exv10w2






Exhibit 10.2








CERTAIN
CONFIDENTIAL PORTIONS OF THIS EXHIBIT WERE OMITTED AND REPLACED WITH “[***]”. A COMPLETE VERSION
OF THIS EXHIBIT HAS BEEN FILED SEPARATELY WITH THE SECRETARY OF THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO AN APPLICATION
REQUESTING CONFIDENTIAL TREATMENT UNDER RULE 24b-2 OF THE SECURITIES
EXCHANGE ACT OF 1934.





Quality Agreement

Commercial Product




Between



Avanir Pharmaceuticals, Inc.

a corporation existing under the laws of Delaware,

(hereinafter referred to as the “Client”)



-and-



Patheon Inc.,

a corporation existing under the laws of Ontario,



Specific sites covered by this Agreement:



[***]



(hereinafter referred to as “Patheon”)



Effective Date: January 19, 2010









 









 








               WHEREAS Patheon and Avanir have entered into a manufacturing services agreement dated January
4, 2006, as amended (the “MSA”), to which this Quality Agreement will form part of, wherein Patheon
agrees to provide pharmaceutical manufacturing services in respect of certain Products (as
described in Schedule A hereto);



               AND WHEREAS pursuant to the MSA, Avanir is required to provide the Specifications to Patheon
in order for Patheon to provide Manufacturing Services;



               AND WHEREAS pursuant to the MSA, Patheon is required to perform the Manufacturing Services in
accordance with the Specifications as provided;



               AND WHEREAS the parties desire to allocate the responsibility for procedures and
specifications impacting on the identity, strength, quality and purity of the Products;



               NOW THEREORE in consideration of the rights conferred and the obligations assumed under the
MSA and herein, and for other good and valuable consideration (the receipt and sufficiency of which
are acknowledged by each party), and intending to be legally bound the parties agree as follows:



SECTION I: RESPONSIBILITIES





1.1 Subject to the terms and conditions hereinafter set out the parties agree that
Patheon shall be responsible for all the operations that are marked with “X” in the column
titled “Patheon” and that Avanir shall be responsible for all the operations that are
marked with “X” in the column titled “Avanir.” If marked with “(X)”, cooperation is
required from the designated party.



 









 






	 	(a)	 	General





	 	 	 	 	 	 	 
	 	 	 	 	Avanir	 	Patheon
	1.

	 	Provide Specifications
	 	X	 	 
	 
	 	 	 	 	 	 
	2.

	 	Manufacture and package Product in strict adherence
to the Specifications.
	 	 	 	X
	 
	 	 	 	 	 	 
	3.

	 	Permit audits of all relevant premises, procedures
and documentation by Avanir, and permit inspection by
regulatory authorities.
	 	 	 	X
	 
	 	 	 	 	 	 
	4.

	 	Patheon may arrange for subcontractors to perform
specific testing services for Products and
Components; provided that (1) all such subcontractors
will be duly qualified by Patheon under GMP and
applicable Laws to perform such testing; (2) Patheon
will at all times remain fully responsible to Avanir
for the performance of all obligations pursuant to
the MSA related to such subcontracted testing
services; and (3) no subcontractors will be utilized
to perform release testing of the Product.
	 	 	 	X
	 
	 	 	 	 	 	 
	5.

	 	Provide copies of all information and correspondence
regarding Annual Product Reviews when requested by
Avanir.
	 	 	 	X
	 
	 	 	 	 	 	 
	6.

	 	Notify and obtain approval from Avanir prior to
implementation of any proposed changes to the
process, materials, testing, equipment or premises
that may affect the Product, such Avanir approval not
to be unreasonably withheld.
	 	 	 	X
	 
	 	 	 	 	 	 
	7.

	 	Notify Avanir within [***] of receipt of
any Form 483’s, warning letters or the like from
applicable regulatory agencies relating to: (i) the
Product, or (ii) if the supply of Products will be
affected, the facilities used to produce, test or
package the Product. Responses related to the product
shall be reviewed and approved by Avanir prior to
submission to the applicable regulatory agency,
provided that Patheon reserves the right to respond
to such regulatory agencies without approval, if, in
the reasonable opinion of Patheon’s counsel, it is
required to do so.
	 	 	 	X
	 
	 	 	 	 	 	 
	8.

