(Logo of XXXX IMAGING appears here)
A XXXX GROUP COMPANY
000 XXXXX XXXXX XXXX X.X. XXX 0000 XXXXXXXXXXX, XXXXXXX 00000 X.X.X.
PHONE: 000-000-0000 TELEFAX 000-000-0000
Clinical Product Development Agreement
THIS AGREEMENT is effective as of the 3rd day of January, 1997.
BY AND BETWEEN:
ACUTE THERAPEUTICS, INC., a corporation organized and existing under the laws
of Pennsylvania, with its principal offices located at 0000 Xxxxxx Xxxx,
Xxxxxxxxxx, XX 00000 (hereinafter referred to as "CLIENT")
AND:
XXXX IMAGING CORPORATION, a corporation organized under the laws of Indiana,
with its principal place of business located at 000 Xxxxx Xxxxx Xxxx xx
Xxxxxxxxxxx, Xxxxxxx 00000 (hereinafter referred to as "XXXX");
WHEREAS CLIENT is the owner of patents, trademarks, formulations and know-how
related to the pharmaceutical product KL4 Pulmonary Lung Surfactant
(hereinafter referred to as the "Drug Product");
WHEREAS XXXX has the expertise and the manufacturing facility suitable for
the pharmaceutical preparation and production of the Drug Product;
WHEREAS, CLIENT wishes to have XXXX manufacture the Drug Product and XXXX
wishes to supply the Drug Product to CLIENT;
NOW, THEREFORE, in consideration of the premises and the undertakings, terms,
conditions and covenants set forth below, the parties hereto agree as follows:
DEFINITIONS
1.1 DRUG PRODUCT shall mean the pharmaceutical product "KL4 Pulmonary
Lung Surfactant" as described in the Manual in finished dosage form for
clinical use.
1.2 SPECIFICATIONS shall mean those specifications set forth in Attachment
I to the Manual.
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1.3 DEVELOPMENT shall mean all work necessary to develop a process to
manufacture the Drug Product in full accord with cGMP and to supply the Drug
Product conforming to the Specifications set forth in Attachment I to the
Manual. Development activities shall include, but not be limited to, research,
pilot batches, scale-up batches, qualification of Xxxx Quality Control
Laboratories, validation of the manufacturing process, and successful
completion of the Drug Product manufacture and delivery as defined in Schedule
I attached hereto.
1.4 LABELING shall mean all labels and other written, printed, or
graphic matter upon: (i) the Drug Product or any container or wrapper utilized
with the Drug Product or (ii) any written material accompanying the Drug
Product, including without limitation, package inserts.
1.5 IND shall mean an Investigational New Drug Exemption Application
for the Drug Product, as defined in the United States Food and Drug
Administration (FDA) rules and regulations, 21 CFR.
1.6 DMF shall mean Drug Master File, as defined in the FDA rules and
regulations.
1.7 cGMP shall mean current Good Manufacturing Practices as
defined in the FDA rules and regulations, 21 CFR Part 211.
1.8 MANUAL shall mean the Manufacturing Project Manual attached hereto
as Schedule II to this Agreement and reviewed and accepted by CLIENT and XXXX,
the terms and provisions of which are incorporated by reference as though fully
set forth herein.
1.9 BULK DRUG SUBSTANCE shall mean the [***] used as the raw material
in the Drug Product.
1.10 STOCK RECOVERY shall mean the removal or correction of a product
that has not been marketed or that has not left the direct control of the
CLIENT, i.e., the product is located on premises owned by, or under the control
of, the firm and no portion of the lot has been released for sale or use.
DEVELOPMENT PROVISIONS
2.1 INITIATION: Upon execution of this Agreement, XXXX shall proceed
with the schedule for Development of the Drug Product as set forth in Schedule
I appended hereto.
2.2 DOCUMENTATION: XXXX shall provide CLIENT with required supporting
documentation for the Development for the Drug Product in a form suitable for
CLIENT's submission to the FDA.
