Exhibit 10.38
CONFIDENTIAL
PORTSMOUTH QUALITY AGREEMENT
RELATING TO
THE MANUFACTURING SERVICES AGREEMENT DATED NOVEMBER 21, 2005
BETWEEN
LONZA BIOLOGICS ***.
AND
TRUBION PHARMACEUTICALS, INC.
Page 1 of 15
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 ***, the registered office of
which is at *** (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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SPECIFIC RESPONSIBILITIES
RESPONSIBILITIES AND RIGHTS
------------------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
------------------------------------ ----------------------------------------------- ----------------------------------------
1.0 Organisation and Personnel - Ensure adequate number of personnel with - Right to audit
appropriate training, skills, knowledge
and experience to manufacture and test
Product in accordance with cGMP
2.0 Facilities, Utilities and - Ensure facilities, environment, utilities, - Right to audit
Equipment equipment, computerised systems and
software are properly designed, validated
and maintained in accordance with cGMP
- Ensure Product is manufactured and tested - Right to audit
only at sites as agreed with Customer
- Make available for review by Customer - Right to audit
relevant SOPs of LB related to the
Agreement and services of LB
- Provide Customer with Site Master File - Include Drug Master File reference
reference that will allow regulatory into regulatory submissions, as
agencies the ability to cross-reference appropriate
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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RESPONSIBILITIES AND RIGHTS
------------------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
------------------------------------ ----------------------------------------------- ----------------------------------------
3.0 Raw Materials for Process and - Source, test and release raw materials and - Right to audit; right to review all
Packaging of Product / Vendor primary packaging of appropriate quality raw material specifications, grades
Qualification Process for processing of Product and vendors used in manufacture of
Product
- Customer to provide LB with list of
critical raw materials used in
Customer process; update with
changes as necessary
- Propose and jointly agree to - Right to approve vendor, grade and
specifications, vendors and grade of specifications of critical raw
critical raw materials used in Customer materials used in Customer process,
process in accordance with LB policy, with including excipients, and raw
preference for non-animal and non-human materials of animal or human origin
derived raw 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 samples - Right to audit
(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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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 specifications - Jointly agree on testing
and test methods to enable release of cell specifications and test methods to
banks for use in LB's multi-product enable Product manufactured from
manufacturing facility cell banks to be used in the clinic
- Perform stability testing of cell bank(s) - Right to audit
if contracted by Customer and share data
with Customer
IF CELL BANK SUPPLIED BY CUSTOMER
- Review and approve characterisation data. - Supply cell bank characterisation
Store working stock or cell bank data for review and approval.
Transfer cell bank (or portion
thereof) to LB
- Provide shipping validation data if - Right to audit
requested by Customer
IN ALL CASES
- Provide inventory levels periodically upon
request by Customer
5.0 Product Specification - With the Customer determine and approve - With LB determine and approve the
the following Product specification(s) as following Product specification(s)
required: as required:
- Drug substance (including testing - Drug substance (including
performed on fermenter contents for testing performed on fermenter
adventitious agents) contents for adventitious
agents)
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RESPONSIBILITIES AND RIGHTS
------------------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
------------------------------------ ----------------------------------------------- ----------------------------------------
6.0 Production and Process - Make available for review by Customer - Right to review
Control documents relating to facility, equipment,
Process and test methods, and GMP systems - Jointly review and approve Process
descriptions
- Jointly review and approve Process
descriptions - Agree in-process testing strategy
- Define and perform an in-process control - Right to review and comment on
and testing program strategy master batch records
- Using LB templates prepare master batch - Right to audit
records for each processing step and
provide to Customer for review and - Right to audit
comment. Retain final master batch record
on site at LB - Relevant sections of Customer's
regulatory submissions to be made
- Designate unique batch numbers for raw available to LB as appropriate
materials, process materials and Product
- Right to audit
- Manufacture of Product in accordance with
Product Specifications, cGMP standards, - Right to designate 1 of its
batch records, in-process controls and employees or consultants as
in-progress specifications Customer's person on plant, to be
present in LB's facility during
- Ensure QA representatives on-site or normal business hours to observe
available at all times during manufacture the Runs and observe LB's
and testing of Product performance, at times and for
durations to be agreed. While at
- Permit Customer's person on plant to be LB's facility, Customer's
present in LB's facility during normal representative shall comply with
business hours to observe the Runs and all of LB's applicable policies and
observe LB's performance, at times and for procedures, and, at LB's option,
durations to be agreed. While at LB's shall be escorted by LB personnel.