	 	Notify Avanir within [***] of any
regulatory authority requests for Product samples,
Batch documentation, or other information related to
the Product.
	 	 	 	X
	 
	 	 	 	 	 	 
	9.

	 	Conduct operations in compliance with applicable
environmental, occupational health and safety laws
and cGMP regulations.
	 	 	 	X
	 
	 	 	 	 	 	 
	10.

	 	Investigate and resolve all medical and non-medical
Product complaints.
	 	X
	 	(X)
	 
	 	 	 	 	 	 
	11.

	 	Investigate all manufacturing type Product complaints.
	 	X
	 	X
	 
	 	 	 	 	 	 
	12.

	 	Initiate and control a Product recall.
	 	X
	 	(X)
	 
	 	 	 	 	 	 
	13.

	 	Liaise with Regulatory Authorities for approval,
maintenance and updating of marketing approval in a
timely manner.
	 	X
	 	(X)






 









 






	 	(b)	 	Validation and Process Testing Activities





	 	 	 	 	 	 	 
	 	 	 	 	Avanir	 	Patheon
	1.

	 	Establish applicable master validation plans and
maintain a validation program for the Product.
	 	X
	 	X
	 
	 	 	 	 	 	 
	2.

	 	Qualify (IQ/OQ) facilities, utilities and process
equipment.
	 	 	 	X
	 
	 	 	 	 	 	 
	3.

	 	Calibrate instrumentation and qualify computer
systems used in the manufacture and testing of the
Product.
	 	 	 	X
	 
	 	 	 	 	 	 
	4.

	 	Prepare and approve all performance qualification and
process validation protocols and reports, for
manufacturing, packaging, and analytical testing
operations.
	 	(X)
	 	X
	 
	 	 	 	 	 	 
	5.

	 	Review and approve master validation plan,
performance qualification and process validation
protocols and reports for the Product.
	 	X
	 	X
	 
	 	 	 	 	 	 
	6.

	 	Maintain an appropriate cleaning and cleaning
validation program.
	 	 	 	X
	 
	 	 	 	 	 	 
	7.

	 	Provide toxicological information to be used in the
development of a cleaning program.
	 	X	 	 
	 
	 	 	 	 	 	 
	8.

	 	Validate analytical test methods for finished Product.
	 	(X)
	 	X







	 	(c)	 	Raw Materials





	 	 	 	 	 	 	 
	 	 	 	 	Avanir	 	Patheon
	1.

	 	Provide the master formula.
	 	X	 	 
	 
	 	 	 	 	 	 
	2.

	 	Provide approved supplier list. Avanir to audit
and approve Component and Active Material
supplies and ensure cGMP compliance where Avanir
stipulates the supplier. Avanir stipulated
supplier shall be included on Avanir’s approved
supplier list (attached hereto as Schedule D).
Patheon to audit and approve Component and
Active Material suppliers and ensure cGMP
compliance as per Patheon SOP where Patheon
stipulates the supplier. Patheon stipulated
supplier shall be included on Patheon’s approved
supplier list (Schedule C). Avanir to audit and
approve, in its sole discretion, all Patheon
stipulated suppliers.
	 	X
	 	X
	 
	 	 	 	 	 	 
	3.

	 	Qualify and approve Active Materials supplier(s).
	 	X
	 	(X)
	 
	 	 	 	 	 	 
	4.

	 	Provide Active Materials specifications
(including Certificates of Analysis).
	 	X	 	 
	 
	 	 	 	 	 	 
	5.

	 	Procure Active Materials (including Certificates
of Analysis).
	 	X	 	 
	 
	 	 	 	 	 	 
	6.

	 	Provide test methods for Active Materials (if
non-Compendial).
	 	X
	 	X






 









 






	 	 	 	 	 	 	 
	 	 	 	 	Avanir	 	Patheon
	7.

	 	Validate non-Compendial testing methods for
Active Materials.
	 	X
	 	X
	 
	 	 	 	 	 	 
	8.

	 	Analyze and release Active Materials (including
documentation and Certificates of Analysis).
	 	(X)
	 	X
	 
	 	 	 	 	 	 
	9.

	 	Retain reference sample of Active Material for
[***] past the expiration date of the
last Batch of Product manufactured with that
material in the Product or such longer period
required by law.
	 	 	 	X
	 
	 	 	 	 	 	 
	10.