2.3 BULK DRUG SUBSTANCE SUPPLY: CLIENT, at its sole cost and expense
(including, without limitation, shipping costs), shall supply to XXXX, in a
timely manner, all Bulk Drug Substance required to satisfy the terms of this
Agreement.
2.4 SUPPLY OF COMPONENTS: XXXX shall be responsible for the supply of
materials (except Bulk Drug Substance) necessary for the Development of the
Drug Product. [***]
2.5 DELIVERY TERMS: XXXX shall ship all Drug Product to CLIENT
or to CLIENT's designated consignee, after satisfaction of the conditions in
Paragraph 4.1 hereto. All shipments shall be F.O.B.
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Bloomington, Indiana. CLIENT shall, within fifteen (15) working days after its
receipt of any shipment, notify XXXX in writing, of any claim relating to
non-conforming Drug Product and, failing such notification, notwithstanding
Paragraph 5.1 of this Agreement, CLIENT shall be deemed to have accepted the
Drug Product, holding XXXX free and harmless therefrom.
2.6 PAYMENT FOR THE DRUG PRODUCT AND DEVELOPMENT: at the time of each
shipment, XXXX shall invoice CLIENT for CLIENT's purchase of the Drug Product
and Development costs, as set forth in Schedule I. Upon execution of this
Agreement, CLIENT shall pay XXXX the amount of [***]. The foregoing amount
shall be applied to the first invoice pursuant to the terms and conditions set
forth in Schedule I. Payment not received within thirty (30) days for any
invoice shall bear interest at one and one-half percent (1.5%) per month.
TERM AND TERMINATION
3.1 TERM: This Agreement shall commence on the date first above
written and will continue until the Development, as described in Schedule I,
has been completed, but not more than [***], unless sooner terminated pursuant
to Paragraph 3.2 herein (the "Term").
3.2 TERMINATION: This Agreement may be terminated at any time
upon the occurrence of any of the following events:
(a) Default: Forty-five (45) days written notice, by either party to the other
party, in the event that the other party breaches any provision of this
Agreement, and such party fails to remedy the breach prior to the expiration of
the forty-five (45) day period.
(b) Insolvency: Written notice by either party to the other upon insolvency or
bankruptcy of the other party, and the failure of any such insolvency or
bankruptcy to be dismissed within sixty (60) days.
(c) If, as a result of causes described in Paragraph 7.1, either party is
unable to fully perform its obligations hereunder for a period of sixty (60)
consecutive days, the other party shall have the right to terminate this
Agreement upon at least thirty (30) days prior written notice.
Termination, expiration, cancellation or abandonment of this Agreement, through
any means and for any reason, shall not relieve the parties of any obligation
accruing prior thereto and shall be without the prejudice to the rights and
remedies of either party with respect to any antecedent breach of any of the
provisions of this Agreement or CLIENT's purchase order issued hereunder.
3.3 PAYMENT ON TERMINATION: In the event of the termination or
cancellation of this Agreement, CLIENT shall reimburse XXXX for all raw
materials and components, that are unique to this project, ordered prior to
termination and not cancelable at no cost to XXXX. CLIENT shall pay prices as
described in Schedule I for (a) all work-in-process commenced by XXXX and (b)
all finished goods of XXXX. CLIENT shall be responsible for any other expenses
or losses incurred by XXXX because of the termination. XXXX shall ship such
materials to CLIENT at CLIENT's cost and per CLIENT's instructions. CLIENT
shall make payment for all expenses described in Paragraph 3.3 net thirty (30)
days from the invoice date.
3.4 Survival: Sections headed Warranties, Drug Product Recalls,
Confidentiality, and Indemnification shall survive the termination or
cancellation of this Agreement for any reason.
