Exhibit
10.1
Form
8-K
Bio-Path
Holdings, Inc.
File No.
000-53404
Drug Product Development and Clinical Supply Agreement
THIS
AGREEMENT is effective as
of the 24 th
day of June, 2008 (“Effective
Date”).
Bio-Path
Holdings, Inc., a corporation organized and existing under the laws
of the State of Utah, with its principal offices located at 3293
Harrison Blvd., Suite 230, Ogden, UT 84403
(hereinafter referred to as “CLIENT”).
ALTHEA
TECHNOLOGIES, INC. , a
Delaware corporation, with a place of business located at 11040
Roselle Street, San Diego, CA 92121 (hereinafter referred to as
“ALTHEA”);
WHEREAS CLIENT has formulations and/or know-how related
to each Drug Product, as defined below;
WHEREAS ALTHEA has the expertise and the manufacturing
facility suitable for the Production of Drug Product;
WHEREAS , CLIENT wishes to have ALTHEA Produce Drug
Product and ALTHEA wishes to Produce Drug Product for
CLIENT;
NOW,
THEREFORE , in
consideration of the premises and the undertakings, terms,
conditions and covenants set forth below, the parties hereto agree
as follows:
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AFFILIATE of a party hereto shall mean any entity that
controls or is controlled by such party, or is under common control
with such party. For purposes of this definition, an
entity shall be deemed to control another entity if it owns or
controls, directly or indirectly, at least fifty percent (50%) of
the voting equity of another entity (or other comparable interest
for an entity other than a corporation).
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ALTHEA
SOPs shall mean
ALTHEA’S Standard Operating Procedures which shall be deemed
reviewed and approved by CLIENT unless prior to manufacture of
CLIENT’s Drug Product CLIENT’s representative audits
ALTHEA’s SOPS and has modifications deemed necessary for the
manufacture of CLIENT’s Drug Product.
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BATCH shall mean a specific quantity of a Drug Product
comprising a number of units mutually agreed upon between CLIENT
and ALTHEA, and that (a) is intended to have uniform character and
quality within specified limits, and (b) is produced according to a
single manufacturing order during the same cycle of
manufacture.
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BULK DRUG
SUBSTANCE shall mean the
active compound, as set forth in the Project Plan, to be supplied
by CLIENT for use in Production of Drug Product.
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cGMP shall mean current Good Manufacturing Practices
as defined in the FDA rules and regulations, 21 CFR Parts
210-211.
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CANCELLATION
FEES shall mean the fees
payable by CLIENT in the event that CLIENT cancels the Production
of any Batch of Drug Product set forth in the Project Plan, except
in the event of a default by ALTHEA as set forth in Section
3.3.
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COMPONENTS shall mean all Components used by ALTHEA in
Production of Drug Product under this
Agreement. Components are listed in the Project
Plan, such Components identified as Components supplied by CLIENT
(“CLIENT Supplied Components”) and Components supplied
by ALTHEA (“ALTHEA Supplied Components”).
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CONFIDENTIAL
INFORMATION shall mean
all information and data provided by one party to the other party
except any portion of such information and data which:
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is known to the
recipient as evidenced by its written records before receipt
thereof from the disclosing party;
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is disclosed to
the recipient by a third person who has the right to make such
disclosure;
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is or becomes
part of the public domain through no fault of the recipient;
or
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the recipient
can reasonably establish has been independently developed by
recipient without use of the information disclosed by the
disclosing party.
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DEVELOPMENT shall mean studies conducted by ALTHEA to
develop a process to Produce Drug Product, in accordance with the
Specifications and cGMP. Development activities shall be
identified in the Project Plan.
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DRUG
PRODUCT shall mean each
pharmaceutical product set forth in a development & regulatory
Plan, if applicable, and a Project Plan to be Produced by ALTHEA in
bulk or finished dosage form for development and/or clinical use
only.
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FDA shall mean the United States Food and Drug
Administration or any successor entity thereto.
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FD&C
ACT shall mean the United
States Federal Food, Drug and Cosmetic Act, as may be amended from
time to time.
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IND shall mean an Investigational New Drug
Application for Drug Product, as defined in the United States Food
and Drug Administration (FDA) rules and regulations, 21
CFR.
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LABELING shall mean all labels and other written,
printed, or graphic matter upon: (i) Drug Product or any container,
carton, or wrapper utilized with Drug Product or (ii) any written
material accompanying Drug Product.
