Exhibit 10.18
SUPPLY AGREEMENT
BY AND BETWEEN
OMRIX BIOPHARMACEUTICALS, LTD,
TEL AVIV, ISRAEL
AND
TALECRIS BIOTHERAPEUTICS, INC.
RALEIGH, NORTH CAROLINA, USA
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PORTIONS OF THIS EXHIBIT MARKED BY AN *** HAVE BEEN OMITTED PURSUANT TO A
REQUEST FOR CONFIDENTIAL TREATMENT FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION.
TABLE OF CONTENTS
Page
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SECTION 1 TERM OF AGREEMENT 4
SECTION 2 PURCHASE AND SALE OF CRYO 4
2.1 Volume Requirements 4
2.2 Forecasts 5
2.3 Right of First Refusal 5
2.4 Purchase Orders 6
2.5 Shipments 6
2.6 Cooperation of the Parties 6
2.7 Meetings 7
SECTION 3 QUALITY AND SPECIFICATIONS 7
3.1 Specifications 7
3.2 Testing 7
3.3 Acceptance 7
3.4 Latent Defects 7
3.5 Records 8
3.6 Alternate Facility 8
SECTION 4 PRICE AND PRICE ADJUSTMENT 8
4.1 Price 8
4.2 Adjustment to Price 8
4.3 Price Adjustment Calculation 8
SECTION 5 BILLING AND PAYMENT 8
5.1 Payments 8
5.2 Payment Disputes 9
SECTION 6 REGULATORY REQUIREMENTS 9
6.1 Compliance with Regulations 9
6.2 Audit 9
6.3 Regulatory Approvals 9
SECTION 7 NONCONFORMING CRYO AND RECALLS 10
7.1 Nonconforming Cryo 10
7.2 General Requirements 10
7.3 Distribution and Use Records 10
7.4 Adverse Events 10
7.5 Customer Notification of Adverse Reactions 10
7.6 Withdrawals and Recalls 11
7.7 Complaints 11
SECTION 8 FORCE MAJEURE 11
SECTION 9 REPRESENTATIONS AND WARRANTIES AND DISCLAIMER 11
9.1 Regulatory Requirements 11
9.2 Debarment 11
9.3 Compliance 12
9.4 Intellectual Property 12
9.5 Representation and Warranties 12
9.6 Disclaimer 14
SECTION 10 TERMINATION 14
10.1 Termination for Cause 14
10.2 Termination for Talecris' Force Majeure 14
10.3 Other Termination Provisions 15
10.4 Effect of Termination 15
10.5 Remedies 15
10.6 Survival 15
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SECTION 11 INDEMNIFICATION 15
11.1 Indemnification: Talecris 15
11.2 Indemnification: Customer 16
11.3 Joint Responsibility 16
SECTION 12 CONFIDENTILITY 16
12.1 Confidentiality Obligations 16
12.2 Exceptions 16
12.3 Other Confidentiality Agreements 16
SECTION 13 INSURANCE 17
SECTION 14 MISCELLANEOUS 17
14.1 Consent to Assignment 17
14.2 Entire Agreement and Amendments 17
14.3 Notices 17
14.4 Independent Contractor 18
14.5 Non-Waiver 18
14.6 Choice of Law 18
14.7 Captions 18
14.8 Severability 19
14.9 Dispute Resolution 19
14.10 Set Off 20
14.11 Conflicting Terms 20
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SUPPLY AGREEMENT
THIS SUPPLY AGREEMENT (this "AGREEMENT") is entered into as of September, 2006
(the "EFFECTIVE DATE"), by and between Talecris Biotherapeutics, Inc., with
offices at 4101 Research Commons, 79 X. X. Xxxxxxxxx Drive, Research Xxxxxxxx
Xxxx, Xxxxx Xxxxxxxx 00000 ("TALECRIS") and Omrix Biopharmaceutical, Ltd., an
Israeli company, with its principal place of business located at MDA Xxxxx
Xxxxxx, Xxx Xxxxxxxx Xxxxxxxx, Xxx Xxxx 00000 Israel ("CUSTOMER"). Customer and
Talecris are the ("PARTIES").
WITNESSETH
WHEREAS, Talecris is engaged in the manufacture and distribution of
plasma-derived biological products;
WHEREAS, Talecris fractionates plasma into biological products at its Precision
Pharma Services facility and one of the components of the fractionation process
is a licensed intermediate blood fraction known as Cryoprecipitate ("CRYO");
WHEREAS, Customer is in the business of producing and selling fibrin sealant
products (the "Products");
WHEREAS, Customer desires to purchase from Talecris Cryo derived from plasma
fractionated at the Precision Pharma Services, Inc.'s ("Precision Pharma
Services") facility located in Melville, New York (the "Precision Pharma
Services Facility") to be qualified with various Regulatory Authorities (as
defined herein) for use in the manufacture and development of the Products; and
WHEREAS, Customer and Talecris wish to set forth their mutual agreements and
understandings regarding the sale by Talecris and the purchase by Customer of
the Cryo hereunder.
NOW, THEREFORE, for and in consideration of the premises and the mutual
covenants contained herein, and other good and valuable consideration, the
receipt and sufficiency of which are hereby acknowledged, the Parties hereto do
hereby agree as follows:
SECTION 1 TERM OF AGREEMENT
This Agreement shall have an initial term commencing on the Effective Date and
ending on December 31, 2007 ("Initial Term"), unless earlier terminated as
provided in Section 10 or otherwise in this Agreement. In the event that (i)
Customer obtains US FDA approval for use of the Cryo in the Products or Customer
is prepared to assume the Required Quantity obligations of Exhibit A without
such approval and (ii) Talecris has broadly implemented HAV testing on source
plasma during this time period (the occurrence of the fulfillment of the
conditions of clauses (i) and (ii), will initiate the "Commencement Date"), then
the Initial Term shall be extended by three (3) years from the Commencement
Date. The Initial Term may be renewed for two consecutive two (2) year periods
at the option of Customer. Customer must give Talecris at least one (1) year's
written notice prior to the end of each expiring term of its intent to renew
(each an "EXTENDED TERM", along with the Initial Term, the "TERM").
SECTION 2: PURCHASE AND SALE OF CRYO
2.1 Volume Requirements. With respect to each twelve (12) month period during
the Term, effective with issuance of the initial forecast described in Section
2.2, Talecris shall make available to Customer, and Customer shall purchase, the
volumes of Cryo set forth in EXHIBIT A, attached hereto (the "REQUIRED
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QUANTITY"). Such volumes may be adjusted as set forth in Section 2.3 and 2.4.
Upon providing a notice of renewal for an Extended Term in accordance with
Section 1, the Required Quantity for the Extended Term shall not be less than
the Required Quantity set forth in EXHIBIT A. All volumes of Cryo to be sold to
Customer shall be determined after deducting quantities representing
Nonconforming Cryo (as defined in Section 7.1 below).
2.2 Forecasts. Within thirty (30) days of the Commencement Date, Customer shall
provide Talecris with an initial twelve (12) month rolling forecast of
Customer's estimated requirements of Cryo by calendar month. Such forecast shall
be deemed attached and incorporated hereto as EXHIBIT B. Customer shall provide
an updated rolling twelve (12) month forecast on or about the commencement of
each calendar month, in form as set forth in EXHIBIT B. Subject to Sections 2.3
and 2.4, the first six (6) months of each rolling twelve (12) month forecast
shall be a firm binding order (a "BINDING FORECAST"). Talecris agrees to deliver
Cryo in the quantities ordered hereunder within +/- 5% of the requirements of
the Binding Forecast (a "DELIVERY DEVIATION"), on such delivery dates as are
specified in the Purchase Orders issued by Customer pursuant to Section 2.5.
Notwithstanding the above, the Delivery Deviation will not accumulate to more
than 10% over any three (3) month period. The Parties agree and acknowledge
that, only after Customer obtains approval from the FDA for use of the Cryo on
the Products, shall Customer be obligated to purchase the Cryo. To the extent
that the aggregate volume of Cryo purchased by Omrix in any (twelve) 12 month
period after the Commencement Date (each, an "Anniversary Year") does not at
least equal the Required Quantity applicable to such Anniversary Year, Talecris
may, within thirty (30) days of the end of such year, invoice Customer for the
total price attributed to such difference (based on the Price set forth in
Section 4 below) and deliver to Customer the invoiced Cryo in accordance with
Section 2.6. Except as otherwise provided under Section 2.3, forecasts for
volumes exceeding the Required Quantity shall require the prior written approval
of Talecris.
2.2.1 On an annual basis starting within thirty (30) days after the Effective
Date, and at least six (6) months prior to the beginning of each Anniversary
Year, Talecris shall provide Customer with written notice of the total quarterly
volumes of Cryo to be manufactured and made available during the following year
(the "AVAILABLE QUANTITY"). Upon six (6) months prior written notice, Customer
may (i) increase the Required Quantity by an amount up to the Available Quantity
and applicable Purchase Orders shall be adjusted to account for such increase,
or (ii) if prior to the Commencement Date, Customer may issue a Purchase Order
for up to the Available Quantity.
2.3 Right of First Refusal
2.3.1 Fee. Upon payment of one million dollars ($1,000,000), and the five (5)
subsequent payments on the anniversary of the Effective Date of this
Agreement of one hundred thousand dollars ($100,000) for the remainder of
the Term ("ROFR Fee"), Talecris grants Customer a right of first refusal
("ROFR") during the Term for additional Cryo as detailed below.
2.3.2 Available Quantity. Within thirty days (30) days prior to the beginning of
each calendar year Talecris shall provide Customer with written notice of
the total Cryo not already subject to an existing contractual obligation
that Talecris expects to manufacture and make available to third parties
for that upcoming year ("Available Quantity"). The Available Quantity shall
be updated and communicated in writing to Customer (each an "Update") upon
the following occurrences: 1) six months from the original forecast for
that year, and 2) if Talecris intends to provide greater volumes of Cryo to
third parties than those specified in the last Available Quantity forecast
or Update submitted to Customer.
2.3.3 Purchase Right. Customer shall have fifteen (15) days upon receipt of the
Available Quantity or any subsequent Update to purchase all or part of the
available Cryo at the then
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current price per kilogram called for in this Agreement. Whatever volumes
Customer has not elected to purchase Talecris shall be free to dispose of
in its sole discretion. Any additional Cryo Customer purchases pursuant to
this ROFR shall be added to Customer's binding forecast and minimum volume
obligations.
2.3.4 Refund of ROFR Fee. If Talecris does not routinely implement HAV testing
by December 31, 2007, Talecris shall either a) provide HAV testing for all
Cryo purchased by Customer at no additional cost to Customer, or b) will
refund entire ROFR Fee paid by Customer. Furthermore, if (i) If Cryo does
not receive FDA approval and Customer has not exercised any of its rights
under the ROFR during the Term, or Talecris makes changes to the batch
production records or the Specification, as described in Section 3.1, such
that the Cryo is no longer in compliance with the FDA approval received by
Customer, and Customer did not receive FDA approval for such batch
production record or Specification change, (ii) Customer terminates this
Agreement pursuant to Section 6.2, or (iii) Talecris ceases to manufacture
Cryo, then Talecris shall pay Customer the pro rata share of the RFR Fee
equal to the ratio between (A) the period since the Commencement Date and
the date of termination, and (B) six (6) years.
2.3.5 Exclusion of Cryo. For purposes of clarification, Cryo sent to third party
toll manufacturers for the benefit of Talecris (i.e., not sold to such
third parties), are not subject to the ROFR provisions contained herein.
2.4 Purchase Orders. Within thirty (30) days after the Commencement Date,
Customer shall deliver to Talecris a purchase order reflecting the aggregate
Cryo volume in the initial Binding Forecast and with each subsequent forecast
set forth in Section 2.2 above, Customer shall deliver a purchase order
reflecting the aggregate Cryo ordered for the six (6) months of the Binding
Forecast (in each case, a "PURCHASE ORDER"). Each Purchase Order shall specify
the volumes of Cyro ordered and the delivery dates. The Parties shall cooperate
to ensure that the Cryo to be purchased by Customer is ordered in a manner so as
to reasonably allow Talecris to produce such Cryo efficiently, without material
swings in volume over the course of any twelve (12) month period.
2.5 Shipments. Talecris agrees that it shall provide Cryo in conformance with
the delivery schedule provided by Customer based on issued Purchase Orders.
Talecris shall include copies of production and test records with each shipment
as specified in the Specifications (EXHIBIT C). Customer shall be responsible
for making the necessary shipping arrangements. All Cryo purchased and sold
hereunder shall be delivered Ex Works (Precision Pharma Services Facility)
(INCOTERMS 2000). Risk of loss for Ciyo in transit shall lie with Customer. All
financial arrangements for shipping and handling of Cryo shall be the
responsibility of Customer.
2.6 Cooperation of the Parties. Talecris shall inform Customer promptly of any
problems that could reasonably be expected to prevent Talecris from providing
timely deliveries of Cryo and the Parties shall cooperate in resolving such
problems relating to the manufacture and supply of Cryo under this Agreement.
The Parties shall use their commercially reasonable efforts to coordinate
maintenance outages and shut-downs of Customer's facility and Precision Pharma
Services Facility, which coordination could include making temporary changes to
the Binding Forecast. Consistent with Section 6.3 below, Talecris will provide
reasonable support to Customer in response to any questions raised by
"Regulatory Authorities" (i.e., all applicable governmental and regulatory
authorities, including, but not limited to, the FDA, subject to Section 6.1)
regarding the production of Cryo at the Precision Pharma Services Facility. For
purposes of clarification, this Section 2.7 does not diminish or expand the
Parties' respective aggregate obligations over any 12- month period to supply
and purchase Cryo in accordance with the Binding Forecast set forth in
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Section 2.2. If Talecris fails to deliver Cryo in accordance within a delivery
schedule, and is unable to make up the quantity in a rolling three (3) month
period, set forth in a Purchase Order, then for each week of delay beyond such
three (3) month period from the delivery schedule date, the Price for the
undelivered quantity shall be reduced by five percent (5%) per each additional
week of delay.
