Section 7.01, whenever in the administration of the provisions of this Indenture the Trustee shall deem it reasonably necessary or desirable that a matter be proved or established prior to taking or suffering or omitting to take any action hereunder, such matter (unless other evidence in respect thereof be herein specifically prescribed) may, in the absence of negligence or bad faith on the part of the Trustee, be deemed to be conclusively proved and established by an Officers’ Certificate delivered to the Trustee and such certificate, in the absence of negligence or bad faith on the part of the Trustee, shall be full warrant to the Trustee for any action taken, suffered or omitted to be taken by it under the provisions of this Indenture upon the faith thereof.
Section 7.08    Disqualification; Conflicting Interests.
If the Trustee has or shall acquire any “conflicting interest” within the meaning of Section 310(b) of the Trust Indenture Act, the Trustee and the Company shall in all respects comply with the provisions of Section 310(b) of the Trust Indenture Act.
Section 7.09    Corporate Trustee Required; Eligibility.
There shall at all times be a Trustee with respect to the Securities issued hereunder which shall at all times be a corporation organized and doing business under the laws of the United States of America or any state or territory thereof or of the District of Columbia, or a corporation or other Person permitted to act as trustee by the Securities and Exchange Commission, authorized under such laws to exercise corporate trust powers, having a combined capital and surplus of at least fifty million U.S. dollars ($50,000,000), and subject to supervision or examination by federal, state, territorial, or District of Columbia authority.
If such corporation or other Person publishes reports of condition at least annually, pursuant to law or to the requirements of the aforesaid supervising or examining authority, then for the purposes of this Section, the combined capital and surplus of such corporation or other Person shall be deemed to be its combined capital and surplus as set forth in its most recent report of condition so published.  The Company may not, nor may any Person directly or indirectly controlling, controlled by, or under common control with the Company, serve as Trustee.  In case at any time the Trustee shall cease to be eligible in accordance with the provisions of this Section, the Trustee shall resign immediately in the manner and with the effect specified in Section 7.10.
Section 7.10    Resignation and Removal; Appointment of Successor.
(a)    The Trustee or any successor hereafter appointed may at any time resign with respect to the Securities of one or more series by giving written notice thereof to the Company and by transmitting notice of resignation by mail, first class postage prepaid, to the Securityholders of such series, as their names and addresses appear upon the Security Register.  Upon receiving such notice of resignation, the Company shall promptly appoint a successor trustee with respect to Securities of such series by written instrument, in duplicate, executed by order of the Board of Directors, one copy of which instrument shall be delivered to the resigning Trustee and one copy to the successor trustee.  If no successor trustee shall have been so appointed and have accepted appointment within 30 days after the mailing of such notice of 

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resignation, the resigning Trustee may petition any court of competent jurisdiction for the appointment of a successor trustee with respect to Securities of such series, or any Securityholder of that series who has been a bona fide holder of a Security or Securities for at least six months may on behalf of himself and all others similarly situated, petition any such court for the appointment of a successor trustee.  Such court may thereupon after such notice, if any, as it may deem proper and prescribe, appoint a successor trustee.
(b)    In case at any time any one of the following shall occur:
(i)    the Trustee shall fail to comply with the provisions of Section 7.08 after written request therefor by the Company or by any Securityholder who has been a bona fide holder of a Security or Securities for at least six months; or
(ii)    the Trustee shall cease to be eligible in accordance with the provisions of Section 7.09 and shall fail to resign after written request therefor by the Company or by any such Securityholder; or
(iii)    the Trustee shall become incapable of acting, or shall be adjudged a bankrupt or insolvent, or commence a voluntary bankruptcy proceeding, or a receiver of the Trustee or of its property shall be appointed or consented to, or any public officer shall take charge or control of the Trustee or of its property or affairs for the purpose of rehabilitation, conservation or liquidation;
then, in any such case, the Company may remove the Trustee with respect to all Securities and appoint a successor trustee by written instrument, in duplicate, executed by order of the Board of Directors, one copy of which instrument shall be delivered to the Trustee so removed and one copy to the successor trustee, or any Securityholder who has been a bona fide holder of a Security or Securities for at least six months may, on behalf of that holder and all others similarly situated, petition any court of competent jurisdiction for the removal of the Trustee and the appointment of a successor trustee.  Such court may thereupon after such notice, if any, as it may deem proper and prescribe, remove the Trustee and appoint a successor trustee.
(c)    The holders of a majority in aggregate principal amount of the Securities of any series at the time Outstanding may at any time remove the Trustee with respect to such series by so notifying the Trustee and the Company and may appoint a successor Trustee for such series with the consent of the Company.
(d)    Any resignation or removal of the Trustee and appointment of a successor trustee with respect to the Securities of a series pursuant to any of the provisions of this Section shall become effective upon acceptance of appointment by the successor trustee as provided in Section 7.11.
(e)    Any successor trustee appointed pursuant to this Section may be appointed with respect to the Securities of one or more series or all of such series, and at any time there shall be only one Trustee with respect to the Securities of any particular series.
Section 7.11    Acceptance of Appointment By Successor.

