TOPICAL INTERFERON ALPHA-2b GMP PROCESS DEVELOPMENT, SCALE UP AND CLINICAL SUPPLIES MANUFACTURING AGREEMENT BETWEEN HELIX BIOPHARMA CORP. AND CONTRACT PHARMACEUTICALS LIMITED NIAGARA April _3__, 2008 CONFIDENTIAL TREATMENT REQUESTED
Exhibit
4.2
TOPICAL
INTERFERON ALPHA-2b GMP PROCESS DEVELOPMENT, SCALE UP AND
CLINICAL
SUPPLIES MANUFACTURING AGREEMENT
BETWEEN
AND
CONTRACT
PHARMACEUTICALS LIMITED NIAGARA
April _3__,
2008
CONFIDENTIAL TREATMENT
REQUESTED
INFORMATION
FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN REQUESTED IS OMITTED AND IS IDENTIFIED
BY THREE ASTERISKS, AS FOLLOWS “* * *”, AN UNREDACTED VERSION OF THIS DOCUMENT
HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION.
PROJECT
OPTIMIZATION, SCALE UP AND GMP MANUFACTURING AGREEMENT
THIS AGREEMENT is made as of
April _3__,
2008 (the “Effective Date”)
BY
AND BETWEEN:
Helix
BioPharma Corp., a corporation organized and existing under the laws of Canada,
with its principal offices located at 000 Xxxxxxxxxx Xxxxxxx Xxxxx, Xxxx 0,
Xxxxxx, Xxxxxxx, X0X 0X0, (hereinafter referred to as “Helix”)
and
Contract
Pharmaceuticals Limited Niagara, a corporation organized and existing under the
laws of Delaware, with a place of business located at 000 Xxxxxx Xxxxxx,
Xxxxxxx, Xxx Xxxx, 00000 - 1091 (hereinafter referred to as “CPL”)
(each, a
Party and together the Parties).
WHEREAS
CPL and Helix intend that the terms and conditions of this Agreement shall
govern the general manufacturing process development, scale-up and the GMP
manufacturing of clinical supplies of Helix’s Topical Interferon Alpha-2b (also
referred to as Interferon Alpha-2b Cream).
NOW,
THEREFORE, in consideration of the mutual promises and covenants herein
contained and other good and valuable consideration, the receipt and sufficiency
of which is hereby acknowledged, CPL and Helix agree as follows:
ARTICLE
1 DEFINITIONS
AND SCHEDULES
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1.1
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Definitions
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The
following capitalized terms, whether used in the singular or plural, shall have
the meanings assigned to them below for purposes of this Agreement, including
the Schedules hereto:
Actual &
Reasonable, in relation to acquisition or other costs incurred by CPL,
means, in the case of property acquired by CPL from, or costs incurred to, an
arm’s length Third Party, CPL’s actual acquisition cost of such property or
actual costs incurred, and in the case of property acquired by CPL from, or
costs incurred to, a non-arm’s length Third Party or a person, firm, corporation
or other entity or individual which is not a Third Party, the lesser of CPL’s
actual acquisition or other costs and the fair market value of the property or
other consideration acquired or rendered in consideration of such
costs.
Affiliate means, with
respect to either Party, any other corporation or business entity that directly,
or indirectly through one or more intermediaries, controls, is controlled by or
is under common control with such Party. For purposes of this definition, the
term control means direct or indirect ownership of more than fifty percent (50%)
of the securities or other ownership interests representing the equity voting
stock or general partnership or membership interest of such entity or the power
to direct or cause the direction of the management or policies of such entity,
whether through the ownership of voting securities, by contract, resolution or
otherwise.
Batch means a
specific quantity of Product produced pursuant to a CPL Estimate.
Production Record
means all of the documentation associated with the production of a given Batch,
including the manufacture, testing, packaging, storage, and labeling of such
Batch. This documentation
shall
include: (a) all manufacturing batch documents and packaging batch documents
referred to in the Quality Assurance Agreement or otherwise pertaining to the
Batch; (b) any change control documents, deviation reports and other quality
investigation reports; and (c) CPL's Certificate of cGMP
Compliance.
Certificate of cGMP
Compliance means, for each clinical Batch and each Batch produced for
stability testing, a document prepared by CPL in form and substance reasonably
satisfactory to Helix:
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(a)
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listing
the manufacturing date, unique Batch number, and quantity of Product in
such Batch,
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(b)
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certifying
that such Batch was manufactured in accordance with the Master Formula,
the Master Packaging Formula / Procedure and
cGMP;
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(c)
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certifying
that all required quality assurance investigations are completed and
listing the same; and
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(d)
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certifying
that the Batch meets all CPL Specifications and cGMP quality control
requirements.
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Confidential
Information means Helix Confidential Information or CPL Confidential
Information, as the context requires.
cGMP or GMP shall mean the
good manufacturing practices as required by the FD&C Act and regulations
thereunder, including without limitation, applicable requirements of the U.S.
Code of Federal Regulations 21 CFR Parts 210 and 211 and all FDA policies, or
guidelines in effect at a particular time, for the manufacture and testing of
pharmaceutical materials as applied to bulk pharmaceuticals, and the
corresponding requirements of each Regulatory Authority.
CPL Confidential
Information means all technical and other information, whether patented
or unpatented, relating to the CPL Facility or CPL processes (including General
Process Improvements), methods, operations, technologies, forecasts and business
information, that is disclosed or supplied to, or used on behalf of, Helix by
CPL pursuant to this Agreement, or of which Helix may become aware through the
presence of their employees or agents at CPL offices or at the CPL Facility,
including, without limitation, trade secrets, know-how, processes, concepts,
experimental methods and results and business and scientific plans and
information and facility layout and schematics, but does not include the Helix
Confidential Information. Notwithstanding the foregoing, CPL
Confidential Information shall not include any information that:
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(i)
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is
known publicly or hereafter becomes known publicly through no fault of
Helix, its Affiliates or agents;
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(ii)
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becomes
available to Helix from a Third Party which is not legally prohibited from
disclosing such information, provided such information was not acquired
directly or indirectly from Helix;
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(iii)
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was
developed by Helix independently of information obtained from CPL as
evidenced by written records;
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(iv)
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was
already known to Helix before receipt from CPL, as shown by its prior
written records, provided that such information was not acquired directly
or indirectly from CPL; or
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(v)
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is
released with the prior written consent of CPL
hereunder.
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In the
event any CPL Confidential Information has entered the public domain, only that
portion of said Confidential Information that has become public shall be
excluded under this definition and portions remaining confidential shall retain
their status as CPL Confidential Information.
CPL Estimates means
the CPL Estimates #0542 to 0000-0 Xxx-0 dated November 2, 2007 and attached
hereto as Schedule A, and any other quotations developed and issued by CPL and
approved by Helix from time to time relating to the manufacture of Product
pursuant to this Agreement.
CPL Facility means
the manufacturing facility owned and operated by CPL at 000 Xxxxxx Xxxxxx,
Xxxxxxx, Xxx Xxxx.
CPL Intellectual
Property means all Intellectual Property owned or controlled by
CPL.
CPL Specifications
means the CPL Raw Material specifications, the CPL packaging materials
specifications, the CPL bulk product specifications and the CPL finished product
specifications all as referred to in the Quality Assurance Agreement and as
approved by Helix or by PDL on behalf of Helix.
EMEA means the
European Agency for the Evaluation of Medicinal Products, or any successor
agency.
FDA means the United
States Food and Drug Administration, or any successor agency
thereto.
FD&C Act shall
mean the United States Federal Food, Drug and Cosmetic Act and regulations
thereunder, as amended from time to time.
Force Majeure Event
has the meaning set forth in Section 18.1.
Governmental
Authority means any:
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(a)
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nation,
province, county, city, town, village, district or other jurisdiction of
any nature,
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(b)
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federal,
provincial, local, municipal, foreign or other
government,
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(c)
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governmental
or quasi-governmental authority of any nature (including any governmental
agency, branch, department, official or entity and any court or other
tribunal, including an arbitral tribunal, such as EMEA and Health Canada
as are described in this
Agreement),
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(d)
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multi-national
organization or body, or
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(e)
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body
exercising, or entitled to exercise, any administrative, executive,
judicial, legislative, police, regulatory or taxing power of any
nature.
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Health Canada shall
mean the Canadian Federal government department known as Health Canada or its
successor agency.
Helix Confidential
Information means, but is not limited to, the Product, all Helix Records,
and all clinical data and information, business plans, regulatory and product
strategies and all technical and other information, whether patented or
unpatented, relating to the products, processes, test methods, operations,
technologies, forecasts and business information of Helix or any of its
Affiliates that is disclosed or supplied to CPL by or on behalf of Helix or any
of its Affiliates pursuant to this Agreement or that is Intellectual Property
owned by Helix as referred to in Section 10.1, or information of
which CPL may become aware of through the presence of its employees or agents at
the offices or facilities of Helix or any of its Affiliates or at facilities
that manufacture the Product, including, without limitation, trade secrets,
know-how, processes, concepts, experimental, analytical and test methods and
results, and business and scientific plans and information and facility layout
and schematics. Notwithstanding the foregoing, Helix Confidential
Information shall not include any information that:
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(i)
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is
known publicly or hereafter becomes known publicly through no fault of
CPL, its Affiliates or agents;
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(ii)
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becomes
available to CPL from a Third Party which is not legally prohibited from
disclosing such information, provided such information was not acquired
directly or indirectly from CPL;
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(iii)
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was
developed by CPL independently of information obtained from Helix as
evidenced by written records;
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(iv)
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was
already known to CPL before receipt from Helix, as shown by its prior
written records, provided that such information was not acquired directly
or indirectly from CPL; or
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(v)
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is
released with the prior written consent of Helix
hereunder.
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In the
event any Helix Confidential Information has entered the public domain, only
that portion of said Confidential Information that has become public shall be
excluded under this definition and portions remaining confidential shall retain
their status as Helix Confidential Information.
Helix Intellectual Property
means any Intellectual Property owned or controlled by Helix, and shall
include, but not be limited to, the Helix Confidential Information.
Helix Records means
all Records as defined in section 6.3, other than those that relate
specifically to the CPL Confidential Information.
INDA shall mean an
Investigational New Drug Application, as defined in the FD&C
Act.
Intellectual
Property means all
Patents and other Patent rights, copyrights, trade secrets, know-how, processes
and all other intellectual property rights, including all applications and
registrations with respect thereto, and all information, data,
concepts, designs, processes, software, algorithms, inventions, and all relevant
documents, instruments and other records, whether or not the subject, or capable
of being the subject, of patent, copyright, industrial, trade secret, trademark
or other forms of protection, and includes all trademarks, trade names, service
marks, logos and other corporate identifiers.
Manufacturing Process
means the production process for the manufacture of Product pursuant to this
Agreement, as described in the Master Formula, as such process may be changed
from time to time in accordance with this Agreement.
Master Formula means
the document approved by Helix or PDL in writing, that defines the manufacturing
methods, test methods, materials, and other procedures, directions and controls
associated with the manufacture and testing of Product. The Master Formula shall
also include or be deemed to incorporate by reference, without limitation, such
information as materials specifications, in process and final Product sampling
standards and specifications, equipment and instrumentation specifications and
CPL’s standard operating procedures, including, without limitation, standard
operating procedures for in-process quality control testing.
Master Packaging Formula /
Procedure means the document, approved by Helix or PDL in writing, that
defines the filling and packaging methods, test methods, materials, and other
procedures, directions and controls associated with the filling, packaging and
testing of Product. The Master Packaging Formula /
Procedure
shall also include or be deemed to incorporate by reference, without limitation,
such information as materials specifications, in process and final Product
sampling standards, equipment and instrumentation specifications and CPL’s
standard operating procedures, including, without limitation, standard operating
procedures for in-process quality control testing.
Non-Conforming
Product or non-conforming means
Product or similar material that fails to conform to all of the warranties set
forth in Section 11.1
or Product or similar material that was manufactured at a time when the CPL
Facility failed to conform to the warranties set forth in Section 11.2.
Patents shall mean,
with respect to an invention, any patent or patent application, and any patent
issuing therefrom, together with any extensions, reissues, reexaminations,
substitutions, renewals, divisions, continuations and continuations-in-part
thereof, and any patent or patent application claiming priority to any
application in common with any such patent containing a disclosure substantially
similar to any such patent, all to the extent the foregoing contain claims
covering such invention.
PDL means PharmaDerm
Laboratories Ltd., a wholly-owned subsidiary and agent of Helix for purposes of
this Agreement.
Process Improvements
has the meaning set forth in Section 10.3.
Product means Helix’s
Topical Interferon Alpha-2b, and includes the developmental batch, clinical
batch (placebo), clinical batch (active) and Stand Alone Independent Active
Batch referred to in the CPL Estimates, or any other batch hereinafter
contemplated, whether placebo or active, for Helix’s planned clinical
trials.
Quality Assurance
Agreement means the Quality Assurance Agreement between CPL and PDL, as
agent for Helix, which is attached as Schedule B hereto and hereby incorporated
into this Agreement by reference.
Raw Materials means
all materials, including without limitation, raw materials and packaging
components, acquired by CPL for use in manufacturing the Product or performing
the Services under this Agreement.
Records has the
meaning set forth in Section 6.3.