facility, Customer's representative shall Lonza must agree to all consultants
comply with all LB's applicable policies used by Trubion for person on plant
and procedures, and, at LB's option, shall activities
be escorted by LB personnel
- Review and comment on LB's policy
- Perform Product changeover testing of for Product changeover testing of
Product-contacting equipment in accordance Product-contacting equipment
with LB policy
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RESPONSIBILITIES AND RIGHTS
------------------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
------------------------------------ ----------------------------------------------- ----------------------------------------
7.0 Product Storage, Labelling - Store, label and package the Product - Right to audit
and Packaging Prior to (including samples) as defined in the
Shipment Product Specification - Provide information on shipping
requirements
8.0 Shipment Requirements - Ship Product on behalf of Customer to - Jointly agree with LB on process
locations designated by Customer in for shipping requirements
accordance with jointly agreed process for
shipping requirements - Right to audit
- With Customer agree on shipment date for - Acknowledge receipt of Product
Product
- Right to audit
- Provide shipping validation data for
Product if contracted by Customer
9.0 Laboratory Controls (QC) - Perform Product release testing against - Right to audit
Bulk Drug Substance Specifications
- Jointly agree on SOP's describing
- Jointly agree on SOP's describing Product-specific analytical testing
Product-specific analytical testing methods
methods
- Provide LB with Product-specific
- Retesting, where required, will be information as it relates to sample
performed in accordance with LB's retest storage, handling and testing
procedure. Out of specification (OOS) requirements
Product release testing results will be
notified to the Customer as soon as - Review and comment on LB retest
possible within 3 business days of the OOS procedure. Review OOS reports;
being confirmed comment on corrective and
preventative actions
- Send samples to Customer for additional
testing (including potency testing) in - Perform Product potency testing and
accordance with jointly approved SOP provide data to LB; such data will
be provided for LB's 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 QC - Retain representative samples of bulk - Right to audit
(Continued) Product from each batch in accordance with
LB SOP - Right to receive copies of raw data
and testing records
- If requested by Customer, provide copies
of raw data and testing records - Request additional samples to be
shipped as required
- Take additional representative samples if
requested and ship to Customer - Jointly approve Product reference
standard Protocol
- Prepare and characterise Product reference
standard in accordance with jointly agreed - Right to audit
Protocol, if contracted by Customer
- Jointly approve Product reference
- Jointly approve Product reference standard standard report
report
10.0 Use of Contract Testing - Qualify Contract Testing Laboratories for - Right to jointly audit
Laboratories Product release testing in accordance with
LB policy - Consent or reject to the proposed
use of Contract Testing
- Notify Customer of Contract Testing Laboratories
Laboratories intended to be used for
Product release testing - Right to audit
- Facilitate audit by Customer if requested - Right to request, receive and use
from time to time copies of LB's audits of Contract
Testing Laboratories when possible,
- If not prohibited by Contract Testing unless prohibited by Contract
Laboratory, provide Customer with copies Testing Laboratories
of LB's audits of Contract Testing
Laboratories when possible, if requested
11.0 Product Release and Lot - Review batch record for compliance with - Right to review completed and
Review cGMP, manufacturing controls, and with the reviewed Product batch records
Product Specifications
- Right to review
- Provide Customer with an 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
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RESPONSIBILITIES AND RIGHTS
------------------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
------------------------------------ ----------------------------------------------- ----------------------------------------
11.0 Product Release and Lot - If requested by Customer, send full - Right to request and receive full
Review (Continued) electronic copies of actual deviation copies of actual deviations
- Prepare manufacturer's Certificate of - Prepare Certificate of Analysis and
Analysis, including related Certificate of Certificate of Compliance for
Compliance release 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 Failed Run - Initiate investigations, evaluate and - Right to audit
Investigations and Reports define follow up actions and final
approval of deviations and failure - Review significant deviations;
investigations comment on corrective and
preventative actions
- Notify Customer of all significant
deviations within 24 hours or at least 3 - Review failure investigation report
business days of the event being assigned and comment on corrective and
as significant, and send Customer the preventative actions
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 runs within 24
hours or at least 3 business days of
failure being identified
- 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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RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
----- ----------------------------------------- -------------------------------------
13.0 Change Control Procedures CUSTOMER PROPOSED CHANGES
- Process Product-specific change - Propose Customer
through change control and notify Product-specific changes and
Customer of change approval. If provide rationale in writing
change rejected, discuss reasons for
rejection with Customer
- Approve proposed Product-specific
changes prior to implementation
LB PROPOSED CHANGES
- Propose Product-specific changes and - Process Product-specific change
provide rationale for change to through change control and
process descriptions; test methods; notify LB of change approval.
sampling plans; specifications for Customer approval for change
key raw materials (animal and / or controls will be needed 10 days
human derived raw materials, , from receipt If change rejected,
chromatography resins and final discuss reasons for rejection
formulation excipients); Product with LB
specification(s) and stability
programme, in-process controls and - Approve proposed
other key processing steps Product-specific change prior to
implementation
- Inform Customer of changes to key - Right to audit
personnel as identified in Appendix
1
- Inform Customer of changes to major - Right to audit
items of equipment, premises and
utilities used for manufacture of
Product
ALL CHANGES
- With Customer define strategy for - With LB define strategy for
notifying change to Regulatory. notifying change to Regulatory.