2.7 Meetings. Unless otherwise mutually agreed, the manufacturing representative
of each Party shall meet (either in person or via conference call) no less than
monthly to discuss the forecasts delivered by Customer pursuant to this
Agreement and other matters relevant to the supply of Cryo hereunder. In
addition, a senior manager of each Party shall meet (either in person or via
conference call) on a quarterly basis to discuss matters relevant to the supply
of Cryo hereunder. At least three (3) business days prior to each meeting, each
Party shall deliver to the other Party a written report regarding the issues to
be discussed at such meeting.
SECTION 3 QUALITY AND SPECIFICATIONS
3.1 Specifications. Talecris shall manufacture, process, store, distribute,
test, transport, dispose and otherwise handle Cryo at all times in compliance
with cGMPs (as defined in Section 6.1) and other applicable Regulations (as
defined in Section 6.1 below), the Cryo Specifications and Requirements
(attached hereto as EXHIBIT C and incorporated herein by reference the
"SPECIFICATIONS"), and the SOPs as defined in Sections 6.2. All Cryo shall be
produced only at the Precision Pharma Services Facility. The Specifications
shall be renewed annually, consistent with the Term of this Agreement, with each
such renewal deemed attached hereto as EXHIBIT C and incorporated herein by
reference. In the event of a conflict between the provisions of this Agreement
and the provisions of the Specifications, the provisions of this Agreement shall
prevail. Talecris/Precision shall not make changes to the key process parameters
EXHIBIT D that require prior approval from the FDA or the Specifications without
prior reasonable notice to Customer, which prior notice shall be at least six
(6) months unless otherwise required by a regulatory body. Such notice shall be
sufficiently prior to implementation of the changes so as to allow Customer to
amend its regulatory filings and to purchase additional inventory of Cryo. The
key process parameters in effect at the Precision Pharma Services Facility as of
the Effective Date are set forth in EXHIBIT D, attached hereto. If Talecris
changes to EXHIBIT D or the Specifications in such a manner that the Cryo will
no longer be in compliance with the FDA approval received by Customer, then
Customer may upon written notice terminate this Agreement. Additionally, the
Customer agrees to the terms and conditions set forth in the Manufacturing
Agreement, attached hereto as EXHIBIT E.
3.2 Testing. With respect to each shipment of Cryo to be shipped to Customer,
Talecris shall test such Cryo to ensure compliance with the Specifications.
Talecris shall include a certificate of analysis ("COA") as well as all other
documentation described in the Specifications with each shipment of Cryo
disclosing the results of such testing and showing conformance with the
Specifications. Customer shall not perform any additional testing for human
pathogens (Nucleic Acid Testing (NAT) or otherwise) on the Cryo or any
derivatives therefrom without the prior written authorization of Talecris unless
this testing is approved by both parties and is listed in the Specifications.
3.3 Acceptance. Subject to Section 3.4 below, Customer shall have a period of
thirty (30) days from date of its receipt of a shipment of Cryo at Customer's
Israel plant to inspect the delivered Cryo and the accompanying COA (and
documentation described in EXHIBIT C) and reject all or part of the
corresponding shipment of Cryo for nonconformity with the Specifications. If
Customer rejects all or part of such shipment, it shall promptly notify Talecris
and the provisions of Sections 7.1 below shall apply.
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3.4 Latent Defects. If after accepting a shipment of Cryo, Customer subsequently
discovers latent material defects (including without limitation, nonconformance
to the Specifications) not reasonably discoverable during the acceptance period
set forth in Section 3.3, Customer may revoke its acceptance of such shipment of
Cryo by giving written notice and disclosing the nature of any defects to
Talecris as soon as practicable after discovering such defects. In such event,
such Cryo shall be considered a Nonconforming Cryo (as defined in 7.1) to the
extent latent material defects in fact are present and the provisions of Section
7.1 below shall apply.
3.5 Records. Talecris shall maintain production records and other records
required by cGMPs and the Regulations for such time periods referenced thereby.
Talecris shall make such records available to Customer for Customer's inspection
promptly following a written request by Customer.
3.6 Alternative Facility. Talecris represents and warrants that Talecris has no
current plans for closing the Precision Pharma Services Facility during the
Term. If at anytime during the Term, Talecris decides to close the Precision
Pharma Services Facility, then (1) Talecris will provide Customer with twelve
(12) months notice prior to such closing to allow Customer to purchase
additional inventory of Cryo and (2) the parties will negotiate in good faith
terms for transferring the manufacturing of Cryo to an alternative Talecris
facility, which terms shall include allocation of costs necessary for enabling
such alternative facility to manufacture Cryo in accordance with this Agreement,
and Customer's requirements assuming a shared manufacturing arrangement may be
put into place between Omrix and the new manufacturing facility. If the parties
are unable to negotiate an alternative facility, then Customer may terminate
this Agreement upon written notice. Additionally, if Talecris transfers
ownership or control of the Precision Pharma Services Facility, Talecris shall
require the transferee to be bound by the terms of this Agreement, on the same
terms and specifications as applicable to Talecris and Precisions Pharma
Services.
SECTION 4 PRICE AND PRICE ADJUSTMENT
4.1 Price. During the Term of this Agreement, Customer shall pay *** per kg of
Cryo for any Cryo purchased hereunder, as adjusted pursuant to Section 4.2 below
("PRICE"). All payments hereunder shall be made in U.S. Dollars. If Cryo from
Precision Pharma Services receives EU regulatory approval, Customer shall have
the option to purchase such Cryo for the European market and the Price for such
Cryo to be sold into the European market shall be *** per kg.
4.2. Adjustment to Price The Price shall be adjusted annually by Talecris on the
first day of each Anniversary Year. Such adjustment to Price (the "PRICE
ADJUSTMENT") shall reflect the change in the CPI-U or increases in acquisition
cost of raw material, which ever is the greater number. For purposes of the
foregoing, "CPI-IF shall mean the unadjusted percentage change for the previous
twelve-month period as published in the Consumer Price Index for all urban
consumers by the U.S. Department of Labor, Bureau of Labor Statistics. For the
avoidance of doubt, the first such Price Adjustment shall become effective at
the end of the first Anniversary Year.
4.3 Price Adjustment Calculations. On the first day of each Anniversary Year or
as soon thereafter as possible, Talecris shall provide for Customer's review and
approval the computation of the Price Adjustment (as determined in accordance
with Section 4.2 above) to be applied in the following Anniversary Year, and the
methodology used in making such computation. Disagreements as to the adjustment
calculation shall be resolved in accordance with Section 14.9.
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SECTION 5 BILLING AND PAYMENT
5.1 Payments. Talecris shall deliver to Customer at the address set forth in
Section 14.3 an invoice for shipments of Cryo to Customer as the same is
shipped. Each invoice shall reflect the actual quantity of the Cryo shipped and
the price thereof, as computed in accordance with Section 4. The amount invoiced
by Talecris and payable by Customer during each Binding Forecast period will not
be less than that charge associated with such Binding Forecast, as computed in
accordance with Section 4, unless the actual Cryo delivered is less than the
Binding Forecast due to a Delivery Deviation or Talecris' failure to perform its
obligations under this Agreement, including due to Nonconforming Cryo. Within
thirty (30) days following the receipt of such invoice, Customer shall pay to
Talecris the amount specified therein.
5.2 Payment Disputes. All billing and payment disputes between Customer and
Talecris shall be resolved in accordance with Section 14.9 below.
SECTION 6 REGULATORY REQUIREMENTS
6.1 Compliance with Regulations. Talecris shall comply in all material respects
with all applicable laws, requirements, regulations, guidelines, licenses and
directives, including applicable current Good Manufacturing Practices ("CGMPS")
as defined in national and international laws and internationally accepted GMP
compendia including PIC/C and WHO GMP Guide, including all specifications and
procedures for plasma sourcing, plasma testing, and in process testing and all
regulations, specifications, and procedures contained therein, as well as the
contract manufacturing arrangements described in the CBER: "Guidance for
Industry Cooperative Manufacturing Arrangements for Licensed Biologics and
specifically all requirements under section V "Shared Manufacturing
Arrangements" (collectively, "REGULATIONS"). These shall include all applicable
US FDA laws, requirements, regulations, guidelines, licenses and directives,
including applicable cGMPs and FD&C Act (21 USC 301). Talecris commits to
promptly inform Customer of any FDA citation of a deviation from cGMP that may
impact the ability to meet all Specifications of Cryo.
6.2 Audit. Customer shall have the right, on reasonable written advance notice,
and during normal business hours, to inspect and audit the Precision Pharma
Services Facility, and any other Talecris owned facility involved in the
production of Cryo, Standard Operating Procedures (as in effect as of the
Effective Date and amended from time to time upon mutual agreement of the
Parties, and any replacement or successor thereof, "SOPS"), production,
operations, testing, storage and books and records to confirm compliance with
Section 6.1 and Talecris compliance with the terms and conditions of this
Agreement, provided that such inspection or audit does not unreasonably
interfere with the conduct of business of Talecris. Talecris shall use its
commercially reasonable efforts to accommodate any reasonable request made by
Customer to inspect such facility. Talecris shall respond in writing to Customer
regarding any items of noncompliance identified by Customer during such
inspections or audits within fifteen (15) days of Customer's notice thereof and
shall develop a plan, reasonably satisfactory to Customer, to remedy any such
items of noncompliance within sixty (60) days of notice thereof and shall remedy
such items of noncompliance as set forth in such plan, the failure of which
shall entitle Customer to terminate this Agreement in accordance with Section
10.1 hereof. Provided, however, at the election of either party, any dispute
concerning compliance or non-compliance can be referred to arbitration in
accordance with Section 14.9.
6.3 Regulatory Approvals. Talecris/Precision is responsible for maintaining the
FDA license for the cryo intermediate. Customer is solely responsible for
obtaining and maintaining all necessary regulatory approvals from all Regulatory
Authorities necessary to sell and market the Products. Talecris shall, upon
request by Customer, and as reasonably necessary, promptly (in any case, not
longer than thirty (30) days of any such request) provide a plan detailing when
and how all documents or information requested by Customer to support Customer's
efforts to obtain, maintain, or defend the regulatory approvals necessary to
sell the Products in the US will be provided to the Customer.
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Furthermore, the price of the Cryo includes cost associated with fair and
reasonable efforts by Talecris to assist Customer in obtaining US FDA Regulatory
approval. Any information or documents that are not generated as part of
Talecris' normal business practices will be provided at a cost to the Customer.
In the event that the Customer requires additional regulatory support from
Talecris, regulatory support may be provided at an hourly rate of $250 (US
dollars).
SECTION 7 NONCONFORMING CRYO AND RECALLS
7.1. Nonconforming Cryo. In the event that Talecris provides Cryo that does not
meet the Regulations or does not conform to the Specifications, or contains
latent defects, or that has not been manufactured, processed, stored,
distributed, tested, transported, disposed of or otherwise handled in accordance
with applicable SOPs, the Specifications, cGMPs and the Regulations
("NONCONFORMING CRYO"), Talecris will at no cost to Customer, and within ninety
(90) days, replace such Nonconforming Cryo with an equivalent amount of
conforming Cryo. If not so replaced, then such Nonconforming Cryo will be
considered a delayed delivery, and the penalties set forth in Section 2.7 will
begin after such ninety (90) day period.
Upon discovery of Nonconforming Cryo, Customer will immediately notify Talecris
of the identification of the Cryo that is rejected by the Customer. The reason
for the rejection will be provided to Talecris. An investigation will be
initiated at Talecris to determine if they concur with the Customer's rejection
and to determine the cause of the Nonconformance. Talecris may request a visit
to the Customer's facility to inspect the Cryo, to sample the Cryo or other
investigational activities as necessary. Talecris must initiate their internal
investigation within fifteen (15) days of notification of Nonconformance from
the Customer.
If Talecris agrees that the material in Nonconforming, Talecris will provide a
written notification to the Customer to destroy the Cryo. The Customer will not
destroy the Cryo without receiving written notification from Talecris.
If Talecris does not agree that the product is Nonconforming and the Customer
and Talecris cannot agree to acceptability a third party arbitrator will
determine the final disposition.
7.2 General Requirements. Customer shall maintain accurate records of the
quantities of Cryo received and the intermediate and final commercial Products
derived from such Cryo.
7.3 Distribution and Use Records. Talecris/ Precision shall maintain and give
Customer access, upon advance notice and at reasonable times, to, production,
donor records and test results with respect to each unit of plasma included in
Cryo delivered to Customer. Such records and results shall be maintained such
that they can rapidly and unequivocally be accounted for and made available to
Customer within fourteen (14) days from the date of request. All such records
will be maintained by Talecris for a time period at or greater than required by
the FDA. Customer shall maintain and give Talecris access, upon advance notice
and at reasonable times, to, records identifying the use of each lot of Cryo and
the Products from which such Cryo was processed. Such records shall be
maintained such that the use of each lot of Cryo can be rapidly and
unequivocally accounted for and made available to Talecris within fourteen (14)
days from the date of request. All such records will be maintained by Customer
for a time period at or greater than required by the FDA. Customer shall assist
Talecris in identifying, tracking and controlling the use of any Cryo identified
in post-donation information as contaminated or otherwise unsuitable for
processing into Products.