Regulatory
Authority or
Regulatory Authorities means the FDA, EMEA or Health Canada, or all of
the foregoing, as the case requires.
Regulatory Filing
means any or all applications, correspondence or petitions, to Regulatory
Authorities in connection with the development, testing, manufacture or sale of
Product, or modifying or supplementing existing filings and subsequent
amendments and supplements thereto, including any foreign counterparts thereof
and any other filings required by Regulatory Authorities relating to the
manufacture, testing, sale or distribution of the Product under this
Agreement.
Regulatory
Requirements means:
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(a)
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obtaining
and maintaining any and all permits, licenses, filings and certifications
required by the Regulatory
Authorities,
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(b)
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compliance
with the cGMP applicable to any manufacturing or processing activities
hereunder or the CPL Facility or other facilities at which any of the
Manufacturing Process is performed,
and
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(c)
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any
laws, rules, guidelines, regulations, guidance, points to consider
documents and standards of any Governmental Authority, that apply to the
activities to be carried out under the CPL Estimates or to the CPL
Facility or other facilities at which any of the Manufacturing Process is
performed.
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Services has the
meaning set forth in Section 2.1
Subcontractor means
any independent entity that CPL contracts with to perform any services or meet
any obligations that are required under the terms and conditions of this
Agreement.
Term means the term
of five (5) years commencing on the Effective Date, unless terminated sooner
pursuant to the terms of this Agreement.
Third Party means any
party other than Helix, CPL, their respective Affiliates and their respective
directors, officers, employees and agents.
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1.2
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Schedules
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The
following Schedules are attached hereto and incorporated into this Agreement by
reference:
Schedule
A – CPL Estimates
Schedule
B – Quality Assurance Agreement
Schedule
C -- Estimated Timelines
In the
event of a conflict between the provisions of the body of this Agreement and the
provisions of a Schedule, the provisions of the body of this Agreement shall
prevail.
ARTICLE
2 THE
SERVICES
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2.1
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The
Services
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CPL
agrees to provide to Helix the services (the “Services”) described in the CPL
Estimates, the services described in the Quality Assurance Agreement as being
the responsibility of CPL, and otherwise as set forth herein, and such other
services as the parties may agree upon from time to time, PROVIDED HOWEVER that
CPL shall not render any Services described in or related to a CPL Estimate
unless and until Helix notifies CPL to do so in writing by submitting a written
purchase order for such Services to CPL. Upon such notification, CPL
shall use commercially reasonable efforts to commence and complete the
applicable Services within the time frame set out by Helix in its notification,
or within such other time frame as the parties may otherwise agree
upon. The Parties acknowledge that the timing and results of the
Services can not be guaranteed and hereby agree that reasonable deviations shall
not be deemed a failure to adequately perform the Services.
It is
understood and agreed that Helix may require the Services described in or
related to any or all of Estimates 0542 through 0542-4 to be repeated or
modified from time to time, in Helix’s discretion, and that CPL will duly
perform such Services each time Helix notifies CPL that it wishes the Estimate
repeated. Helix shall pay CPL the price identified in the applicable
Estimate for each Service repeated pursuant to this provision. In the
event an Estimate requires modification, CPL shall issue a new quotation for
approval to Helix and Helix shall pay the approved revised price for Services
related to each new quotation.
Specifically,
it is Helix’s intention to require CPL to:
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(a)
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Initially
commence the necessary packaging line improvements, storage facility
preparations and equipment procurement, installation and qualification per
CPL Estimates #0542-5, 0542-6 and
0542-7;
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(b)
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Thereafter,
produce a Small Scale Development (Placebo) Batch per CPL Estimate
#0542. If necessary, Helix may require CPL to produce
successive additional Small Scale Development (Placebo) Batches per CPL
Estimate #0542 until Helix indicates that it is satisfied with the
resultant Product quality.
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(c)
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Thereafter,
produce Small Scale Clinical Batches (Placebo), Small Scale Clinical
Batches (Active) per CPL Estimate #0542-1, 0542-2 and, if necessary, Stand
Alone Independent Active Batches per CPL Estimate 0542-3. In
parallel with these activities, CPL shall develop and implement the
necessary cleaning validation processes per CPL Estimate
#0542-4. The parties acknowledge that these batches are
intended to be used for clinical testing in humans, for which CPL may be
required to produce successive clinical batches per CPL Estimates #0542-1,
0542-2 and, if necessary, 0542-3 to support multiple clinical trials
and/or to furnish fresh Product through the course of any given trial
depending on Product expiration
dates.
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Schedule
“C” attached sets forth Helix’s estimated timelines for the CPL Estimates set
forth in Schedule “A”. CPL confirms that these timelines are
reasonable and that it expects to be able to fully perform the Services within
such timelines.
For
greater certainty, Helix has no obligation to notify CPL to provide any
Services, or, if Helix has so notified CPL in respect of a particular CPL
Estimate, no obligation to notify CPL to provide any Services described in or
related to any other CPL Estimate.
Notification
to CPL to provide any Services will come from Helix in the form of a written
purchase order for Product or Services consistent with a CPL
Estimate.
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2.2
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Service
Standard
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CPL will
provide the Services with due care and diligence, and, without limiting the
generality of the foregoing, in accordance with (i) this Agreement; (ii) all
applicable Regulatory Requirements; (iii) the Quality Assurance
Agreement; (iv) cGMP; and (iv) accepted industry standards.
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2.3
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Quality Assurance
Agreement
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The
Quality Assurance Agreement specifies certain services, including certain
testing, storage, release, cGMP, regulatory and other quality assurance
requirements to be performed by CPL as part of the Services, all of which shall
be deemed a material part of this Agreement.
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2.4
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Additional
Services
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CPL will
use reasonable commercial efforts to accommodate any request which Helix may
make for services not contemplated at the date hereof, and should CPL and Helix
agree upon the provision and pricing of such services, such additional services
shall be deemed to form part of the Services hereunder and shall be governed by
the provisions of this Agreement.
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2.5
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Helix Personnel on
Site
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From
time-to-time and upon reasonable advance notice, Helix may designate selected
Helix personnel to be present at the CPL Facility during the execution of the
Services. CPL shall allow such designated personnel access to those
portions of the CPL Facility where Services are conducted for the purposes
contemplated in this Agreement, provided that the Helix personnel are
accompanied by CPL staff and
comply
with all applicable rules, protocols and safety measures at all times while they
are present at the CPL Facility.
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2.6
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Dispute
Resolution.
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In the
event of a disagreement or decision-deadlock between the Parties as to any
material matter within the scope of this Agreement, or matters that a Party
considers to be, or potentially cause, a breach of a material term hereunder, or
matters requiring the consent or agreement of both Parties, the Parties will
diligently and in good faith seek to resolve the matter in dispute, and each
Party shall act diligently and in good faith in seeking to resolve the matter.
In the event that no mutual agreement is reached by the Parties, neither Party
shall incur any liability to the other Party solely as a result of failing to
resolve a disagreement or decision-deadlock under this 2.6.
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2.7
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Approval of
Subcontracting
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CPL shall
not have the right to subcontract, sublicense or otherwise delegate all or any
portion of its obligations under this Agreement without Helix's prior written
approval. Notwithstanding the foregoing, CPL may propose certain pre-defined,
non-essential or routine tasks that CPL desires to subcontract out, and Helix
will review and reasonably approve CPL to subcontract any or all of such tasks
to the Subcontractors of CPL's choosing. To the extent such approvals are
granted, CPL shall
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(i)
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fully
qualify each such Subcontractor, and Helix shall have the right to
participate in such qualification
process;
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(ii)
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ensure
that all such qualified Subcontractors comply with the provisions of this
Agreement, including, but not limited to, the confidentiality provisions;
and
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(iii)
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be
responsible for each such Subcontractors performance hereunder (including,
without limitation, any breach of this Agreement by such Subcontractor),
as if CPL were itself performing such
activities.
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ARTICLE
3 PRICING
AND PAYMENT
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3.1
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Estimates
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Subject
to section 3.3, the parties agree that the
price set out in each CPL Estimate includes compensation for all Services to be
rendered by CPL in connection with such Estimate, including all Services as set
out in the Quality Assurance Agreement, excepting only stability testing
Services which shall be priced separately at a price to be agreed upon between
the Parties.
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3.2
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Invoicing and
Payment
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CPL may
invoice Helix for the price set out in an Estimate at anytime on or after CPL’s
completion of all Services to be rendered in connection with such Estimate,
excepting only Services to be performed or which may be required following
release of finished Product, for which CPL shall continue to remain responsible
(such as, without limitation, Services related to shipping, product recall,
sample retention, document retention, and investigation of clinical
complaints). Invoices so rendered by CPL will be paid by Helix within
thirty (30) days of receipt. Invoices relating to Services for
the production of a Batch will reference the Helix purchase order number, the
corresponding CPL Estimate number, and the Batch or lot number and will be
supported by a copy of, or reference to, the appropriate Production
Record.
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3.3
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Capital
Requirements
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The
capital requirement pricing estimates set out in Schedule “A” are estimates of
equipment cost only and the actual cost shall be approved and paid for directly
by Helix with the vendor, pursuant to section 10.7. Any applicable
acceptance testing and/or qualification costs will be quoted and invoiced
separately.
ARTICLE 4 DELIVERIES
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4.1
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Delivery
Responsibilities
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Delivery
responsibilities are as set out in the Quality Assurance
Agreement. The delivery date for each batch of Product shall be
commercially reasonably determined by Helix.
Delivery
of any Product shipped from CPL shall be FCA CPL (i.e. the loading dock at CPL’s
Facility) to Helix or Helix’s designee in accordance with applicable
law. Freight, duty, taxes, and insurance shall be for the account of
Helix, and title and the risk of loss, delay, damage in transit shall be passed
to Helix upon delivery to Helix’s or Helix’s designee’s designated
carrier. CPL shall package the Product for shipment in accordance
with its customary practices therefore, unless otherwise specified in writing by
Helix, in which event any extra reasonable cost incurred by CPL on account of
changes requested by Helix will be incorporated into the price of Product CPL
charged to Helix. CPL shall include the following for each shipment
of Product: (a) the purchase order number; (b) the lot and batch numbers; (c)
the quantity of Product; and (d) the Certificate of cGMP
Compliance.
ARTICLE
5 COMPLIANCE
AUDITS
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5.1
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Manufacturing
Audits
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Helix
shall have the right to perform, directly or through its representatives,
certain manufacturing compliance audits as set forth in the Quality Assurance
Agreement, or as otherwise agreed in writing by CPL and Helix from time to
time. Helix shall be responsible for all Third Party costs of all
compliance audits.
ARTICLE
6 RECORDS AND REGULATORY MATTERS
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6.1
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Permits
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CPL shall
secure and maintain in good order, at its sole cost and expense, such current
governmental registrations, permits and licenses and other Regulatory
Requirements as are required by Governmental Authorities in order for CPL to
perform all of its obligations under this Agreement.
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6.2
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Compliance with
cGMP
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CPL shall
monitor and maintain reasonable records respecting its compliance with cGMP,
including those referenced in the Quality Assurance Agreement, or as Helix may
otherwise reasonably request from time to time. CPL further
agrees to comply with any and all corrective actions mutually agreed to by the
Parties pursuant to any audit performed pursuant to section 5.1.
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6.3
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Access to
Records
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CPL shall
maintain all records required by the terms and conditions of the Quality
Assurance Agreement, or as Helix may otherwise reasonably request from time to
time. Helix shall have access, on reasonable prior written notice, and the right
to duplicate and use all documents, information, batch records, or other records
otherwise prepared or compiled and associated with the Services or undertaken
pursuant to, or required by, this Agreement (collectively referred to as the
“Records”), and CPL shall provide Helix with copies of the foregoing upon
request. CPL shall make such Records available to Helix and, subject to section
15.2. Helix
may use the information contained in the Records as it sees fit, including the
disclosure of such information to third parties. CPL will notify Helix before
destroying any Records developed under this Agreement and Helix retains the
option of having the Records delivered to Helix. All Helix
Records shall be maintained by CPL in confidence and shall only be disclosed in
accordance with this Agreement.
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6.4
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Record
Maintenance
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CPL will
maintain adequate and accurate Records in order to ensure the Products’
development and manufacturing activities are documented in compliance with
applicable Regulatory Requirements.
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6.5
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Accurate
Documentation
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Each
Party shall use diligent efforts to ensure all Records and documentation
provided to the other Party in connection with the Services shall be accurate in
all material respects, as more precisely described in the Quality Assurance
Agreement, or as otherwise agreed in writing by CPL and Helix.
