EXHIBIT 10.35
CONFIDENTIAL
PORTSMOUTH QUALITY AGREEMENT
RELATING TO
THE MANUFACTURING SERVICES AGREEMENT DATED NOVEMBER 21, 2005
BETWEEN
LONZA BIOLOGICS, INC.
AND
TRUBION PHARMACEUTICALS, INC.
CONFIDENTIAL TREATMENT
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CONFIDENTIAL
PORTSMOUTH QUALITY AGREEMENT
This Portsmouth Quality Agreement ("Portsmouth Quality Agreement") is dated
effective as of November 21,2005, and it defines the roles and responsibilities
for the quality operations between LONZA BIOLOGICS INC., the registered office
of which is at INTERNATIONAL DRIVE, PORTSMOUTH, XX 00000 XXX (herein after
referred to as ("LB") and TRUBION PHARMACEUTICALS, INC., of 0000 0xx Xxxxxx,
Xxxxx 0000, Xxxxxxx, XX 00000, XXX (herein referred to as the "Customer") with
respect to manufacture of Customer's proprietary Small Modular
lmmunoPharmaceutical (SMIP) known as TRU-015 ("TRU-015") under that certain
manufacturing services agreement between the parties of even date herewith (the
"Services Agreement") in preparation for regulatory filings and for human
clinical use.
When used in this Portsmouth Quality Agreement, the term "Product" shall have
the meaning given in the Service Agreement, and refers to TRU-015 and/or to the
form of TRU-015 manufactured under the Services Agreement, as the context
requires.
This is the Portsmouth Quality Agreement referred to in Exhibit A of the
Services Agreement. Capitalized terms used but not defined in this Portsmouth
Quality Agreement shall have the meaning given in the Services Agreement. This
Portsmouth Quality Agreement may be amended by written agreement of the parties.
In the event of a conflict between the Portsmouth Quality Agreement and the
Services Agreement, the Services Agreement shall control. This Portsmouth
Quality Agreement may be executed in any number of counterparts, each of which
shall for all purposes be deemed an original and all of which, taken together,
shall constitute one and the same instrument. A facsimile signature shall be
deemed to be and shall be as effective as an original signature.
The responsibilities and rights of the parties under this Portsmouth Quality
Agreement are set forth below.
a. OVERALL RESPONSIBILITIES
This Portsmouth Quality Agreement outlines the responsibilities of the Customer
and LB with respect to the quality assurance of Product manufactured and
supplied by LB for the Customer under the terms of the Agreement.
This Portsmouth Quality Agreement takes the form of a detailed list of
activities associated with the manufacture, testing and disposition of Product.
Responsibility for each activity is assigned to either the Customer or LB, or is
assigned to both the Customer and LB. Additional details are provided in the
Services Agreement and in the SOP's referred to in this Portsmouth Quality
Agreement.
This detailed list describes generic quality activities that would be performed
by both parties for Product used in clinical trial supply. The specific services
to be provided by LB are set out in the Services Agreement (and any Amendments
to the Agreement).
LB is responsible for ensuring that the quality requirements for Product are as
specified in the approved Product Specifications, and that Product is
manufactured, tested and stored by LB in accordance with current Good
Manufacturing Practices (cGMP) and all applicable US and EU laws, regulations
and ICH guidelines.
The Customer is responsible for shipping and the final review, approval, and
disposition of product for use in the clinic. The Customer is responsible for
Product development, technical oversight, product specifications and regulatory
agency filings.