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MASTER BATCH
RECORD (MBR) shall mean
the formal set of instructions for Production of Drug
Product. The MBR shall be developed and maintained in
ALTHEA’s standard format by ALTHEA, using CLIENT’s
master formula and technical support.
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PRODUCTION
or PRODUCE shall mean the
formulation, filling, packaging, inspection, labeling, and testing
of Drug Product by ALTHEA.
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PRODUCT
SPECIFICATION SHEET shall
mean a listing of the analytical testing and corresponding
Specifications, to be performed on the Bulk Drug Substance and Drug
Product in connection with the stability program.
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PROJECT
PLAN shall mean the
document containing the parameters for Production of Drug Product
which shall be developed by ALTHEA and agreed to in writing by
CLIENT for each Drug Product under this Agreement. Prior
to commencing Production of any Drug Product, ALTHEA shall deliver
two (2) signed originals of the Project Plan to
CLIENT. CLIENT shall sign both originals of the Project
Plan and return one (1) fully executed original to
ALTHEA. Each fully executed Project Plan shall be
incorporated herein by reference and made a part of this
Agreement. ALTHEA shall have no obligation for
Production of a Drug Product until CLIENT has executed and returned
the Project Plan for such Drug Product to ALTHEA.
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PURCHASE
PRICE shall mean the
amount to be paid by CLIENT as specified in each Project
Plan.
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REGULATORY
AUTHORITY shall mean
those agencies or authorities responsible for regulation of Drug
Product in the United States and overseas. ALTHEA shall
have no obligation to Produce Drug Product in compliance with the
requirements of a Regulatory Authority not specified in the
applicable Project Plan.
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RELEASED
EXECUTED BATCH RECORD shall mean the completed batch record and
associated deviation reports, investigation reports, and
Certificates of Analysis created for each Batch of Drug
Product.
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SPECIFICATIONS shall mean those specifications set forth in
Product Specification Sheet and the Master Batch Record for Drug
Product, and to the extent that ALTHEA is required to test the Bulk
Drug Substance, for the Bulk Drug Substance.
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Article 2,
DEVELOPMENT AND PRODUCTION OF DRUG PRODUCT.
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Initiation: Upon execution of this Agreement and
the corresponding Project Plan for each Drug Product, ALTHEA shall
commence Development of such Drug Product pursuant to the timeline
set forth in the Project Plan. Upon execution of this
Agreement and the corresponding Project Plan for each Drug Product,
ALTHEA shall commence Production of such Drug Product pursuant to
the Project Plan. ALTHEA shall diligently perform the
work necessary to complete the Development and Production of such
Drug Product in accordance with the Project Plan.
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Documentation: The Master Batch Record shall be
reviewed and approved by ALTHEA and by CLIENT prior to commencement
of Production. Any material change to an approved Master
Batch Record will be reviewed and approved by ALTHEA and by CLIENT
prior to said change being implemented. Each Batch of
Drug Product shall be Produced by using a copy of the Master Batch
Record. Each copy of the Master Batch Record for such
Batch of Drug Product shall be assigned a unique batch
number. Any deviation from the manufacturing process
specified in the Master Batch Record must be documented in the copy
of the Master Batch Record for that Batch. ALTHEA shall
provide CLIENT with required supporting Development and Production
documentation in a form reasonably suitable for CLIENT's submission
to the FDA.
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Bulk Drug
Substance and Components Supply:
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2.3.1 CLIENT
Responsibilities: CLIENT,
at its sole cost and expense (including, without limitation,
shipping costs), shall supply to ALTHEA, in a timely manner, (a)
all Bulk Drug Substance required to satisfy the terms of this
Agreement and (b) all other CLIENT Supplied Components, all to be
delivered to ALTHEA as set forth in the applicable Project Plan for
Production of such Drug Product. Except as may
specifically be set forth in the Project Plan, on receipt of the
Bulk Drug Substance and CLIENT Supplied Components as set forth
above, ALTHEA’s sole obligation with respect to evaluation of
the Bulk Drug Substance and CLIENT Supplied Components shall be to
review the accompanying certificate of analysis to confirm that the
Bulk Drug Substance and CLIENT Supplied Components (if applicable)
conform with the Specifications and component specifications,
respectively.