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6.6
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Claims and
Complaints
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Helix
shall have responsibility for reporting any complaints relating to the Product
to Regulatory Authorities, including, but not limited to, complaints relating to
the manufacture of the Product and adverse drug experience or event reports in
accordance with the terms and conditions of the Quality Assurance Agreement, or
as otherwise agreed in writing by CPL and Helix. Helix shall pay CPL for all
Actual & Reasonable costs and expenses incurred by CPL in
connection with any assistance that CPL provides with respect to such reporting,
except in the event and to the extent that such complaints are directly
attributable to CPL's breach of the warranties set forth in Sections 11.1
and 11.2.
|
6.7
|
Regulatory
Communications and
Correspondence
|
Any and
all communications from and to Regulatory Authorities related to this Agreement
or the Services hereunder shall be handled as agreed in writing by CPL and
Helix.
|
6.8
|
New Regulatory
Requirements
|
Either
party shall promptly notify the other party new Regulatory Requirements of which
it obtains actual knowledge and which are relevant to the Services under this
Agreement and which are required by the FDA, other applicable Regulatory
Authority, or other applicable laws or governmental regulations and the parties
shall confer with each other with respect to the best means to comply with such
requirements.
|
6.9
|
Manufacturing Records
and Maintenance
|
CPL shall
prepare and maintain all manufacturing records, certificates, authorizations,
data and other records that directly or indirectly pertain to the manufacture of
the Product, as further set forth in the Quality Assurance Agreement or as
otherwise agreed in writing by CPL and Helix.
|
6.10
|
Cooperation in
Obtaining Government
Approvals
|
As set
forth in the Quality Assurance Agreement, or as otherwise agreed to in writing
by CPL and Helix, at Helix's request, CPL shall provide Helix with such existing
documents and information (or copies thereof) held by CPL to assist Helix in
securing and maintaining Regulatory Authority approvals for the Product. In
addition, CPL shall provide Helix with such information as is reasonably
requested in writing by Helix relating to the Manufacturing Process, the Master
Formula, the Master Packaging Formula / Procedure, the CPL Services performed
under this Agreement or other Product-related documentation. Any Helix requests
for documents or other work product that do not exist as of the date of such
request and are not otherwise required by this Agreement, including the CPL
Estimates or Quality Assurance Agreement, or any other substantive requests for
assistance in compiling any Regulatory Filing shall be conducted at Helix’s
expense.
|
6.11
|
Ownership of
Regulatory Filings
|
Helix
shall prepare, maintain, share with CPL as appropriate, and be the sole owner of
all applicable or relevant Regulatory Filings and all governmental approvals
granted by any Regulatory Authority with respect to the Product, including all
copyright and CPL waives all moral rights therein.
|
6.12
|
Safety and Efficacy
Claims
|
CPL shall
promptly notify Helix of any information or notice of which it becomes aware
concerning the safety or efficacy claims of the Product, including, without
limitation, any threatened or pending action by any Regulatory Authority. Helix
shall be responsible for handling all complaints and communications from
Regulatory Authorities with respect to the Product. CPL shall cooperate in
resolving such complaints and responding to such communications to the extent
they pertain to Product and are reasonably requested by Helix in connection
therewith. Helix shall pay CPL for all Actual & Reasonable costs and
expenses incurred by CPL in connection with the performance of CPL's obligations
under this Section 6.12
except in the event and to the extent that such complaints or communications are
directly attributable to CPL's breach of the warranties set forth in Sections 11.1
and 11.2.
|
6.13
|
Accident
Reports
|
Each
Party shall report to the other as soon as possible all material accidents
related to the manufacture, handling, use or storage of any Raw Materials or
Product, including, without limitation:
|
(a)
|
accidents
resulting in significant personal injury requiring more than first aid
treatment,
|
|
(b)
|
accidents
resulting in chronic illness or loss of
consciousness,
|
|
(c)
|
accidents
resulting in material property
damage,
|
|
(d)
|
accidents
resulting in material environmental release,
and
|
|
(e)
|
accidents
that result in regulatory, safety, health or environmental
audits.
|
ARTICLE
7 QUALITY ASSURANCE; QUALITY CONTROL; VALIDATION
|
7.1
|
Responsibility for
Quality Assurance and Quality
Control
|
Responsibility
for quality assurance and quality control of Product shall be allocated between
Helix and CPL as set forth in the Quality Assurance Agreement and in those CPL
standard operating procedures which have been agreed upon in writing by Helix
and CPL from time to time.
|
7.2
|
Validation of CPL
Facility; Utilities and
Equipment
|
CPL shall
maintain cGMP validation status of the CPL Facility, as well as the utilities
and equipment used in the manufacture of Product at the CPL Facility, and shall
make relevant validation reports applicable thereto (edited, if deemed necessary
by CPL, to remove information not related to the manufacture of Product)
available to Helix for review at CPL's Facility, at Helix's reasonable
request.
ARTICLE
8 NON-CONFORMANCE
|
8.1
|
Non-Conformance
|
Helix may
reject any Product on the ground that it is non-conforming by giving written
notice thereof to CPL (an “NC Notice”) within sixty (60) days after the Delivery
Date for such Product. Such written notice shall specify the manner in which
such Product fails to conform to the warranties set forth in Sections 11.1
and 11.2 and shall be
accompanied by any test results or reports evidencing such
non-conformity. For a period of twenty-one (21) days following CPL’s
receipt of an NC Notice, the Parties shall diligently and in good faith seek to
reach agreement on whether a nonconformity exists and, if so, whether such
nonconformity was caused by CPL’s breach of the warranties set forth in Sections
11.1
and 11.2.
|
8.2
|
No CPL Liability for
Non-Conforming Product
|
If it is
determined by agreement of the Parties that either: (i) there is no
nonconformity, or (ii) there is nonconformity but the nonconformity was not
caused by CPL's breach of the warranties set forth in Sections 11.1
and 11.2 and CPL shall have no liability to
Helix with respect thereto.
|
8.3
|
CPL Liability for
Non-Conforming Product;
Replacement
|
If it is
determined by agreement of the Parties that any nonconformity claimed by Helix
pursuant to Section 8.1 was caused by CPL's breach of any warranty set forth in
Section 11.1
or 11.2, CPL shall replace such Non-Conforming Product with
conforming Product at CPL’s sole expense within such timeframe as Helix may
reasonably require. For greater clarity, it is understood by the
Parties that under such circumstances CPL shall bear the expense of the
non-conforming Product and Helix shall bear the expense of the conforming
replacement Product.
|
8.4
|
Cooperation in
Investigations; Disposition of Non-Conforming
Product
|
If Helix
desires to make a claim against CPL with respect to and causing the rejection of
a Batch of Non-Conforming Product pursuant to Section 8.1, Helix agrees that it
shall not dispose of or allow such Product to be disposed of without written
authorization and instructions from CPL either to dispose of or return to CPL
such Non-Conforming Product. Upon written request by Helix, CPL agrees promptly
to give Helix such authorization and instructions within a reasonable period of
time. Each Party shall act in good faith and shall cooperate with the other
Party and with any Third Party or arbitrator appointed pursuant to Section 8.5
in connection with an investigation as to the existence of or source of any
Non-Conforming Product supplied under this Agreement. At the request of Helix,
CPL will provide all Non-Conforming Product to Helix at a price (including
shipping and delivery expenses) to be agreed upon between the Parties and in
accordance with the delivery terms set forth in Section 3
hereof. Helix may make whatever further use of such Non-Conforming
Product as it shall determine; provided, however, that Helix agrees
that:
|
(a)
|
such
Non-Conforming Product shall not be used in humans,
and
|
|
(b)
|
CPL shall
dispose of any Non-Conforming Product returned by Helix in accordance with all
relevant Regulatory Requirements for such disposal, at CPL's expense, if CPL was
liable for such Non-Conforming Product in accordance with Section 8.3 and at Helix's expense if CPL was not
liable for such Non-Conforming Product in accordance with Section 8.2.
|
8.5
|
Third Party /
Arbitration
|
In the
event the parties are unable to come to an agreement within 21 days of the date
Helix first gave notice to CPL under Section 8.1,
the matter may be referred by either Party to a mutually acceptable, qualified
and independent Third Party whose fees shall be paid by the non-prevailing
Party. If the parties are unable to agree upon a qualified and
independent Third Party within twenty-one (21) calendar days of the date a Party
first notifies the other that it wishes to so refer the matter, then the matter
shall be resolved by arbitration conducted in English in Toronto, Ontario in
accordance with the Arbitration Act (Ontario) as
the same may be amended from time to time. The arbitration shall be
conducted as follows: (a) either Party may require arbitration by giving
written notice to arbitrate to the other Party; (b) if the Parties are
able to agree upon a single arbitrator, the arbitration shall be conducted
before the single arbitrator; (c) if the Parties have been unable to agree
upon the selection of a single arbitrator within fourteen (14) calendar days
after receipt of the notice requiring arbitration, each Party shall
within seven (7) further calendar days by notice in writing given
to the other Party nominate one (1) neutral arbitrator. If either Party
fails to nominate an arbitrator, the single arbitrator nominated by the other
Party shall
proceed
to conduct the arbitration alone. If both Parties nominate neutral
arbitrators, the two arbitrators so nominated shall nominate a third arbitrator
within seven (7) calendar days of their nomination. The Parties agree that
it is important that the matter be resolved promptly and the Parties agree that
the arbitration will be required to be conducted expeditiously and that the
final disposition shall be accomplished within fourteen (14) calendar days of
the appointment of the single arbitrator or the third arbitrator. The
Parties shall ensure that the arbitrator or arbitrators upon accepting
nomination agree that they have the time available for the timely handling of
the arbitration in order to achieve the final disposition within fourteen (14)
calendar days. The decision of the arbitrator or arbitrators shall be
rendered in writing, without reasons and shall be binding upon the
Parties.
ARTICLE
9 LICENSE GRANTS
|
9.1
|
Helix Licenses to
CPL
|
During
the Term (subject to early termination in accordance with ARTICLE
17 hereof), Helix hereby grants to CPL a royalty-free, non-exclusive,
non transferable license under any and all Helix Intellectual Property that is
necessary for CPL to perform its obligations under this Agreement, including,
without limitation, all rights necessary for the development and use of the
Helix Confidential Information for the sole and limited purpose of CPL's
performance of its obligations under this Agreement, including, without
limitation, to manufacture Product for Helix.
|
9.2
|
CPL Licenses to
Helix
|
CPL
hereby grants to Helix a perpetual, fully paid, royalty-free, non-exclusive,
license, with the right to grant and authorize sub-licenses, under any and all
CPL Intellectual Property that CPL uses for the performance of the Services or
that is necessary to the practice of the Services solely for the limited purpose
of manufacturing the Product. Helix shall include a provision in all
agreements with Third Party contractors for the manufacture of the Product that
clearly states that such Third Party contractor’s right to use such
CPL Intellectual Property is exclusively limited to the Product.
ARTICLE
10 OWNERSHIP OF INTELLECTUAL PROPERTY, MATERIALS AND
EQUIPMENT
|
10.1
|
Intellectual
Property
|
Subject
to section 10.4, CPL
acknowledges and agrees that Helix shall own exclusively all Intellectual
Property that is made, created, conceived or reduced to practice in the course
of or resulting from performance of the Services by either Party or its
employees or agents and CPL waives any moral rights therein.
|
10.2
|
Confidential
Information
|
Helix
shall own all Helix Confidential Information, and CPL shall own all CPL
Confidential Information.
|
10.3
|
Process
Improvements
|
The
parties acknowledge that CPL may develop improvements to the manufacturing
process or procedure in the course of performing the Services under
this Agreement (“Process Improvements”). CPL agrees to promptly disclose all
Process Improvements to Helix as they occur.
|
10.4
|
Product-Specific
Process Improvements
|
CPL
agrees that all Process Improvements specific to the manufacture of the Product
(“Product-Specific Process Improvements”) shall be owned solely by Helix and
Helix may obtain patent, copyright and other proprietary protection
therewith.
|
10.5
|
General Process
Improvements
|
All
Process Improvements that are not specific to the manufacture of the Product
that have general application to the contract manufacturing of chemical or
pharmaceutical compounds (“General Process Improvements”) shall be owned by
CPL.
|
10.6
|
Helix
Materials
|
Helix
shall own all rights in and title to the Helix Intellectual Property, and any
and all improved or enhanced versions of the foregoing that are created by
either Party in the course of or resulting from this Agreement, including,
without limitation, any derivatives or variants of the foregoing. CPL hereby
assigns to Helix any improvements that directly relate to the Helix Intellectual
Property or the Product and shall not provide them to any third party without
Helix’s prior written consent and CPL waives all moral rights
therein.
|
10.7
|
Helix
Equipment
|
All
equipment procured by CPL or Helix pursuant to any CPL Estimate shall be paid
for directly by Helix to the vendor of the equipment, and shall become the
property of Helix. Where practical, CPL will obtain two to three
quotes for all equipment purchases for presentation to Helix Any
costs related to, without limitation, qualification, installation,
de-installation, preparation for shipping, insurance and transportation of such
equipment shall be paid for directly by Helix. These activities will
be co-ordinated by CPL.
|
10.8
|
CPL
Assistance
|
CPL
agrees to provide all reasonable assistance, including without limitation,
executing documents and supplying information necessary, to secure,
perfect or prosecute Helix’s legal rights and worldwide ownership of any
Intellectual Property, materials or equipment owned or licensed by Helix as
provided in this Agreement, including but not limited to documents relating to
patent, trademark and copyright assignments and applications and CPL waives all
moral rights therein, provided however, that such assistance shall not include
(i) any requirement of CPL to pay money to a Third Party, commence, defend or
participate in any litigation with a Third Party or offer or grant any
accommodation (financial or otherwise) to any Third Party, or (ii) any action
that would unreasonably interfere with the conduct of CPL’s business,
unreasonably disrupt its normal operations, violate confidentiality obligations
to a Third Party or void any right of privilege on behalf of
CPL. Helix shall pay CPL for all Actual & Reasonable costs and
expenses incurred by CPL in connection with any assistance that CPL provides
pursuant to this provision.
|
10.9
|
Limitation
|
Notwithstanding
any provision of this Article 10 or this Agreement to the contrary, but subject
to section 10.4, CPL’s proprietary manufacturing or other processes
and related know-how shall not become or be deemed to be Helix Intellectual
Property or Helix Confidential Information and shall not be subject to any
ownership or other rights of Helix or a Third Party.
|
10.10
|
CPL Employee
Agreements
|
CPL
agrees that no employee, consultant or other agent of CPL who is in a position
to make, create, conceive, or reduce to practice, any Intellectual Property in,
or resulting from, the performance of the Services shall perform any Services
unless and until CPL has obtained an appropriate legal agreement from such
person assigning to CPL, and agreeing to promptly disclose to CPL, all such
Intellectual Property upon its creation by such person, and waiving all moral
rights of such person therein. CPL shall hold such Intellectual
Property to be dealt with as between CPL and Helix in accordance with the terms
of this Agreement.