	 	Procure inactive ingredients (including
Certificates of Analysis).
	 	 	 	X
	 
	 	 	 	 	 	 
	11.

	 	Provide test methods and method validation for
inactive ingredients (if non-Compendial).
	 	X
	 	(X)
	 
	 	 	 	 	 	 
	12.

	 	Analyze and release inactive ingredients
(including documentation and Certificates of
Analyses).
	 	 	 	X
	 
	 	 	 	 	 	 
	13.

	 	Retain reference samples of inactive ingredients
for [***] past the expiration date of
the last Batch manufactured with that material
in the Product or such longer period as required
by law.
	 	 	 	X
	 
	 	 	 	 	 	 
	14.

	 	Provide to Avanir, at Avanir’s request, by means
of aBSE/TSE or melamine certificate of
compliance from the raw material vendor,
confirmation of any bovine, caprine, or ovine
derived raw materials purchased by Patheon for
the manufacture of Products.
	 	 	 	X







	 	(d)	 	Bulk Manufacture





	 	 	 	 	 	 	 
	 	 	 	 	Avanir	 	Patheon
	1.

	 	Create, control, issue and execute master batch record.
	 	 	 	X
	 
	 	 	 	 	 	 
	2.

	 	Approve master batch record.
	 	X
	 	X
	 
	 	 	 	 	 	 
	3.

	 	Document, investigate and resolve deviations from
approved manufacturing instructions or Specifications.
Report and obtain approval from Avanir representative
regarding Quality Deviation Report (“DR”) type
deviations (incidents where there is a potential to
affect Product quality). Provide copies of all DR’s to
Avanir as part of the executed master batch record.
	 	 	 	X







	 	(e)	 	Bulk Packaging





	 	 	 	 	 	 	 
	 	 	 	 	Avanir	 	Patheon
	1.

	 	Create, control, issue and execute master batch record.
	 	 	 	X
	 
	 	 	 	 	 	 
	2.

	 	Approve master packaging batch record.
	 	X
	 	X
	 
	 	 	 	 	 	 
	3.

	 	Provide specifications for packaging components.
	 	X
	 	X
	 
	 	 	 	 	 	 
	4.

	 	Qualify and approve packaging component suppliers.
Patheon to audit and approve packaging component
suppliers and ensure cGMP compliance as per Patheon
SOP where Patheon stipulates the supplier.
	 	(X)
	 	X






 









 






	 	 	 	 	 	 	 
	 	 	 	 	Avanir	 	Patheon
	 

	 	Patheon
stipulated supplier shall be included on its approved
supplier list (Schedule C). Avanir to audit and
approve, in its sole discretion, all Patheon
stipulated suppliers	 	 	 	 
	 
	 	 	 	 	 	 
	5.

	 	Provide test methods and method validation for
packaging components. Where applicable, Patheon will
provide such test methods and validation for packaging
components purchased from suppliers on the Patheon
approved supplier list only (Schedule C).
	 	(X)
	 	X
	 
	 	 	 	 	 	 
	6.

	 	Procure packaging components.
	 	 	 	X
	 
	 	 	 	 	 	 
	7.

	 	Analyze and release packaging components.
	 	 	 	X
	 
	 	 	 	 	 	 
	8.

	 	Retain reference samples of bulk Product for
[***] past Product expiry or such longer
period as required by law.
	 	(X)
	 	X
	 
	 	 	 	 	 	 
	9.

	 	Document, investigate and resolve any deviation from
approved packaging instructions or specifications.
Report and obtain approval from Avanir representative
regarding DR type deviations. Provide copies of all
DRs to Avanir as part of the executed master batch
packaging record.
	 	(X)
	 	X







	 	(f)	 	Testing & Release of Finished Product





	 	 	 	 	 	 	 
	 	 	 	 	Avanir	 	Patheon
	1.

	 	Provide finished Product specifications.
	 	X	 	 
	 
	 	 	 	 	 	 
	2.

	 	Supply/develop analytical test methods
for finished Product.
	 	X
	 	X
	 
	 	 	 	 	 	 
	3.

	 	Test finished Product.
	 	 	 	X
	 
	 	 	 	 	 	 
	4.

	 	Maintain all Batch records for a minimum
of [***] past Product expiry
date and supply all such records to
Avanir upon request.
	 	 	 	X
	 
	 	 	 	 	 	 
	5.