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CERTIFICATES OF ANALYSIS AND MANUFACTURING COMPLIANCE
4.1 CERTIFICATES OF ANALYSIS: XXXX shall test, or cause to be tested,
in accordance with the Specifications, each batch of the Drug Product
manufactured 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. XXXX shall also indicate on the
certificate of analysis that all batch production and control records have been
reviewed and approved by the appropriate quality control unit. XXXX shall send,
or cause to be sent, such certificates to CLIENT prior to the shipment of the
Drug Product. CLIENT shall test, or cause to be tested, for final release, each
batch of the Drug Product as meeting the Specifications. As required by the FDA
(see Paragraph 5.2 below), CLIENT shall assume full responsibility for final
release of each lot of the Drug Product.
4.2 MANUFACTURING COMPLIANCE: XXXX shall advise CLIENT immediately if
an authorized agent of any regulatory body visits XXXX'x manufacturing facility
and makes an inquiry regarding XXXX'x method of manufacture of the Drug Product
for CLIENT.
WARRANTIES
5.1 CONFORMITY WITH SPECIFICATIONS: XXXX warrants that, at the time of
manufacture, the Drug Product is prepared and tested in accordance with the
Specifications, including cGMP. If the drug product does not meet
specifications, and the reason being solely due to XXXX'x performance, then
CLIENT will not be billed for the batch. Because of individual biological
differences, no product is 100% effective under all circumstances. In addition,
because XXXX has no control of the conditions under which the Drug Product is
used, the diagnosis of the patient before or after treatment with the Drug
Product, the method of use or administration of the Drug Product, and handling
of the Drug Product after it leaves XXXX'x possession, XXXX does not warrant
either a good effect, or against an ill effect, following the use of the Drug
Product. The foregoing warranty is exclusive and in lieu of all other
warranties either written, oral, or implied. THERE ARE NO WARRANTIES OF
MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. No representative of XXXX
may change any of the foregoing warranties and CLIENT accepts the Drug Product
subject to all terms hereof.
5.2 COMPLIANCE: Client assumes responsibility for all contact
with the FDA and other regulatory bodies, pertaining specifically to Drug
Product.
DRUG PRODUCT STOCK RECOVERY
6.1 DRUG PRODUCT STOCK RECOVERY: In the event CLIENT reasonably
determines that the Drug Product should be recovered because the Drug Product
does not conform to Specifications, the parties shall take all appropriate
corrective actions. In no event, however, shall XXXX have responsibility for
regulatory compliance in connection with any recovery, except to the extent and
under the circumstances set forth in the Manual or as required by law. All
costs and expenses incurred in connection with such recovery shall be the
responsibility of CLIENT unless caused solely by the negligence of XXXX. In no
event shall XXXX have any liability for consequential damages incurred by
CLIENT which arise out of, or in connection with, any Drug Product recovery.
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FORCE MAJEURE; FAILURE TO SUPPLY
7.1 FORCE MAJEURE EVENTS: failure of either party to perform under
this agreement (except the obligation to make payments) shall not subject such
party to any liability to the other if such failure is caused by acts such as,
but not limited to, acts of God, fire, explosion, flood, drought, war, riot,
sabotage, embargo, strikes or other labor trouble, compliance with any order or
regulation of any government entity, or by any cause beyond the reasonable
control of the parties, whether or not foreseeable, provided that written
notice of such event is promptly given to the other party.
7.2 FAILURE TO SUPPLY: If XXXX fails to supply all or any material
part of the Drug Product ordered by CLIENT, CLIENT may require XXXX to
supply the undelivered Drug Product or a lesser quantity at a future date
agreed upon by CLIENT. The provisions of this Paragraph 7.2 shall be without
prejudice to CLIENT's rights under paragraph 3.2 and remedies provided for
thereunder.
IMPROVEMENTS
8.1 CHANGES BY CLIENT: If CLIENT requests a change to the Drug Product
Specifications and XXXX agrees that such change is feasible with regard to the
manufacture of the Drug Product, such change shall be incorporated within the
Specifications pursuant to a written amendment to this Agreement. The price of
the Drug Product shall be adjusted for such change, and CLIENT shall pay XXXX
the costs associated with such change, including any development work, if
necessary, based upon XXXX'x then-prevailing development rates. Such prices and
costs shall be set forth in a written amendment to this Agreement. It is the
responsibility of CLIENT to ensure that proper regulatory agencies approve the
suggested changes.