7.4 Adverse Events. Customer shall record and investigate all reports of adverse
events in which Products manufactured from Cryo have been implicated. If
Customer determines that a Cryo lot has caused adverse reactions as a result of
such Cryo being manufactured using Cryo, Customer shall immediately
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notify the applicable Regulatory Authorities as required by the Regulations, and
shall promptly notify Talecris. Talecris shall promptly notify Customer of any
adverse event resulting in a market withdrawal or recall involving viral,
bacterial or prion transmission associated with other fractions processed from
the same plasma units as the Cryo or associated with a specific plasma donor
whose plasma was used in the manufacture of Cryo.
7.5 Customer Notification of Adverse Reactions. In the event that during the
course of a preliminary investigation related to a report of any serious adverse
reaction associated with any Customer Products, Customer obtains preliminary
evidence indicating that, according to indications and dosage, the Cryo used in
the manufacture of such commercial Products may have caused such specific
adverse reaction, each customer that received any such commercial Products shall
be notified by Customer and cautioned that any unused containers of the suspect
lots should be withheld from use, pending the outcome of more definitive
investigations and evaluations, with a copy of such notice to the applicable
Regulatory Authority if required. Customer shall promptly provide Talecris with
a copy of such notice. Any and all of the foregoing actions will be executed
with the concurrence of all relevant Regulatory Authority, to the extent
required by law.
7.6 Withdrawals and Recalls. Customer shall make all contacts with the relevant
Regulatory Authority and shall be responsible for coordinating all activities in
connection with any recall or withdrawal of any Products. In the event that
Talecris believes a recall or withdrawal of any Cryo may be necessary or
appropriate, Talecris shall promptly notify Customer in writing. In the event
that Customer initiates a recall or withdrawal of any Products, Customer shall
promptly notify Talecris. If Customer initiates a withdrawal or recall because
the Cryo used in the manufacture of Products caused adverse reactions, then the
cost of such withdrawal or recall shall be reimbursed by Talecris.
7.7 Complaints. Customer and Talecris will cooperate in the reporting,
investigation and evaluation of customer complaints according to
policies/procedures currently in place at Talecris and Omrix.
SECTION 8 FORCE MAJEURE
For the purpose of this Agreement, "FORCE MAJEURE" shall mean (i) acts of God,
acts of the public enemy, insurrections, riots, sabotage, strike, work-stoppage
or other labor dispute and natural disasters; (ii) explosions, fires, flood
damage, or loss of electric power not resulting from the negligence of the Party
invoking Force Majeure; (iii) regulatory actions not attributable to any
violation of law on the part of Talecris or Customer, as the case may be and
(iv) in the case of Talecris, events, circumstances, conditions and actions
outside of the control of Talecris that materially and adversely affect the
plasma-derived products industry generally, including, but not limited to,
interruptions of supply of raw plasma due to viral outbreaks, eruption of new
viruses and similar events that are reasonably likely to be subject to action by
any Regulatory Authority; any of (i), (ii), (iii) or (iv) of which, in the case
of Talecris, prevents Talecris from performing its obligations under this
Agreement, or, any of (i), (ii) or (iii) of which, in the case of Customer,
prevents Customer from producing and/or marketing its Products or performing its
obligations under this Agreement. Notwithstanding anything in this Agreement to
the contrary, except Section 11 and Section 12, the party experiencing the Force
Majeure shall be excused from the performance of each of its obligations under
this Agreement upon a Force Majeure, but only to the extent performance of any
such obligation is necessarily prevented, hindered or delayed thereby and only
during the continuance of any such Force Majeure, and shall have no liability
for damages arising from non-performance of any obligation excused by a Force
Majeure. Furthermore, if Customer terminates this Agreement pursuant to Section
10.2, there shall be no further damages arising from any non-performance excused
by a Force Majeure. The Party suffering such Force Majeure shall invoke this
provision by promptly notifying the other Party in writing of the nature and
estimated duration of the suspension period, as well as the extent to which it
will be unable to fulfill its obligations under the Agreement. Each Party shall
be relieved of performance of its obligations under this Agreement during the
time when it is prevented from performing by the failure of the other party to
perform its obligations or because of any event of Force Majeure.
Page 11 of 30
SECTION 9 REPRESENTATIONS AND WARRANTIES AND DISCLAIMER
9.1 Regulatory Requirements. Talecris represents and warrants that Talecris has
all applicable government approvals, permits and licenses required in the
performance of its obligations under this Agreement, including the US FDA.
9.2 Debarment. Talecris certifies it will not use in any capacity the services
of any person, including any firm or individual that has been debarred or is
subject to debarment under the Generic Drug Enforcement Act of 1992, amending
the Food, Drug, and Cosmetic Act of 21 U.S.C. 335a (a) or (b). Talecris agrees
to notify Customer promptly in the event any person providing services to
Talecris under the scope of this Agreement is debarred or becomes subject to
debarment.
9.3 Compliance. Talecris represents and warrants that the manufacture,
processing, distribution, testing, transport, storage, disposal and other
handling of Cryo by Talecris until delivery to and processing by Customer shall
(i) conform to applicable SOPs, the Specifications, cGMPs and the Regulations,
and (ii) be free from defects in materials and workmanship and shall not be
adulterated or misbranded within the meaning of the applicable Regulations.
9.4 Intellectual Property. Talecris represents and warrants that the
manufacture, processing, testing, distribution, transport, storage, disposal and
other handling of Cryo does not infringe the intellectual property rights of any
third party and that Talecris validly possesses all licenses to third party
intellectual property necessary or appropriate for the manufacture, processing,
testing, distribution, transport, storage, disposal and other handling of Cryo.
9.5 Representations and Warranties.
a) Customer hereby represents and warrants to Talecris that:
(i) Due Organization, Good Standing and Power. Customer is a duly
organized, validly existing and in good standing under the laws of the
jurisdiction in which it was organized. Customer has all requisite
corporate or other power and authority to own or lease and to operate its
assets and to conduct the business now being conducted by it. Customer is
duly authorized, qualified or licensed to do business as a foreign
corporation or other organization in good standing in each of the
jurisdictions in which its ownership of property or the conduct of its
business requires such authorization, qualification or licensing, except
where the failure to have such authorization, qualification or licensing
could not reasonably be expected to have a material adverse effect on
Customer or on the consummation of the transactions contemplated hereunder.
Customer has all requisite corporate power and authority under applicable
law and its charter documents to enter into this Agreement and to perform
its obligations hereunder and to consummate the transactions contemplated
hereby.
(ii) Authorization and Validity of Agreement. The execution and delivery of
this Agreement by Customer and the consummation by it of the transactions
contemplated hereby have been duly authorized and approved by all necessary
corporate action under applicable law and the relevant charter documents on
the part of Customer and do not require the approval of the stockholders of
Customer. This Agreement has been duly executed and delivered by Customer
and constitutes the legal, valid and binding obligation of Customer
enforceable against it in accordance with its terms, except as that
enforceability may be (i) limited by any applicable bankruptcy, insolvency,
reorganization, moratorium or similar laws affecting the enforcement of
creditors' rights generally, (ii) subject to general principles of equity
(regardless of whether that enforceability is considered in a proceeding in
equity or at law) and (iii) limited
Page 12 of 30
by general principles of applicable law regarding the enforceability of
arbitral awards and judicial decisions.
(iii) Lack of Conflicts. Neither the execution and delivery of this
Agreement by Customer or the consummation by it or the transactions
contemplated hereby, does or will (i) conflict with, or result in the
breach of any provision of, the charter documents of Customer or (ii)
violate any applicable law or any permit, order, award, injunction, decree
or judgment of any governmental authority applicable to or binding upon
Customer or to which any of its properties or assets is subject.
(iv) No Consents. The execution, delivery and performance of this Agreement
by Customer and the consummation of the transactions contemplated by this
Agreement do not require any governmental approval. No consent (other than
governmental approvals) will be required to be obtained by Customer for the
consummation of the transactions contemplated by this Agreement.
(b) Talecris hereby represents and warrants to Customer that:
(i) Due Organization, Good Standing and Power. Talecris is a corporation
duly organized validly existing and in good standing under the laws of
the state of Delaware. Talecris has all requisite corporate or other
power and authority to own or lease and to operate its assets and to
conduct the business now being conducted by it. Talecris is duly
authorized, qualified or licensed to do business as a foreign
corporation or other organization in good standing in each of the
jurisdictions in which its ownership of property or the conduct of its
business requires such authorization, qualification or licensing,
except where the failure to have such authorization, qualification or
licensing could not reasonably be expected to have a material adverse
effect on Talecris or on the consummation of the transactions
contemplated hereunder. Talecris has all requisite corporate power and
authority under applicable law and its charter documents to enter into
this Agreement and to perform its obligations hereunder and to
consummate the transactions contemplated hereby.
(ii) Authorization and Validity of Agreement. The execution and delivery of
this Agreement by Talecris and the consummation by it of the
transactions contemplated hereby have been duly authorized and
approved by all necessary corporate action under applicable law and
the relevant charter documents on the part of Talecris and do not
require the approval of the stockholders of Talecris. This Agreement
has been duly executed and delivered by Talecris and constitutes the
legal, valid and binding obligation of Talecris enforceable against it
in accordance with its terms, except as that enforceability may be (i)
limited by any applicable bankruptcy, insolvency, reorganization,
moratorium or similar laws affecting the enforcement of creditors'
rights generally, (ii) subject to general principles of equity
(regardless of whether that enforceability is considered in a
proceeding in equity or at law) and (iii) limited by general
principles of
Page 13 of 30
applicable law regarding the enforceability of arbitral awards and
judicial decisions.
(iii) Lack of Conflicts. Neither the execution and delivery of this
Agreement by Talecris or the consummation by it to the transactions
contemplated hereby, does or will (i) conflict with, or result in the
breach of any provision of, the charter documents of Talecris or (ii)
violate any applicable law or any permit, order, award, injunction,
decree or judgment of any governmental authority applicable to or
binding upon Talecris or to which any of its properties or assets is
subject.
(iv) No Consents. The execution, delivery and performance of this Agreement
by Talecris and the consummation of the transactions contemplated by
this Agreement do not require any governmental approval. No consent
(other than governmental approvals) will be required to be obtained by
Talecris for the consummation of the transactions contemplated by this
Agreement.
9.6 Disclaimer. TALECRIS MAKES NO REPRESENTATIONS OR WARRANTIES, EXPRESS OR
IMPLIED OTHER THAN THOSE EXPRESSLY MADE IN THIS AGREEMENT. ALL OTHER WARRANTIES,
EXPRESS OR IMPLIED, INCLUDING, WITHOUT LIMITATION, THE IMPLIED WARRANTIES OF
MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE, ARE HEREBY DISCLAIMED.
SECTION 10: TERMINATION
10.1 Termination for Cause. If either Party commits a substantial violation of
any material provision of this Agreement (which means (i) in the case of
Customer, nonpayment of amounts owing to Talecris in accordance with Section 5.1
or any other material breach of any representation, warranty, covenant or
performance obligations under this Agreement by Customer and (ii) in the case of
Talecris, any material breach of any representation, warranty, covenant or
performance obligation under this Agreement), the other Party may, without
prejudice to any other right or remedy, and after giving the breaching Party
thirty (30) days' written notice of the breach, terminate this Agreement. This
Agreement shall not be so terminated if the breaching Party has cured the
breach, or submitted a plan for curing the breach reasonably acceptable to the
non-breaching Party within thirty (30) days after the non-breaching Party's
notice. If the breaching Party fails to cure the breach as set forth in the
aforementioned plan in accordance with the deadlines set forth therein, the
non-breaching Party may terminate this Agreement without further notice. The
non-breaching Party shall have the right to recover all damages and losses
arising as a result of any such material breach, provided that any such recovery
shall be reduced by the amount that such non-breaching Party actually recovers
under any insurance it maintains.
10.2 Termination for Talecris' Force Majeure. Customer may terminate this
Agreement in its sole discretion upon written notice in the event of any failure
or inability of Talecris extending beyond sixty (60) days to provide Cryo
hereunder due to Force Majeure. In the event of termination under this Section
10.2, Talecris shall have no liability for damages arising solely from such
termination or otherwise excused by a Force Majeure.
Page 14 of 30
10.3 Other Termination Provisions, By Customer if Talecris or by Talecris if
Customer:
(i) admits in writing that it is unable to pay its debts as they become
due;
(ii) starts a proceeding, or indicates its acquiescence to a proceeding
started by another, relating to it under any bankruptcy,
reorganization, rearrangement, insolvency, readjustment or debt,
dissolution, liquidation or similar law;
(iii) makes an assignment for the benefit of creditors;
(iv) consents to the appointment of a receiver, trustee or liquidator for a
substantial part of its property;
(v) files, or has filed against it, a petition in bankruptcy,
reorganization, rearrangement or insolvency which, if filed against
it, is not dissolved or dismissed within ninety (90) days after
filing; or
(vi) had entered against it an order by a court of competent jurisdiction
appointing a receiver, trustee or liquidator for it or a substantial
part of its property, or approving its dissolution or termination, and
if not consented to or acquiesced in by such Party, such order in not
vacated or set aside or stayed within ninety (90) days.
Notwithstanding anything to the contrary herein, no Party shall take or cause to
be taken any action relating to the voluntary liquidation or dissolution of such
Party.
10.4 Effect of Termination. Upon termination of this Agreement, Talecris shall
immediately cease delivery of all Cryo under this Agreement, and Talecris shall
prepare and submit to Customer an invoice for all Cryo shipped by Talecris and
not paid for by Customer. Customer shall within thirty (30) days of receipt
thereof pay the full amount of such invoice and all other sums owed to Talecris;
provided, however, that if the aggregate total of the Purchase Orders placed by
Customer prior to the effective date of such termination does not meet the
Binding Forecast for the then current calendar year in the event that this
Agreement is terminated by Talecris pursuant to Section 10.1, Customer shall be
obligated to pay amounts associated with Cryo to be delivered under the then
current Binding Forecast and, at Customer's sole discretion, Talecris shall be
obligated to deliver the same.