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(a)    In case of the appointment hereunder of a successor trustee with respect to all Securities, every such successor trustee so appointed shall execute, acknowledge and deliver to the Company and to the retiring Trustee an instrument accepting such appointment, and thereupon the resignation or removal of the retiring Trustee shall become effective and such successor trustee, without any further act, deed or conveyance, shall become vested with all the rights, powers, trusts and duties of the retiring Trustee; but, on the request of the Company or the successor trustee, such retiring Trustee shall, upon payment of its charges, execute and deliver an instrument transferring to such successor trustee all the rights, powers, and trusts of the retiring Trustee and shall duly assign, transfer and deliver to such successor trustee all property and money held by such retiring Trustee hereunder.
(b)    In case of the appointment hereunder of a successor trustee with respect to the Securities of one or more (but not all) series, the Company, the retiring Trustee and each successor trustee with respect to the Securities of one or more series shall execute and deliver an indenture supplemental hereto wherein each successor trustee shall accept such appointment and which (i) shall contain such provisions as shall be necessary or desirable to transfer and confirm to, and to vest in, each successor trustee all the rights, powers, trusts and duties of the retiring Trustee with respect to the Securities of that or those series to which the appointment of such successor trustee relates, (ii) shall contain such provisions as shall be deemed necessary or desirable to confirm that all the rights, powers, trusts and duties of the retiring Trustee with respect to the Securities of that or those series as to which the retiring Trustee is not retiring shall continue to be vested in the retiring Trustee, and (iii) shall add to or change any of the provisions of this Indenture as shall be necessary to provide for or facilitate the administration of the trusts hereunder by more than one Trustee, it being understood that nothing herein or in such supplemental indenture shall constitute such Trustees co-trustees of the same trust, that each such Trustee shall be trustee of a trust or trusts hereunder separate and apart from any trust or trusts hereunder administered by any other such Trustee and that no Trustee shall be responsible for any act or failure to act on the part of any other Trustee hereunder; and upon the execution and delivery of such supplemental indenture the resignation or removal of the retiring Trustee shall become effective to the extent provided therein, such retiring Trustee shall with respect to the Securities of that or those series to which the appointment of such successor trustee relates have no further responsibility for the exercise of rights and powers or for the performance of the duties and obligations vested in the Trustee under this Indenture, and each such successor trustee, without any further act, deed or conveyance, shall become vested with all the rights, powers, trusts and duties of the retiring Trustee with respect to the Securities of that or those series to which the appointment of such successor trustee relates; but, on request of the Company or any successor trustee, such retiring Trustee shall duly assign, transfer and deliver to such successor trustee, to the extent contemplated by such supplemental indenture, the property and money held by such retiring Trustee hereunder with respect to the Securities of that or those series to which the appointment of such successor trustee relates.
(c)    Upon request of any such successor trustee, the Company shall execute any and all instruments for more fully and certainly vesting in and confirming to such successor trustee all such rights, powers and trusts referred to in paragraph (a) or (b) of this Section, as the case may be.
(d)    No successor trustee shall accept its appointment unless at the time of such acceptance such successor trustee shall be qualified and eligible under this Article.

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Section 7.12    Merger, Conversion, Consolidation or Succession to Business.
Any corporation into which the Trustee may be merged or converted or with which it may be consolidated, or any corporation resulting from any merger, conversion or consolidation to which the Trustee shall be a party, or any corporation succeeding to the corporate trust business of the Trustee, including the administration of the trust created by this Indenture, shall be the successor of the Trustee hereunder, provided that such corporation shall be qualified under the provisions of Section 7.08 and eligible under the provisions of Section 7.09, without the execution or filing of any paper or any further act on the part of any of the parties hereto, anything herein to the contrary notwithstanding.  In case any Securities shall have been authenticated, but not delivered, by the Trustee then in office, any successor by merger, conversion or consolidation to such authenticating Trustee may adopt such authentication and deliver the Securities so authenticated with the same effect as if such successor Trustee had itself authenticated such Securities.
Section 7.13    Preferential Collection of Claims Against the Company.
The Trustee shall comply with Section 311(a) of the Trust Indenture Act, excluding any creditor relationship described in Section 311(b) of the Trust Indenture Act.  A Trustee who has resigned or been removed shall be subject to Section 311(a) of the Trust Indenture Act to the extent included therein.
Section 7.14    Notice of Default.
If any Default or any Event of Default occurs and is continuing and if such Default or Event of Default is known to a Responsible Officer of the Trustee, the Trustee shall mail to each Securityholder in the manner and to the extent provided in Section 313(c) of the Trust Indenture Act notice of the Default or Event of Default within 45 days after it occurs, unless such Default or Event of Default has been cured; provided, however, that, except in the case of a default in the payment of the principal of (or premium, if any) or interest on any Security, the Trustee shall be protected in withholding such notice if and so long as the board of directors, the executive committee or a trust committee of directors and/or Responsible Officers of the Trustee in good faith determine that the withholding of such notice is in the interest of the Securityholders.
ARTICLE 8
CONCERNING THE SECURITYHOLDERS
Section 8.01    Evidence of Action by Securityholders.
Whenever in this Indenture it is provided that the holders of a majority or specified percentage in aggregate principal amount of the Securities of a particular series may take any action (including the making of any demand or request, the giving of any notice, consent or waiver or the taking of any other action), the fact that at the time of taking any such action the holders of such majority or specified percentage of that series have joined therein may be evidenced by any instrument or any number of instruments of similar tenor executed by such holders of Securities of that series in person or by agent or proxy appointed in writing.