8.2 CHANGES BY XXXX: XXXX agrees that any changes developed by XXXX
which may be incorporated into the Drug Product shall be set forth in a written
amendment to this Agreement prior to such incorporation and approved by CLIENT
in writing. At the time of such incorporation, such changes shall become part
of the Specifications. It is the responsibility of CLIENT to ensure that proper
regulatory agencies approve the suggested changes.
CONFIDENTIALITY
9.1 This Agreement, by reference, incorporates the Confidentiality
Agreement signed by CLIENT and XXXX on January 3, 1996, and is made a part
hereof as though fully set forth herein.
9.2 Any invention made, conceived or reduced to practice by XXXX in
connection with the performance of the obligations under this Agreement, during
the term of this Agreement or thereafter, whether derived from XXXX or CLIENT,
shall be considered confidential information and shall be the exclusive
property of XXXX; provided, however, that any invention made, conceived of, or
reduced to practice during the Term of this Agreement, of (a) a pharmaceutical
product with the same composition as the Drug Product, or (b) an improvement to
the Drug Product, shall be the exclusive property of CLIENT. Each party, in its
sole discretion, may file for patent protection of its invention as set forth
above in its own name, and the other party, upon request by the owner, shall
promptly sign and deliver any and all documents or information necessary for
the securing of such invention in any country as determined by the owner.
9.3 The parties agree that contents of this Agreement shall not be
disclosed to any third party except (i) the controlling companies of the
parties, (ii) the companies controlled by the parties, and (iii) governmental
regulatory agencies, including, but not limited to, environmental protection
authorities, without prior written consent of the other party.
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9.4 Upon termination of this Agreement for whatever reason, each party
shall return to the other originals, copies, and derivative forms of disclosed
or developed information relating to the purpose of this Agreement; except that
one copy of such information may be retained as required by regulatory law for
a period of ten (l0) years for future reference. The confidential information
shall remain confidential and not be disclosed by either party for a period of
ten (l0) years following the date of expiration or termination of this
Agreement.
INDEMNIFICATION
10.1 INDEMNIFICATION BY CLIENT: CLIENT shall indemnify and hold XXXX
(and any parent, subsidiary, or affiliate company or corporation, and their
officers, directors, shareholders, agents, and the employees and insurers of
any of them and/or their successors and assigns thereto), free and harmless
from any and all claims, demands, liability, actions or causes of actions, or
any fines or penalties, and any and all expenses associated therewith
(including, without limiting the generality of the foregoing, defense costs and
attorney's fees), arising out of or in connection with, are the result of, or
are otherwise related to: (i) any act or omission of CLIENT; (ii) the
promotion, distribution, use, misuse or sale of the Drug Product (including,
without limiting the generality of the foregoing, any claims, express, implied
or statutory, made as to the efficacy or safety thereof); (iii) any Drug
Product labeling or packaging; (iv) CLIENT's compliance or noncompliance with
any applicable Federal or State laws or regulations; or, (v) any failure of
CLIENT to perform, in whole or in part, any of its obligations hereunder,
unless caused solely by the acts or omissions of XXXX.
CLIENT also will indemnify and hold XXXX (and all others
indemnified in Paragraph l0.1 hereof) free and harmless against any and all
claims, demands, liability, actions or causes of action, and any and all
expenses associated therewith (including, without limiting the generality of
the foregoing, defense costs and attorney's fees), for damages on account of
personal injury (including death) or property damage arising out of or in
connection with CLIENT's manufacture or handling of the Bulk Drug Substance.
10.2 INDEMNIFICATION BY XXXX: XXXX will indemnify and hold CLIENT free
and harmless against any and all claims, demands, actions or causes of action,
and any and all expenses associated therewith (including, without limiting the
generality of the foregoing, defense costs and attorney's fees), for damages on
account of personal injury (including death) or property damage caused solely
by the acts or omissions of XXXX.