10.5 Remedies. The rights of a Party to this Agreement to recover monetary
damages from the other Party to this Agreement with respect to termination of
this Agreement are exclusively set forth in this Section 10.
10.6 Survival. Provisions of this Agreement, which by their nature would
continue beyond the termination, expiration or ending in any other way of this
Agreement shall survive the termination, expiration or ending in any other way
of this Agreement.
Page 15 of 30
SECTION 11: INDEMNIFICATION
11.1 Indemnification: Talecris, Talecris hereby agrees to save, defend and hold
Customer and its affiliates and its or their directors, officers, managers,
employees, representatives, consultants, stockholders, controlling persons and
agents and each of the heirs, executors, successors and assigns of any of the
foregoing (together, the "CUSTOMER GROUP") harmless from and against any and all
claims, suits, actions, liabilities, expenses and/or losses, including punitive
or exemplary damages and reasonable attorneys' fees and expenses ("CLAIMS")
asserted by a person or entity other than a member of the Customer Group arising
from any material breach of obligations under this Agreement by Talecris Group
(as defined below).
11.2 Indemnification: Customer. Customer hereby agrees to save, defend and hold
Talecris and its affiliates and its or their directors, officers, managers,
employees, representatives, consultants, stockholders, controlling persons and
agents and each of the heirs, executors, successors and assigns of any of the
foregoing (together, the "TALECRIS GROUP") harmless from and against any and all
Claims asserted by a person or entity other than a member of the Talecris Group
arising from any material breach of obligations under this Agreement by the
Customer Group.
11.3 Joint Responsibility. Where a Claim arises directly or indirectly from acts
or omissions of both (i) the Talecris Group and (ii) the Customer Group, the
obligation of the Talecris or Customer to indemnify the other shall not exceed
the extent of the indemnifying party's contribution to the harm giving rise to
the Claim.
SECTION 12: CONFIDENTIALITY
12.1 Confidentiality Obligations. All information provided by one Party to the
other Party in connection with this Agreement (including without limitations,
the Specifications and forecasts provided by Customer) shall be maintained in
strict confidence by the receiving Party. Such information shall remain the
property of the providing Party, and the receiving Party shall not make use of
any such information except for the purposes for which it was provided. At the
termination of this Agreement, the receiving Party shall promptly return to the
providing Party any physical embodiments (including copies) of any such
information. Each Party agrees to keep confidential the existence of this
Agreement, as well as all of its terms and conditions; provided that if a public
announcement-or disclosure is required by law, rule, regulation, court order,
subpoena, interrogatory or other discovery request (including without limitation
applicable securities laws or stock exchange regulations), and subject to
Section 12.2(vi), the Party required to make the public announcement or
disclosure shall be permitted to make such disclosure and shall provide prompt
prior written notice of such requirement to the other Party, and the Parties
shall thereafter negotiate in good faith, to the extent appropriate and
feasible, the contents of the public announcement or disclosure.
12.2 Exceptions. The covenants of the receiving Party contained in Section 12.1
shall not apply to information which: (i) is already in the public domain at the
time of disclosure; (ii) becomes part of the public domain through no action or
omission of the receiving Party after disclosure to the receiving Party; (iii)
is already known to the receiving Party at the time of disclosure, as evidenced
by the receiving Party's written records; (iv) has been or is disclosed to the
receiving Party in good faith by a third party who was or is not, at the time of
disclosure, under any obligation of confidence to the other Party hereto at the
time the third party disclosed such information; (v) is independently developed
by the receiving Party, without reliance on information provided by the
disclosing party, as evidenced by the receiving Party's written records, or (vi)
is required to be disclosed by law, provided that the receiving Party shall
cooperate with the disclosing Party (at the disclosing Party's expense) in
obtaining any available protection for such information to be disclosed.
Talecris acknowledges that Customer currently manufactures its own Cyo and uses
know how developed by Customer or received from third parties for such
purchases.
Page 16 of 30
12.3 Other Confidentiality Agreements. In the event that the Parties are bound
by more than one confidentiality agreement, then the obligations contained
therein shall be deemed cumulative.
SECTION 13 INSURANCE
Each Party shall procure and maintain, at its own expense, in full force and
effect at all times during the term, product liability insurance written by a
responsible insurance carrier, Best Rated A, with a combined single limit of not
less than five million U.S. dollars (U.S. $5,000,000). Such insurance policy
shall name both Parties hereto as additional insureds and will provide for at
least thirty (30) days prior written notice to the other Party of the
cancellation or substantial adverse modification thereof. Each Party hereto
shall deliver a certificate of such insurance to the other Party promptly upon
issuance of the policy and shall, from time to time as reasonably requested by
such other Party, furnish such other Party with evidence of the maintenance
thereof. If any of the insurance policies described herein are written on a
claims made basis, the applicable Party maintaining such insurance agrees either
to (a) continue to purchase such coverage or (b) purchase an extended reporting
period endorsement ("tail" insurance), in either instance for the entire Term,
and for a period of five (5) years after the end of such Term.
SECTION 14 MISCELLANEOUS
14.1. Consent to Assignment. This Agreement and all of the provisions hereof
shall be binding upon and inure to the benefit of the parties hereto and their
respective successors and assigns, and are not intended to confer upon any other
person any rights or remedies hereunder. Neither this Agreement nor any of the
rights, interests or obligations hereunder may be assigned by any of the parties
without the prior written consent of the other party hereto, except that each
party may at any time assign any or all of its rights or obligations hereunder
to one of its wholly owned subsidiaries (but no such assignment shall relieve
such party of any obligations under this Agreement). Notwithstanding the
foregoing, Talecris may assign this Agreement and any or all rights or
obligations hereunder to (i) any affiliate of Talecris, provided that any such
affiliate becomes a party to this Agreement prior to such assignment or (ii) any
successor in interest to Talecris, it being understood that any such successor
shall commit to Customer to continue to supply Cryo under this Agreement from
the Precision Pharma Services Facility; and provided that any such successor
becomes a party to this Agreement. No assignment under (i) or (ii) above shall
relieve Talecris from any obligation hereunder. Customer may assign this
Agreement and any or all rights or obligations hereunder to (i) any affiliate of
Customer provided that any such affiliate becomes a party to this Agreement or
(ii) any successor in interest to Customer of its fibrin sealant business,
provided that any such successor becomes a party to this Agreement. No
assignment under (i) or (ii) above shall relieve Customer nom any obligation
hereunder. Any purported assignment in contravention of this Section 14.1 shall
be void.
14.2 Entire Agreement and Amendments. Except with regards to additional
confidentiality agreements, this Agreement, together with the Exhibits,
constitutes the entire agreement between the Parties regarding the supply of
Cryo, whether oral or written, relating to the subject matter hereof. In the
event that this Agreement conflicts with any Purchase Order, invoice or other
written document, the terms and conditions of this Agreement shall apply. No
amendment, modification or interpretation of this Agreement will have any effect
unless it is reduced to writing, makes specific reference to this Agreement and
is signed by all of the Parties.
14.3 Notices. All notices, requests, demands and other communications required
or permitted hereunder shall be in writing and if mailed by prepaid first class
mail or certified mail, return receipt requested, at any time other than during
a general discontinuance of postal service due to strike, lockout or otherwise,
shall be deemed to have been received on the earlier of the date shown on the
receipt or three (3) business days after the postmarked date thereof and, if
telexed or faxed, the original notice shall be mailed
Page 17 of 30
by prepaid first class mail within twenty-four (24) hours after sending such
notice by telex or fax, and shall be deemed to have been received on the
business day following dispatch and acknowledgment of receipt the recipient's
telex or telecopy machine. In addition, notices hereunder may be delivered by
hand, in which event the notice shall be deemed effective when delivered, or by
overnight courier, in which event the notice shall be deemed to have been
received on the next business day following delivery to such courier. All
notices and other communications under this Agreement shall be given to the
parties hereto at the following addresses:
(a) If to Customer:
Omrix Biopharmaceuticals, Ltd
MDA Xxxxx Xxxxxx, Xxx Xxxxxxxx
Xxxxxxxx, Xxx Xxxx 00000 Israel
Attn: Xxxxxx Xxxx
President and CEO
(b) If to Talecris:
Talecris Biotherapeutics, Inc.
79 XX Xxxxxxxxx Drive
4101 Research Commons
Research Triangle Park
Xxxxxxx, XX 00000 XXX
Fax: (000)000-0000
Attention: Law and Public Affairs Department
And to:
Talecris Biotherapeutics, Inc.
0000 X.X. 00 Xxxx
Xxxxxxx, XX 00000 XXX
Attn.: Xxxx Xxxxx
Any Party hereto may change its address specified for notices herein by
designating a new address by notice in accordance with this Section 14.3.
14.4 Independent Contractor. This Agreement does not create an employer-employee
relationship between the Parties, and is not an agency, joint venture or
partnership. Neither Party shall have the authority to act for the other or to
bind the other in any way, nor to sign the name or to represent that the other
is in any way responsible for the acts or omissions of the other. Talecris shall
maintain its status as an independent contractor engaged in the selling of Cryo
to Customer.
14.5 Non-Waiver. The waiver by either party of any breach of any term, covenant,
condition or agreement contained herein or any default in the performance of any
obligations hereunder shall not be deemed to be a waiver of any other breach or
default of the same or of any other term, covenant, condition, agreement or
obligation.
14.6 Choice of Law. The rights and obligations of the Parties arising out of the
Agreement shall be governed in all respects by the laws of the State of New
York, without giving effect to its conflict of laws provisions.
Page 18 of 30
14.7 Captions. All captions are inserted for convenience only, and will not
affect any construction or interpretation of this Agreement.
14.8 Severability. Any provision of this Agreement which is or may become
prohibited or unenforceable, as a matter of law or regulation, will be
ineffective only to the extent of such prohibition or unenforceability and shall
not invalidate the remaining provisions hereof if the essential purposes of this
Agreement may be given effect despite the prohibition or unenforceability of the
affected provision.
14.9 Dispute Resolution.
(a) Resolution by the Parties. The Parties shall attempt to resolve any
dispute, controversy, claim or difference arising out of, or in connection
with, this Agreement amicably and promptly by negotiations between
executives who have authority to settle the controversy. Either Party may
give written notice of any dispute not resolved in the normal course of
business ("NOTICE OF DISPUTE"). Within seven (7) days after delivery of
such Notice of Dispute, executives of the Party shall agree to meet at a
mutually acceptable time and place, and thereafter as often as they
reasonably deem necessary, to attempt to resolve the dispute. If the matter
has not been resolved within ten (10) days of the first meeting of such
executives (or, if the Parties are unable to mutually agree upon an
acceptable time and place to meet, within ten (10) days of the disputing
Party's Notice of Dispute) either Party may, by notice to the other Party
("DISPUTE ESCALATION NOTICE"), refer the matter to the respective officers
of the Parties designated below.
For Customer:
Omrix Biopharmaceuticals, Ltd
MDA Xxxxx Xxxxxx,
Xxx Xxxxxxxx Xxxxxxxx, Xxx Xxxx 00000 Israel
Attn: Xxxxxx Xxxx
President and CEO
For Talecris:
Talecris Biotherapeutics, Inc.
79 XX Xxxxxxxxx Drive
4101 Research Commons
Xxxxxxxx Xxxxxxxx Xxxx
Xxxxxxx, XX 00000
Fax: (000)000-0000
Attn: Chief Executive Officer of Talecris
Biotherapeutics, Inc.
With a copy to: VP, General Counsel
And to:
Talecris Biotherapeutics, Inc.
0000 X.X. 00 Xxxx
Xxxxxxx, XX 00000 XXX
Attn.: Xxxx Xxxxx
Such officers shall negotiate in good faith to resolve the matter in an
amicable manner within ten (10) days of the Dispute Escalation Notice. In
the event the matter is not resolved within such ten (10) days, either
Party may initiate arbitration of the dispute as provided for in this
Section 14.9.
(b) Binding Arbitration. In any event, if any dispute is not resolved in
accordance with Section 14.9(a) within thirty (30) days of the date in
which such dispute arose, either Party may
Page 19 of 30
Association (the "RULES"). If the arbitrator is not agreed by the Parties
within a thirty (30) day period, then the arbitrator will be selected by
the American Arbitration Association. The arbitration shall be held in the
English language in New York, New York (U.S.) in accordance with the
substantive law of the State of New York, without giving effect to its
conflict of laws provisions. Notwithstanding the provisions of this Section
14.9, Party shall be entitled to seek injunctive relief or specific
performance in a court of competent jurisdiction in cases where a breach of
this Agreement may cause the other Party extensive and irreparable harm and
damage.
14.10 Set-Off. No Party to this Agreement shall have any right of set off with
respect to amounts it has an obligation to pay hereunder.
14.11 Conflicting Terms. In the event any terms of the exhibits conflict with
this Agreement, the terms of this Agreement shall control.
IN WITNESS WHEREOF, the Parties have caused their duly authorized
representatives to execute this Agreement as of the Effective Date.
OMRIX
By: /s/ Xxxxxx Xxxx
------------------------------------
Name: Xxxxxx Xxxx
Title: President and CEO
TALECRIS BIOTHERAPEUTICS, INC.
By: /s/ Xxxx X Xxxx
------------------------------------
Name: Xxxx X Xxxx
Title: SVP Operations
(STAMP)
Page 20 of 30
EXHIBIT A
Required Quantity*
Anniversary Year after Commencement Date Kgs of Cryo
---------------------------------------- -----------
1 ***
2 ***
3 ***
4 ***
5 ***
6 ***
7 ***
* Such quantities may be adjusted in accordance with Section 2.