ARTICLE
11 CPL PRODUCT WARRANTIES
|
11.1
|
Product
Warranties
|
CPL
warrants to Helix that all Product manufactured hereunder will:
|
(a)
|
have
been manufactured, tested, stored, packaged, labeled and
controlled in conformance with the CPL Specifications, the
Master Formula and the Master Packaging Formula /
Procedure;
|
|
(b)
|
have
been transferred to Helix with a Certificate of cGMP Compliance, which is
accurate and complete with respect to each
Batch;
|
|
(c)
|
have
been manufactured, packaged, handled, stored and labeled in accordance
with cGMP and all applicable Regulatory
Requirements;
|
|
(d)
|
not
be adulterated or misbranded by CPL within the meaning of the FD&C
Act; and
|
|
(e)
|
have
been transferred free and clear of any liens or encumbrances of any
kind.
|
Notwithstanding
the foregoing, the parties may agree to except out any of the above warranties
in respect of one or more trial developmental batches.
|
11.2
|
CPL
Facility
|
CPL
hereby warrants that it owns or lawfully controls the CPL Facility, and that,
provided the Manufacturing Process is successfully implemented including the
procurement and installation of all required product-specific equipment, and
provided no Force Majeure Event shall occur, CPL has sufficient manufacturing
capacity to enable CPL to conduct the Services required by this
Agreement. CPL hereby warrants that the CPL Facility shall be
maintained in accordance with cGMP and in such condition as will allow CPL to
conduct the Services in compliance with cGMP, all applicable laws, and in
conformance with the Master Formula.
ARTICLE
12 REPRESENTATIONS AND WARRANTIES; COVENANTS
|
12.1
|
Mutual Representations
and Warranties
|
Each
Party hereby represents and warrants to the other Party that:
|
(i)
|
this
Agreement, as executed and delivered, constitutes the valid and binding
agreement of such Party, its successors and assigns, and is enforceable in
accordance with its terms;
|
|
(ii)
|
the
execution, delivery and performance of this Agreement does not conflict
with any agreement, instrument or understanding, oral or written, to which
such Party may be bound, nor violate any law or regulation of any court,
governmental body or administrative or other agency having jurisdiction
over it; and
|
|
(iii)
|
it
has obtained all necessary authorizations and consents required to enter
into this Agreement and to perform its obligations
hereunder.
|
|
12.2
|
Representations and
Warranties of Helix
|
Helix
hereby represents and warrants to CPL, as of the date hereof and throughout the
term of this Agreement, that:
|
(a)
|
To
the best of Helix's knowledge as of the Effective Date, after reasonable
inquiry, Helix is free to supply to CPL the Helix Confidential Information
and any other information supplied by Helix to
CPL;
|
|
(b)
|
To
the best of Helix's knowledge as of the Effective Date, after reasonable
inquiry, there is no lawsuit pending against Helix that alleges patent
infringement based on the manufacture, use or sale of the Product, and as
of the Effective Date, Helix has not received any written notice alleging
infringement of a Third Party Patent based on the manufacture, use or sale
of the Product;
|
|
(c)
|
To
the best of Helix's knowledge as of the Effective Date, after reasonably
inquiry, Helix's supply to CPL of the Helix Confidential Information and
any other information Helix intends to supply to CPL hereunder, and CPL's
use thereof in accordance with the terms of and in performance of its
obligations under this Agreement, does not infringe any intellectual
property rights of any Third Party for which Helix lacks the right to
grant CPL a valid sublicense to manufacture the
Product;
|
|
(d)
|
To
the best of Helix’s knowledge as of the Effective Date, after reasonably
inquiry, the Manufacturing Process for the Product in effect as of the
Effective Date does not infringe any intellectual property rights of any
Third Party for which Helix lacks the right to grant CPL a valid
sublicense to manufacture the
Product;
|
|
(e)
|
there
is no fact known to Helix which it has not disclosed to CPL or included in
its public documents filed on SEDAR at xxx.xxxxx.xxx
which adversely affects, or which may adversely affect, the
assets, liabilities (contingent or otherwise), capital, affairs, business,
prospects, operations or condition (financial or otherwise) of Helix or
the ability of Helix to perform its obligations under this
Agreement;
|
|
(f)
|
To
the best of Helix’s knowledge as of the Effective Date, after reasonable
inquiry, Helix has made CPL aware of any known hazards involved in
handling the Helix Intellectual Property;
and
|
|
(g)
|
Helix
has the financial capacity to enter into and carry out this entire
Agreement.
|
|
12.3
|
Representations and
Warranties of CPL
|
CPL
hereby represents and warrants to Helix, as at the date hereof and throughout
the term of this Agreement, that:
|
(a)
|
To
the best of CPL's knowledge, of the Effective Date, after reasonable
inquiry, CPL is free to supply CPL Confidential Information to Helix and
any other information supplied by Helix to
CPL;
|
|
(b)
|
CPL
has the financial capacity to enter into and carry out this entire
Agreement;
|
|
(c)
|
CPL’s
employees are not unionized as at the date of this
Agreement;
|
|
(d)
|
To
the best of CPL's knowledge after reasonable
inquiry,
|
|
(i)
|
CPL
has the legal right to grant Helix the licenses set forth in Section 9.2 above;
|
|
(ii)
|
|
(iii)
|
CPL
has not and will not use in any capacity the services of any persons
prohibited in any way in connection with its development or manufacture of
the Product;
|
|
(iv)
|
neither
CPL nor any CPL official or employee has been convicted of a felony under
U.S. federal law for conduct relating to the development or approval,
including the process for development or approval, of any drug, product,
INDA, or any other drug product application;
and
|
|
(v)
|
no
CPL official or employee has been convicted under Canadian law for conduct
otherwise relating to the regulation of any drug substance or drug
product;
|
|
(vi)
|
there
is no fact known to CPL which it has not disclosed to Helix
which adversely affects, or which may adversely affect, the
assets, liabilities (contingent or otherwise), capital, affairs, business,
prospects, operations or condition (financial or otherwise) of CPL or the
ability of CPL to perform its obligations under this
Agreement;
|
|
(vii)
|
with
the exception of a disability discrimination complaint filed with the New
York State Division of Human Rights against which CPL is currently
defending, there are no legal or governmental actions, suits, proceedings
or investigations pending or, to the knowledge of CPL, threatened, to
which CPL is or may be a party or of which property owned or leased by CPL
is or may be the subject, or related to environmental or discrimination
matters. Except to the extent the terms of a consent decree
dated 1995 (as amended) among the State of New York, the owner of the land
on which the CPL Facility is located and others relating to environmental
conditions on a portion of the premises are applicable to CPL or its
operations, CPL is not a party to or subject to the provisions of any
injunction, judgment, decree or order of any court, regulatory body,
administrative agency or other governmental body;
and
|
|
(viii)
|
CPL
is not in violation of or in default under, any lien, mortgage, lease,
agreement or instrument, including without limitation, its financial
arrangements with any Third Party.
|
|
(e)
|
CPL
has and will maintain in place all equipment, personnel, facilities, and
supply agreements necessary to perform its obligations
hereunder.
|
|
12.4
|
Additional
Covenants
|
|
(a)
|
Helix
shall comply with all applicable laws and regulations in the performance
of Helix's obligations under this
Agreement.
|
|
(b)
|
CPL
shall comply with all applicable laws and regulations in the performance
of CPL's obligations under this
Agreement.
|
|
(c)
|
Each
Party shall notify the other in writing immediately in the event that any
representation and warranty contained in this Agreement becomes
untrue.
|
ARTICLE
13 INDEMNIFICATION
|
13.1
|
Indemnification By
Helix
|
Subject
to Section 13.2,
Helix agrees to indemnify, defend and hold CPL and its directors, officers,
employees and agents harmless from and against any damages, claims, liabilities
and expenses (including, but not limited to, reasonable legal fees)
(collectively, “Liabilities”) resulting from any Third Party claims, suits,
actions or proceedings (collectively, “Claims”) against CPL arising out
of
|
(a)
|
Helix's
breach of any of its representations, warranties or covenants contained in
this Agreement; or
|
|
(b)
|
Helix's
negligent acts or omissions or willful
misconduct.
|
|
13.2
|
Exception
|
Notwithstanding
Section 13.1,
Helix will not be required to indemnify, defend and hold CPL or its directors,
officers, employees and agents harmless from or against any Liabilities in
connection with any Claims to the extent arising out of:
|
(i)
|
CPL's
breach of any of its representations, warranties, or covenants contained
in this Agreement; or
|
|
(ii)
|
CPL's
negligent acts or omissions or willful
misconduct.
|
|
13.3
|
Indemnification By
CPL
|
CPL
agrees to indemnify, defend and hold Helix and its directors, officers,
employees and agents harmless from and against any Liabilities resulting from
any Claims against Helix arising out of
|
(a)
|
CPL's
breach of any of its representations, warranties or covenants contained in
this Agreement; or
|
|
(b)
|
CPL's
negligent acts or omissions or willful
misconduct.
|
Notwithstanding
the foregoing, CPL will not be required to indemnify, defend and hold Helix or
its directors, officers, employees and agents harmless from or against any
Liabilities in connection with any Claims to the extent arising out
of
|
(i)
|
Helix's
breach of any of its representations, warranties or covenants contained in
this Agreement; or
|
|
(ii)
|
Helix's
negligent acts or omissions or willful
misconduct.
|
|
13.4
|
Indemnification
Procedures
|
Where
either party to this Agreement (the “Indemnitee”) seeks indemnification from the
other (the “Indemnitor”) in respect of any Claim, the Indemnitee shall provide
written notice of the Claim to the Indemnitor as soon as reasonably practicable
upon becoming aware of the Claim, provided, however, the failure to provide such
notice within a reasonable period of time shall not relieve the Indemnitor of
any of its obligations hereunder except to the extent the Indemnitor is
prejudiced by such failure. The Indemnitor shall be entitled, but
shall not be obligated, to participate in or assume the defence of the Claim,
provided that if the defence is assumed, it shall be through legal counsel
acceptable to the Indemnitee, acting reasonably, and the Indemnitee shall also
have the right, but not the obligation, to employ separate counsel, in which
event the fees and expenses of such counsel shall be borne by the
Indemnitee. Each Indemnitee shall reasonably cooperate with the
Indemnitor and its legal representatives in the investigation or defence of any
Claims covered under this Agreement. No Claim may be settled by an
Indemnitee or an Indemnitor without the prior written consent of the other,
which consent shall not be unreasonably withheld, unless in the case of a
settlement by an Indemnitor, the settlement acknowledges in writing that no
liability, negligence, guilt or other wrongful act or omission of the Indemnitee
is admitted or assumed, and such settlement acts as a complete bar to future or
other claims of, by or under the parties with whom such settlement is reached,
arising or which may arise out of any act, matter or thing prior to the date of
settlement.
ARTICLE
14 INSURANCE
|
14.1
|
CPL
Insurance
|
CPL shall
maintain in full force and effect, at its own expense:
|
(a)
|
At
all times during the period in which CPL is making any of the
Products, general liability insurance coverage in an amount not
less than USD $10,000,000 per occurrence (annual general aggregate of not
less than USD $10,000,000) covering bodily injury, broad-form property
insurance and including blanket contractual
coverage;
|
|
(b)
|
At
all times during the period in which CPL is making any of the Products
and, if the insurance is on a “claims made” basis, for a period of three
(3) years thereafter, products liability / completed operations hazard
insurance coverage in an amount not less than USD $10,000,000 per claim
(annual general aggregate of not less than USD $10,000,000) covering
bodily injury, broad-form property insurance and including blanket
contractual coverage.
|
CPL shall
maintain the foregoing insurance coverage comparable to coverage maintained by
bulk pharmaceutical manufacturing companies of similar size with a responsible
insurance carrier. These policies will provide that the insurer shall give Helix
thirty (30) days notice of any termination or cancellation of such coverage. CPL
will add Helix as a named insured and will provide Helix with
such reasonable proof of the existence and maintenance of this
insurance coverage as Helix may request from time to time.
|
14.2
|
Helix
Insurance
|
Helix
shall maintain in full force and effect, at its own expense:
|
(a)
|
At
all times during the period in which CPL is making any of the Products,
general liability insurance coverage in an amount not less than CDN
$5,000,000 per occurrence (annual general aggregate of not less than CDN
$5,000,000) covering bodily injury, broad-form property insurance and
including blanket contractual
coverage;
|
|
(b)
|
At
all times during the period in which CPL is making any of the Products
and, if the insurance is on a “claims made” basis, for a period of three
(3) years thereafter, products liability / completed operations hazard
insurance coverage in an amount not less than CDN $5,000,000 per claim
(annual general aggregate of not less than CDN $5,000,000) covering bodily
injury, broad-form property insurance and including blanket contractual
coverage.
|
Helix
shall maintain the foregoing insurance coverage comparable to coverage
maintained by other biopharmaceutical companies of similar size and stage of
development with a responsible insurance carrier. These policies will provide
that the insurer shall endeavor to give CPL thirty (30) days notice of any
termination or cancellation of such coverage. Helix will provide CPL with such
reasonable proof of the existence and maintenance of this insurance coverage as
CPL may request from time to time.
|
14.3
|
Evidence of
Insurance
|
Upon
request, each Party shall provide to the other Party evidence of the insurance
required under this Article.