10.3 PATENT INDEMNITY: CLIENT further warrants that manufacture, use
and sale of the Drug Product and Bulk Drug Substance will not infringe any
patent or other proprietary rights and that CLIENT will indemnify, defend and
hold XXXX free and harmless from any damage, judgment, liability, loss, cost or
expense, including legal expenses, arising from claims that the Drug Product
and Bulk Drug Substance infringe patent or other proprietary rights of a third
party.
10.4 CONDITIONS OF INDEMNIFICATION: If either party seeks
indemnification from the other under Paragraphs l0.1, 10.2, or 10.3, it shall
promptly give written notice to the other party of any such claim or suit
threatened, made or filed against it, which forms the basis for such claim of
indemnification and shall cooperate fully with the other party in the defense
of all such claims or suits. No settlement or compromise shall be binding on a
party hereto without its prior written consent.
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GENERAL PROVISIONS
11.1 NOTICES: Any notice permitted or required by this Agreement may
be sent by facsimile with the original document being sent by certified (or
registered) mail, return receipt requested, or overnight delivery and shall be
effective when received (or refused) via facsimile or mail or overnight if
faxed and sent and addressed as follows (or to such other facsimile number or
address as may be designated by a party in writing):
If to CLIENT: Acute Therapeutics, Inc.
0000 Xxxxxx Xxxx
Xxxxxxxxxx, XX 00000
Attn: Xx. Xxxxx Xxxxxxxx
Telephone: (000) 000-0000
Facsimile: (000) 000-0000
If to XXXX: Xxxx Imaging Corporation
000 Xxxxx Xxxxx Xxxx
X.X. Xxx 0000
Xxxxxxxxxxx, XX 00000
Attn: Xxxxxx X. Xxxx, Project Coordinator
Telephone: (000) 000-0000
Facsimile: (000) 000-0000
11.2 ENTIRE AGREEMENT: AMENDMENT: The parties hereto acknowledge that
this Agreement sets forth the entire agreement and understanding of the parties
and supersedes all prior written or oral agreements or understandings with
respect to the subject matter hereof. No modification of any of the terms of
this Agreement, or any amendments thereto, shall be deemed to be valid unless
in writing and signed by both parties hereto. No course of dealing or usage of
trade shall be used to modify the terms and conditions herein.
11.3 WAIVER: None of the provisions of this Agreement shall be
considered waived by any party hereto unless such waiver is agreed to, in
writing, by both parties. The failure of a party to insist upon strict
conformance to any of the terms and conditions hereof, or failure or delay to
exercise any rights provided herein or by law shall not be deemed a waiver of
any rights of any party hereto.
11.4 OBLIGATIONS TO THIRD PARTIES: Each party warrants and
represents that this Agreement is not inconsistent with any contractual
obligations, expressed or implied, undertaken with any third party.
11.5 ASSIGNMENT: This Agreement shall be binding upon and inure to the
benefit of the successors or permitted assigns of each of the parties and may
not be assigned or transferred by either party without the prior written
consent of the other, which consent will not be unreasonably withheld or
delayed, except that no consent shall be required in the case of a transfer to
a wholly-owned subsidiary or transaction involving the merger, consolidation or
sale of substantially all of the assets of the party seeking such assignment
or transfer and such transaction relates to the business covered by this
Agreement and the resulting entity assumes all the obligations under this
Agreement.
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11.6 INDEPENDENT CONTRACTOR: XXXX shall act as an independent
contractor for CLIENT IN providing the services required hereunder and shall
not be considered an agent for joint venture with CLIENT. Unless otherwise
provided herein to the contrary, XXXX shall furnish all expertise, labor,
supervision, machining and equipment necessary for performance hereunder and
shall obtain and maintain all building and other permits and licenses required
by public authorities.
11.7 GOVERNING LAW: This Agreement is subject to and shall be
governed by the laws of the State of Indiana.
11.8 SEVERABILITY: In the event that any term or provision of this
Agreement shall violate any applicable statute, ordinance, or rule of law in
any jurisdiction in which it is used, or otherwise be unenforceable, such
provision shall be ineffective to the extent of such violation without
invalidating any other provision hereof.