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If the Company shall solicit from the Securityholders of any series any request, demand, authorization, direction, notice, consent, waiver or other action, the Company may, at its option, as evidenced by an Officers’ Certificate, fix in advance a record date for such series for the determination of Securityholders entitled to give such request, demand, authorization, direction, notice, consent, waiver or other action, but the Company shall have no obligation to do so.  If such a record date is fixed, such request, demand, authorization, direction, notice, consent, waiver or other action may be given before or after the record date, but only the Securityholders of record at the close of business on the record date shall be deemed to be Securityholders for the purposes of determining whether Securityholders of the requisite proportion of Outstanding Securities of that series have authorized or agreed or consented to such request, demand, authorization, direction, notice, consent, waiver or other action, and for that purpose the Outstanding Securities of that series shall be computed as of the record date; provided, however, that no such authorization, agreement or consent by such Securityholders on the record date shall be deemed effective unless it shall become effective pursuant to the provisions of this Indenture not later than six months after the record date.
Section 8.02    Proof of Execution by Securityholders.
Subject to the provisions of Section 7.01, proof of the execution of any instrument by a Securityholder (such proof will not require notarization) or his agent or proxy and proof of the holding by any Person of any of the Securities shall be sufficient if made in the following manner:
(a)    The fact and date of the execution by any such Person of any instrument may be proved in any reasonable manner acceptable to the Trustee.
(b)    The ownership of Securities shall be proved by the Security Register of such Securities or by a certificate of the Security Registrar thereof.
The Trustee may require such additional proof of any matter referred to in this Section as it shall deem necessary.
Section 8.03    Who May be Deemed Owners.
Prior to the due presentment for registration of transfer of any Security, the Company, the Trustee, any paying agent and any Security Registrar may deem and treat the Person in whose name such Security shall be registered upon the books of the Company as the absolute owner of such Security (whether or not such Security shall be overdue and notwithstanding any notice of ownership or writing thereon made by anyone other than the Security Registrar) for the purpose of receiving payment of or on account of the principal of (and premium, if any) and (subject to Section 2.03) interest on such Security and for all other purposes; and neither the Company nor the Trustee nor any paying agent nor any Security Registrar shall be affected by any notice to the contrary.
Section 8.04    Certain Securities Owned by Company Disregarded.
In determining whether the holders of the requisite aggregate principal amount of Securities of a particular series have concurred in any direction, consent or waiver under this Indenture, the Securities of 

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that series that are owned by the Company or any other obligor on the Securities of that series or by any Person directly or indirectly controlling or controlled by or under common control with the Company or any other obligor on the Securities of that series shall be disregarded and deemed not to be Outstanding for the purpose of any such determination, except that for the purpose of determining whether the Trustee shall be protected in relying on any such direction, consent or waiver, only Securities of such series that the Trustee actually knows are so owned shall be so disregarded.  The Securities so owned that have been pledged in good faith may be regarded as Outstanding for the purposes of this Section, if the pledgee shall establish to the satisfaction of the Trustee the pledgee’s right so to act with respect to such Securities and that the pledgee is not a Person directly or indirectly controlling or controlled by or under direct or indirect common control with the Company or any such other obligor.  In case of a dispute as to such right, any decision by the Trustee taken upon the advice of counsel shall be full protection to the Trustee.
Section 8.05    Actions Binding on Future Securityholders.
At any time prior to (but not after) the evidencing to the Trustee, as provided in Section 8.01, of the taking of any action by the holders of the majority or percentage in aggregate principal amount of the Securities of a particular series specified in this Indenture in connection with such action, any holder of a Security of that series that is shown by the evidence to be included in the Securities the holders of which have consented to such action may, by filing written notice with the Trustee, and upon proof of holding as provided in Section 8.02, revoke such action so far as concerns such Security.  Except as aforesaid any such action taken by the holder of any Security shall be conclusive and binding upon such holder and upon all future holders and owners of such Security, and of any Security issued in exchange therefor, on registration of transfer thereof or in place thereof, irrespective of whether or not any notation in regard thereto is made upon such Security.  Any action taken by the holders of the majority or percentage in aggregate principal amount of the Securities of a particular series specified in this Indenture in connection with such action shall be conclusively binding upon the Company, the Trustee and the holders of all the Securities of that series.
ARTICLE 9
SUPPLEMENTAL INDENTURES
Section 9.01    Supplemental Indentures Without the Consent of Securityholders.
In addition to any supplemental indenture otherwise authorized by this Indenture, the Company and the Trustee may from time to time and at any time enter into an indenture or indentures supplemental hereto (which shall conform to the provisions of the Trust Indenture Act as then in effect), without the consent of the Securityholders, for one or more of the following purposes:
(a)    to cure any ambiguity, defect, or inconsistency herein or in the Securities of any series;
(b)    to comply with Article Ten;
(c)    to provide for uncertificated Securities in addition to or in place of certificated Securities;