ARTICLE
15 CONFIDENTIALITY
|
15.1
|
CPL Confidentiality
Obligations
|
CPL shall
not use Helix Confidential Information except as authorized under this Agreement
and shall not disclose Helix Confidential Information to anyone else other
than:
|
(i)
|
its
employees or employees of its Affiliates who are bound by similar
obligations of confidentiality and non-use and who have a need to know
such information in order to perform their duties in carrying out CPL's
obligations under this Agreement;
|
|
(ii)
|
contractors
who are bound by similar obligations of confidentiality and non-use and
who have a need to know such information in order to provide direction to
CPL or Helix regarding their respective obligations under this Agreement;
or
|
|
(iii)
|
Regulatory
Authorities, to the extent required by law or as necessary to perform the
Services.
|
|
15.2
|
Helix Confidentiality
Obligations
|
Helix
shall not use CPL Confidential Information except as authorized under this
Agreement and shall not disclose any CPL Confidential Information to anyone else
other than:
|
(i)
|
employees,
consultants, agents or contractors of Helix or Helix's Affiliates who are
bound by similar obligations of confidentiality and nonuse and who have a
need to know such information in order to perform their duties in carrying
out Helix's obligations under this Agreement, or in order to provide
direction to
|
Helix
regarding production, testing, storage or quality of the Product or regulatory
or compliance issues related to the Product; or
|
(ii)
|
Regulatory
Authorities, to the extent required by law or as Helix considers necessary
in connection with the development, manufacturing, distribution or sale of
the Product; or
|
|
(iii)
|
to
Third Parties in accordance with the exercise of the licenses granted to
Helix under ARTICLE
9.
|
|
15.3
|
Responsibility for
Compliance with Confidentiality and Non-Use
Obligations
|
Each
Party shall be responsible for any intentional misuse or misappropriation, by
such Party, its Affiliates, or the employees, consultants, agents or contractors
of such Party or such Party's Affiliates, of the other Party's Confidential
Information.
|
15.4
|
Terms of
Agreement
|
Except
for any disclosure that is deemed necessary, in the reasonable judgment of the
responsible Party, to comply with national, federal, state or provincial laws or
regulations (including the rules and regulations of any national stock exchange
on which such Party's securities are traded) or disclosure to a Party's
employees, consultants, advisors, agents, contractors, partners, potential
partners, potential acquirers, investors or potential investors under reasonable
conditions of confidentiality, neither Party shall, without the prior written
consent of the other Party, disclose in any manner to any Third Party the terms
and conditions of this Agreement.
|
15.5
|
Notification of
Mandatory Disclosure
|
|
(a)
|
Notification and
Consultation In the event that a Party (in such case, the Notifying
Party) believes it is required by applicable statute or regulation
(including the rules and regulations of any national stock exchange on
which such Party's securities are traded), or by judicial or
administrative process to disclose any part of the other Party's (in such
case, the Notified Party) Confidential Information which is disclosed to
it under this Agreement, the Notifying Party
shall:
|
|
(i)
|
promptly
notify the Notified Party of each such requirement and identify the
documents so required thereby, so that the Notified Party may seek an
appropriate protective order or other remedy or waive compliance by the
Notifying Party with the provisions of this Agreement,
and
|
|
(ii)
|
consult
with the Notified Party on the advisability of taking legally available
steps to resist or narrow the scope of such
requirement.
|
|
(b)
|
Limited
Disclosure If, in the absence of such a protective order or such a
waiver by the Notified Party of the provisions of this Agreement, the
Notifying Party is nonetheless required by mandatory applicable law to
disclose any part of the Notified Party's Confidential Information which
is disclosed to it under this Agreement, the Notifying Party may disclose
such Confidential Information without liability under this Agreement,
except that the Notifying Party shall furnish only that portion of the
Confidential Information which is legally
required.
|
15.6 No
Licenses
Except as
expressly provided in ARTICLE
9 hereof, no right or license, either express or implied, is granted
under any intellectual property right or by virtue of the disclosure of
Confidential Information under this Agreement, or otherwise.
15.7 Equitable
Relief
Each
Party agrees that
|
(i)
|
the
other Party and their respective Affiliates would be irreparably injured
by a material breach of the confidentiality and nonuse provisions of this
Agreement by the breaching Party or by its employees or the employees of
its Affiliates, consultants, agents or
contractors,
|
|
(ii)
|
that
monetary remedies would be inadequate to protect the other Party against
any actual or threatened material breach of the provisions of
this
ARTICLE
15 by the breaching Party or by its employees or the
employees of its Affiliates, consultants, agents or contractors,
and,
|
|
(iii)
|
without
prejudice to any other rights and remedies otherwise available to the
other Party, the breaching Party agrees, upon proof of any such actual or
threatened material breach, to the granting of equitable relief, including
injunctive relief and specific performance, in the other Party's favor
without proof of actual damages. It is further understood and agreed that
no failure or delay by either Party in exercising any right, power or
privilege hereunder shall operate as a waiver thereof, nor shall any
single or partial exercise thereof preclude any other or further exercise
thereof or the exercise of any other right, power or privilege
hereunder.
|
15.8 Prior Confidentiality
Agreement
The
Parties acknowledge that the Confidentiality Agreement dated on or about June 5,
2007 between CPL and PDL shall survive the execution and delivery of this
Agreement and shall remain in full force and effect in accordance with its
terms.
ARTICLE
16 PRESS RELEASES; USE OF NAMES
|
16.1
|
Press
Releases
|
CPL shall
not originate any publicity, news releases, public statements or announcements,
whether written or oral, relating to this Agreement without the prior written
consent of Helix, which consent may not be unreasonably withheld or unduly
delayed, provided however, that CPL shall not be prevented from complying with
any duty of disclosure it may have pursuant to any law or regulation or as
required by the Regulatory Authorities.
|
16.2
|
Use of
Names
|
CPL shall
not make use of Helix’s or PDL’s name in any advertising or promotional material
in connection with this Agreement or any related agreements, without the prior
written consent of Helix.
ARTICLE
17 TERMINATION & CANCELLATION
|
17.1
|
Termination
|
This
Agreement may be terminated as follows:
|
(a)
|
At the Discretion of
Helix This Agreement may be terminated in its entirety by Helix
upon ninety (90) days written notice thereof to CPL at Helix’s sole
discretion.
|
|
(b)
|
CPL Material
Breach This
Agreement may be terminated in its entirety by Helix upon written notice
thereof to CPL in the event of a material breach by CPL which, if capable
of being cured, is not cured within thirty (30) days after receipt of
written notice from Helix to CPL specifying in reasonable detail the
nature of such breach or, if such breach cannot be cured within such
30-day period but is capable of being cured within a reasonable time, if
CPL does not commence and diligently continue actions to cure such breach.
CPL shall not render any Services during such cure period other than those
which are necessary to cure such breach, provided that the breach is
capable of being cured within such cure period. In the event such breach
is not cured within such cure period, this Agreement shall terminate as
set forth in Helix's notice of breach and in accordance with the terms of
this ARTICLE
17; provided, however, that this Agreement shall not be
terminated prior to the end of such cure period. Breach of any
of the provisions of ARTICLE
15 or the
Confidentiality Agreement referred to therein, or of any representation or
warranty of CPL contained herein, or any such representation or warranty
ceasing to be true, shall be deemed to constitute a material breach for
purposes of this ARTICLE
17 not capable of being cured, and accordingly, Helix may
terminate this Agreement immediately upon notice in any such
event.
|
|
(c)
|
Helix Material
Breach This Agreement may be terminated by CPL upon
written notice thereof to Helix in the event of a material breach by Helix
that is not cured within thirty (30) days after receipt of written notice
from CPL to Helix specifying in reasonable detail the nature of such
breach. In the event such breach is not cured within such cure period,
this Agreement shall terminate as set forth in CPL's notice of breach and
in accordance with the terms of this ARTICLE
17; provided, however, that this Agreement shall not be
terminated prior to the end of such cure
period.
|
|
(d)
|
Force
Majeure A Party shall have the right to terminate this
Agreement, upon providing written notice thereof to the other Party, if,
as a result of a Force Majeure Event suffered by such other Party, (i)
such other Party is unable fully to perform its obligations under this
Agreement for any consecutive period of sixty (60) days; (ii) it is
reasonably foreseeable at the time notice of the Force Majeure Event is
given or is required to be given pursuant to Section 18.2
that such other Party will be unable fully to perform its obligations
under this Agreement for any consecutive period of sixty (60) days; or
(iii) it is reasonably uncertain, (such as in the case of a labour dispute
that could continue for an indeterminate amount of time) at the time
notice of the Force Majeure Event is given or is required to be given
pursuant to Section 18.2,
whether such other Party will be able to fully to perform its obligations
under this Agreement within the next following sixty (60)
days.
|
|
(e)
|
Insolvency
Either Party may terminate this Agreement upon notice to the other
Party,
|
|
(i)
|
upon
the institution by or against that other Party of insolvency, receivership
or bankruptcy proceedings or any other proceedings for the settlement of
such Party's debts, which proceedings are not dismissed within sixty (60)
days,
|
|
(ii)
|
upon
that other Party making a general assignment for the benefit of
creditors, taking the benefit of any statute for bankrupt or
insolvent debtors, making any proposal, assignment or arrangements with
its creditors, or taking any steps with
|
a view to
readjustment, rescheduling or deferral of that Party's indebtedness or
suspending making payments to that Party's creditors; or
|
(iii)
|
upon
that other Party's dissolution or cessation of
business.
|
|
17.2
|
Consequences of
Termination
|
|
(a)
|
Payment of Amounts Due
Expiration or termination of this Agreement for any
reason shall not exempt any Party from paying to any other Party any
amounts owing to such Party at the time of such expiration or
termination.
|
|
(b)
|
Payment for Partial
Services Within 30 days of termination of this Agreement pursuant
to sections 17.1(a), (c), (d), or (e),
Helix shall pay CPL that portion of the price set forth in the relevant
Estimate(s) equal to the portion of Services provided up to the time of
such termination and not previously paid by Helix (excluding the cost of
Raw Materials which are dealt with separately in section 17.2(d)), provided that in no
event shall such proportionate price, plus the cost of any Raw Materials
purchased under section 17.2(d), exceed the full price set out in
the CPL Estimate(s) in respect of which such Services were
rendered.
|
|
(c)
|
Cumulative
Remedies Except as expressly stated otherwise herein, a Party’s
right to terminate this Agreement, and any other remedies under this
Agreement, are cumulative, and nothing in this Agreement shall prevent any
Party, in the case of a breach (after expiration of any applicable cure
period and notice periods), from terminating this Agreement pursuant to
Section 17.1
and pursuing all other rights and remedies such Party may otherwise have
at law or in equity in respect of such
breach.
|
|
(d)
|
Raw Materials
Upon expiration of this Agreement or termination by Helix pursuant to
Section 17.1(b)(CPL
material breach) or 17.1(e)
(Insolvency of CPL) or Section 17.1(d)
(Force Majeure), Helix may elect (but shall have no obligation) to
purchase from CPL, at CPL's Actual & Reasonable acquisition cost plus
10%, all remaining usable Raw Materials acquired and paid for by CPL for
the manufacture of Product under this Agreement, and not previously paid
for by Helix, and which cannot be used for other CPL clients in full
within ninety (90) days. Upon termination of this Agreement by
Helix pursuant to Section 17.1(a) (At the
Discretion of Helix) or by CPL pursuant to Section 17.1(c)
(Helix Material Breach) or 17.1(e)
(Helix Insolvency), Helix shall purchase from CPL, at CPL's Actual &
Reasonable acquisition cost plus 10%, all remaining Raw Materials acquired
and paid for by CPL, but not previously paid for by Helix or included in
the price payable by Helix under section 17.2(b), for the manufacture of Product
under this Agreement and which cannot be used for other CPL clients in
full within ninety (90) days, except as may be necessary for completion of
any portion of CPL's Services hereunder that are not immediately
terminated.