11.9 HEADINGS, INTERPRETATION: The headings used in this Agreement
are for convenience only and are not part of this Agreement.
11.10 CONFLICT: In the event of a conflict between the terms and
provisions of this Agreement and the terms and provisions of the Manual, the
terms of this Agreement shall control.
IN WITNESS WHEREOF, the parties hereto have each caused this Agreement to be
executed by their duly authorized representatives as of the date first above
written.
ACUTE THERAPEUTICS, INC. XXXX IMAGING CORPORATION
(Signature of Xxxxxx Xxxxxxxx) (Signature of Xxxxx X. Xxxxxx)
Authorized Signature Authorized Signature
Xxxxxx Xxxxxxxx Xxxxx X. Xxxxxx
Printed Name Printed Name
(handwritten January 9, 1997) January 8, 1997
Date Date
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SCHEDULE I
DEVELOPMENT ACTIVITIES AND PRICING
DEVELOPMENT of the Drug Product for use in Clinical Studies will consist of the
following: [***]
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SCHEDULE II
MANUFACTURING PROJECT MANUAL
The policies and procedures outlined herein have been reviewed and will be
adhered to in the manufacturing and/or finishing of the Drug Product pursuant
to the Clinical Product Development Agreement (the "Agreement").
I. POLICY:
XXXX'x policy is to assure that the Drug Product manufactured and/or packaged
for CLIENT will be processed under a total quality control system which ensures
that the Drug Product will meet all warranties set forth in Section 5.1 of the
Agreement.
II. PURPOSE:
The purpose of this Manual is to address and delineate the responsibilities
between XXXX and CLIENT and to provide a vehicle for implementation of the
policy stated above.
III. SCOPE:
This Manual applies to all contract manufacturing activities for which XXXX has
manufacturing and/or finishing responsibility as set forth below.
RAW MATERIALS
All raw materials are defined by the Specifications outlined in Attachment I
hereto which is made a part hereof by reference. An Approved Vendor List shall
be jointly developed and approved by XXXX and by CLIENT for the supply of these
raw materials. The Approved Vendor List shall contain, but not be limited to,
the following information:
Raw Material Name
Vendor Name
Manufacturing Location
DMF Information
Acceptance Criteria
More than one vendor may appear on the Approved Vendor List for each raw
material item as long as the material supplied by each listed vendor meets the
Specifications.
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CLIENT shall supply to XXXX, in a timely manner, all Bulk Drug Substance
necessary to satisfy XXXX'x obligations under the Agreement. At some point,
CLIENT wishes for XXXX to supply the excipients, namely Palmitic Acid, DPPC,
and POPG. When this occurs, a price will be negotiated and agreed to jointly
by both parties.
XXXX will use standard operating procedures which define the sampling
methodology and the analytical methods used to assure that the raw materials
meet the Specifications. XXXX and CLIENT agree that a vendor's certificate of
analysis may be used in lieu of testing, where testing by XXXX or CLIENT has
validated the vendor. XXXX and CLIENT will maintain supporting documentation.
XXXX will notify CLIENT in writing of any changes to the Specifications,
sampling, or test methods of those raw materials listed in Attachment I that
are included in the current USP/NF, and of any changes in the Approved Vendor
List.
For all raw materials listed in Attachment I which are not included in the
current USP/NF, and for Bulk Drug Substance supplied by CLIENT or its agents,
XXXX shall obtain CLIENT's approval prior to instituting any changes to the
Specifications, sampling, or test methods for that material.
PACKAGING MATERIALS
CLIENT shall be responsible for, and shall provide to XXXX, all copy content,
artwork and mechanicals for all printed materials associated with the Drug
Product. This includes, but is not limited to, container labels, container
cartons, package inserts, and promotional material. CLIENT shall be responsible
for compliance with all Federal, State and Local laws and regulations
concerning packaging and labeling materials, and for obtaining any necessary
regulatory approvals of printed materials, artwork, and copy. Refer to Schedule
I for details.
