Exhibit 10.1

 

THE SYMBOL “[**]” INDICATES MATERIAL WHERE CERTAIN IDENITIFIED INFORMATION HAS BEEN EXCLUDED BECAUSE IT IS BOTH (i) NOT MATERIAL AND (ii) WOULD LIKELY CAUSE COMPETITIVE HARM TO THE COMPANY IF PUBLICLY DISCLOSED.

 

 

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 Valles, 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/ Victor Grifols Deu
    
	
 
    	
 
    	
 
    	
 
    	
 
    
	
Title:
    	
Co-CEO
    	
 
    	
Title:
    	
Co-CEO
    


 

[Plasma – ARA to PSA Signatures Pages]

 











 

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 Valles, 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

 

1.2                               [**].

 

1.3                               [**].

 











 

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.

 

1.4                               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.

 

2.3.1                     [**].

 

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.

 

2.5                               Term of the Agreement.  The term of this Agreement shall be of thirty (30) years, starting on the Effective Date [**]. [**].

 

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

 

(b)                                 [**],

 

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 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 PLAN