|
|
(e)
|
Return of Materials
and of Helix Confidential Information; Transfer of Equipment Upon
expiration or termination of this Agreement, unless otherwise directed by
Helix, CPL shall promptly:
|
|
(i)
|
return
or, at Helix's election, destroy all quantities of the Product, with any
such destruction to be certified in writing to Helix by an authorized CPL
officer,
|
|
(ii)
|
return
all Helix Confidential Information to Helix, except for a single copy
and/or sample which may be retained for documentation purposes only and
which shall remain subject to the obligations of non-use and
confidentiality set forth in this
Agreement,
|
|
(iii)
|
return
to Helix all retention and reserve samples being held by CPL, provided
that CPL may retain one set of such samples for documentation and
regulatory purposes only;
|
|
(iv)
|
deliver
to Helix all equipment in its possession which is the property of Helix
pursuant to this Agreement; and
|
|
(v)
|
return
to Helix all interferon alpha-2b previously provided by Helix to
CPL.
|
Helix
shall pay CPL for all Actual & Reasonable costs incurred by CPL in carrying
out CPL’s obligations under this Section 17.2(e), unless this Agreement has been
terminated pursuant to Section 17.1(b), in which event
all such costs shall be for CPL’s account.
|
(f)
|
Return of CPL
Confidential Information Upon expiration or termination of this
Agreement, Helix shall promptly return all CPL Confidential Information to
CPL, except for a reasonable number of copies to be retained by Helix to
exercise its rights under this Agreement in relation to such CPL
Confidential Information, but which shall otherwise remain subject to the
obligations of non-use and confidentiality set forth in this
Agreement.
|
|
(g)
|
Accrued Rights
Except as otherwise expressly set forth herein, any termination or
expiration of this Agreement shall be without prejudice to any right which
shall have accrued to the benefit of either Party and shall not relieve
either Party of any obligation which has accrued prior to the effective
date of such termination or expiration, which obligations shall remain in
full force and effect for the period provided therein or, if no period is
provided therein, then such obligations shall remain in full force and
effect indefinitely.
|
|
17.3
|
Surviving
Rights
|
All terms
of this Agreement, which by their nature are intended to survive termination of
this Agreement, shall survive termination of this Agreement.
|
17.4
|
Cancellation of
Services
|
Helix
may, upon at least thirty (30) days advance written notice, cancel an Estimate
or purchase order for which it previously notified CPL to provide Services, and
CPL shall cease providing Services in relation to such Estimate or purchase
order as of the effective date of such cancellation. Within 30
days of providing notice of cancellation, Helix will pay to CPL that portion of
the price set forth in the relevant Estimate equal to the portion of Services
provided by CPL in respect of the cancelled Estimate prior to the effective date
of such notice, plus CPL’s Actual & Reasonable cost of remaining usable Raw
Materials specifically obtained by CPL for purposes of the cancelled Estimate,
the cost of which has not been included in the portion of Services payable by
Helix, provided that in no event, except for the following sentence, shall such
combined payment exceed, in the aggregate, the price set out in the cancelled
Estimate. Notwithstanding the foregoing however, residual Raw
Materials with value greater than an Estimate may exist and become the financial
responsibility of Helix due to vendor minimum order quantities and pack sizes of
Raw Materials reasonably demonstrated by CPL. All remaining usable
Raw Materials obtained by CPL for purposes of the cancelled Estimate and paid
for by Helix, shall become the
property
of Helix upon the effective date of Helix’s notice of cancellation and shall be
returned to Helix or otherwise dealt with, at the expense of Helix, as Helix may
direct.
ARTICLE
18 FORCE MAJEURE
|
18.1
|
Effects of Force
Majeure
|
No Party
shall be in breach of this Agreement if there is any failure of performance
under this Agreement (except for payment of any amounts due under this
Agreement) occasioned by any reason beyond the control and without the fault or
negligence of the Party affected thereby, including, without limitation, an act
of God, fire, act of government or state, war, civil commotion, insurrection,
embargo, an infectious virus which cannot be detected by testing and which
causes a shutdown for a substantial period of a large portion of the CPL
Facility due to contamination despite commercially reasonable efforts by CPL to
prevent such occurrence, prevention from or hindrance in obtaining energy or
other utilities, a market-wide shortage of Raw Materials or other necessary
components, labor disputes (excluding any disputes that may arise at CPL) of
whatever nature, or any other reason beyond the control and without the fault or
negligence of the Party affected thereby (a “Force Majeure Event”). Such excuse
shall continue as long as the Force Majeure Event continues, and any estimated
completion date affected by such Force Majeure event shall be extended
accordingly. Upon cessation of such Force Majeure Event, the affected Party
shall promptly resume performance under this Agreement as soon as it is
commercially reasonable for the Party to do so.
|
18.2
|
Notice of Force
Majeure;
Obligations of Parties During Force Majeure
Event
|
Each
Party agrees to give the other Party prompt written notice of the occurrence of
any Force Majeure Event, the nature thereof, and the extent to which the
affected Party will be unable to fully perform its obligations under this
Agreement. Each Party further agrees to use commercially reasonable efforts to
correct the Force Majeure Event as quickly as practicable and to give the other
Party prompt written notice when it is again fully able to perform such
obligations. In the event that the Force Majeure cannot be corrected
quickly, the parties will work together to ensure that the Services will carry
forward to the extent practicable, even if this means transfer of materials to
another facility on a temporary or permanent basis. Any proceeds
received from Business interruption or similar insurance will be applied to this
action.
|
18.3
|
Termination
|
This
Agreement may be terminated as a result of a Force Majeure Event in accordance
with Section 17.1(d)
hereof.
ARTICLE
19 ASSIGNMENT; TRANSFER
|
19.1
|
Assignment
|
This
Agreement shall be binding upon the successors and assigns of the Parties and
the name of a Party appearing herein shall be deemed to include the names of its
successors and assigns. Neither Party may assign its interest under this
Agreement without the prior written consent of the other Party, such consent not
to be unreasonably withheld; provided, however, either Party may assign its
interest under this Agreement, without the prior written consent of the other,
(a) to an Affiliate or (b) to a successor of the business by reason of merger,
sale of all or substantially all of its assets or other form of acquisition. Any
permitted assignment of this Agreement by either Party will be conditioned upon
that Party's permitted assignee agreeing in writing to comply with all the terms
and restrictions contained in this Agreement. Any purported assignment without a
required consent shall be void. No assignment shall relieve any Party of
responsibility for the performance of any obligation that accrued prior to the
effective date of such assignment.
ARTICLE
20 MISCELLANEOUS
|
20.1
|
Notices
|
Any
notice required or permitted to be given under this Agreement by any Party shall
be in writing and shall be (a) delivered personally, (b) sent by registered
mail, return receipt requested, postage prepaid, (c) sent by a
nationally-recognized courier service guaranteeing next-day or second day
delivery, charges prepaid, or (d) delivered by facsimile (with the original
promptly sent by any of the foregoing manners), to the addresses or facsimile
numbers of the other Parties set forth below, or at such other addresses as may
from time to time be furnished by similar notice by any Party. The effective
date of any notice under this Agreement, other than a termination notice
pursuant to ARTICLE
17, shall be the date of receipt by the receiving Party.
0-000
Xxxxxxxxxx Xxxxxxx X.
Xxxxxx,
XX
Xxxxxx,
X0X 0X0
Fax #
(000) 000-0000
CPL
Niagara
000
Xxxxxx Xxxxxx,
Xxxxxxx,
Xxx Xxxx, XXX
00000
Attention:
General Manager
Fax #
(000) 000-0000
With copy
to:
CPL
0000
Xxxxxx Xxxxxxxx,
Xxxxxxxxxxx,
Xxxxxxx, Xxxxxx
X0X
0X0
Attention:
CEO
Fax #
(000) 000-0000
|
20.2
|
Applicable
Law
|
This
Agreement shall be construed, interpreted and enforced in accordance with the
laws in force in the Province of Ontario.
|
20.3
|
20.3 Headings
|
All
headings in this Agreement are for convenience of reference only and shall not
affect the interpretation of this Agreement.
|
20.4
|
Exhibits
|
All
exhibits referred to herein form an integral part of this Agreement and are
incorporated into this Agreement by such reference.
|
20.5
|
Severability
|
Each
Party hereby expressly agrees that:
|
(a)
|
it
has no intention to violate any public policy, statutory or common laws,
rules, regulations, treaty or decision of any government agency or
executive body thereof of any country or community or association of
countries;
|
|
(b)
|
that
if any word, sentence, paragraph, clause or combination thereof in this
Agreement is found by a court or executive body with judicial powers
having jurisdiction over this Agreement or any Party hereto, in a final
unappealed order, to be in violation of any such provisions in any country
or community or association of countries, such words, sentences,
paragraphs, clauses or combination shall be inoperative in such country or
community or association of countries and the remainder of this Agreement
shall remain binding upon the Parties, so long as enforcement of the
remainder does not violate the Parties overall intentions in this
transaction.
|
|
20.6
|
Independent
Contractors
|
Each of
the Parties is an independent contractor and nothing herein contained shall be
deemed to constitute the relationship of partners, joint venturers, nor of
principal and agent between the Parties. Neither Party shall hold itself out to
Third Parties as purporting to act on behalf of, or serving as the agent of, the
other Party.
|
20.7
|
Waiver
|
No waiver
of any term, provision or condition of this Agreement whether by conduct or
otherwise in any one or more instances shall be deemed to be or construed as a
further or continuing waiver of any such term, provision or condition or of any
other term, provision or condition of this Agreement. The
failure of either Party to assert a right hereunder or to insist upon compliance
with any term or condition of this Agreement shall not constitute a waiver of
that right or excuse a similar subsequent failure to perform any such term or
condition by the other Party.
|
20.8
|
Counterparts
|
This
Agreement and any amendment hereto may be executed in any number of
counterparts, each of which shall for all purposes be deemed an original and all
of which shall constitute the same instrument. This Agreement shall be effective
upon full execution by facsimile or original, and a facsimile signature shall be
deemed to be and shall be as effective as an original signature.
|
20.9
|
Entirety;
Amendments
|
This
Agreement, including any exhibits attached hereto and referenced herein,
constitutes the full understanding of the Parties and a complete and exclusive
statement of the terms of their agreement with respect to the specific subject
matter hereof, and no terms, conditions, understandings or agreements purporting
to modify or vary the terms thereof shall be binding unless it is hereafter made
in writing and signed by each of the Parties. No modification to this Agreement
shall be effected by the acknowledgment or acceptance of any purchase order or
shipping instruction forms or similar documents containing terms or conditions
at variance with or in addition to those set forth herein. This Agreement may be
amended and supplemented only by a written instrument signed by each of the
Parties.
|
20.10
|
Preference
|
The terms
of this Agreement shall prevail in the event of a conflict between this
Agreement and any Schedule hereto.
|
20.11
|
Limitation on
Damages
|
Except
for (i) the parties’ obligations under ARTICLE
13 or any breach
of such obligations; or (ii) a breach of the obligations of a party under ARTICLE
15, in no event shall either Party be liable to the
other
Party for incidental, special, punitive, exemplary or consequential damages,
including, but not limited to, any claim for damages based upon lost
profits.
|
20.12
|
Time
|
Time is
of the essence of this Agreement.
20.13 Currency
Unless
otherwise specifically noted herein, all references to dollar amounts in the
Agreement and any attached Schedules and/or Appendices are in U.S.
dollars.
IN
WITNESS WHEREOF, the Parties have caused this Agreement to be executed as of the
Effective Date.
|
CONTRACT
PHARMACEUTICALS LIMITED NIAGARA
|
||||
|
Per:
|
/s/
Xxxx Xxxxxxxx
|
Per:
|
/s/
Xxxx Xxxx
|
|
|
Xxxx
Xxxxxxxx
Director
and President
|
Xxxx
Xxxx
General
Manager, Niagara Operations
|
|||
|
Per:
|
Per:
|
/s/
Xxxx Xxxxxxx
|
||
|
[Name]
[Title]
|
Xxxx
Xxxxxxx
CEO
|
|||
Schedule
A
November
2, 2007
Xxxxxxx
Xxxxx, PhD
PharmaDerm
Laboratories Ltd
#301 111
Research Dr.
Innovation
Xxxxx Xxxxxxxx Xxxx
Xxxxxxxxx,
XX Xxxxxx X0X 0X0
306-934-7471
ext. 230
Estimate
#0542 to 0542-7 Rev-1a (Bulk Capital Equipment)
Interferon
alpha 2B Cream
(Supercedes
#542 to 0542-7Rev-1 Dated 10/26/2007)
Dear
Praveen,
Thank you
for allowing CPL the opportunity to provide a price estimate for PharmaDerm’s
Interferon alpha 2-B Cervical Cancer Cream.
Considering
the bulk manufacturing equipment needs, including the MMU or equivalent tank,
the chiller system and the Microfluidizer are to be finalized we have listed
these items in the capital section below but have omitted costs. We will re-vise
the capital costs upon completion of the design specifications.
We have
carefully considered the requirements necessary to meet your expectations and
submit the following responses and price estimates below.