CLIENT shall provide XXXX with specifications for all packaging components
including, without limitation, purchase description (general specifications for
a class of packaging supplies; e.g., bottles, caps, cartons, etc.), acceptance
criteria (including incoming inspection and sampling plans), and test methods
used to determine conformance to specifications.
CLIENT shall approve the specifications for product container closure
components.
XXXX shall review and certify, by comparison to a master supplied by CLIENT,
each receipt of printed components. Non-printed packaging components shall be
tested by XXXX according to XXXX specifications.
XXXX shall notify CLIENT in writing of any changes to the specifications for
any components used in the Drug Product prior to use in manufacture.
XXXX shall obtain prior approval from CLIENT before revising any printed
packaging components, primary container components, and all CLIENT supplied
packaging components used in the Drug Product.
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MASTER PRODUCTION RECORDS
A Master Batch Record (MBR) is the formal set of instructions for the
preparation of the Drug Product. A MBR shall be developed by XXXX, using
CLIENT's master formula and technical support provided by CLIENT.
The MBR shall be maintained by the Document Control/Quality Assurance group
within XXXX. The MBR shall be written in the standard XXXX format.
The MBR shall be reviewed and approved by XXXX and by CLIENT. Any change to an
approved MBR will be reviewed and approved by XXXX and by CLIENT prior to said
change being implemented. Each batch of the Drug Product is produced by using a
copy of the MBR. Each batch record is assigned a unique batch number.
Any deviation from the specified manufacturing process must be documented in
the batch record. XXXX shall have a system to document the deviation, the
investigation that was undertaken, and the conclusion drawn from that
investigation. Appropriate departmental reviews and approvals by XXXX shall be
required prior to release of the Drug Product. The documentation associated
with any deviation in the manufacturing process shall become part of the batch
record.
SAMPLING, TESTING AND RELEASE OF THE DRUG PRODUCT
Each batch of the Drug Product manufactured and/or packaged by XXXX shall be
sampled in-process and at the completion of the manufacturing and packaging
operations, as agreed to by XXXX and CLIENT.
All in-process and completed Drug Product testing shall be conducted by XXXX or
a third party designated by XXXX using approved test methods, following receipt
of written approval by CLIENT.
All test methodologies shall be validated. For those procedures which appear in
the current USP/NF, or other recognized standard reference, a statement
indicating the reference shall suffice. For those test methods which are
developed by XXXX, documentation supporting the validation of the test method
shall be documented. For test methods developed by CLIENT, CLIENT shall supply
XXXX with the supporting validation documentation.
XXXX shall provide CLIENT with a certificate of analysis indicating each test
parameter, test result, and the corresponding acceptance criteria for each
batch of the Drug Product manufactured or packaged, as well as a statement
indicating that all associated documentation has been reviewed and approved by
the appropriate quality control unit.
Final Drug Product release shall be made by CLIENT pursuant to the provisions
of the Agreement.
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RESERVE SAMPLES AND ANNUAL QUALITY REVIEW
CLIENT Shall Be Responsible For Obtaining And Maintaining Sufficient Quantities
of Bulk Drug Substance and Drug Product Reserve Samples as Defined in Good
Manufacturing Practices Regulations 21 CFR, Section 211.170.
CLIENT shall be responsible for evaluating, at least annually, the quality
standards of the Drug Product to determine the need for changes in the Drug
Product specifications, manufacturing processes, or controlled documents. XXXX
shall provide CLIENT with access to all appropriate batch records for each
batch of the Drug Product. CLIENT shall supply to XXXX a copy of the
examination results and recommendations, if any.
STABILITY, STORAGE, VALIDATION AND ENVIRONMENTAL MONITORING
Stability: XXXX shall be responsible for the stability testing outlined in
Schedule I.