Page 21 of 30
EXHIBIT B
FIRST ANNIVERSARY YEAR CRYO FORECAST
Cryo
Month (kgs)
----- -----
XX
XX+1
XX+2
XX+3
XX+4
XX+5
XX+6
XX+7
XX+8
XX+9
XX+10
XX+11
Total
Approved by
-----------------------------
Talecris
Approved by
-----------------------------
Customer
Page 22 of 30
EXHIBIT B (CONT'D.)
SECOND ANNIVERSARY YEAR CRYO FORECAST
Cryo
Month (kgs)
----- -----
XX
XX+1
XX+2
XX+3
XX+4
XX+5
XX+6
XX+7
XX+8
XX+9
XX+10
XX+11
Total
Approved by
-----------------------------
Talecris
Approved by
-----------------------------
Customer
Page 23 of 30
EXHIBIT B (CONT'D.)
THIRD ANNIVERSARY YEAR CRYO FORECAST
Cryo
Month (kgs)
----- -----
XX
XX+1
XX+2
XX+3
XX+4
XX+5
XX+6
XX+7
XX+8
XX+9
XX+10
XX+11
Total
Approved by
-----------------------------
Talecris
Approved by
-----------------------------
Customer
Page 24 of 30
EXHIBIT B CONTINUED
FOURTH ANNIVERSARY YEAR CRYO FORECAST
Cryo
Month (kgs)
----- -----
XX
XX+1
XX+2
XX+3
XX+4
XX+5
XX+6
XX+7
XX+8
XX+9
XX+10
XX+11
Total
Approved by
-----------------------------
Talecris
Approved by
-----------------------------
Customer
Page 25 of 30
EXHIBIT B (CONT'D.)
FIFTH ANNIVERSARY YEAR CRYO FORECAST
Cryo
Month (kgs)
----- -----
XX
XX+1
XX+2
XX+3
XX+4
XX+5
XX+6
XX+7
XX+8
XX+9
XX+10
XX+11
Total
Approved by
-----------------------------
Talecris
Approved by
-----------------------------
Customer
Page 26 of 30
EXHIBIT B (CONT'D.)
SIXTH ANNIVERSARY YEAR CRYO FORECAST
Cryo
Month (kgs)
----- -----
XX
XX+1
XX+2
XX+3
XX+4
XX+5
XX+6
XX+7
XX+8
XX+9
XX+10
XX+11
Total
Approved by
-----------------------------
Talecris
Approved by
-----------------------------
Customer
Page 27 of 30
EXHIBIT C
CRYOPRECIPITATE ("CRYO")
SPECIFICATIONS AND REQUIREMENTS
Page 28 of 30
(TALECRIS BIOTHERAPEUTICS LOGO) STANDARD OPERATING PROCEDURES SOP#: CS-000-AD-218
REVISION: 04
TITLE: Preparation Of PAGE 1 of 1
Manufacturing Agreements ATTACHMENT 2
For The Purchase And
Sale Of Plasma
Intermediates
INTERMEDIATE PRODUCT SPECIFICATION APPROVAL
Supercedes: N/A
The attached specifications for Cryoprecipitate that is purchased from Talecris
--------------- --------
Intermediate Seller
by Omrix have been found acceptable.
-----
Buyer
These specifications will be effective: 11 Sept. 2006.
---------------------
Date
The revision number of these specifications will be: NEW.
---------------------
Associated Change Control Number: 1.
---------------------
N/A if not applicable
Talecris SAP Number: 1
Talecris Biotherapeutics, Inc. Omrix approval:
approval:
/s/ Xxxx Xxxxx
------------------------------------- Refer to attached EAD 9-5-06
Date: 8-21-06 Date:
Sr. Contract Manager ----------------------------------
Title:
---------------------------------
/s/ Xxx X. Xxxxxx
------------------------------------- N/A EAD 9-11-06
Date: 8-30-06 Date:
QO Manager ----------------------------------
Title:
---------------------------------
Comments: (1) A change control will be initiated at Talecris to create a SAP
number for traceability of material sold to Omrix. This CCR must be closed prior
to first shipment. EAD 8-21-06.
(TALECRIS BIOTHERAPEUTICS LOGO) STANDARD OPERATING PROCEDURES SOP#: CS-000-AD-218
REVISION: 04
TITLE: Preparation Of PAGE 1 of 1
Manufacturing Agreements ATTACHMENT 2
For The Purchase And
Sale Of Plasma
Intermediates
INTERMEDIATE PRODUCT SPECIFICATION APPROVAL
Supercedes: N/A
The attached specifications for Cryoprecipitate that is purchased from Talecris
--------------- --------
Intermediate Seller
by Omrix have been found acceptable.
-----
Buyer
These specifications will be effective: .
---------------------
Date
The revision number of these specifications will be: NEW.
---------------------
Associated Change Control Number: 1.
---------------------
N/A if not applicable
Talecris SAP Number: 1
Talecris Biotherapeutics, Inc. Omrix approval:
approval:
/s/ Xxxx Xxxxx /s/ Xxxxx Xxxx
------------------------------------- ----------------------------------------
Date: 8-21-06 Date: Sept 3, 2006
Sr. Contract Manager Title: Director QA
/s/ Xxx X. Xxxxxx
------------------------------------- ----------------------------------------
Date: 8-30-06 Date:
QO Manager ----------------------------------
Title:
---------------------------------
Comments: (1) A change control will be initiated at Talecris to create a SAP
number for traceability of material sold to Omrix. This CCR must be closed prior
to first shipment. EAD 8-21-06
CRYOPRECIPITATE ("CRYO")
SPECIFICATIONS AND REQUIREMENTS
/s/ Xxx X. Xxxxxx Aug. 30, 2006 Refer to attached. EAD 9-5-06
------------------------ ------------- ---------------------- ----------
Talecris Quality Manager Date Omrix Quality Director Date
/s/ Xxxxx X. Xxxxxxx 09/08/2006
------------------------ ----------
Precision Pharma Date
Services, Director,
Regulatory Affairs and
Quality Assurance
Revision: NEW Date Effective: 11 Sept 2006
1. PURPOSE
To provide specifications for Cryo manufactured by the Precision
Pharma Services Inc USA on behalf of and from plasma provided by
Talecris Biotherapeutics, Inc USA, to assure that the starting raw
material (Human Normal Source Plasma) and the manufactured material
(Cryo) meets specifications and established guidelines and standards.
2. REFERENCES
U.S. Code of Federal Regulations 21 CFR part 640 (appropriate
sections).
3. PLASMA REQUIREMENTS
The Cryo must be manufactured from Human Normal Source Plasma meeting
all current FDA requirements, including testing and screening
requirements. Source Plasma donations can only be accepted from
regular, repeat (Qualified) donors. Anti D reclassified Plasma is not
acceptable.
3.1 Human Normal Source Plasma for the manufacturing of Cryo must be
harvested from FDA licensed and approved collection centers,
currently certified under the Plasma Protein Therapeutics
Association's (PPTA)
The Centers and all associated testing laboratories (including
Talecris' NAT test lab) have received the Clinical Laboratory
Inspection Act (CLIA) licensure and approval.
3.2 Donor selection as well as collection, production, quality
control and storage of plasma are in compliance with the current
WHO and FDA regulations and standards. No plasma is collected
from high risks populations; epidemiological data is available
for each collection center. The information will be provided on
an annual basis as part of the plasma master file.
3.3 The anticoagulant and container quality is in compliance with the
FDA requirements.
3.4 The Plasma used for the Cryo production must be less than three
(3) years from date of donation.
3.5 The plasma once collected must be frozen rapidly at not warmer
than -20 degrees C, within one (1) hour and maintained at or
below minus
Page 1 of 7
CRYOPRECIPITATE ("CRYO")
SPECIFICATIONS AND REQUIREMENTS
/s/ Xxx X. Xxxxxx Aug. 30, 2006 /s/ Xxxxx Xxxx Sept. 3, 2006
---------------------------- ------------- ---------------------- -------------
Talecris Quality Manager Date Omrix Quality Director Date
---------------------------- -------------
Precision Pharma Services, Date
Director, Regulatory Affairs
and Quality Assurance
Revision: NEW Date Effective:
-----------------
1. PURPOSE
To provide specifications for Cryo manufactured by the Precision Pharma
Services Inc USA on behalf of and from plasma provided by Talecris
Biotherapeutics, Inc USA, to assure that the starting raw material (Human
Normal Source Plasma) and the manufactured material (Cryo) meets
specifications and established guidelines and standards.
2. REFERENCES
U.S. Code of Federal Regulations 21 CFR part 640 (appropriate sections).
3. PLASMA REQUIREMENTS
The Cryo must be manufactured from Human Normal Source Plasma meeting all
current FDA requirements, including testing and screening requirements.
Source Plasma donations can only be accepted from regular, repeat
(Qualified) donors. Anti D reclassified Plasma is not acceptable.
3.1 Human Normal Source Plasma for the manufacturing of Cryo must be
harvested from FDA licensed and approved collection centers, currently
certified under the Plasma Protein Therapeutics Association's (PPTA)
The Centers and all associated testing laboratories (including
Talecris' NAT test lab) have received the Clinical Laboratory
Inspection Act (CLIA) licensure and approval.
3.2 Donor selection as well as collection, production, quality control and
storage of plasma are in compliance with the current WHO and FDA
regulations and standards. No plasma is collected from high risks
populations; epidemiological data is available for each collection
center. The information will be provided on an annual basis as part of
the plasma master file.
3.3 The anticoagulant and container quality is in compliance with the FDA
requirements.
3.4 The Plasma used for the Cryo production must be less than three (3)
years from date of donation.
3.5 The plasma once collected must be frozen rapidly at not warmer than
-20 degrees C, within one (1) hour and maintained at or below minus
Page 1 of 7
20 degrees C (-20 degrees C) during storage and transportation
according to current CFR regulations.
3.6 A certification for each Cryo shipment will be provided, indicating
that the plasma was stored and shipped at a temperature at or below
minus 20 degrees C. (-20 degrees C).
3.7 Testing Required for each Unit of Plasma
3.7.1 Each unit of plasma used for manufacture of the Cryo must be
tested and found non-reactive for: hepatitis B surface antigen
(HBsAg), antibodies to human immunodeficiency virus types 1 and 2
(anti-HIV I/II), antibody to hepatitis C virus (anti-HCV) by
current generation FDA-approved test methods. Additionally, once
every four months the plasma donors are tested for Syphilis and
found to be negative.
3.7.2 Each plasma unit must be NAT/PCR tested and found negative for
HAV, HBV, HIV-1, HCV and non-elevated for Parvo B19.
Test Requirements for each unit:
TEST TYPE Test Requirements
--------- -----------------------------------------------------
HBsAg(1) Non-Reactive(2)
Anti-HIV 1/2(1) Non-Reactive(2)
Anti-HCV(1) Non-Reactive(2)
Syphilis(3) Negative or Non-reactive for donor (test performed on
donor initially and every four (4) months)
Atypical Antibody(6) Negative for donor (initial donation)
HIV-1 NAT(1) Not Implicated(4)
HAV NAT(5) Not Implicated(4)
HBV NAT(1) Not Implicated(4)
HCV NAT(1) Not Implicated(4)
Parvo B19 NAT(5) Non-Elevated
Notes:
(1.) Current generation, FDA approved test method must be used.
(2.) Some manufacturer's package inserts use the term "negative" and
"non-reactive" interchangeably.
(3.) FDA approved syphilis test.
(4.) Some manufacturer's package inserts use the term "negative" and
"not-implicated" interchangeably.
(5.) Currently not FDA approved test method. Upon approval, FDA approved methods
must be used.
(6.) Test reagents for atypical antibody screening tests must minimally include
specific anti-D antibody.
3.8 Testing required for Plasma Pool
3.8.1 The plasma pool used for manufacture of the cryoprecipitate must
be tested and found non-reactive for HBsAg, anti-HIV I/II and
HIV-1,
Page 2 of 7
HBV, HAV and HCV-RNA by PCR/NAT. The plasma pool must be tested
and found non-elevated for Parvo B19.
3.8.2 Talecris will test each Plasma Pool to ensure the following
quality limits (Omrix limits) are met:
PLASMA POOL QUALITY LIMITS:
TEST TYPE Test Requirements
--------- -------------------------------------
HBsAg Non-reactive
Anti HIV-1/2 Negative
Anti-D Non-Detectable (<1:1)
HIV-1 NAT Negative
HAV NAT Negative
HBV NAT Negative
HCV NAT Negative
Parvo B19 NAT Non-Elevated (< or = 1 x 10(5) IU/mL)
3.8.3 Omrix will test each Plasma Pool to ensure Omrix internal
specifications are met prior to authorizing shipment of specific
batches. Omrix will perform the following tests.
PLASMA POOL:
TEST TYPE
Protein (Biuret)
TVC
3.9 Representative pre-delivery samples (3 x 10 mL) of the Manufacturing
Pool associated with each batch of Cryoprecipitate offered for sale to
Omrix will be supplied to Omrix for evaluation.
Based on the plasma pool certification and results of testing by
Talecris/Precision and Omrix, Omrix will approve the shipment no later
than 30 days after receipt of samples.
3.10 The actual number of donors represented in the plasma pool from which
an amount of approximately 20 kg of Cryo is derived does not exceed
5700 donors.
4. CRYO REQUIREMENTS
4.1 The Cryo must be manufactured by Precision Pharma Services Inc USA
under the responsibility of Talecris Biotherapeutics, Inc. USA. The
manufacturing process must be approved and licensed by the FDA.
4.2 The Cryo batch size (derived from one plasma pool only) should be as
big as possible, but not less than 10kg.
4.3 The Cryo to be sent to Omrix must be less than 6 months old from
production date.
Page 3 of 7
4.4 The storage and shipping temperature of Cryo must be minus 20 degrees
C (-20 degrees C) or colder.