Pre-Commercial
Price Estimate # 0542 to 0542-7
|
|
1.
|
Small
Scale Developmental Batch (Placebo)
|
|
Estimate
#
|
Description
|
Price
|
|
0542
|
Manufacture
and package one (1) 120 kg
developmental
placebo batch (without active)
|
***
|
Price
Assumptions/Conditions:
|
1.
|
Placebo
batch size is 120 kg.
|
|
2.
|
Cost
includes excipient raw material, applicator and foil lined
pouch.
|
|
3.
|
Raw
materials will be tested by COA.
|
|
4.
|
All
bulk and finished goods analytical testing to be conducted by PharmaDerm
Labs Ltd.
|
|
5.
|
Limited
bulk testing to include physicals for one sample per location from
top-middle-bottom of bulk batch. (See item 4
above)
|
|
6.
|
Includes
packaging product into approximately 5,000 vaginal applicators and pouches
for packaging equipment
qualification.
|
|
7.
|
Limited
packaged testing to include physicals for one sample per location from
beginning-middle-end of packaging run. (See item 4
above)
|
|
8.
|
Includes
labor for manufacturing, packaging and related
activities.
|
|
9.
|
Includes
residual product disposal costs.
|
|
10.
|
Product
not intended for commercial
distribution.
|
|
|
2.
|
Small
Scale Clinical Batch (Placebo)
|
|
Estimate
#
|
Description
|
Price
|
|
0542
– 1
|
Manufacture
and package one (1) 120 kg clinical placebo batch (without
active)
|
***
|
Price
Assumptions/Conditions:
|
1.
|
Placebo
batch size is 120 kg.
|
|
2.
|
Cost
includes excipient raw material, applicator, foil lined pouch and
miscellaneous corrugate packaging
components.
|
|
3.
|
Clinical
labeling of product not included.
|
|
4.
|
Includes
full testing of excipient raw materials based on compendial
methods.
|
|
5.
|
All
bulk and finished goods analytical testing to be conducted by PharmaDerm
Labs Ltd.
|
|
6.
|
Limited
bulk testing to include physicals for one sample per location from
top-middle-bottom of bulk batch. (See item 5
above)
|
|
7.
|
Includes
packaging product into approximately 25,000 vaginal applicators and
pouches for clinical supply
studies.
|
|
8.
|
Limited
packaged testing to include physicals for one sample per location from
beginning-middle-end of packaging run. (See item 5
above)
|
|
9.
|
Includes
labor for manufacturing, packaging and related
activities.
|
|
10.
|
Includes
residual product disposal costs.
|
|
11.
|
Product
not intended for commercial
distribution.
|
|
12.
|
Does
not include stability testing.
|
|
|
3.
|
Small
Scale Clinical Batch (Active)
|
|
Estimate
#
|
Description
|
Price
|
|
0542
- 2
|
Manufacture
and package one (1) 120 kg batch (with active Interferon alpha
2-B)
|
***
|
Price
Assumptions/Conditions:
|
1.
|
Active
batch size is 120 kg.
|
|
2.
|
Cost
includes excipient raw material, applicator, foil lined pouch and
miscellaneous corrugate packaging
components.
|
|
3.
|
Clinical
labeling of product not included.
|
|
4.
|
Includes
full testing of excipient raw materials based on compendial
methods.
|
|
5.
|
All
bulk and finished goods analytical testing to be conducted by PharmaDerm
Labs Ltd.
|
|
6.
|
Approved
API will be provided at not cost to CPL by PharmaDerm Labs
Ltd.
|
|
7.
|
Limited
bulk testing to include physicals for one sample per location from
top-middle-bottom of bulk batch. (See item 5
above)
|
|
8.
|
Includes
packaging product into approximately 25,000 vaginal applicators and
pouches for clinical supply
studies.
|
|
9.
|
Limited
packaged testing to include physicals for one sample per location from
beginning-middle-end of packaging run. (See item 5
above)
|
|
10.
|
Includes
labor for manufacturing, packaging and related
activities.
|
|
11.
|
Product
not intended for commercial
distribution.
|
|
12.
|
Does
not include stability testing.
|
|
|
4.
|
Stand
Alone Independent Active Batch
|
|
Estimate
#
|
Description
|
Price
|
|
0542
– 3
|
Manufacture
and package one (1) 120 kg batch (with active Interferon alpha
2-B)
|
***
|
Price
Assumptions/Conditions:
|
1.
|
PharmaDerm
RFQ indicates that multiple batches will be required throughout the course
of the pre-commercial phases. This particular estimate is based on
manufacturing and packaging one (1) stand alone batch with active with no
cost sharing with any previous or subsequent batches. This estimate model
has been selected since timing between batches is unknown and thus raw
material may exceed expiration
dates.
|
|
2.
|
Active
batch size is 120 kg.
|
|
3.
|
Cost
includes excipient raw material, applicator, foil lined pouch and
miscellaneous corrugate packaging
components.
|
|
4.
|
Clinical
labeling of product not included.
|
|
5.
|
Includes
full testing of excipient raw materials based on compendial
methods.
|
|
6.
|
All
bulk and finished goods analytical testing to be conducted by PharmaDerm
Labs Ltd.
|
|
7.
|
Approved
API will be provided at no cost to CPL by PharmaDerm Labs
Ltd.
|
|
8.
|
Includes
packaging product into approximately 25,000 vaginal applicators and
pouches for additional studies.
|
|
9.
|
Includes
labor for manufacturing and packaging
activities.
|
|
10.
|
Product
not intended for commercial
distribution.
|
|
11.
|
Does
not include stability testing.
|
|
|
5.
|
Cleaning
Validation
|
|
Estimate
|
Description
|
Pricing
|
|
0542
– 4
|
Cleaning
Validation For Bulk and Packaging
|
***
|
|
Total
|
***
|
Cleaning
Validation Cost Assumption/Conditions:
1. Activities,
associated with developing the cleaning protocol: Identify
equipment train,
review
detergent and
germicide data, calculate ARL, create data collection sheets
(DCS),
write
protocol
etc.
2. Activities
associated with obtaining swabs: Swab preparation, obtaining swabs
from
equipment
train
etc.
3. Activities
associated with writing the final report. Review DCS, write
report.
4. Includes
execution of required visual, micro and TOC testing.
5. Analytical
testing of swabs for active will be conducted by PharmaDerm Labs
Ltd.
|
|
6.
|
Capital
Requirements
|
|
Estimate
#
|
Description
|
Pricing
Estimate
|
|
0542
– 5
|
Packaging
Line Equipment
|
***
|
|
0542
– 6
|
Raw
Material, Bulk and Packaged Product
Storage
Preparation
|
***
|
|
0542
– 7
|
Bulk
Equipment and Support
|
***
|
|
Total
|
***
|
Cost
Assumptions/Conditions:
|
|
0542-6:
|
Pre-commercial
Packaging Line Equipment includes filler product contact change parts,
associated filler process piping, applicator transfer pucks and stainless
steel Xxxxxx product transfer
drums.
|
|
|
0542-6:
|
Pre-commercial
Raw Material, Bulk and Package Product Storage Preparation includes
retro-fitting CPL’s existing 2C – 8C Refrigerator and -80C Freezer with
appropriate instrumentation and back-up systems to provide exposure
protection for the drug substance and drug
product.
|
|
|
0542-7:
|
Pre-commercial
Bulk Manufacturing Equipment includes but is not limited to: Bulk mixing
tank, chiller system, heating system and installation and
qualification.
|
**Note: Microfluidizer
for bulk manufacturing will be provided by PharmaDerm.
This
price estimate is valid for 90 days from the date of this letter. We look toward
to serving your needs and building our partnership together.
Please
contact me at your earliest convenience for further discussions at 000-000-0000
(fax 000-000-0000).
Sincerely,
Contract
Pharmaceuticals Limited
Xxxxx
Xxxxxxx Xx.
Manager
New Product Transfer
cc: FILE,
X. Xxxxxxxxx, X. Xxxxx, X. Xxxxxx, X. Xxxxxx, X. Xxxxxx, X. Xxxxxx, X.
Xxxx
Schedule
B
QUALITY
ASSURANCE AGREEMENT
Overview
This
Quality Assurance Agreement is between Contract Pharmaceuticals Limited
Niagara (hereinafter referred to as “CPL”) located at 000 Xxxxxx Xxxxxx,
Xxxxxxx, Xxx Xxxx, 00000 and PharmaDerm Laboratories
Limited (hereinafter referred to as “PDL”), located at #301 – 111
Research Drive, Innovation Place Research Park, Saskatoon, SK, Canada, S7N3R2,
as agent for Helix BioPharma Corp., (“Helix”) #3 - 000 Xxxxxxxxxx Xxxxxxx Xxxxx,
Xxxxxx, Xxxxxxx X0X 0X0.
This
Quality Assurance Agreement sets out certain responsibilities of the parties
relating to the manufacturing, packaging, testing, and supply of the products
listed in Appendix I. This document has been drawn up according to
cGMP regulations and will apply to product manufactured for Helix pursuant to
the Topical Interferon Alpha-2b GMP Process Development, Scale Up and Clinical
Supplies Manufacturing Agreement dated the date hereof between CPL and Helix
(the “Manufacturing Agreement”), to which this Quality Assurance Agreement is
being attached as Schedule “B”. All terms used in this Quality
Assurance Agreement which are defined in the Manufacturing Agreement shall have
the meanings ascribed in the Manufacturing Agreement.
Confidentiality
Without
limiting the generality of any confidentiality agreement(s) in effect between
the parties, each party agrees to hold all information furnished, disclosed or
made known to either of them or their respective representatives by the other
party or by the examination of the records of the other or otherwise obtained,
whether such information is furnished, disclosed or made known orally, in
writing or by any other means whatsoever, confidential and shall not disclose,
or permit disclosure of such information. Each party agrees that it
has no right, title or interest whatsoever in or to the confidential information
of the other and that no right or license in such confidential information is
implied or granted.
Duration of
Agreement
This
Agreement shall commence upon the execution and delivery hereof by the parties
and will terminate at such time as the Manufacturing Agreement is
terminated.
Revisions to
Agreement
No
amendment to the terms of this Agreement shall be binding on the parties hereto
unless made in writing and signed by an authorized representative of each of the
parties.
Communication
The
parties have identified and listed in Appendix II a list of personnel
responsible for the administration of this Agreement. Personnel may
be added or deleted to Appendix II upon written notice to the other
party.
Standard
Responsibilities
CPL
specifications (raw materials, packaging, bulk product, finished product, etc.)
prepared by CPL shall not be effective until approved by PDL.
CPL may
only release materials (raw, packaging, bulk product, finished product,
etc.):
(a) if
the materials meet CPL specifications approved by PDL; and
(b) after
PDL has confirmed that any testing to be done by it is complete and
satisfactory.