Storage: CLIENT shall indicate the appropriate storage conditions for the Bulk
Drug Substance and the Drug Product. XXXX shall comply with these
specifications and will monitor the storage conditions for the Bulk Drug
Substance and the Drug Product. XXXX shall provide CLIENT access to the
monitoring records.
Validation: Process/product and cleaning validation shall be performed by XXXX
using protocols developed and approved by XXXX. XXXX shall be responsible for
conducting the validation studies and maintaining validation reports and/or
drug product specific XXXX Standard Operating Procedures.
Environmental Monitoring: Where particulate and microbial levels are required
for the Drug Product, then the facilities and raw materials used during the
manufacturing and packaging process shall be monitored for these factors. XXXX
will be responsible for the establishment and institution of a monitoring
program to assure that the Drug Product will meet the required particulate and
microbial levels and shall maintain the records obtained from this monitoring
program.
DISTRIBUTION RECORDS AND RETURNS
Distribution Records: XXXX shall maintain distribution records which contain
all of the appropriate information as specified in the Good Manufacturing
Practices regulations 21 CFR, Section 211.196.
Product Returns: Returned Drug Product is the responsibility of CLIENT pursuant
to the terms of the Agreement.
Xxxx Imaging Corporation Development Agreement - 129; 1/8/97 - 02
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COMPLAINTS
Complaint files, as required by 21 CFR, Section 211.198 of the Good
Manufacturing Practices regulations, shall be maintained by CLIENT. All
complaints received by XXXX shall be forwarded to CLIENT. CLIENT shall be
responsible for the review of the complaint to determine the need for an
investigation as specified in 21 CFR, Section 211.192, or the need to report to
the United States Food and Drug Administration (FDA) as required by 21 CFR,
Section 310.305 and 312.32. CLIENT shall send to XXXX all Drug Product
performance or manufacturing-related complaints which require investigation.
XXXX shall conduct an investigation for each Drug Product performance or
manufacturing-related complaint and shall report the findings and follow-up of
each investigation to CLIENT.
CLIENT shall make these complaint files available to XXXX in the event they are
required during an FDA inspection.
STOCK RECOVERY
CLIENT shall be responsible for drug product recoveries pursuant to the terms
of the Agreement.
For manufacturing-related recoveries, XXXX shall conduct an investigation to
determine the cause of such Drug Product defect and shall report the findings
to CLIENT.
XXXX shall provide to CLIENT distribution records and current inventory levels
for any recalled Drug Product.
AUDITS AND REGULATORY COMPLIANCE
Audits: Except with respect to information and operations which constitute XXXX
trade secrets, CLIENT, upon prior written notice and during normal business
hours, shall have the right to inspect XXXX batch records and the portions of
XXXX'X facility used for the manufacturing, finishing, holding, and testing of
the Drug Product.
Regulatory Compliance: Unless otherwise stated in this document, XXXX is
responsible for compliance to all Federal, State and Local laws and regulations
as they apply solely to XXXX'x business and not to the manufacture of Drug
Product.
Xxxx Imaging Corporation Development Agreement -129; 1/8/97 - 02
18
ATTACHMENT I
DRUG PRODUCT SPECIFICATIONS
AND PROCEDURES
[***]
Xxxx Imaging Corporation Development Agreement - 129; 1/8/97 - 02
[***] Confidential treatment requested.
19
ACUTE THERAPEUTICS, INC.
[***]
Authorized by: Signature of Xxxxx X. Xxxxxxxx Date: Handwritten 1/9/97
[***] Confidential treatment requested.
ACUTE THERAPEUTICS, INC.
[***]
Authorized by: Signature of Xxxxx X. Xxxxxxxx Date: Handwritten 1/9/97
[***] Confidential treatment requested.
ACUTE THERAPEUTICS, INC.
[***]
Authorized by: Signature of Xxxxx X. Xxxxxxxx Date: Handwritten 1/9/97
[***] Confidential treatment requested.
ACUTE THERAPEUTICS, INC.
[***]
Authorized by: Signature of Xxxxx X. Xxxxxxxx Date: Handwritten 1/9/97
[***] Confidential treatment requested.