	 	Maintain records and evidence on the
testing of raw materials and
packaging/labelling materials for
[***] after the materials were
last used in the manufacture or
packaging/labelling of the Product.
	 	 	 	X
	 
	 	 	 	 	 	 
	6.

	 	Notify Avanir representative of
confirmed out-of-Specification results
(“OOS”) within [***]; Patheon
to generate DR and obtain approval of
the DR from Avanir representative.
	 	(X)
	 	X
	 
	 	 	 	 	 	 
	7

	 	Retain reference samples of finished
Product for two years past Product
expiry or such longer period as required
by law.
	 	(X)
	 	X







	 	(g)	 	Stability Testing (if required)





	 	 	 	 	 	 	 
	 	 	 	 	Avanir	 	Patheon
	1.

	 	Store stability samples.
	 	 	 	X
	 
	 	 	 	 	 	 
	2.

	 	Develop and validate stability indicating assay.
	 	(X)
	 	X






 









 






	 	 	 	 	 	 	 
	 	 	 	 	Avanir	 	Patheon
	3.

	 	Provide stability testing protocol for finished Product.
	 	X
	 	(X)
	 
	 	 	 	 	 	 
	4.

	 	Perform stability testing.
	 	 	 	X
	 
	 	 	 	 	 	 
	5.

	 	Notify Avanir of any stability failure for Product
supplied to Avanir within one business day.
	 	 	 	X






ARTICLE 2: COMPLIANCE BETWEEN PRODUCT REGISTRATION
AND THE MANUFACTURING PROCESS



2.1 Technical Changes





	 	(a)	 	     All proposed process changes shall be communicated to Avanir for initial review
and approval, such Avanir approval not to be unreasonably withheld. Avanir shall be
responsible for determining whether or not to initiate registration variation procedures
and for maintaining adequate control over the quality commitments of the marketing
authorization made to the regulatory authorities by Avanir for Products.
	 
	 	(b)	 	     Following validation of a process change, Patheon shall deliver a copy of the
related validation report to Avanir and the associated stability data, if applicable, as
it becomes available.




2.2 Labeling / Packaging Material Changes



Avanir may initiate changes and shall review and approve all Patheon-proposed changes to labeling
or packaging, including a change in the supplier of any labeling or packaging materials before any
such change may be implemented.



2.3 Other Changes



Patheon will not make any changes in storage, shipping, facilities or equipment that affect the
Product, or process or procedure used to manufacture the Product, without first obtaining written
approval from Avanir (such approval not to be unreasonably withheld).



2.4 Permits



Avanir shall be solely responsible for obtaining and maintaining, on a timely basis, any permits or
other regulatory approvals in respect of the Products or the Specifications, including, without
limitation, all marketing and post-marketing approvals.





 











 





SECTION 3: GENERAL





	3.1	 	Any communications about the subject matter of this Agreement will be directed, in the first
instance, to the person(s) identified in Appendix B.
	 
	3.2	 	Capitalized terms not otherwise defined herein will have the meaning specified in the MSA.
	 
	3.3	 	If any provision of this Agreement should be or found invalid, or unenforceable by law, the
rest of the Agreement will remain valid and binding and the parties will negotiate a valid
provision which meets as close as possible the objective of the invalid provision.
	 
	3.4	 	If this Agreement requires modification such that either party affected cannot be reasonably
expected to continue to perform under this Agreement, then the parties will negotiate and
revise the Agreement accordingly
	 
	3.5	 	Any amendment of this Agreement will be made in writing and signed by both parties.
	 
	3.6	 	This Agreement will start on the Effective Date that is set forth on the cover page of this
Agreement and will remain valid until all Quality obligations under all applicable MSA’s have
been fulfilled.




 









 











SECTION 4: DESCRIPTION OF RESPONSIBILITIES




4.1 Quality Management





	4.1.1	 	GMP, Health and Safety Compliance
	 
	 	 	Patheon will conduct operations in compliance with applicable environmental, occupational
health and safety laws, and cGMP regulations.
	 
	4.1.2	 	Client Audit Rights
	 
	 	 	Patheon will permit audits on reasonable prior written notice, of all relevant premises,
procedures and documentation by the Client; to the extent such audits are related to Client’s
Product. Client audits are limited to [***] per [***] unless for cause.
	 