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(d)    to add to the covenants, restrictions, conditions or provisions relating to the Company for the benefit of the holders of all or any series of Securities (and if such covenants, restrictions, conditions or provisions are to be for the benefit of less than all series of Securities, stating that such covenants, restrictions, conditions or provisions are expressly being included solely for the benefit of such series), to make the occurrence, or the occurrence and the continuance, of a default in any such additional covenants, restrictions, conditions or provisions an Event of Default, or to surrender any right or power herein conferred upon the Company;
(e)    to add to, delete from, or revise the conditions, limitations, and restrictions on the authorized amount, terms, or purposes of issue, authentication, and delivery of Securities, as herein set forth;
(f)    to make any change that does not adversely affect the rights of any Securityholder in any material respect; provided that any amendment made solely to conform the provisions of this Indenture to the corresponding description of the Securities contained in the applicable prospectus or prospectus supplement shall be deemed to not adversely affect the interests of the Securityholders; provided further that, any amendment made pursuant to this Section 9.01(f), the Company shall provide the Trustee with an Officers’ Certificate certifying that such amendment will not adversely affect the right or interests of Securityholders;
(g)    to provide for the issuance of and establish the form and terms and conditions of the Securities of any series as provided in Section 2.01, to establish the form of any certifications required to be furnished pursuant to the terms of this Indenture or any series of Securities, or to add to the rights of the holders of any series of Securities;
(h)    to evidence and provide for the acceptance of appointment hereunder by a successor trustee; or
(i)    to comply with any requirements of the Securities and Exchange Commission or any successor in connection with the qualification of this Indenture under the Trust Indenture Act.
The Trustee is hereby authorized to join with the Company in the execution of any such supplemental indenture, and to make any further appropriate agreements and stipulations that may be therein contained, but the Trustee shall not be obligated to enter into any such supplemental indenture that affects the Trustee’s own rights, duties or immunities under this Indenture or otherwise.
Any supplemental indenture authorized by the provisions of this Section may be executed by the Company and the Trustee without the consent of the holders of any of the Securities at the time Outstanding, notwithstanding any of the provisions of Section 9.02.
Section 9.02    Supplemental Indentures With Consent of Securityholders.
With the consent (evidenced as provided in Section 8.01) of the holders of not less than a majority in aggregate principal amount of the Securities of each series affected by such supplemental indenture or indentures at the time Outstanding, the Company, when authorized by a Board Resolution, and the Trustee 

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may from time to time and at any time enter into an indenture or indentures supplemental hereto (which shall conform to the provisions of the Trust Indenture Act as then in effect) for the purpose of adding any provisions to or changing in any manner or eliminating any of the provisions of this Indenture or of any supplemental indenture or of modifying in any manner not covered by Section 9.01 the rights of the holders of the Securities of such series under this Indenture; provided, however, that no such supplemental indenture shall, without the consent of the holders of each Security then Outstanding and affected thereby,
(i)    extend the fixed maturity of any Securities of any series, or reduce the principal amount thereof, or reduce the rate or extend the time of payment of interest thereon, or reduce any premium payable upon redemption thereof;
(ii)    reduce the aforesaid percentage of Securities, the holders of which are required to consent to any such supplemental indenture;
(iii)    change any obligation to pay additional amounts;
(iv)    reduce the amount of principal of an original issue discount security or any other Security payable upon acceleration of the maturity thereof;
(v)    change currency in which any Security or any premium or interest is payable;
(vi)    impair the right to enforce any payment on or with respect to any Security;
(vii)    adversely change the right to convert or exchange, including decreasing the conversion rate or increasing the conversion price of, such Security (if applicable);
(viii)    if the Securities are secured, change the terms and conditions pursuant to which the Securities are secured in a manner adverse to the holders of the Securities;
(ix)    reduce the percentage in principal amount of outstanding Securities of any series, the consent of whose holders is required for modification or amendment of the indenture or for waiver of compliance with certain provisions of the indenture or for waiver of certain defaults;
(x)    reduce the requirements contained in the indenture for quorum or voting;
(xi)    change any obligations of the Company to maintain an office or agency in the places and for the purposes required by the indentures; or
(xii)    modify any of the above provisions.
It shall not be necessary for the consent of the Securityholders of any series affected thereby under this Section to approve the particular form of any proposed supplemental indenture, but it shall be sufficient if such consent shall approve the substance thereof.
Section 9.03    Effect of Supplemental Indentures.