4.5 Cryo must meet the Material specifications as detailed by Precision
Pharma Services Inc USA under the responsibility of Talecris
Biotherapeutics, Inc. USA and which are to be provided to Omrix.
4.6 Representative pre-delivery samples (5 x l0gr) of each batch of Cryo
(prior to freezing) will be supplied to Omrix to be tested by Omrix
prior to purchasing Cryo for further manufacturing in a Fibrin Sealant
product. Precision Pharma Services will release individual batches of
Cryo based on their FDA BLA requirements. Omrix will authorize
shipment of individual batches of Cryo based on the batch meeting the
following quality limits (Omrix limits) after re-suspension and
testing of the pre-delivery samples is performed at Omrix:
PARAMETERS LIMITS
---------- --------------
Total protein 30-60mg/ml
% Clottable Protein > or = 60%
Fibrinogen 20-40mg/ml
Factor XIII 2-9IU/ml
Factor VIII 5-20IU/ml
Fibronectin 0.5-6.0
VWFAg 15-40IU/ml
TWC <3000 CFU/mL
Based on Cryo sample results tested by Omrix, and Plasma Pool results
(tested by Talecris/Omrix), Omrix will approve the shipment of the
Cryo batch no later than 30 days after receipt of samples.
5. GENERAL REQUIREMENTS:
5.1 The following Plasma supplier information must be maintained for each
center currently supplying plasma to Talecris by the Quality
Organization at Talecris.
1. FDA approved ELA, PLA or BLA
2. CLIA registration certificate for the facility
3. Individual state licenses, as required
4. iQPP certification for the collection facility
5. FDA approved SOP manual
6. Viral Marker Rates - provided no less than quarterly
7. US FDA Form 483, inspection observations and
follow-up/corrective actions
8. Talecris Quality Compliance Audits - conducted on a periodic
basis, not less than once every 24 months.
5.2 U.S. Plasma Master File should be submitted once to Omrix and then
when versions are updated or new versions are issued.
Page 4 of 7
The Plasma Master File should include the following information:
1. A list of names and addresses of blood/plasma collection
establishments including any subcontractors and any separate
sites for testing of individual donations.
NOTE: The Plasma Master File is updated on an annual basis. The
list of centers currently supplying plasma to Talecris is
maintained by Talecris' Quality Organization.
2. Conditions of storage and transportation of the plasma
3. Epidemiological data on blood transmissible infections.
4. Selection/Exclusion Criteria
5. Donation traceability
6. Suitability of donors
7. Donor record system
8. Test result Management for laboratory results
9. Donor frequency and volume.
10. Screening of donations
List of all tests performed (including NAT testing) on individual
donations, minipools and plasma pools (if relevant), the test
method, brand name of test kit, manufacturer, generation of test,
license number and countries where licensed, plus validation of
screening test methods.
11. Donor registration and applicant donor system
12. Donor deferral system
13. Look back procedures.
14. Post collection information system.
15. Batch numbering system
16. Information on the containers used for collection and of the
anticoagulant solution.
17. Confirmation that all preventive measures are taken to reduce the
possible risk of transmission of Creutzfeldt -Jacob disease (CJD)
and variant Creutzfeldt -Jacob disease (vCJD) in blood and blood
products.
5.3 Any changes to the test kits used for the plasma testing must be
notified in writing to Omrix at least 60 days prior to the shipment of
any plasma using such changed test kits. Documentation on the test
kits validation must be provided.
5.4 A full description of the process for Cryo production must be provided
to Omrix.
5.5 Precision Pharma must receive written approval prior to shipment of a
Cryo batch to Omrix.
5.6 Manufacturing records for the production of Cryo including
traceability to the individual plasma units will be kept on file per
all FDA regulations.
Manufacturing records and Bleeding lists (electronic data/hard copy)
for each plasma pool are available for inspection by Omrix upon
request.
5.7 Consistent with Section 6.2 of the Supply Agreement, Omrix has the
right to inspect/audit relevant areas of the facilities and the
relevant documentation associated with the supply of plasma and for
the
Page 5 of 7
manufacturing of Cryo typically once per year This rate may be
adjusted whenever considered necessary. Omrix will notify Talecris and
Precision Pharma three weeks prior to the proposed audit. Talecris
will notify Omrix if the audit date is acceptable. If the audit date
is not acceptable an alternate date will be provided.
Talecris/Precision and Omrix will use commercially reasonable efforts
to accommodate the audit date.
5.8 Talecris Biotherapeutics Inc./Precision Pharma must inform Omrix about
each change in the Manufacturing Process affecting any Key Process
Parameters as defined in Exhibit D of the Supply Agreement that
requires FDA prior approval. Notification must be made to Omrix at
least six (6) months prior to implementation. This allows time for
Omrix to evaluate the impact of the change to the product being
processed by Omrix. Omrix may not accept batches of Cryo if they will
not comply with the approved requirements and specifications.
6. STORAGE AND SHIPPING REQUIREMENTS
6.1 Packaging - The cryoprecipitate from a single batch must be frozen in
separate entities weighing < or = 5 kg. These separate entities will
be grouped into shipments of NMT 25 kg. Each shipment will be double
bagged using two plastic liners. Cryoprecipitate will be shipped in
plastic sealable containers. Each container is to be labeled inside
and outside.
6.2 Storage and Shipping - Cryoprecipitate must be stored at -20 degrees C
or colder and shipped upon request to Omrix. Cryoprecipitate must be
shipped at -20 degrees C or colder. The temperature of each shipment
must be monitored by Omrix. If temperature monitoring devices are
required, Omrix will provide the devices and instructions on
activation. Shipments from Precision to Omrix will be made Ex Works.
7.0 CERTIFICATIONS
7.1 For each batch of Cryo shipped to Omrix, Precision Pharma/Talecris
must submit the following documentation:
1. Proforma-Invoice (to be sent prior to shipment).
2. Certificate of Quality which will include the following data (to
be sent prior to shipment):
- Tests and results performed on each contributing plasma unit
and all plasma pools
- A statement certificating that the Cryo is of the same
quality as required for the marketing and human use of
plasma derivatives products in USA and certificating that
the Cryo was processed by Precision Pharma Services Inc USA
current U.S. licenses approved by United States Food and
Drug Administration (FDA) regulations, including that there
were no manufacturing deviations or discrepancies for this
batch that could adversely affect the safety, purity, or
potency of the Cryo and that the Cryo has not been reworked
or reprocessed. Complete data indicating the initial
Page 6 of 7
plasma volume, calculated numbers of donors in the pool,
date of plasma pooling, oldest and recent donation date,
Plasma pool batch number, total amount of Cryo produced,
date of Cryo manufacture.
8.0 ATTACHMENTS
8.1 Example - Cryoprecipitate Certification of Analysis
Page 7 of 7
Attachment 1 - Example Certificate of Cryoprecipitate
PRECISION PHARMA SERVICES. INC.
000 Xxxxxx Xxxx
Xxxxxxxx, Xxx Xxxx 00000
Phone: 000-000-0000
Fax: 000-000-0000
Certificate of Cryoprecipitate
For Omrix
Paste Batch #: _____________ Date of Manufacture: _____________
Plasma Pool #: _____________ Plasma Volume: L
SAP#: _____________ Number of Pooled Units: __________
Paste Weight: kg __________
This paste was fractionated from Precision plasma pool # XXXXXXX. The paste
contained only the material from Talecris shipment pool # XXXXXXX. All plasma
units processed in this pool were 100% inspected. No additional units were added
to the pre-selected pool except as authorized in writing by Talecris (Copy
attached) and noted on the Plasma Packing List.
The plasma units used in the manufacture of this batch of Paste are collected in
the United States in facilities licensed by the U.S Food and Drug Administration
and inspected and approved by the FDA. These plasma units were collected from
healthy donors who met the criteria prescribed in 21 CFR, part 640.
All contributing plasma to this manufacturing pool has been tested and found
negative for HBsAg, anti-HIV-1/2, anti-HCV, HCV/HIV-1/HAV and HBV by NAT.
Donors, associated with these plasma units, were screened and found negative for
syphilis and undetectable for Anti-D, Additionally, the plasma units were
screened for parvovirus B19 by NAT and found non-elevated.
Oldest donation date: __________________
Most recent donation date: _____________
Manufacturing pool samples were tested by Talecris and found
negative/non-reactive for the following: HBsAg, Anti-D, HIV-1 & 2 Antibody, HCV/
HIV-1/HAV and HBV by NAT. Additionally, the manufacturing pool was tested for
parvovirus B19 by NAT and found non-elevated.
All lookback, positive, and other discrepant units were removed prior to
pooling.
This paste was processed in a manner minimizing microbial load and endotoxin
load.
The Cryoprecipitate batch has not been reworked for any reason.
The raw plasma was stored at -20 degrees C or less prior to Fractionation. The
intermediate stages were held at the required temperature ranges during the
process. Additionally, plasma was shipped from Talecris to Precision at
-20 degrees C or colder.
This paste was processed according to Precision procedures and BLA's and BLA
Amendments filed with and approved by CBER/FDA. The finished Cryoprecipitate was
held at -20 degrees C or colder prior to shipment.
Changes and/or variations in the process from those outlined on the production
records at Precision but with the constraints of the BLA and/or BLA Amendments
have been reviewed and approved by Precision and are appropriately documented in
the records. There were no significant deviations for this batch.
The Product Records for this batch are located at the Precision facility and are
available for further review by authorized personnel.
The plasma and the Paste are of the same quality as required for the marketing
and human use of plasma derivatives products in USA.
This batch was released by Precision Pharma Services, Inc.
I certify that the above information is correct.
------------------------------------- ----------------------------------------
Quality Assurance Date
EXHIBIT D
KEY PROCESS PARAMETERS - PRECISION PHARMA CRVOPRECIPITATE: FDA LICENSE 1633
The following steps are considered to be the critical steps:
1. Pre-thawing of plasma
a. Batch Size: Not defined in license
b. Temperature range: Plasma units are stored < or = -20 degrees C
c. Time: Not defined in license
2. Thawing
a. Temperature: Plasma is pooled and thawed at 0-4 degrees C
b. Agitation speed: Not defined in license
3. Centrifugation
a. Type of centrifuge/name: Westfalia BKA-28 or AS-26 Sharpies
b. Flow rate to centrifuge: Not defined in license
c. Centrifugation revolutions (rpm): Not defined in license
d. Plasma inlet temperature: Thawed plasma is 0 - 4 degrees C
e. Supernatant outlet temperature: Effluent temperature is 0 - 4
degrees C
4. Cryo blast freezing
a. Freezer temperature: Not defined in license
b. Time limitation until freezing: Not defined in license
c. Minimal time for freezing: Not defined in license
d. Packaging material and cake height: Not defined in license
5. General:
a. Copy of Cleaning Procedures (including manual OP/SIP as
applicable)
b. Thawing tank, centrifuge or freezer change
Page 29 of 30
EXHIBIT E--MANUFACTURING AGREEMENT
Page 30 of 30
Precision Pharma Services, Talecris Biotherapeutics, Inc. Page 1 of 4
and Omrix Biopharmaceuticals Ltd.
Manufacturing Agreement (Cryoprecipitate)
MANUFACTURING AGREEMENT
This Manufacturing Agreement (Agreement) is between Omrix Biopharmaceuticals
Ltd. (Omrix) located at MDA Bloodbank, Sheba Hospital, Ramat Gan, POB 888,
Kiryat Ono 55000, Israel, Precision Pharma Services (Precision), located at 000
Xxxxxx Xxxx, Xxxxxxxx, Xxx Xxxx 00000, and Talecris Biotherapeutics, Inc.
(Talecris), located at 79 X.X. Xxxxxxxxx Drive, 4101 Research Commons, Research
Xxxxxxxx Xxxx, Xxxxx Xxxxxxxx 00000. Precision manufactures Cryoprecipitate for
Talecris from US licensed Source Plasma (Human) supplied by Talecris to
Precision. The "Effective Date" is determined by the last date of the signature
of the authorized representatives of each party at the end of this Agreement.
Whereas the United States Food and Drug Administration (FDA) regulations allow
that a shipment or other delivery of a drug (biologic) which is, in accordance
with the practice of the trade, to be processed, labeled, or repacked in
substantial quantity at an establishment other than that where originally
processed or packed, shall be exempt, during the time of introduction and
movement in interstate commerce and the time of holding such establishment, from
compliance with the labeling and packaging requirements of Sections 501(b) and
502(b),(e),(f) and (g) of the Federal Food, Drug and Cosmetic Act [21 U.S.C.
351(b) and 352(b), (e), (f) and (g)], if the requirements of 21 CFR Section
201.150 are met and that a partially processed biological product may be
exported if requirements of Section 351(h) of the Public Health Service Act and
Section 801 (e)(1) of the Federal Food, Drug and Cosmetic Act are met.
NOW, THEREFORE, it is agreed as follows:
1. INTENT OF PARTIES
It is the express intent of the parties hereto to adhere to all of the
requirements set forth at 21 CFR Section 201.150.
It is the intent of Precision/Talecris to distribute Cryoprecipitate
to Omrix solely for use in the manufacture of "Fibrin Sealant" under
a shared manufacturing arrangement according to the CBER draft
guideline "Cooperative Manufacturing Arrangements for Licensed
Biologics". The cryoprecipitate may not be sold or used in the
manufacture of any other product.
2. MAINTENANCE OF PROPER RECORDS
Each party agrees to maintain complete and adequate records, where
applicable, pertaining to the methods used in and the facilities and
controls used for the manufacture, processing, packing, labeling and
holding of drugs and pertaining to the disposition of Plasma
Cryoprecipitate (Cryoprecipitate), as may be required by applicable
regulations.