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2.3.2 ALTHEA
Responsibilities: ALTHEA,
at its sole cost and expense (including, without limitation,
shipping costs), shall supply, in a timely manner, all ALTHEA
Supplied Components as set forth in the applicable Project Plan for
Production of such Drug Product.
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Bulk Drug
Substance and Component Delivery Delays : ALTHEA shall have no responsibility
for delays in delivery of Drug Product caused by delays in receipt
of Bulk Drug Substance or CLIENT Supplied Components.
Notwithstanding anything in this Agreement to the contrary, in the
event that ALTHEA receives the Bulk Drug Substance for Production
of Drug Product from CLIENT with less time than requested in the
applicable Project Plan prior to the scheduled date of Production
of such Drug Product, but within sufficient time to Produce such
Drug Product on such scheduled date as determined by ALTHEA in its
sole discretion, ALTHEA shall Produce such Drug Product as per the
original schedule. Notwithstanding anything in this
Agreement to the contrary, in the event that ALTHEA receives the
Bulk Drug Substance for Production of Drug Product from CLIENT with
less time than requested in the applicable Project Plan prior to
the scheduled date of Production of such Drug Product, and without
sufficient time to Produce such Drug Product on the scheduled date
as determined by ALTHEA in its sole discretion, ALTHEA shall
reschedule Production of such Drug Product and shall charge CLIENT
the applicable Cancellation Fee, provided, however, in the event
CLIENT has provided notice to ALTHEA a minimum of forty five (45)
days prior to the date scheduled for Production that delivery of
the Bulk Drug Substance to Althea will be delayed, Althea shall
reschedule the date for Production based on the new date for
delivery of the drug substance and no fees will be owed by
CLIENT.
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Importer of
Record: In
the event any material or equipment to be supplied by CLIENT,
including without limitation CLIENT Supplied Components and Bulk
Drug Substance, is imported into the United States for delivery to
ALTHEA ("Imported Goods"), CLIENT shall be the “Importer of
Record” of such Imported Goods. As the
Importer of Record, CLIENT shall be responsible for all aspects of
the Imported Goods including, without limitation (a) customs and
other regulatory clearance of Imported Goods, (b) payment of all
tariffs, duties, customs, fees, expenses and charges payable in
connection with the importation and delivery of the Imported Goods,
and (c) keeping all records, documents, correspondence and tracking
information required by applicable laws, rules and regulations
arising out of or in connection with the importation or delivery of
the Imported Goods.
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Material
Safety Data Sheet : CLIENT shall provide ALTHEA a
Material Safety Data Sheet for Bulk Drug Substance and for each
Drug Product. ALTHEA shall immediately notify CLIENT of
any unusual health or environmental occurrence relating to Drug
Product, including, but not limited to any claim or complaint by
any employee of ALTHEA or any of its Affiliates or third party that
the operations of ALTHEA pursuant to this Agreement have resulted
in any adverse health or safety effect on an employee or third
party. ALTHEA agrees to advise CLIENT immediately of any
safety or toxicity problems of which it becomes aware regarding the
Drug Product.
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Vendor and
Supplier Audit and Certification : CLIENT shall certify and audit all
Drug Product- related vendors and suppliers, or approve
ALTHEA’S selection of vendors and suppliers by way of signing
this agreement.
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ALTHEA
Progress Reports : ALTHEA shall provide CLIENT
with at least monthly written Microsoft Project reports on the
progress of the Development and Production of a Drug Product,
comparing actual accomplishments to the objectives set forth in the
applicable Project Plan..
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Delivery
Terms: ALTHEA
shall ship all Drug Product to CLIENT or to CLIENT's designated
consignee. All shipments shall be shipped FOB ALTHEA, by
a common carrier designated by CLIENT, at CLIENT’s expense;
provided, however, ALTHEA shall be responsible for the loading of
the Drug Product on departure and shall bear risk of loss and all
costs of such loading. CLIENT shall procure, at its cost, insurance
covering damage or loss of Drug Product during
shipping. All shipping instructions of CLIENT shall be
accompanied by the name and address of the recipient and the
shipping date.
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Exporter of
Record: CLIENT shall be the exporter of record for any
Product shipped out of the United States, as CLIENT remains the
owner of the Product. CLIENT warrants that all shipments
of Product exported from the United States will be
made in compliance with all applicable United States export laws
and regulations and all applicable import laws and regulations into
the country of deportation.