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Upon the execution of any supplemental indenture pursuant to the provisions of this Article or of Section 10.01, this Indenture shall, with respect to such series, be and be deemed to be modified and amended in accordance therewith and the respective rights, limitations of rights, obligations, duties and immunities under this Indenture of the Trustee, the Company and the holders of Securities of the series affected thereby shall thereafter be determined, exercised and enforced hereunder subject in all respects to such modifications and amendments, and all the terms and conditions of any such supplemental indenture shall be and be deemed to be part of the terms and conditions of this Indenture for any and all purposes.
Section 9.04    Securities Affected by Supplemental Indentures.
Securities of any series affected by a supplemental indenture, authenticated and delivered after the execution of such supplemental indenture pursuant to the provisions of this Article or of Section 10.01, may bear a notation in form approved by the Company, provided such form meets the requirements of any securities exchange upon which such series may be listed, as to any matter provided for in such supplemental indenture.  If the Company shall so determine, new Securities of that series so modified as to conform, in the opinion of the Board of Directors, to any modification of this Indenture contained in any such supplemental indenture may be prepared by the Company, authenticated by the Trustee and delivered in exchange for the Securities of that series then Outstanding.
Section 9.05    Execution of Supplemental Indentures.
Upon the request of the Company, accompanied by its Board Resolutions authorizing the execution of any such supplemental indenture, and upon the filing with the Trustee of evidence of the consent of Securityholders required to consent thereto as aforesaid, the Trustee shall join with the Company in the execution of such supplemental indenture unless such supplemental indenture affects the Trustee’s own rights, duties or immunities under this Indenture or otherwise, in which case the Trustee may in its discretion but shall not be obligated to enter into such supplemental indenture.  The Trustee, subject to the provisions of Section 7.01, may receive an Officers’ Certificate or an Opinion of Counsel as conclusive evidence that any supplemental indenture executed pursuant to this Article is authorized or permitted by, and conforms to, the terms of this Article and that it is proper for the Trustee under the provisions of this Article to join in the execution thereof; provided, however, that such Officers’ Certificate or Opinion of Counsel need not be provided in connection with the execution of a supplemental indenture that establishes the terms of a series of Securities pursuant to Section 2.01 hereof.
Promptly after the execution by the Company and the Trustee of any supplemental indenture pursuant to the provisions of this Section, the Trustee shall transmit by mail, first class postage prepaid, a notice, setting forth in general terms the substance of such supplemental indenture, to the Securityholders of all series affected thereby as their names and addresses appear upon the Security Register.  Any failure of the Trustee to mail such notice, or any defect therein, shall not, however, in any way impair or affect the validity of any such supplemental indenture.
ARTICLE 10
SUCCESSOR ENTITY

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Section 10.01    Company May Consolidate, Etc.
Except as provided pursuant to Section 2.01 pursuant to a Board Resolution, and set forth in an Officers’ Certificate, or established in one or more indentures supplemental to this Indenture, nothing contained in this Indenture shall prevent any consolidation or merger of the Company with or into any other Person (whether or not affiliated with the Company) or successive consolidations or mergers in which the Company or its successor or successors shall be a party or parties, or shall prevent any sale, conveyance, transfer or other disposition of the property of the Company or its successor or successors as an entirety, or substantially as an entirety, to any other corporation (whether or not affiliated with the Company or its successor or successors) authorized to acquire and operate the same; provided, however, (a) the Company hereby covenants and agrees that, upon any such consolidation or merger (in each case, if the Company is not the survivor of such transaction), sale, conveyance, transfer or other disposition, the due and punctual payment of the principal of (and premium, if any) and interest on all of the Securities of all series in accordance with the terms of each series, according to their tenor, and the due and punctual performance and observance of all the covenants and conditions of this Indenture with respect to each series or established with respect to such series pursuant to Section 2.01 to be kept or performed by the Company shall be expressly assumed, by supplemental indenture (which shall conform to the provisions of the Trust Indenture Act, as then in effect) reasonably satisfactory in form to the Trustee executed and delivered to the Trustee by the entity formed by such consolidation, or into which the Company shall have been merged, or by the entity which shall have acquired such property and (b) in the event that the Securities of any series then Outstanding are convertible into or exchangeable for shares of common stock or other securities of the Company, such entity shall, by such supplemental indenture, make provision so that the Securityholders of Securities of that series shall thereafter be entitled to receive upon conversion or exchange of such Securities the number of securities or property to which a holder of the number of shares of common stock or other securities of the Company deliverable upon conversion or exchange of those Securities would have been entitled had such conversion or exchange occurred immediately prior to such consolidation, merger, sale, conveyance, transfer or other disposition.
Section 10.02    Successor Entity Substituted.
(a)    In case of any such consolidation, merger, sale, conveyance, transfer or other disposition and upon the assumption by the successor entity by supplemental indenture, executed and delivered to the Trustee and satisfactory in form to the Trustee, of the obligations set forth under Section 10.01 on all of the Securities of all series Outstanding, such successor entity shall succeed to and be substituted for the Company with the same effect as if it had been named as the Company herein, and thereupon the predecessor corporation shall be relieved of all obligations and covenants under this Indenture and the Securities.
(b)    In case of any such consolidation, merger, sale, conveyance, transfer or other disposition, such changes in phraseology and form (but not in substance) may be made in the Securities thereafter to be issued as may be appropriate.
(c)    Nothing contained in this Article shall require any action by the Company in the case of a consolidation or merger of any Person into the Company where the Company is the survivor of such 