Precision Pharma Services, Talecris Biotherapeutics, Inc. Page 2 of 4
and Omrix Biopharmaceuticals Ltd.
Manufacturing Agreement (Cryoprecipitate)
It is further agreed that each party will maintain a copy of all
records required pursuant to this Agreement until five (5) years after
the final shipment or delivery of the Cryoprecipitate hereunder from
the Precision manufacturing facility, and shall make copies available
for inspection at any reasonable hour to any authorized representative
of the Department of Health and Human Services.
3. SPECIFICATIONS
Cryoprecipitate will be manufactured under contract by Precision for
Talecris from US licensed Source Plasma (Human) supplied by Talecris
to Precision. Cryoprecipitate is a licensed intermediate for further
manufacturing use manufactured by Precision.
Precision will manufacture and ship bulk quantities of Cryoprecipitate
to Omrix. Said material will be furnished in bulk containers, per
Specifications, and will be labeled to indicate that further
manufacturing, processing or repacking is intended. Cryoprecipitate
will be fractionated by Precision from US Collected Source Plasma
obtained in accordance with the provisions 21 CFR Section 640, Subpart
G, and other applicable FDA guidelines and regulations including but
not limited to 21 CFR Section 610.40, 610.41 and 610.46.
Cryoprecipitate shall meet the current Specifications an example of
which is attached hereto as Exhibit C (Specifications). If
Specifications are revised during the term of this Agreement both
parties will agree to all revisions prior to implementation.
Each unit of plasma used in the manufacture of this material will be
certified to have been tested and found nonreactive for Hepatitis B
Surface Antigen (HBsAg), antibodies to Human Immunodeficiency Virus
(HIV-1/HIV-2), antibodies to Hepatitis C virus (anti-HCV). Each unit
of plasma used in the manufacture of Cryoprecipitate will also be
certified by Talecris to have been NAT tested in mini-pools and found
non-reactive for HAV, HIV-1, HBV, HCV. Furthermore, each plasma unit
used in the manufacture of Cryoprecipitate will also be certified by
Talecris to have been NAT tested in a mini-pools format for Parvovirus
B19 and have shown no highly viraemic titers of Parvovirus B19,
avoiding manufacturing pools exceeding 10(5) IU B19 DNA per mL, and
will also meet any other applicable FDA testing and screening
requirements.
The plasma pool used in the manufacture of this material will be
certified by Talecris to have been tested and found nonreactive for
Hepatitis B Surface Antigen (HBsAg), antibodies to Human
Immunodeficiency Virus (HIV-1/HIV-2), and HAV, HBV, HCV, and HIV-1 by
NAT. The plasma pool will also be certified to have been tested by NAT
for Parvovirus B19 and did not exceed 10(5) IU B19-DNA per mL.
Precision Pharma Services, Talecris Biotherapeutics, Inc. Page 3 of 4
and Omrix Biopharmaceuticals Ltd.
Manufacturing Agreement (Cryoprecipitate)
The Cryoprecipitate will be stored and shipped at -20 degrees C or
colder. Shipping temperature will be verified for each shipment in
accordance with the Specifications.
Precision will provide Omrix with a test certification for each lot of
Cryoprecipitate shipped, which will be agreed by both parties. Such
certification, an example of which is included with the
Specifications, will specify the tests performed and values or results
obtained. Talecris agrees to inform Omrix in writing of any change in
the manufacturing process that may affect Talecris' ability to supply
Cryoprecipitate in accordance with the Specifications.
Talecris represents and warrants that the Cryoprecipitate provided to
Omrix hereunder is not adulterated or misbranded within the meaning of
the Federal Food, Drug, and Cosmetic Act.
Omrix shall be responsible for ensuring that any Products derived from
Cryoprecipitate meets the applicable specifications and regulations of
the country in which such Product is distributed.
4. DURATION
This Agreement shall apply to all Cryoprecipitate from the process
used by Precision shipped in bulk quantities to Omrix. This Agreement
will be reviewed annually and updated as needed.
5. WARNING
Cryoprecipitate shall be prepared from large pools of human plasma.
Products made from human plasma may contain infectious agents, such as
viruses, that can cause disease. Talecris represents and warrants that
the plasma of each donor used to manufacture Cryoprecipitate has been
screened and found negative for markers indicating prior exposure to
certain viruses, and for the presence of certain current virus
infections. Plasma pools have been screened and certain viruses are
inactivated and/or removed during the manufacturing process. Despite
these measures, such products can still potentially transmit disease.
There is also the possibility that unknown infectious agents may be
present in such products. Appropriate care should be used in handling
this material.
6. ADDITIONAL PROVISIONS
Cryoprecipitate purchased under this Agreement is for export from the
US only. Cryoprecipitate may not be returned to the US nor may any
product derived from Cryoprecipitate be returned to the US unless the
Cryoprecipitate was used as a raw material for FDA licensed Products
or Products under a current IND. Omrix clearly understands that no
Precision and/or Talecris US
Precision Pharma Servises, Talecris Biotherapeutics, Inc. Page 4 of 4
and Omrix Biopharmaceuticals Ltd.
Manufacturing Agreement (Cryoprecipitate)
license number or any other reference to Precision and/or Talecris may
appear on the labeling of final product.
Omrix shall be responsible for the export of Cryoprecipitate as a partially
processed biological product for further manufacture and shall comply with
all applicable FDA laws and regulations.
Cryoprecipitate is for further manufacture use only and is not to be
represented as suitable for use as a finished human drug.
No additional testing for human pathogens outside of the testing agreed
upon in the agreements may be performed on the Cryoprecipitate, any
derivatives there from, or in-process samples, or resulting final
containers without prior written approval of Talecris.
Talecris will provide Regulatory documents consistent with Section 6.3 of
the Supply Agreement.
All requests for retrospective information, additional testing or samples
outside of what is agreed upon in the agreements and specifications will be
negotiated separately and will be in accordance with applicable regulations
for partially processed biological products.
IN WITNESS THEREOF, the parties thereto have caused this Agreement to be
executed by their duly authorized representatives.
PRECISION PHARMA SERVICES OMRIX BIOPHARMACEUTICALS LTD.
By /s/ Xxxxx X. Xxxxxxxx By /s/ Xxxxxx Xxxx
------------------------------------- ----------------------------------
Xxxxx Xxxxxxxx Name/Title
Dir. Regulatory Affairs & QA
Xxxxxx Xxxx
Print Name/Title
Date 09/08/2006 Date 09/27/2006
TALECRIS BIOTHERAPEUTICS, INC.
By /s/ Xxxx Xxx Xxxx
-------------------------------------
Xxxx Xxx Xxxx, Ph.D.
Vice President, Regulatory Affairs
Date 09/16/2006
(SEAL)
(TALECRIS BIOTHERAPEUTICS LOGO) STANDARD OPERATING PROCEDURE SOP #: CS-000-AD-218
REVISION: 04
TITLE: Preparation Of Manufacturing Agreements For The PAGE 1 of 1
Purchase And Sale Of Plasma Intermediates ATTACHMENT 2
INTERMEDIATE PRODUCT SPECIFICATION APPROVAL
Supercedes: N/A
The attached specifications for Cryoprecipitate that is purchased from Talecris
--------------- --------
Intermediate Seller
by Omrix have been found acceptable.
-----
Buyer
These specifications will be effective: 11 Sept. 2006.
---------------------
Date
The revision number of these specifications will be: NEW.
---------------------
Associated Change Control Number: (1).
---------------------
N/A if not applicable
Talecris SAP Number: (1)
Talecris Biotherapeutics, Inc. approval: Omrix approval:
/s/ Xxxx Xxxxx Refer to attached EAD 9-5-06
---------------------------------------- -------------------------------------
Date: 8-21-06 Date:
Sr. Contract Manager -------------------------------
Title:
------------------------------
/s/ Xxx X. Xxxxxx N/A EAD 9-11-06
---------------------------------------- -------------------------------------
Date: 8-30-06 Date:
QO Manager -------------------------------
Title:
------------------------------
Comments: (1) A Change Control will be initiated at Talecris to create a SAP
number for traceability of material sold to Omrix. This CCR must be closed prior
to first shipment. EAD 8-21-06.
(TALECRIS BIOTHERAPEUTICS LOGO) STANDARD OPERATING PROCEDURE SOP #: CS-000-AD-218
REVISION: 04
TITLE: Preparation Of Manufacturing Agreements For The PAGE 1 of 1
Purchase And Sale Of Plasma Intermediates ATTACHMENT 2
INTERMEDIATE PRODUCT SPECIFICATION APPROVAL
Supercedes: N/A
The attached specifications for Cryoprecipitate that is purchased from Talecris
--------------- --------
Intermediate Seller
by Omrix have been found acceptable.
-----
Buyer
These specifications will be effective: .
---------------------
Date
The revision number of these specifications will be: NEW.
---------------------
Associated Change Control Number: (1).
---------------------
N/A if not applicable
Talecris SAP Number: (1)
Talecris Biotherapeutics, Inc. approval: Omrix approval:
/s/ Xxxx Xxxxx /s/ Xxxxx Xxxx
---------------------------------------- -------------------------------------
Date: 8-21-06 Date: Sept. 3, 2006
Sr. Contract Manager Title: Director QA
/s/ Xxx X. Xxxxxx
---------------------------------------- -------------------------------------
Date: 8-30-06 Date:
QO Manager -------------------------------
Title:
------------------------------
Comments: (1) A Change Control will be initiated at Talecris to create a SAP
number for traceability of material sold to Omrix. This CCR must be closed prior
to first shipment. EAD 8-21-06.
CRYOPRECIPITATE ("CRYO")
SPECIFICATIONS AND REQUIREMENTS
/s/ Xxx X. Xxxxxx Aug. 30, 2006 Refer to attached. EAD 9-5-06
----------------------------- -------------- ---------------------- ----------
Talecris Quality Manager Date Omrix Quality Director Date
/s/ Xxxxx X. Xxxxxxx 09/08/2006
----------------------------- ----------
Precision Pharma Services, Date
Director, Regulatory Affairs
and Quality Assurance
Revision: NEW Date Effective: 11 Sept. 2006
1. PURPOSE
To provide specifications for Cryo manufactured by the Precision
Pharma Services Inc USA on behalf of and from plasma provided by
Talecris Biotherapeutics, Inc USA, to assure that the starting raw
material (Human Normal Source Plasma) and the manufactured material
(Cryo) meets specifications and established guidelines and standards.
2. REFERENCES
U.S. Code of Federal Regulations 21 CFR part 640 (appropriate
sections).
3. PLASMA REQUIREMENTS
The Cryo must be manufactured from Human Normal Source Plasma meeting
all current FDA requirements, including testing and screening
requirements. Source Plasma donations can only be accepted from
regular, repeat (Qualified) donors. Anti D reclassified Plasma is not
acceptable.
3.1 Human Normal Source Plasma for the manufacturing of Cryo must be
harvested from FDA licensed and approved collection centers,
currently certified under the Plasma Protein Therapeutics
Association's (PPTA)
The Centers and all associated testing laboratories (including
Talecris' NAT test lab) have received the Clinical Laboratory
Inspection Act (CLIA) licensure and approval.
3.2 Donor selection as well as collection, production, quality
control and storage of plasma are in compliance with the current
WHO and FDA regulations and standards. No plasma is collected
from high risks populations; epidemiological data is available
for each collection center. The information will be provided on
an annual basis as part of the plasma master file.
3.3 The anticoagulant and container quality is in compliance with the
FDA requirements.
3.4 The Plasma used for the Cryo production must be less than three
(3) years from date of donation.
3.5 The plasma once collected must be frozen rapidly at not warmer
than -20 degrees C, within one (1) hour and maintained at or
below minus
Page 1 of 7
CRYOPRECIPITATE ("CRYO")
SPECIFICATIONS AND REQUIREMENTS
/s/ Xxx X. Xxxxxx Aug. 30, 2006 /s/ Xxxxx Xxxx Sept. 3, 2006
----------------------------- -------------- ---------------------- -------------
Talecris Quality Manager Date Omrix Quality Director Date
----------------------------- --------------
Precision Pharma Services, Date
Director, Regulatory Affairs
and Quality Assurance
Revision: NEW Date Effective: _____________
1. PURPOSE
To provide specifications for Cryo manufactured by the Precision
Pharma Services Inc USA on behalf of and from plasma provided by
Talecris Biotherapeutics, Inc USA, to assure that the starting raw
material (Human Normal Source Plasma) and the manufactured material
(Cryo) meets specifications and established guidelines and standards.
2. REFERENCES
U.S. Code of Federal Regulations 21 CFR part 640 (appropriate
sections).
3. PLASMA REQUIREMENTS
The Cryo must be manufactured from Human Normal Source Plasma meeting
all current FDA requirements, including testing and screening
requirements. Source Plasma donations can only be accepted from
regular, repeat (Qualified) donors. Anti D reclassified Plasma is not
acceptable.
3.1 Human Normal Source Plasma for the manufacturing of Cryo must be
harvested from FDA licensed and approved collection centers,
currently certified under the Plasma Protein Therapeutics
Association's (PPTA).
The Centers and all associated testing laboratories (including
Talecris' NAT test lab) have received the Clinical Laboratory
Inspection Act (CLIA) licensure and approval.
3.2 Donor selection as well as collection, production, quality
control and storage of plasma are in compliance with the current
WHO and FDA regulations and standards. No plasma is collected
from high risks populations; epidemiological data is available
for each collection center. The information will be provided on
an annual basis as part of the plasma master file.
3.3 The anticoagulant and container quality is in compliance with the
FDA requirements.
3.4 The Plasma used for the Cryo production must be less than three
(3) years from date of donation.
3.5 The plasma once collected must be frozen rapidly at not warmer
than -20 degrees C, within one (1) hour and maintained at or
below minus
Page 1 of 7
20 degrees C (-20 degrees C) during storage and transportation
according to current CFR regulations.