Agency as appropriate (see Section Agency as appropriate (see
20.0, below, Regulatory Submissions) Section 20.0, below, Regulatory
Submissions)
- Inform Customer of Product batches
manufactured with the change until - Ensure Product is not
regulatory approval obtained, if distributed until Regulatory
required approval obtained, if required
- Cooperate with Customer in
connection with change controls; - Cooperate with LB in connection
respect Customer's change controls, with change controls; respect
and, as appropriate, use it to LB's change controls, and, as
initiate LB's change controls appropriate, use it to initiate
Customer's change controls
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RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
---- ----------------------------------------- -------------------------------------
14.0 Reprocessing / Rework - Processing to be performed in - Review and comment on LB's
accordance with LB SOP. With reprocessing / rework SOP; with
Customer agree on and approve LB agree on reprocessing /
reprocessing / rework procedures, rework procedures, where
where possible prior to execution possible prior to execution
- Provided documented reason and - Right to audit
justification for reprocessing /
rework event
- With Customer agree on the - With LB agree on the appropriate
appropriate testing required prior testing required prior to
to Product release Product release
15.0 Audit - Permit Customer representatives - Provide reasonable notice of
access as reasonably required to intention to audit
conduct a cGMP compliance audit,
including access to warehousing, - Right to 2 standard cGMP
manufacturing areas, laboratories, compliance audits per year, plus
and manufacturing records and right to additional "for cause"
documents, including SOPS (unless audits
they contain specific LB proprietary
information eg media formulations), - Right to audit each batch record
and personnel, for audit purposes.
Customer representatives to be - Hold an exit meeting to discuss
accompanied at all times by LB observations
personnel
- Provide an audit report within
- *** cGMP compliance audits permitted 30 days of completion of audit
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 data to - Receive and investigate Product
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RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
---- ----------------------------------------- -------------------------------------
and Recall assist Customer in their complaints and instigate Product
investigation. Agree a time scale recall as appropriate
for response
17.0 Batch Records - Retain records associated with - Right to audit
manufacture and testing records of
Product including records associated - Customer to approve destruction
with the inspection and release of or request receipt of records
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 to destroy
records with option to send records
to Customer
18.0 Process Validation / - With Customer define process - With LB define process
Stability Studies validation plans for Product validation plans for Product
including analytical validation and including 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) including
protocol(s) for approval prior to stability protocols
execution
- Review and comment on
- Provide Customer with draft Product-specific validation
Product-specific validation report(s) including stability
report(s) for review and comment reports
- Issue Customer with copy of final
Product specific validation
report(s)
WHERE PROCESS VALIDATION IS PERFORMED BY
CUSTOMER
- Incorporate specifications in cGMP - Provide LB with process
documentation and regulatory validation reports
submissions
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RESPONSIBILITIES AND RIGHTS
---------------------------------------------------------------------------------
ITEM LB CUSTOMER(1)
------------------------------------ ----------------------------------------- -------------------------------------
19.0 Regulatory Agency Inspection GMP INSPECTIONS
- Inform Customer of Regulatory Agency - For Regulatory Agency
inspections or regulatory action inspections of regulatory action
affecting manufacture, testing or affecting Product, provide
storage of Product assistance when requested by LB
- Notify Customer of inspection - Common on proposed inspection
observations (including Deficiency responses to observations
Letters) affecting the Product, relevant to Product
process or systems relating to the
Product
20.0 Regulatory Submissions WHERE A DATA PACK IS PROVIDED BY LB TO
SUPPORT CUSTOMER'S CLINICAL TRIAL
APPLICATION
INITIAL APPLICATION, AMENDMENTS AND
RESPONSES TO QUESTIONS
- Provide Customer with data pack - Prepare and provide LB with copy
covering activities performed by LB of relevant sections of clinical
trial application for review and
- Review and comment on relevant comment prior to submission to
sections of clinical trial Regulatory Agency
application
- Provide LB with copy of relevant
sections as submitted to
Regulatory Agencies
TELECONFERENCES AND MEETINGS WITH THE
REGULATORY AGENCIES
- Attend teleconferences and meetings - Arrange for LB personnel to have
between the Customer and Regulatory option to attend teleconferences
Agencies arranged to specifically and meetings between Customer
discuss topics relating to LB's and Regulatory Agencies to
responsibilities specifically discuss topics
relating to LB's
responsibilities
[signatures on following page]
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QUALITY APPROVAL
LONZA BIOLOGICS ***
Name: *** Signature: ***
--------------------------- -----------------------------
Title: Date: December 5, 2005
--------------------------
TRUBION PHARMACEUTICALS, INC.
Name: Xxxxx Xxxxx Signature: /s/ Xxxxx Xxxxx
-----------------------------
Title: Senior Director Date: December 1, 2005
Page 14 of 15
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: _________
Page 15 of 15