39

transaction, or the acquisition by the Company, by purchase or otherwise, of all or any part of the property of any other Person (whether or not affiliated with the Company).
Section 10.03    Evidence of Consolidation, Etc. to Trustee.
The Trustee, subject to the provisions of Section 7.01, may receive an Officers’ Certificate or an Opinion of Counsel as conclusive evidence that any such consolidation, merger, sale, conveyance, transfer or other disposition, and any such assumption, comply with the provisions of this Article.
ARTICLE 11
SATISFACTION AND DISCHARGE
Section 11.01    Satisfaction and Discharge of Indenture.
If at any time:  (a) the Company shall have delivered to the Trustee for cancellation all Securities of a series theretofore authenticated and not delivered to the Trustee for cancellation (other than any Securities that shall have been destroyed, lost or stolen and that shall have been replaced or paid as provided in Section 2.07 and Securities for whose payment money or Governmental Obligations have theretofore been deposited in trust or segregated and held in trust by the Company and thereupon repaid to the Company or discharged from such trust, as provided in Section 11.05); or (b) all such Securities of a particular series not theretofore delivered to the Trustee for cancellation shall have become due and payable, or are by their terms to become due and payable within one year or are to be called for redemption within one year under arrangements satisfactory to the Trustee for the giving of notice of redemption, and the Company shall deposit or cause to be deposited with the Trustee as trust funds the entire amount in moneys or Governmental Obligations or a combination thereof, sufficient in the opinion of a nationally recognized firm of independent public accountants expressed in a written certification thereof delivered to the Trustee, to pay at maturity or upon redemption all Securities of that series not theretofore delivered to the Trustee for cancellation, including principal (and premium, if any) and interest due or to become due to such date of maturity or date fixed for redemption, as the case may be, and if the Company shall also pay or cause to be paid all other sums payable hereunder with respect to such series by the Company then this Indenture shall thereupon cease to be of further effect with respect to such series except for the provisions of Sections 2.03, 2.05, 2.07, 4.01, 4.02, 4.03 and 7.10, that shall survive until the date of maturity or redemption date, as the case may be, and Sections 7.06 and 11.05, that shall survive to such date and thereafter, and the Trustee, on demand of the Company and at the cost and expense of the Company shall execute proper instruments acknowledging satisfaction of and discharging this Indenture with respect to such series.
Section 11.02    Discharge of Obligations.
If at any time all such Securities of a particular series not heretofore delivered to the Trustee for cancellation or that have not become due and payable as described in Section 11.01 shall have been paid by the Company by depositing irrevocably with the Trustee as trust funds moneys or an amount of Governmental Obligations sufficient to pay at maturity or upon redemption all such Securities of that series not theretofore delivered to the Trustee for cancellation, including principal (and premium, if any) 

40

and interest due or to become due to such date of maturity or date fixed for redemption, as the case may be, and if the Company shall also pay or cause to be paid all other sums payable hereunder by the Company with respect to such series, then after the date such moneys or Governmental Obligations, as the case may be, are deposited with the Trustee the obligations of the Company under this Indenture with respect to such series shall cease to be of further effect except for the provisions of Sections 2.03, 2.05, 2.07, 4,01, 4.02, 4,03, 7.06, 7.10 and 11.05 hereof that shall survive until such Securities shall mature and be paid.
Thereafter, Sections 7.06 and 11.05 shall survive.
Section 11.03    Deposited Moneys to be Held in Trust.
All moneys or Governmental Obligations deposited with the Trustee pursuant to Sections 11.01 or 11.02 shall be held in trust and shall be available for payment as due, either directly or through any paying agent (including the Company acting as its own paying agent), to the holders of the particular series of Securities for the payment or redemption of which such moneys or Governmental Obligations have been deposited with the Trustee.
Section 11.04    Payment of Moneys Held by Paying Agents.
In connection with the satisfaction and discharge of this Indenture all moneys or Governmental Obligations then held by any paying agent under the provisions of this Indenture shall, upon demand of the Company, be paid to the Trustee and thereupon such paying agent shall be released from all further liability with respect to such moneys or Governmental Obligations.
Section 11.05    Repayment to Company.
Any moneys or Governmental Obligations deposited with any paying agent or the Trustee, or then held by the Company, in trust for payment of principal of or premium, if any, or interest on the Securities of a particular series that are not applied but remain unclaimed by the holders of such Securities for at least two years after the date upon which the principal of (and premium, if any) or interest on such Securities shall have respectively become due and payable, or such other shorter period set forth in applicable escheat or abandoned or unclaimed property law, shall be repaid to the Company on May 31 of each year or upon the Company’s request or (if then held by the Company) shall be discharged from such trust; and thereupon the paying agent and the Trustee shall be released from all further liability with respect to such moneys or Governmental Obligations, and the holder of any of the Securities entitled to receive such payment shall thereafter, as a general creditor, look only to the Company for the payment thereof.