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CONFIDENTIAL
SPECIFIC RESPONSIBILITIES
RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------
ITEM LB CUSTOMER(1)
------------------------- -------------------------------- -----------------------------
1.0 Organisation and - Ensure adequate number of - Right to audit
Personnel personnel with appropriate
training, skills, knowledge
and experience to
manufacture and test
Product in accordance with
cGMP
2.0 Facilities, - Ensure facilities, - Right to audit
Utilities and environment, utilities,
Equipment equipment, computerised
systems and software are
properly designed,
validated and maintained in
accordance with cGMP
- Ensure Product is - Right to audit
manufactured and tested
only at sites as agreed
with Customer
- Make available for review - Right to audit
by Customer relevant SOPs
of LB related to the
Agreement and services of
LB
- Provide Customer with Site - Include Drug Master File
Master File reference that reference into
will allow regulatory regulatory submissions,
agencies the ability to as appropriate
cross-reference other
products that are
manufactured at LB's
manufacturing and testing
locations
- Provide Customer with Lonza
Policy that no penicillin
is manufactured or tested
at site
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CONFIDENTIAL
RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------
ITEM LB CUSTOMER(1)
------------------------- -------------------------------- -----------------------------
3.0 Raw Materials for - Source, test and release - Right to audit; right to
Process and raw materials and primary review all raw material
Packaging of packaging of appropriate specifications, grades
Product / Vendor quality for processing of and vendors used in
Qualification Product manufacture of Product
Process
- Customer to provide LB
with list of critical
raw materials used in
Customer process; update
with changes as
necessary
- Propose and jointly agree - Right to approve vendor,
to specifications, vendors grade and specifications
and grade of critical raw of critical raw
materials used in Customer materials used in
process in accordance with Customer process,
LB policy, with preference including excipients,
for non-animal and and raw materials of
non-human derived raw animal or human origin
materials
- Acknowledge and support
Customer's goal not to use
any raw materials of animal
or human origin in the
development of Customer
process
- Retain representative - Right to audit
samples
(1) Throughout the Portsmouth Quality Agreement, Customer's column includes the
phrase "right to audit" - the use of this phrase in certain instances but
not in others does not and shall not imply that Customer's audit rights
pursuant to Clause 15 below are limited to those boxes where "right to
audit" appears
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CONFIDENTIAL
RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------
ITEM LB CUSTOMER(1)
------------------------- -------------------------------- -----------------------------
4.0 Cell Banks - Prepare, characterise and
store cell bank(s) if
contracted by Customer
- Jointly agree on testing - Jointly agree on testing
specifications and test specifications and test
methods to enable release methods to enable
of cell banks for use in Product manufactured
LB's multi-product from cell banks to be
manufacturing facility used in the clinic
- Perform stability testing - Right to audit
of cell bank(s) if
contracted by Customer and
share data with Customer
IF CELL BANK SUPPLIED BY
CUSTOMER
- Review and approve - Supply cell bank
characterisation data. characterisation data
Store working stock or cell for review and approval.
bank Transfer cell bank (or
portion thereof) to LB
- Provide shipping validation - Right to audit
data if requested by
Customer
IN ALL CASES
- Provide inventory levels
periodically upon request
by Customer
5.0 Product - With the Customer determine - With LB determine and
Specification and approve the following approve the following
Product specification(s) as Product specification(s)
required: as required:
- Drug substance (including - Drug substance
testing performed on (including testing
fermenter contents for performed on fermenter
adventitious agents) contents for
adventitious agents)
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RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------
ITEM LB CUSTOMER(1)
------------------------- -------------------------------- -----------------------------
6.0 Production and - Make available for review - Right to review
Process Control by Customer documents
relating to facility,
equipment, Process and test
methods, and GMP systems
- Jointly review and approve - Jointly review and
Process descriptions approve Process
descriptions
- Define and perform an - Agree in-process testing
in-process control and strategy
testing program strategy
- Using LB templates prepare - Right to review and
master batch records for comment on master batch
each processing step and records
provide to Customer for
review and comment. Retain
final master batch record
on site at LB
- Designate unique batch - Right to audit
numbers for raw materials,
process materials and
Product
- Manufacture of Product in - Right to audit
accordance with Product
Specifications, cGMP - Relevant sections of
standards, batch records, Customer's regulatory
in-process controls and submissions to be made
in-progress specifications available to LB as
appropriate
- Ensure QA representatives - Right to audit
on-site or available at all
times during manufacture
and testing of Product
- Permit Customer's person on - Right to designate 1 of
plant to be present in LB's its employees or
facility during normal consultants as
business hours to observe Customer's person on
the Runs and observe LB's plant, to be present in
performance, at times and LB's facility during
for durations to be agreed. normal business hours to
While at LB's facility, observe the Runs and
Customer's representative observe LB's
shall comply with all LB's performance, at times
applicable policies and and for durations to be
procedures, and, at LB's agreed. While at LB's
option, shall be escorted facility, Customer's
by LB personnel representative shall
comply with all of LB's
applicable policies and
procedures, and, at LB's
option, shall be
escorted by LB
personnel. Lonza must
agree to all consultants
used by Trubion for
person on plant
activities
- Perform Product changeover - Review and comment on
testing of LB's policy for Product
Product-contacting changeover testing of
equipment in accordance Product-contacting
with LB policy equipment
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RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------
ITEM LB CUSTOMER(1)
------------------------- -------------------------------- -----------------------------
7.0 Product Storage, - Store, label and package - Right to audit
Labelling and the Product (including
Packaging Prior to samples) as defined in the - Provide information on
Shipment Product Specification shipping requirements
8.0 Shipment - Ship Product on behalf of - Jointly agree with LB on
Requirements Customer to locations process for shipping
designated by Customer in requirements
accordance with jointly
agreed process for shipping - Right to audit
requirements
- Acknowledge receipt of
Product
- With Customer agree on
shipment date for Product
- Provide shipping - Right to audit
validation data for Product
if contracted by Customer
9.0 Laboratory Controls - Perform Product release - Right to audit
(QC) testing against Bulk Drug
Substance Specifications
- Jointly agree on SOP's - Jointly agree on SOP's
describing Product-specific describing
analytical testing methods Product-specific
analytical testing
methods
- Provide LB with
Product-specific
information as it
relates to sample
storage, handling and
testing requirements
- Retesting, where required, - Review and comment on LB
will be performed in retest procedure. Review
accordance with LB's retest OOS reports; comment on
procedure. Out of corrective and
specification (OOS) Product preventative actions
release testing results
will be notified to the
Customer as soon as
possible within 3 business
days of the OOS being
confirmed
- Send samples to Customer - Perform Product potency
for additional testing testing and provide data
(including potency testing) to LB; such data will be
in accordance with jointly provided for LB's
approved SOP information only and not
for inclusion into LB's
Certificate of Analysis.