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CLIENT shall be
responsible for obtaining and paying for any licenses or other
governmental authorization(s) necessary for the exportation from
the United States. CLIENT shall select and pay the
freight forwarder who shall solely be CLIENT’s
agent. CLIENT and its freight forwarder shall be solely
responsible for preparing and filing the Shipper’s Export
Declaration and any other documentation required for the
export.
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Foreign
Corrupt Practices Act . CLIENT acknowledges that it is not
the agent of ALTHEA and represents and warrants that it has not,
and covenants that it will not, pay anything of value to any
government employee in connection with the resale of the
Product.
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Deposits and
Payment for Drug Product and Development: Promptly upon execution of each Project Plan,
CLIENT shall pay to ALTHEA forty percent (40%) of the total fees of
this agreement, and thereafter will be invoiced monthly based on
the specific services completed during the month. The
final invoice for the Drug Product will be issued upon the delivery
of released Drug Product to CLIENT by ALTHEA CLIENT shall pay all
invoices within thirty (30) days of the invoice date
therefore. Any payment due under this Agreement not
received within the times noted above shall bear interest at the
lesser of (a) the maximum rate permitted by law, and (b) 1.5% per
month on the outstanding balance compounded monthly.
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Default in
Payment Obligations: In
addition to all other remedies available to ALTHEA in the event of
a CLIENT default, if CLIENT fails to make payments as required
hereunder, ALTHEA may take appropriate measures to assure prompt
and full payment, including refusal to Produce any Drug Product
until CLIENT’s account is paid in full, modify the foregoing
terms of payment, place the account on a letter of credit basis,
require full or partial payment in advance, suspend deliveries of
Drug Product until CLIENT provides assurance of performance
reasonably satisfactory to ALTHEA, and/or take other reasonable
means as ALTHEA may determine.
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Returns: Drug Product returned by third parties is the
responsibility of CLIENT.
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Article 3,
TERM AND TERMINATION.
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Term: This Agreement shall commence on the date first
above written and will continue until the Development and
Production, as described in the Project Plan, have been completed,
unless sooner terminated pursuant to Section 3.2 herein (the
“Term”).
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Termination: This Agreement may be terminated at
any time upon the occurrence of any of the following
events:
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Termination
for Breach: Either party may terminate this Agreement upon
the breach of any provision of this Agreement by the other party if
such breach is not cured by the breaching party within thirty (30)
calendar days (or such additional time not to exceed ninety (90)
days reasonably necessary to cure such default provided the
breaching party has commenced a cure within the thirty (30) day
period and is diligently pursuing completion of such cure) after
receipt by the breaching party of written notice of such
default. At the option of the non-breaching party, such
termination may be with respect to the entire Agreement, or only
with respect to the Drug Product that is subject to the
breach.
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Termination
for Financial Matters : This Agreement may be terminated
immediately by either party by giving the other party written
notice thereof in the event such other party makes a general
assignment for the benefit of its creditors, or proceedings of a
case are commenced in any court of competent jurisdiction by or
against such party seeking (a) such party’s reorganization,
liquidation, dissolution, arrangement or winding up, or the
composition or readjustment of its debts, (b) the appointment of a
receiver or trustee for or over such party’s property,
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(c) similar
relief in respect of such party under any law relating to
bankruptcy, insolvency, reorganization, winding up or composition
or adjustment of debt, and such proceedings shall continue
undismissed, or an order with respect to the foregoing shall be
entered and continue unstated, for a period of more than sixty (60)
days.
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Termination
by Client : This Agreement may be terminated by
CLIENT at any time by giving ALTHEA notice thereof and payment to
ALTHEA of the Cancellation Fee set forth in Section 3.3.