	4.1.3	 	Subcontracting
	 
	 	 	Patheon will not subcontract tasks to a third party without Client’s consent. Patheon may
subcontract raw material testing to other Patheon facilities and to other qualified third
party laboratories.
	 
	4.1.4	 	Self-Inspection
	 
	 	 	Patheon will perform self-inspections of its premises, facilities, and processes used to
manufacture, package, test, and store the Client’s starting, intermediate, and/or finished
products in accordance with Patheon’s written standard operating procedures (“SOP’s”) to
ensure compliance with cGMP and this Quality Agreement.





4.2 Regulatory Requirements





	4.2.1	 	Permits
	 
	 	 	The Client will be solely responsible for obtaining or maintaining, on a timely basis, any
permits or other regulatory approvals for the Products or the Specifications, including,
without limitation, all marketing and post-marketing approvals.
	 
	 	 	Patheon will obtain and maintain the appropriate manufacturing license(s) to allow for the
Manufacturing services.
	 
	4.2.2	 	Regulatory Filing / Registration Change Control
	 
	 	 	The Client will determine whether changes to the Product or related to the Product will
impact a regulatory filing and will apply for and receive approval for any required
manufacturing amendment, change or addition to their Product marketing authorization. Upon
request, Patheon will provide assistance in the preparation and review of pertinent sections
of new or supplemental regulatory applications before filing. The Client will provide
Patheon copy of sections of product registration/regulatory submissions that




 









 












	 	 	are relevant to the manufacture of the Product. The Client is responsible for all
communications with Regulatory Authorities as well as for the approval, maintenance, and
updating of marketing approval in a timely manner.
	 
	4.2.3	 	Regulatory Compliance
	 
	 	 	Patheon will ensure that Product(s) are manufactured and tested in strict compliance with
current US Federal and EC regulatory and statutory requirements relating to Good
Manufacturing Practices (GMP) (US 21 CFR parts 210 and 211 for the manufacture of finished
medicinal product) as applicable, regulatory approvals and local laws and regulations
applicable at the site(s) of manufacture and/or testing.
	 
	4.2.4	 	Government Agency Inspections, Communication and Requisitions
	 
	 	 	Patheon will permit all relevant inspections by regulatory authorities of premises,
procedures, and documentation.
	 
	 	 	Patheon will notify the Client within [***] of receipt of any notice of inspection
from a regulatory authority and within [***] of any regulatory authority request
for Product samples, batch documentation, or other information related to the Product.
	 
	 	 	Patheon will notify the Client within [***] of receipt of any Form 483’s warning
letter or the like from any regulatory agency that relates to the Product; or if the supply
of Product will be affected, or if the facilities used to produce, test or package the
Product will be affected.
	 
	 	 	The responses from Patheon related to the Product will be reviewed and approved by the Client
prior to submission to the regulatory agency. Notwithstanding, Patheon reserves the right to
respond to the regulatory agency without approval, if, in the reasonable opinion of Patheon’s
Legal counsel, it is required to do so.





4.3 Material Control





	4.3.1	 	Test Methods and Specifications
	 
	 	 	The Client will give Patheon a copy of the Specifications and test methods used if the Client
issues raw material Specifications.
	 
	4.3.2	 	Material Destruction
	 
	 	 	Patheon has the right to either return to the Client or dispose of any outdated or rejected
material. If the material is disposed of, disposal will be consistent with the nature of the
material and sent to a permitted waste disposal facility. Prior to such disposal:




 









 












	 	(i.)	 	Patheon will send notice to the Client about Patheon’s intent to dispose of the
material. If no direction is received from the Client, Patheon will dispose of the
material no sooner than [***] after the date of the notice.
	 
	 	(ii.)	 	The materials will be disposed and destroyed in compliance with local environmental
regulations and performed in a secure and legal manner that prevents unauthorized use or
diversion.






	 	 	Patheon will maintain destruction records in accordance with Patheon SOP’s.





4.3.3 Vendor Audit Responsibility




4.3.3.1 Excipient and API Vendors:





	 	(i.)	 	If the Client stipulates an excipient or API vendor, the Client will audit
and approve the manufacturers and ensure cGMP compliance in accordance with Section
4.3.4 of this Agreement. The Client stipulated vendor(s) will be included on the
Client’s approved vendor list (attached hereto as Appendix D).
	 