Customer to create
Certificate of Analysis
for potency testing
results.
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RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------
ITEM LB CUSTOMER(1)
------------------------- -------------------------------- -----------------------------
9.0 Laboratory Controls - Retain representative - Right to audit
QC (Continued) samples of bulk Product
from each batch in
accordance with LB SOP
- If requested by Customer, - Right to receive copies
provide copies of raw data of raw data and testing
and testing records records
- Take additional - Request additional
representative samples if samples to be shipped as
requested and ship to required
Customer
- Prepare and characterise - Jointly approve Product
Product reference standard reference standard
in accordance with jointly Protocol
agreed Protocol, if
contracted by Customer - Right to audit
- Jointly approve Product - Jointly approve Product
reference standard report reference standard report
10.0 Use of Contract - Qualify Contract Testing - Right to jointly audit
Testing Laboratories Laboratories for Product
release testing in
accordance with LB policy
- Notify Customer of Contract - Consent or reject to the
Testing Laboratories proposed use of Contract
intended to be used for Testing Laboratories
Product release testing
- Facilitate audit by - Right to audit
Customer if requested from
time to time
- If not prohibited by - Right to request,
Contract Testing receive and use copies
Laboratory, provide of LB's audits of
Customer with copies of Contract Testing
LB's audits of Contract Laboratories when
Testing Laboratories when possible, unless
possible, if requested prohibited by Contract
Testing Laboratories
11.0 Product Release - Review batch record for - Right to review
and Lot Review compliance with cGMP, completed and reviewed
manufacturing controls, and Product batch records
with the Product
Specifications
- Provide Customer with an - Right to review
electronic copy of the
Process documentation
including, main operational
steps from the completed
batch record. This will
include Product analysis, a
summary of batch related
deviations and
environmental monitoring
summaries, as well as
process data, as requested
11.0 Product Release - If requested by Customer, - Right to request and
send full receive full
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RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------
ITEM LB CUSTOMER(1)
------------------------- -------------------------------- -----------------------------
and Lot Review electronic copies of actual copies of actual
(Continued) deviation deviations
- Prepare manufacturer's - Prepare Certificate of
Certificate of Analysis, Analysis and Certificate
including related of Compliance for release
Certificate of Compliance of product for use in
human clinical trials
- Release or reject Product - Release or reject
Product for use in
human clinical trials
12.0 Deviations and - Initiate investigations, - Right to audit
Failed Run evaluate and define follow
Investigations and up actions and final
Reports approval of deviations and
failure investigations
- Notify Customer of all - Review significant
significant deviations deviations; comment on
within 24 hours or at least corrective and
3 business days of the preventative actions
event being assigned as
significant, and send
Customer the related action
plan. (A significant
deviation is defined in
Trubion standard operating
procedure 3150 and Lonza
SOP USPO1698)
- If requested by Customer,
send full copies of
deviation and investigation
reports.