3.6 A certification for each Cryo shipment will be provided,
indicating that the plasma was stored and shipped at a
temperature at or below minus 20 degrees C. (-20 degrees C).
3.7 Testing Required for each Unit of Plasma
3.7.1 Each unit of plasma used for manufacture of the Cryo must
be tested and found non-reactive for: hepatitis B surface
antigen (HBsAg), antibodies to human immunodeficiency virus
types 1 and 2 (anti-HIV I/II), antibody to hepatitis C virus
(anti-HCV) by current generation FDA-approved test methods.
Additionally, once every four months the plasma donors are
tested for Syphilis and found to be negative.
3.7.2 Each plasma unit must be NAT/PCR tested and found negative
for HAV, HBV, HIV-1, HCV and non-elevated for Parvo B19.
Test Requirements for each unit:
TEST TYPE Test Requirements
--------- -----------------
HBsAg (1) Non-Reactive (2)
Anti-HIV 1/2 (1) Non-Reactive (2)
Anti-HCV (1) Non-Reactive (2)
Syphilis (3) Negative or Non-reactive for donor (test performed
on donor initially and every four (4) months)
Atypical Antibody (6) Negative for donor (initial donation)
HIV-1 NAT (1) Not Implicated (4)
HAV NAT (5) Not Implicated (4)
HBV NAT (1) Not Implicated (4)
HCV NAT (1) Not Implicated (4)
Parvo B19 NAT (5) Non-Elevated
Notes:
(1.) Current generation, FDA approved test method must be used.
(2.) Some manufacturer's package inserts use the term "negative" and
"non-reactive" interchangeably.
(3.) FDA approved syphilis test.
(4.) Some manufacturer's package inserts use the term "negative" and
"not-implicated" interchangeably.
(5.) Currently not FDA approved test method. Upon approval, FDA approved methods
must be used.
(6.) Test reagents for atypical antibody screening tests must minimally include
specific anti-D antibody.
3.8 Testing required for Plasma Pool
3.8.1 The plasma pool used for manufacture of the cryoprecipitate
must be tested and found non-reactive for HBsAg, anti-HIV
I/II and HIV-1,
Page 2 of 7
HBV, HAV and HCV- RNA by PCR/NAT. The plasma pool must
be tested and found non-elevated for Parvo B19.
3.8.2 Talecris will test each Plasma Pool to ensure the
following quality limits (Omrix limits) are met:
PLASMA POOL QUALITY LIMITS:
TEST TYPE Test Requirements
--------- ------------------------------
HBsAg Non-reactive
Anti HIV-1/2 Negative
Anti-D Non-Detectable (<1:1)
HPV-1 NAT Negative
HAV NAT Negative
HBV NAT Negative
HCV NAT Negative
Parvo B19 NAT Non-Elevated (< or = 1 x 10(5)
IU/mL)
3.8.3 Omrix will test each Plasma Pool to ensure Omrix
internal specifications are met prior to authorizing
shipment of specific batches. Omrix will perform the
following tests.
PLASMA POOL:
TEST TYPE
Protein (Biuret)
TVC
3.9 Representative pre-delivery samples (3 x 10 mL) of the Manufacturing
Pool associated with each batch of Cryoprecipitate offered for sale to
Omrix will be supplied to Omrix for evaluation.
Based on the plasma pool certification and results of testing by
Talecris/Precision and Omrix, Omrix will approve the shipment no later
than 30 days after receipt of samples.
3.10 The actual number of donors represented in the plasma pool from which
an amount of approximately 20 kg of Cryo is derived does not exceed
5700 donors.
4. CRYO REQUIREMENTS
4.1 The Cryo must be manufactured by Precision Pharma Services Inc USA
under the responsibility of Talecris Biotherapeutics, Inc. USA. The
manufacturing process must be approved and licensed by the FDA.
4.2 The Cryo batch size (derived from one plasma pool only) should be as
big as possible, but not less than 10kg.
4.3 The Cryo to be sent to Omrix must be less than 6 months old from
production date.
Page 3 of 7
4.4 The storage and shipping temperature of Cryo must be minus 20 degrees
C (-20 degrees C) or colder.
4.5 Cryo must meet the Material specifications as detailed by Precision
Pharma Services Inc USA under the responsibility of Talecris
Biotherapeutics, Inc. USA and which are to be provided to Omrix.
4.6 Representative pre-delivery samples (5 x l0gr) of each batch of Cryo
(prior to freezing) will be supplied to Omrix to be tested by Omrix
prior to purchasing Cyro for further manufacturing in a Fibrin Sealant
product. Precision Pharma Services will release individual batches of
Cyro based on their FDA BLA requirements. Omrix will authorize
shipment of individual batches of Cryo based on the batch meeting the
following quality limits (Omrix limits) after re-suspension and
testing of the pre-delivery samples is performed at Omrix:
PARAMETERS LIMITS
---------- ------------
Total protein 30-60mg/ml
% Clottable Protein > or = 60%
Fibrinogen 20-40mg/ml
Factor XIII 2-9IU/ml
Factor VIII 5-20IU/ml
Fibronectin 0.5-6.0
VWFAg 15-40IU/ml
TVC <3000 CFU/mL
Based on Cryo sample results tested by Omrix, and Plasma Pool results
(tested by Talecris/Omrix), Omrix will approve the shipment of the
Ciyo batch no later than 30 days after receipt of samples.
5. GENERAL REQUIREMENTS:
5.1 The following Plasma supplier information must be maintained for each
center currently supplying plasma to Talecris by the Quality
Organization at Talecris.
1. FDA approved ELA, PLA or BLA
2. CLIA registration certificate for the facility
3. Individual state licenses, as required
4. iQPP certification for the collection facility
5. FDA approved SOP manual
6. Viral Marker Rates - provided no less than quarterly
7. US FDA Form 483, inspection observations and follow-up/corrective
actions
8. Talecris Quality Compliance Audits - conducted on a periodic
basis, not less than once every 24 months.
5.2 U.S. Plasma Master File should be submitted once to Omrix and then
when versions are updated or new versions are issued.
Page 4 of 7
The Plasma Master File should include the following information:
1. A list of names and addresses of blood/plasma collection
establishments including any subcontractors and any separate
sites for testing of individual donations.
NOTE: The Plasma Master File is updated on an annual basis. The
list of centers currently supplying plasma to Talecris is
maintained by Talecris' Quality Organization.
2. Conditions of storage and transportation of the plasma
3. Epidemiological data on blood transmissible infections.
4. Selection/Exclusion Criteria
5. Donation traceability
6. Suitability of donors
7. Donor record system
8. Test result Management for laboratory results
9. Donor frequency and volume.
10. Screening of donations
List of all tests performed (including NAT testing) on individual
donations, minipools and plasma pools (if relevant), the test
method, brand name of test kit, manufacturer, generation of test,
license number and countries where licensed, plus validation of
screening test methods.
11. Donor registration and applicant donor system
12. Donor deferral system
13. Look back procedures.
14. Post collection information system.
15. Batch numbering system
16. Information on the containers used for collection and of the
anticoagulant solution.
17. Confirmation that all preventive measures are taken to reduce the
possible risk of transmission of Creutzfeldt -Jacob disease (CJD)
and variant Creutzfeldt -Jacob disease (vCJD) in blood and blood
products.
5.3 Any changes to the test kits used for the plasma testing must be
notified in writing to Omrix at least 60 days prior to the shipment of
any plasma using such changed test kits. Documentation on the test
kits validation must be provided.
5.4 A full description of the process for Cryo production must be provided
to Omrix.
5.5 Precision Pharma must receive written approval prior to shipment of a
Cyro batch to Omrix.
5.6 Manufacturing records for the production of Cryo including
traceability to the individual plasma units will be kept on file per
all FDA regulations.
Manufacturing records and Bleeding lists (electronic data/hard copy)
for each plasma pool are available for inspection by Omrix upon
request.
5.7 Consistent with Section 6.2 of the Supply Agreement, Omrix has the
right to inspect/audit relevant areas of the facilities and the
relevant documentation associated with the supply of plasma and for
the
Page 5 of 7
manufacturing of Cryo typically once per year This rate may be
adjusted whenever considered necessary. Omrix will notify Talecris and
Precision Pharma three weeks prior to the proposed audit. Talecris
will notify Omrix if the audit date is acceptable. If the audit date
is not acceptable an alternate date will be provided.
Talecris/Precision and Omrix will use commercially reasonable efforts
to accommodate the audit date.
5.8 Talecris Biotherapeutics Inc./Precision Pharma must inform Omrix about
each change in the Manufacturing Process affecting any Key Process
Parameters as defined in Exhibit D of the Supply Agreement that
requires FDA prior approval. Notification must be made to Omrix at
least six (6) months prior to implementation. This allows time for
Omrix to evaluate the impact of the change to the product being
processed by Omrix. Omrix may not accept batches of Cryo if they will
not comply with the approved requirements and specifications.
6. STORAGE AND SHIPPING REQUIREMENTS
6.1 Packaging - The cryoprecipitate from a single batch must be frozen in
separate entities weighing < or = 5 kg. These separate entities will
be grouped into shipments of NMT 25 kg. Each shipment will be double
bagged using two plastic liners. Cryoprecipitate will be shipped in
plastic sealable containers. Each container is to be labeled inside
and outside.
6.2 Storage and Shipping - Cryoprecipitate must be stored at -20 degrees C
or colder and shipped upon request to Omrix. Cryoprecipitate must be
shipped at -20 degrees C or colder. The temperature of each shipment
must be monitored by Omrix. If temperature monitoring devices are
required, Omrix will provide the devices and instructions on
activation. Shipments from Precision to Omrix will be made Ex Works.
7.0 Certifications
7.1 For each batch of Cryo shipped to Omrix, Precision Pharma/Talecris
must submit the following documentation:
1. Proforma-Invoice (to be sent prior to shipment).
2. Certificate of Quality which will include the following data (to
be sent prior to shipment):
- Tests and results performed on each contributing plasma unit
and all plasma pools
- A statement certificating that the Cryo is of the same
quality as required for the marketing and human use of
plasma derivatives products in USA and certificating that
the Cryo was processed by Precision Pharma Services Inc USA
current U.S. licenses approved by United States Food and
Drug Administration (FDA) regulations, including that there
were no manufacturing deviations or discrepancies for this
batch that could adversely affect the safety, purity, or
potency of the Cryo and that the Cryo has not been reworked
or reprocessed. Complete data indicating the initial
Page 6 of 7
plasma volume, calculated numbers of donors in the pool,
date of plasma pooling, oldest and recent donation date,
Plasma pool batch number, total amount of Cryo produced,
date of Cryo manufacture.
8.0 ATTACHMENTS
8.1 Example - Cryoprecipitate Certification of Analysis
Page 7 of 7
Attachment 1 - Example Certificate of Cryoprecipitate
PRECISION PHARMA SERVICES. INC.
000 Xxxxxx Xxxx
Xxxxxxxx, Xxx Xxxx 00000
Phone: 000-000-0000
Fax: 000-000-0000
Certificate of Cryoprecipitate
For Omrix
Paste Batch #: __________________ Date of Manufacture: ___________________
Plasma Pool #: __________________ Plasma Volume: L
SAP#: ___________________________ Number of Pooled Units: ________________
Paste Weight: kg
This paste was fractionated from Precision plasma pool # XXXXXXX. The paste
contained only the material from Talecris shipment pool # XXXXXXX. All plasma
units processed in this pool were 100% inspected. No additional units were added
to the pre-selected pool except as authorized in writing by Talecris (Copy
attached) and noted on the Plasma Packing List.
The plasma units used in the manufacture of this batch of Paste are collected in
the United States in facilities licensed by the U.S. Food and Drug
Administration and inspected and approved by the FDA. These plasma units were
collected from healthy donors who met the criteria prescribed in 21 CFR, part
640.
All contributing plasma to this manufacturing pool has been tested and found
negative for HBsAg, anti-HIV-1/2, anti-HCV, HCV/HIV-1/HAV and HBV by NAT.
Donors, associated with these plasma units, were screened and found negative for
syphilis and undetectable for Anti-D. Additionally, the plasma units were
screened for parvovirus B19 by NAT and found non-elevated.
Oldest donation date: ______________
Most recent donation date: ______________
Manufacturing pool samples were tested by Talecris and found
negative/non-reactive for the following: HBsAg, Anti-D, HiV-1 & 2 Antibody, HCV/
HIV-1/HAV and HBV by NAT. Additionally, the manufacturing pool was tested for
parvovirus B19 by NAT and found non-elevated.
All lookback, positive, and other discrepant units were removed prior to
pooling.
This paste was processed in a manner minimizing microbial load and endotoxin
load.
The Cryoprecipitate batch has not been reworked for any reason.
The raw plasma was stored at -20 degrees C or less prior to Fractionation. The
intermediate stages were held at the required temperature ranges during the
process. Additionally, plasma was shipped from Talecris to Precision at
-20 degrees C or colder.
This paste was processed according to Precision procedures and BLA's and BLA
Amendments filed with and approved by CBER/FDA. The finished Cryoprecipitate was
held at -20 degrees C or colder prior to shipment.
Changes and/or variations in the process from those outlined on the production
records at Precision but with the constraints of the BLA and/or BLA Amendments
have been reviewed and approved by Precision and are appropriately documented in
the records. There were no significant deviations for this batch.
The Product Records for this batch are located at the Precision facility and are
available for further review by authorized personnel.
The plasma and the Paste are of the same quality as required for the marketing
and human use of plasma derivatives products in USA.
This batch was released by Precision Pharma Services, Inc.
I certify that the above information is correct.
------------------------------------- ----------------------------------------
Quality Assurance Date