|
AREA OF RESPONSIBILITY
|
CPL
|
PDL
|
|
Raw
Materials:
|
||
|
· Establish
& approve specifications (grade, testing parameters, acceptance
criteria)
|
X
|
|
|
· Prepare
CPL raw material specifications (grade, testing parameters, acceptance
criteria) based on PDL requirements
|
X
|
|
|
· Vendor
Selection
|
X
|
X
|
|
· Vendor
Approval
|
X
|
|
|
· Procurement
of excipient raw materials (inactive ingredients)
|
X
|
|
|
· Procurement
of active raw materials
|
X
|
|
|
· Inspection,
testing documents, testing & release/rejection of excipients (inactive
ingredients). (See Appendix III)
|
X
|
|
|
· Inspection,
testing documents, testing & release/rejection of active (See Appendix
III)
|
X
|
X
|
|
· Retention
of excipient raw material samples
|
X
|
|
|
· Retention
of active raw material samples
|
X
|
|
|
Lab
Testing:
|
||
|
· Selection
of lab for testing of raw materials, bulk product & finished
product
|
X
|
X
|
|
· Approval
of Lab
|
X
|
|
|
· Test
method transfer execution – raw materials, bulk & finished product
analytical methodology
|
X
|
X
|
|
· Review
& approve test method transfer data for unique raw materials, bulk
& finished product
|
X
|
|
|
Stability:
|
||
|
· Overall
responsibility for ensuring stability programs comply with applicable
regulatory guidance & product filings. Including the
suitability of the expiry period to the formulation and packaging
system
|
X
|
| AREA OF RESPONSIBILITY |
CPL
|
PDL
|
|
· Generate
stability protocol
|
X
|
|
|
· Approve
stability protocol
|
X
|
X
|
|
· Execute
stability protocol
|
X
|
X
|
|
· Review
stability results
|
X
|
|
|
· Trend
stability data
|
X
|
|
|
Packaging
Materials:
|
||
|
· Artwork
development, review, approval & distribution
|
X
|
|
|
· Establish
& approve specifications (testing parameters, acceptance
criteria)
|
X
|
|
|
· Prepare
CPL packaging materials specifications (testing parameters, acceptance
criteria) based on PDL requirements
|
X
|
|
|
· Vendor
Selection
|
X
|
X
|
|
· Vendor
Approval
|
X
|
|
|
· Packaging
materials procurement
|
X
|
|
|
· Inspection,
inspection documents, testing & release/rejection of packaging
materials
|
X
|
|
|
Manufacturing:
|
||
|
Master
Formula
|
X
|
|
|
Master
manufacturing work order preparation
|
X
|
|
|
Master
manufacturing work order approval
|
X
|
X
|
|
Manufacturing
of bulk products per approved product Master Formula and
procedures
|
X
|
|
|
Control,
review and communicate minor deviation to PDL
|
X
|
|
|
Control,
review & approve major process deviations
|
X
|
X
|
|
Establish
& approve bulk product specifications (testing parameters, acceptance
criteria)
|
X
|
|
|
Prepare
CPL bulk product specifications (grade, testing parameters, acceptance
criteria) based on PDL requirements
|
X
|
|
|
Bulk
product test method validation
|
X
|
|
|
Provide
bulk product sampling plan
|
X
|
|
|
Bulk
product sampling
|
X
|
|
|
Bulk
product testing as per approved specification (See Appendix
III)
|
X
|
X
|
|
Review
of manufacturing batch documents
|
X
|
X
|
|
Release/rejection
of bulk product for filling and packaging at CPL
|
X
|
|
|
Packaging:
|
||
|
Master
Packaging Formula / Procedure
|
X
|
|
|
Master
packaging work order preparation
|
X
|
|
|
Master
packaging work order approval
|
X
|
X
|
|
Allocation
method of lot number of the products
|
X
|
| AREA OF RESPONSIBILITY |
CPL
|
PDL
|
|
Allocation
method of expiry date of the products
|
X
|
|
|
Filling
and packaging of released bulk products per approved packaging work
orders
|
X
|
|
|
Packaging
in-process line inspection and sampling
|
X
|
|
|
Establish
& approve finished product specifications (testing parameters,
acceptance criteria)
|
X
|
|
|
Prepare
CPL finished product specifications (grade, testing parameters, acceptance
criteria) based on PDL requirements
|
X
|
|
|
Finished
product test method validation
|
X
|
|
|
Provide
finished product sampling plan
|
X
|
|
|
Finished
product sampling
|
X
|
|
|
Finished
product testing as per approved specification (See Appendix
III)
|
X
|
X
|
|
Review
of packaging batch documents
|
X
|
X
|
|
Preparation
of Certificate of cGMP Compliance
|
X
|
|
|
Release
of finished product for clinical packaging
|
X
|
|
|
Control,
review and communicate minor deviation to PDL
|
X
|
|
|
Control,
review & approve major process deviations
|
X
|
X
|
|
Validation:
|
||
|
Premises
validation
|
X
|
|
|
Equipment
validation
|
X
|
|
|
Preparation
and approval of cleaning procedures
|
X
|
|
|
Cleaning
validation – residual detergent
|
X
|
|
|
Cleaning
validation – residual API (CPL swab, PDL test)
|
X
|
X
|
|
Test Method Validation:
overall responsibility for ensuring the test method validation complies
with applicable regulatory guidance & product filing as the product
registration holder
|
X
|
|
|
Protocal
development
|
X
|
|
|
Protocol
approval
|
X
|
X
|
|
Execution
of strategy & sampling plan & testing (See App.
III)
|
X
|
X
|
|
Summary
report development
|
X
|
|
|
Summary
report approval
|
X
|
X
|
|
Manufacturing process
validation: overall responsibility for ensuring the validation
program complies with applicable regulatory guidance & product filings
as the product registration holder
|
X
|
|
|
· Protocol
development
|
X
|
|
|
· Protocol
approval
|
X
|
X
|
|
· Execution
of strategy & sampling plan
|
X
|
X
|
|
· Summary
report development
|
X
|
|
|
· Summary
report approval
|
X
|
X
|
|
Packaging process
validation: overall responsibility for ensuring the validation
program complies with applicable regulatory guidance & product filings
as the product registration holder
|
X
|
| AREA OF RESPONSIBILITY |
CPL
|
PDL
|
|
· Protocol
development
|
X
|
|
|
· Protocol
approval
|
X
|
X
|
|
· Execution
of strategy & sampling plan
|
X
|
|
|
· Summary
report development
|
X
|
|
|
· Summary
report approval
|
X
|
X
|
|
Shipping:
|
||
|
Notification
of special storage conditions for intermediate materials and/or finished
product (Shipping specifications and instructions)
|
X
|
|
|
Release/rejection
of finished goods for shipping to sponsor/customer
|
X
|
X
|
|
Selection
of carrier for shipping and shipping conditions
|
X
|
|
|
Preparation
of shipping documents
|
X
|
|
|
Arrangement
of shipping details (e.g. pick up)
|
X
|
|
|
Transmittal
of complete production batch documents
|
X
|
|
|
OOS
Investigations (Bulk/FP/Stability):
|
||
|
Out
of specification investigation – phase I (to be conducted exclusively by
the lab performing the applicable testing – See Appendix
III)
|
X
|
|
|
Out
of specification investigation – phase II (re-sampling /
re-testing)
|
X
|
X
|
|
Out
of specification approval / rejection
|
X
|
|
|
Clinical
Product Release & Recall:
|
||
|
Release
of finished product for clinical distribution
|
X
|
|
|
Product
Recall
|
X
|
|
|
Participate
in product recall investigations
|
X
|
X
|
|
Retains:
|
||
|
Retention
of regulatory retain finished product samples
|
X
|
|
|
Retention
of finished product samples for investigational purposes
|
X
|
|
|
Retention
of batch documents for at least 12 months after the expiry
date. Notify PDL prior to destruction of batch
documents.
|
X
|
|
|
Investigation
of clinical complaints with respect to the following:
|
||
|
· Manufacturing
|
X
|
X
|
|
· Packaging
|
X
|
X
|
|
· Testing,
documentation and results
|
X
|
X
|
|
· Effectiveness
of Product
|
X
|
|
|
· Adverse
effects
|
X
|
|
|
· Reply
to complainant
|
X
|
|
|
Change
Control:
|
||
|
Notification
of all changes to product & process (e.g. changes in raw/packaging
materials, manufacturing processes, test methods, etc.)
|
X
|
X
|
|
Update
of relevant documents affected by changes
|
X
|
X
|
|
Audits:
|
||
|
Audit
of CPL facilities
|
X
|
X
|
Approval
Signatures
On behalf
of Contract Pharmaceuticals
Limited Niagara and PharmaDerm Laboratories Limited,
we agree to the conditions and relative responsibilities as set out in
the above document.
/s/ Xxxxx
XxXxxxxxxx
March 27,
2008
CONTRACT PHARMACEUTICALS LIMITED
NIAGARA
Date
Xxxxx
XxXxxxxxxx
Vice
President, Quality
/s/ Xxxx
Xxxx March 27,
2008
CONTRACT PHARMACEUTICALS LIMITED
NIAGARA
Date
Xxxx
Xxxx
General
Manager, Niagara Operations
/s/ Xxxx
Xxxxxxxx March 20,
2008
PHARMADERM LABORATORIES
LIMITED Date
Xxxx
Xxxxxxxx
President
___________________________________
PHARMADERM LABORATORIES
LIMITED Date
Appendix
I
PRODUCT
LIST
PHARMADERM LABORATORIES
LIMITED
PRODUCT
CODE PRODUCT
NAME
|
TBD
|
Interferon
Alpha 2-b Cream
|
|
TBD
|
Placebo
for Interferon Alpha 2-b Cream
|
Appendix
II
CONTACT
LIST
|
CPL
NIAGARA
|
PDL
|
|
Xxxxxxx
Xxxxx
Manager,
Quality Assurance
T]
(000) 000-0000
F]
(000) 000-0000
E] xxxxxx@xxxxxx.xxx
|
Xxxxxxx
Xxxxx
V.P.
& Head of Product Development
T]
(000) 000 0000 xxx 000
F]
(000) 000 0000
E]
xxxxxx@xxxxxxxxxxxxxx.xxx
|
|
Xxxx
XxXxxxxxx
Associate
Manager, Product Quality
T]
(000) 000-0000
F]
(000) 000-0000
E] xxxxxxxxxx@xxxxxx.xxx
|
Xxx
Xxxxxx
Manager,
Quality Assurance
T]
(000) 000 0000 xxx 000
F]
(000) 000 0000
E]
xxxxxxx@xxxxxxxxxxxxxx.xxx
|
|
Xxxxx
Xxxxxx
Manager,
Quality Technical Services
T]
(000) 000-0000
F]
(000) 000-0000
E] xxxxxxx@xxxxxx.xxx
|
Geriene
XxXxxx
Quality
Control-in-charge & Group Leader, Analytical
T]
(000) 000 0000 xxx 000
F]
(000) 000 0000
E]
xxxxxxx@xxxxxxxxxxxxxx.xxx
|
|
Xxxxxxx
Xxxxxx
Senior
Manager, Lab Operations
T]
(000) 000-0000
F]
(000) 000-0000
E] xxxxxxx@xxxxxx.xxx
|
Xxxxxxxxxxx
Xxxxx
Stability
coordinator & Group Leader,
Product
Development
T]
(000) 000 0000 xxx 000
F]
(000) 000 0000
E]
xxxxxx@xxxxxxxxxxxxxx.xxx
|
|
Xxx
Xxxxxx
Director,
Customer Service, Purchasing & New Product Transfer
T]
(000) 000-0000
F]
(000) 000-0000
E] xxxxxxx@xxxxxx.xxx
|
Appendix
III
|
Ingredient
|
Grade
|
Testing
Requirements
|
Notes
|
|
***
|
COA
review only (CPL)
|
Helix
will provide
API
pre-approved
|
|
|
***
|
USP/NF
|
COA
review & ID only (CPL)
or
full monograph as
appropriate
|
New
raw material
|
|
***
|
NF
|
COA
review & ID only (CPL)
|
Existing
material
@
CPL
|
|
***
|
NF
|
COA
review & ID only (CPL)
|
Existing
material
@
CPL
|
|
***
|
NF
|
COA
review & ID only (CPL)
|
Existing
material
@
CPL
|
|
***
|
USP
|
COA
review & ID only (CPL)
or
full monograph as
appropriate
|
New
raw material
|
|
***
|
USP
|
COA
review & ID only (CPL)
|
Existing
material
@
CPL
|
|
***
|
COA
review & ID only (CPL)
or
full monograph as
appropriate
|
New
raw material
|
|
|
***
|
USP
|
USP
|
CPL
USP Water
|
|
***
|
NF
|
COA
review & ID only (CPL)
or
full monograph as
appropriate
|
New
raw material
|
|
***
|
EP
|
COA
review & ID only (CPL)
|
Existing
material
@
CPL
|
|
***
|
NF
|
COA
review & ID only (CPL)
|
Existing
material
@
CPL
|
|
***
|
NF
|
COA
review & ID only (CPL)
|
Existing
material
@
CPL
|
|
***
|
COA
review & ID only (CPL)
or
full monograph as
appropriate
|
New
raw material
|
|
|
***
|
NF
|
COA
review & ID only (CPL)
or
full monograph as
appropriate
|
New
raw material
|
|
***
|
USP
|
COA
review & ID only (CPL)
|
Existing
material
@
CPL
|
|
***
|
USP
|
COA
review & ID only (CPL)
or
full monograph as
appropriate
|
New
raw material
|
|
***
|
NF
|
COA
review & ID only (CPL)
|
Existing
material
@
CPL
|
|
Test
Parameter
|
Testing
responsibility
|
Notes
|
|
|
***
|
n/a
|
Primary
– Helix
Secondary
– CPL
|
Primary
testing will
be
performed by
|
|
Helix.
CPL may be asked to perform limited physical testing
|
|||
|
***
|
n/a
|
Primary
– Helix
Secondary
– CPL
|
Primary
testing will
be
performed by
Helix. CPL
may be asked to perform limited physical testing.
|
|
***
|
n/a
|
To
Be Determined
|
|
|
Component
|
Test
Responsibility
|
Notes
|
|
|
***
|
n/a
|
CPL
– COA & Spec
|
|
|
***
|
n/a
|
CPL
– COA & Spec
|
Schedule
C – Estimated Timelines
|
Activity
(Task)
|
Start
|
Completion
|
|
Initial
Kick-Off Team Meeting and Process Design Discussions
|
***
|
***
|
|
Tank
Drawing and Specification
|
***
|
***
|
|
Tank
Drawing Review, Comment and Revise
|
***
|
***
|
|
Tank
Drawings Approved
|
***
|
***
|
|
Tank
Fabrication Process
|
***
|
***
|
|
Tank
Delivery To CPL
|
***
|
***
|
|
Uncrate
and Install
|
***
|
***
|
|
IQOQPQ
and DOE Placebo Batch
|
***
|
***
|
|
1st
Placebo
Manufacturing Batch and Analytical Testing
|
***
|
***
|
|
1st
Placebo Packaging
Operation and Analytical Testing
|
***
|
***
|
|
1st
Active
Manufacturing Batch and Analytical Testing
|
***
|
***
|
|
1st
Active Packaging
Operation and Analytical Testing
|
***
|
***
|
|
Stability
Starts – Ends
|
***
|
***
|
The above
is a partial list of activities (critical path) that illustrate a tentative
timeline. There are additional pieces of equipment that would be required to
support this timeline and activities.
The
associated lead times of other equipment is assumed to be less than the main mix
tank. A full timeline will be established as the project
progresses.
This list
of additional equipment includes but is not limited to:
|
-
|
Microfluidizer
and associated installation and qualification
tasks.
|
|
-
|
Filler
change parts and drum emptying system and associated installation and
qualification tasks up to and including packaging line
trials.
|