- Notify Customer of failed - Review failure
runs within 24 hours or at investigation report and
least 3 business days of comment on corrective
failure being identified and preventative actions
- Immediately and within at
least 3 business days of
event being identified,
notify Customer of any
events which may impact
batches previously shipped
or released
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CONFIDENTIAL
RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------
ITEM LB CUSTOMER(1)
------------------------- -------------------------------- -----------------------------
13.0 Change Control CUSTOMER PROPOSED CHANGES
Procedures
- Process Product-specific - Propose Customer
change through change Product-specific changes
control and notify Customer and provide rationale in
of change approval. If writing
change rejected, discuss
reasons for rejection with
Customer
- Approve proposed
Product-specific changes
prior to implementation
LB PROPOSED CHANGES
- Propose Product-specific - Process Product-specific
changes and provide change through change
rationale for change to control and notify LB of
process descriptions; test change approval.
methods; sampling plans; Customer approval for
specifications for key raw change controls will be
materials (animal and / or needed 10 days from
human derived raw receipt If change
materials, , chromatography rejected, discuss
resins and final reasons for rejection
formulation excipients); with LB
Product specification(s)
and stability programme, - Approve proposed
in-process controls and Product-specific change
other key processing steps prior to implementation
- Inform Customer of changes - Right to audit
to key personnel as
identified in Appendix 1
- Inform Customer of changes - Right to audit
to major items of
equipment, premises and
utilities used for
manufacture of Product
ALL CHANGES
- With Customer define - With LB define strategy
strategy for notifying for notifying change to
change to Regulatory. Regulatory. Agency as
Agency as appropriate (see appropriate (see Section
Section 20.0, below, 20.0, below, Regulatory
Regulatory Submissions) Submissions)
- Inform Customer of Product - Ensure Product is not
batches manufactured with distributed until
the change until regulatory Regulatory approval
approval obtained, if obtained, if required
required
- Cooperate with Customer in - Cooperate with LB in
connection with change connection with change
controls; respect controls; respect LB's
Customer's change controls, change controls, and, as
and, as appropriate, use it appropriate, use it to
to initiate LB's change initiate Customer's
controls change controls
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RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------
ITEM LB CUSTOMER(1)
------------------------- -------------------------------- -----------------------------
14.0 Reprocessing / - Processing to be performed - Review and comment on
Rework in accordance with LB SOP. LB's reprocessing /
With Customer agree on and rework SOP; with LB
approve reprocessing / agree on reprocessing /
rework procedures, where rework procedures, where
possible prior to execution possible prior to
execution
- Provided documented reason - Right to audit
and justification for
reprocessing / rework event
- With Customer agree on the - With LB agree on the
appropriate testing appropriate testing
required prior to Product required prior to
release Product release
15.0 Audit - Permit Customer - Provide reasonable
representatives access as notice of intention to
reasonably required to audit
conduct a cGMP compliance
audit, including access to - Right to 2 standard cGMP
warehousing, manufacturing compliance audits per
areas, laboratories, and year, plus right to
manufacturing records and additional "for cause"
documents, including SOPS audits
(unless they contain
specific LB proprietary - Right to audit each
information eg media batch record
formulations), and
personnel, for audit - Hold an exit meeting to
purposes. Customer discuss observations
representatives to be
accompanied at all times by - Provide an audit report
LB personnel within 30 days of
completion of audit
- *** cGMP compliance audits
permitted per year, with an
audit not to exceed *** and
a maximum of ***.
Additionally the Customer
may request "for cause"
audits to address
production of Product
quality issues
- *** audit for each batch
record if requested by
Customer
- Allow the Customer to
observe operations related
to Product manufacturing
and testing providing other
Customer's confidentiality
is respected
- Provide a written response
to all audit findings that
require corrective action
within 30 days of receipt
of the audit report.