	 	(ii.)	 	If Patheon stipulates the excipient vendor, Patheon will audit and approve
the manufacturers and ensure cGMP compliance in accordance with Patheon’s SOP. The
Patheon stipulated vendor(s) will be included on Patheon’s approved vendor list
(attached hereto as Appendix C).





4.3.3.2 Packaging Component Vendors::





	 	(i.)	 	If the Client stipulates a packaging component vendor, the Client will audit
and approve the manufacturer and ensure cGMP compliance. The Client stipulated
vendor(s) will be included on the approved vendor list (attached hereto as Appendix
D).
	 
	 	(ii.)	 	If Patheon stipulates the packaging component vendor, Patheon will audit and
approve the manufacturer and ensure cGMP compliance in accordance with Patheon’s SOP.
The Patheon stipulated vendor(s) will be included on the approved supplier list
(Appendix C).






	4.3.4	 	Client Furnished Materials
	 
	 	The Client is responsible for vendor qualification of Client furnished materials and for
providing a certificate of compliance confirming the following:






	 	(i)	 	That the materials are compliant with the provisions outlined in the “Note for
Guidance on minimizing the risk of transmitting spongiform
encephalopathy agents via human and veterinary medicinal products” (EMEA/410/01, Rev.2
or update) and




 









 












	 	(ii)	 	A residual solvent certificate confirming that there is no potential for
specific toxic solvents listed in the EP / USP / ICH residual solvents Class I, Class II
or Class III to be present and the material, if tested, will comply with established EP
/ USP / ICH requirements. If any of the solvents listed in the EP / USP / ICH residual
solvents Class I, Class II or Class III are used in the manufacture or are generated in
the manufacturing process, solvents of concern will be indicated.






	4.3.5	 	In-Coming Material Release
	 
	 	Prior to its use in the manufacture of any Product all material(s) will be inspected, tested
and released by Patheon against the Specification approved by the Client.





4.4 Building, Facilities, Utilities and Equipment 





	4.4.1	 	General
	 
	 	All buildings and facilities used in the manufacturing, packaging, testing and storage of any
materials and/or Product will be of suitable size, construction and location to facilitate
cleaning, and will be maintained in a good state of repair. Maintenance and cleaning records
will be kept in accordance with Patheon’s SOP’s.
	 
	4.4.2	 	Equipment, Calibration and Preventative Maintenance
	 
	 	All equipment used in the manufacturing, packaging, testing and stage of any materials and/or
Product will be suitable for its intended use and appropriately located to allow for cleaning
and maintenance. Calibration and maintenance records will be kept according to Patheon SOP’s
for all critical equipment. Patheon will calibrate instrumentation and qualify computer
systems used in the manufacture and testing of the Product in accordance with Patheon’s
SOP’s.
	 
	4.4.3	 	Environmental Monitoring Program
	 
	 	Patheon will perform and maintain an environmental monitoring program. The collected data
will be reviewed and interpreted by the responsible person within Patheon’s quality unit.
Any out of limit results will be managed appropriately in accordance with Patheon SOP’s.





4.5 Production Controls





	4.5.1	 	Master Batch Record
	 
	 	 	The Client will provide the Specifications to Patheon and Patheon will manufacture Product in
accordance with the Specifications.




 









 












	 	 	Patheon is responsible for preparing the master batch records for the Product, however, the
Client is responsible to review and approve such master batch records prior to the
manufacture of the Product.
	 
	 	 	Patheon will not make changes to master batch records except through the established Patheon
change control system, and all master document revisions will be approved by the Client .
Any changes made to issued batch records (prior to master revisions) must be reviewed and
approved by the Client’s quality unit prior to implementation unless otherwise agreed to in
writing.






	4.5.2	 	Reprocessing and Rework
	 
	 	Patheon will not reprocess or rework the Product without the prior written consent from the
Client.
	 
	 	Reprocessing is defined as the introduction of material back into the process and repeating a
step, (e.g. redrying, remilling) using the same equipment and techniques of the established
manufacturing process.
	 
	 	Rework is defined as the introduction of material to one or more processing steps that are
different from the established manufacturing process.
	 
	4.5.3	 	Personnel Training
	 
	 	Patheon will provide appropriate training for all employees. Each person engaged in the
manufacture, packaging, testing, storage, and shipping of the Product will have the
education, training, and experience necessary, consistent with current GMP and safety
training requirements.