ARTICLE 12
IMMUNITY OF INCORPORATORS, STOCKHOLDERS, OFFICERS AND 
DIRECTORS

41

Section 12.01    No Recourse.
No recourse under or upon any obligation, covenant or agreement of this Indenture, or of any Security, or for any claim based thereon or otherwise in respect thereof, shall be had against any incorporator, stockholder, officer or director, past, present or future as such, of the Company or of any predecessor or successor corporation, either directly or through the Company or any such predecessor or successor corporation, whether by virtue of any constitution, statute or rule of law, or by the enforcement of any assessment or penalty or otherwise; it being expressly understood that this Indenture and the obligations issued hereunder are solely corporate obligations, and that no such personal liability whatever shall attach to, or is or shall be incurred by, the incorporators, stockholders, officers or directors as such, of the Company or of any predecessor or successor corporation, or any of them, because of the creation of the indebtedness hereby authorized, or under or by reason of the obligations, covenants or agreements contained in this Indenture or in any of the Securities or implied therefrom; and that any and all such personal liability of every name and nature, either at common law or in equity or by constitution or statute, of, and any and all such rights and claims against, every such incorporator, stockholder, officer or director as such, because of the creation of the indebtedness hereby authorized, or under or by reason of the obligations, covenants or agreements contained in this Indenture or in any of the Securities or implied therefrom, are hereby expressly waived and released as a condition of, and as a consideration for, the execution of this Indenture and the issuance of such Securities.
ARTICLE 13
MISCELLANEOUS PROVISIONS
Section 13.01    Effect on Successors and Assigns.
All the covenants, stipulations, promises and agreements in this Indenture made by or on behalf of the Company shall bind its successors and assigns, whether so expressed or not.
Section 13.02    Actions by Successor.
Any act or proceeding by any provision of this Indenture authorized or required to be done or performed by any board, committee or officer of the Company shall and may be done and performed with like force and effect by the corresponding board, committee or officer of any corporation that shall at the time be the lawful successor of the Company.
Section 13.03    Surrender of Company Powers.
The Company by instrument in writing executed by authority of 2/3 (two-thirds) its Board of Directors and delivered to the Trustee may surrender any of the powers reserved to the Company, and thereupon such power so surrendered shall terminate both as to the Company and as to any successor corporation.
Section 13.04    Notices.

42

Except as otherwise expressly provided herein, any notice, request or demand that by any provision of this Indenture is required or permitted to be given, made or served by the Trustee or by the holders of Securities or by any other Person pursuant to this Indenture to or on the Company may be given or served by being deposited in first class mail, postage prepaid, addressed (until another address is filed in writing by the Company with the Trustee), as follows:  Spectrum Pharmaceuticals, Inc., 11500 South Eastern Avenue, Suite 240, Henderson, Nevada 89052, Attn:  Chief Financial Officer.  Any notice, election, request or demand by the Company or any Securityholder or by any other Person pursuant to this Indenture to or upon the Trustee shall be deemed to have been sufficiently given or made, for all purposes, if given or made in writing at the Corporate Trust Office of the Trustee.
Section 13.05    Governing Law.
This Indenture and each Security shall be deemed to be a contract made under the internal laws of the State of New York, and for all purposes shall be construed in accordance with the laws of said State, except to the extent that the Trust Indenture Act is applicable.
Section 13.06    Treatment of Securities as Debt.
It is intended that the Securities will be treated as indebtedness and not as equity for federal income tax purposes.  The provisions of this Indenture shall be interpreted to further this intention.
Section 13.07    Certificates and Opinions as to Conditions Precedent.
(a)    Upon any application or demand by the Company to the Trustee to take any action under any of the provisions of this Indenture, the Company shall furnish to the Trustee an Officers’ Certificate stating that all conditions precedent provided for in this Indenture (other than the certificate to be delivered pursuant to Section 13.12) relating to the proposed action have been complied with and an Opinion of Counsel stating that in the opinion of such counsel all such conditions precedent have been complied with, except that in the case of any such application or demand as to which the furnishing of such documents is specifically required by any provision of this Indenture relating to such particular application or demand, no additional certificate or opinion need be furnished.
(b)    Each certificate or opinion provided for in this Indenture and delivered to the Trustee with respect to compliance with a condition or covenant in this Indenture shall include (i) a statement that the Person making such certificate or opinion has read such covenant or condition; (ii) a brief statement as to the nature and scope of the examination or investigation upon which the statements or opinions contained in such certificate or opinion are based; (iii) a statement that, in the opinion of such Person, he has made such examination or investigation as is reasonably necessary to enable him to express an informed opinion as to whether or not such covenant or condition has been complied with; and (iv) a statement as to whether or not, in the opinion of such Person, such condition or covenant has been complied with.
Section 13.08    Payments on Business Days.
Except as provided pursuant to Section 2.01 pursuant to a Board Resolution, and set forth in an Officers’ Certificate, or established in one or more indentures supplemental to this Indenture, in any case 