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Payment on
Termination: In the event of the termination of
this Agreement by ALTHEA pursuant to Section 3.2.1, CLIENT shall
reimburse ALTHEA for (a) all Components ordered prior to
termination and not cancelable at no cost to ALTHEA, (b) all
work-in-process commenced by ALTHEA, and (c) all finished Drug
Product. In the event of cancellation by CLIENT of the
Production of any Batch set forth in a Project Plan or in the event
of termination of this Agreement, except for termination in the
event of a default by ALTHEA pursuant to Section 3.2.1, CLIENT
shall pay the Cancellation Fees as hereinafter set
forth: (i) CLIENT is subject to a 20% charge if the
Batch is canceled less than nine (9) weeks from the scheduled fill
date, (ii) a 30% charge if the Batch is canceled less than six (6)
weeks from the scheduled fill date, and (iii) a 50% charge if the
Batch is canceled less than three (3) weeks from the scheduled fill
date. In addition, CLIENT must compensate ALTHEA for any
materials ordered or testing completed. For purposes of
the foregoing, one (1) week is equivalent to seven (7)
days. Following expiration or termination, ALTHEA shall
ship such materials to CLIENT at CLIENT's cost and per CLIENT's
instructions. CLIENT shall make payment for all expenses
described in Section 3.3 thirty (30) days from the invoice
date. In the event of termination by CLIENT for a breach
by ALTHEA pursuant to Section 3.2.1, CLIENT shall not owe any
Cancellation Fees.
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Survival: Termination, expiration,
cancellation or abandonment of this Agreement through any means or
for any reason, except as set forth in Section 12.1, shall be
without prejudice to the rights and remedies of either party with
respect to any antecedent breach of any of the provisions of this
Agreement. The provisions of Sections 3, 6, 9, 10, 11,
12, 13, 14, and 15 hereof shall survive expiration or termination
of this Agreement.
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Article 4,
CERTIFICATES OF ANALYSIS AND MANUFACTURING
COMPLIANCE.
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Certificates
of Analysis: At CLIENT’s cost and expense,
ALTHEA shall test, or cause to be tested by third parties
, in accordance with the Specifications, each
Batch of Drug Product Produced pursuant to this Agreement before
delivery to CLIENT. A certificate of analysis for each
Batch delivered shall set forth the items tested, Specifications,
and test results. ALTHEA shall also indicate on the
final page of the Executed Batch Record that all batch Production
and control records have been reviewed and approved by the
appropriate quality control unit. ALTHEA shall send, or
cause to be sent, such certificates to CLIENT prior to the shipment
of Drug Product (unless Drug Product is shipped under
quarantine). CLIENT shall test, or cause to be tested,
for final release, each Batch of Drug Product as meeting the
Specifications. As required by the FDA (see Section 5.2
below), CLIENT assumes full responsibility for final release of
each Batch of Drug Product.
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Manufacturing Compliance:
ALTHEA shall advise
CLIENT immediately if an authorized agent of any Regulatory
Authority visits ALTHEA's manufacturing facility and makes an
inquiry or inspection regarding ALTHEA's Production of Drug Product
for CLIENT. ALTHEA will also forward to CLIENT any
documents of findings of violations, including but not limited to
FDA Form 483. Manufacturing deviations and
investigations which occur during Production of Drug Product and
which do not cause the Production to be non-compliant with cGMP,
shall not be deemed to cause such Drug Product to be non-conforming
as set forth in Section 5.1.
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Reserve
Samples: CLIENT shall be responsible for
obtaining and maintaining sufficient quantities of Bulk Drug
Substance and Drug Product reserve samples pursuant to
cGMP.
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Annual
Quality Review: CLIENT shall be responsible for
evaluating, at least annually, the quality standards of Drug
Product to determine the need for changes in Specifications,
manufacturing processes, and/or controlled
documents. CLIENT shall supply ALTHEA a copy of the
evaluation and recommendations, if any.
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Distribution
Records: ALTHEA shall maintain distribution
records that contain all of the appropriate information as
specified in cGMP.
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Customer
Complaints: CLIENT, as required by cGMP, shall
maintain complaint files. All specific CLIENT Drug
Product-related complaints received by ALTHEA shall be forwarded to
CLIENT. CLIENT shall be responsible for the review of
the complaint to determine the need for an investigation or the
need to report to the FDA as required by cGMP. CLIENT
shall send to ALTHEA all Drug Product performance or
manufacturing-related complaints which require
investigation. ALTHEA shall conduct an investigation for
each Drug Product performance or manufacturing-related complaint
and shall report findings and follow-up of each investigation to
CLIENT. CLIENT shall make these complaint files
available to ALTHEA in the event they are required during an FDA
inspection.
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Audits: CLIENT, upon prior written notice and during
normal business hours, shall have the right to inspect, once
annually for not more than two (2) days, ALTHEA batch records and
the portions of ALTHEA’s facility used for Production of Drug
Product.&n
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