Response to include
expected timelines
16.0 Product Complaints - Respond to requests for - Receive and investigate
data to Product
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RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------
ITEM LB CUSTOMER(1)
------------------------- -------------------------------- -----------------------------
and Recall assist Customer in complaints and
their investigation. Agree instigate Product recall
a time scale for response as appropriate
17.0 Batch Records - Retain records associated - Right to audit
with manufacture and
testing records of Product
including records
associated with the
inspection and release of
raw materials and primary
packaging components of the
Product for 5 years from
the date of manufacture of
Product. Date of
manufacture is defined as
the date Product is
dispensed in to the bulk
product container)
- Notify Customer of intent - Customer to approve
to destroy records with destruction or request
option to send records to receipt of records
Customer
18.0 Process Validation / - With Customer define - With LB define process
Stability Studies process validation plans validation plans for
for Product including Product including
analytical validation and analytical validation
stability studies and stability studies
WHERE PROCESS VALIDATION IS
PERFORMED BY LB
- Provide Customer with - Approve Product-specific
Product-specific validation validation protocol(s)
protocol(s) for approval including stability
prior to execution protocols
- Provide Customer with draft - Review and comment on
Product-specific validation Product-specific
report(s) for review and validation report(s)
comment including stability
reports
- Issue Customer with copy of
final Product specific
validation report(s)
WHERE PROCESS VALIDATION IS
PERFORMED BY CUSTOMER
- Incorporate specifications - Provide LB with process
in cGMP documentation and validation reports
regulatory submissions
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RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------
ITEM LB CUSTOMER(1)
------------------------- -------------------------------- -----------------------------
19.0 Regulatory Agency GMP INSPECTIONS
Inspection
- Inform Customer of - For Regulatory Agency
Regulatory Agency inspections of
inspections or regulatory regulatory action
action affecting affecting Product,
manufacture, testing or provide assistance when
storage of Product requested by LB
- Notify Customer of - Common on proposed
inspection observations inspection responses to
(including Deficiency observations relevant to
Letters) affecting the Product
Product, process or systems
relating to the Product
20.0 Regulatory WHERE A DATA PACK IS PROVIDED BY
Submissions LB TO SUPPORT CUSTOMER'S
CLINICAL TRIAL APPLICATION
INITIAL APPLICATION, AMENDMENTS
AND RESPONSES TO QUESTIONS
- Provide Customer with data - Prepare and provide LB
pack covering activities with copy of relevant
performed by LB sections of clinical
trial application for
- Review and comment on review and comment prior
relevant sections of to submission to
clinical trial application Regulatory Agency
- Provide LB with copy of
relevant sections as
submitted to Regulatory
Agencies
TELECONFERENCES AND MEETINGS
WITH THE REGULATORY AGENCIES
- Attend teleconferences and - Arrange for LB personnel
meetings between the to have option to attend
Customer and Regulatory teleconferences and
Agencies arranged to meetings between
specifically discuss topics Customer and Regulatory
relating to LB's Agencies to specifically
responsibilities discuss topics relating
to LB's responsibilities
[signatures on following page]
CONFIDENTIAL TREATMENT
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CONFIDENTIAL
QUALITY APPROVAL
LONZA BIOLOGICS, Inc.
Name: X. Xxxxxx Signature: /s/ X. Xxxxxx
-----------------------------
Title: President Date: December 5, 2005
TRUBION PHARMACEUTICALS, INC.
Name: Xxxxx Xxxxx Signature: /s/ Xxxxx Xxxxx
-----------------------------
Title: Senior Director Date: December 1, 2005
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CONFIDENTIAL
APPENDIX I TO THE PORTSMOUTH QUALITY AGREEMENT
CUSTOMER LONZA
-------- -----
SENIOR VICE PRESIDENT, HEAD OF LONZA CONTRACT MANUFACTURING:
RESEARCH AND DEVELOPMENT:
Xxxxxxx X Xxxxxx PhD
Senior Vice President
Research and Development
Trubion Pharmaceuticals Inc
0000 Xxxxxx Xxxxxx. Xxxxx 0000
Xxxxxxx, XX 00000
XXX
Tel: x0 000 000 0000 Tel: + _____________________
Fax: x0 000 000 0000 Fax: + _____________________
Email: xxxxxxx@xxxxxxx.xxx Email: _____________________
HEAD OF QUALITY: HEAD OF QUALITY:
Xxxxx X Xxxxx
Senior Director, Regulatory Affairs
Trubion Pharmaceuticals Inc
0000 Xxxxxx Xxxxxx, Xxxxx 0000
Xxxxxxx, XX 00000
XXX
Tel: +1 2I0 0 000 0000 Tel: _______________________
Fax: x0 000 000 0000 Fax: _______________________
Email: xxxxxx@xxxxxxx.xxx Email: _____________________
HEAD OF MANUFACTURING: DIRECTOR OF MANUFACTURING ***:
Xxxx X Xxxxx
Vice President, Development
Trubion Pharmaceuticals Inc
0000 Xxxxxx Xxxxxx, Xxxxx 0000
Xxxxxxx, XX 00000
XXX
Tel: x0 000 000 0000 Tel: _______________________
Fax: x0 000 000 0000 Fax: _______________________
Email: xxxxxx@xxxxxxx.xxx Email: _____________________
QUALITY CONTROL MANAGER: QUALITY CONTROL MANAGER:
Xxx Xxx PhD
Director, Product Development
Trubion Pharmaceuticals Inc
0000 Xxxxxx Xxxxxx, Xxxxx 0000
Xxxxxxx, XX 00000
XXX
Tel: x0 000 000 0000 Tel: _______________________
Fax: x0 000 000 0000 Fax: _______________________
Email: xxxx@xxxxxxx.xxx Email: _____________________
CONFIDENTIAL TREATMENT
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