43

where the date of maturity of interest or principal of any Security or the date of redemption of any Security shall not be a Business Day, then payment of interest or principal (and premium, if any) may be made on the next succeeding Business Day with the same force and effect as if made on the nominal date of maturity or redemption, and no interest shall accrue for the period after such nominal date.
Section 13.09    Conflict with Trust Indenture Act.
If and to the extent that any provision of this Indenture limits, qualifies or conflicts with the duties imposed by Sections 310 to 317, inclusive, of the Trust Indenture Act, such imposed duties shall control.
Section 13.10    Counterparts.
This Indenture may be executed in any number of counterparts, each of which shall be an original, but such counterparts shall together constitute but one and the same instrument.
Section 13.11    Separability.
In case any one or more of the provisions contained in this Indenture or in the Securities of any series shall for any reason be held to be invalid, illegal or unenforceable in any respect, such invalidity, illegality or unenforceability shall not affect any other provisions of this Indenture or of such Securities, but this Indenture and such Securities shall be construed as if such invalid or illegal or unenforceable provision had never been contained herein or therein.
Section 13.12    Compliance Certificates.
The Company shall deliver to the Trustee, within 120 days after the end of each fiscal year during which any Securities of any series were outstanding, an officer’s certificate stating whether or not the signers know of any Default or Event of Default that occurred during such fiscal year.  Such certificate shall contain a certification from the principal executive officer, principal financial officer or principal accounting officer of the Company that a review has been conducted of the activities of the Company and the Company’s performance under this Indenture and that the Company has complied with all conditions and covenants under this Indenture.  For purposes of this Section 13.12, such compliance shall be determined without regard to any period of grace or requirement of notice provided under this Indenture.  If the officer of the Company signing such certificate has knowledge of such a Default or Event of Default, the certificate shall describe any such Default or Event of Default and its status.

ARTICLE 14
SUBORDINATION OF SECURITIES
Section 14.01    Subordination Terms.
The payment by the Company of the principal of, (and premium, if any) and interest on any series of Securities issued hereunder shall be subordinated to the extent set forth in an indenture supplemental hereto relating to such Securities.

44

45

IN WITNESS WHEREOF, the parties hereto have caused this Indenture to be duly executed all as of the day and year first above written.
SPECTRUM PHARMACEUTICALS, INC	
		
	By:
	 

	Name:
	 

	Title:
	 

[TRUSTEE], as Trustee	
		
	By:
	 

	Name:
	 

	Title:
	 

[SIGNATURE PAGE TO SUBORDINATED DEBT SECURITIES]

46

CROSS-REFERENCE TABLE(1)
	
		
	Section of Trust Indenture 
Act of 1939, as Amended
	Section of Indenture

	310(a)
	7.09

	310(b)
	7.08

	 
	7.10

	310(c)
	Inapplicable

	311(a)
	7.13

	311(b)
	7.13

	311(c)
	Inapplicable

	312(a)
	5.01

	 
	5.02(a)

	312(b)
	5.02(b)

	312(c)
	5.02(b)

	313(a)
	5.04(a)

	313(b)
	5.04(b)

	313(c)
	5.04(a)

	 
	5.04(b)

	313(d)
	5.04(c)

	314(a)
	5.03

	 
	13.12

	314(b)
	Inapplicable

	314(c)
	13.07(a)

	314(d)
	Inapplicable

	314(e)
	13.07(b)

	314(f)
	Inapplicable

	315(a)
	7.01(a)

	 
	7.01(b)

	315(b)
	7.14

	315(c)
	7.01

	315(d)
	7.01(b)

	315(e)
	6.07

	316(a)
	6.06

	 
	8.04

	316(b)
	6.04

	316(c)
	8.01

	317(a)
	6.02

	317(b)
	4.03

	318(a)
	13.09

		
	(1)
	This Cross-Reference Table does not constitute part of the Indenture and shall not have any bearing on the interpretation of any of its terms or provisions.

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