4.6 Packaging, Labeling and Printed Materials





	4.6.1	 	Master Batch Packaging Records
	 
	 	The Client will provide Patheon with the Specifications for all packaging components. Patheon
will create, control, issue, and execute in accordance with the master batch packaging record
and the Specifications.
	 
	 	Patheon will not make changes to master batch packaging records except through the
established Patheon change control system, and all master document revisions will be approved
by the Client. Any changes made to issued batch records (prior to Master revisions) must be
reviewed and approved by the Client prior to implementation unless agreed to in writing.
	 
	4.6.2	 	Printed Material and Artwork
	 
	 	The Client will provide artwork and labelling text (blister, carton, leaflet, label etc.)
Specifications to Patheon. The labelling proofs must be reviewed and approved by the Client.




 









 












	4.6.3	 	Test Methods and Method Validation
	 
	 	 	The Client will provide test methods and method validation for packaging components to
Patheon. Where applicable, Patheon will provide test methods and validation for packaging
components purchased from vendors on the Patheon approved vendor list only (Appendix C).





4.7 Exception Reports (Deviations / Investigations) 





	4.7.1	 	Manufacturing Instruction Deviations
	 
	 	 	Patheon will document, investigate and resolve deviations from approved manufacturing
instructions or Specifications in accordance with Patheon’s SOP’s. Patheon will report and
obtain approval from the Client’s responsible person for deviation report (“DR”) type
deviations where there is a potential to affect Product quality. Such Client approval will
not be unreasonably withheld. Patheon will provide copies of all DR’s to the Client as part
of the executed batch record.
	 
	4.7.2	 	Packaging Instructions Deviations
	 
	 	 	Patheon will document, investigate, and resolve any deviation from approved packaging
instructions or Specifications according to Patheon SOP’s. Patheon will report and obtain
approval from the Client’s responsible person for DR type deviations where there is a
potential to affect Product quality. Such Client approval will not be unreasonably withheld.
Patheon will provide copies of all DR’s to the Client as part of the executed batch
packaging record.
	 
	4.7.3	 	Notification of Deviations
	 
	 	 	Patheon will notify the Client within [***] if any significant deviation occurs
during manufacture of the Product, where such deviation affects the quality, efficacy or
availability of the Product.





4.8 Release of Product





	4.8.1	 	Test Methods and Specifications
	 
	 	 	The Client will provide to Patheon the finished Product Specifications and will develop and
supply validated analytical test methods to Patheon for the finished Product.
	 
	4.8.2	 	Batch Release for Shipment
	 
	 	 	Batch review and release for shipment to the Client will be the responsibility of Patheon’s
Quality Assurance department who will act in accordance with Patheon’s SOP’s.




 









 












	4.8.3	 	Certificate of Compliance
	 
	 	 	For each batch released by Patheon for shipment to the Client, Patheon will deliver to the
Client a certificate of compliance that will include a statement that the batch has been
manufactured in accordance with cGMPs and the Specifications.
	 
	4.8.4	 	Product Release
	 
	 	 	The Client will have sole responsibility for release of the Product to the market. When
Patheon qualified person (“QP”) services are employed, Patheon QP may release the Product for
distribution on behalf of the Client.





4.9 Validation





	4.9.1	 	Master Validation Plan
	 
	 	 	Patheon will establish applicable master validation plans and maintain a validation program
for the Product. The Client will review and approve the master validation plan, performance
qualification and process validation protocols and reports for the Product.
	 
	4.9.2	 	Cleaning Validation Program
	 
	 	 	The Client will provide to Patheon toxicological information to be used in the development of
a cleaning program. Patheon will maintain an appropriate cleaning and cleaning validation
program.
	 
	4.9.3	 	Analytical Method and Procedure Validation
	 
	 	 	The Client must ensure that its analytical methods and manufacturing procedures (including
packaging procedures) are validated. If the methods and procedures are not validated by the
Client, then Patheon may assist in validation development with the costs being borne by the
Client.





4.10 change control





	4.10.1	 	General
	 
	 	 	Patheon will notify and obtain approval from the Client before implementing any proposed
changes to the process, materials, testing, equipment or premises, where such changes may
directly affect the Product. This Client approval will not to be unreasonably withheld.
	 
	 	 	The Client will be responsible for determining whether or not to initiate registration
variation procedures and for maintaining adequate control over the quality commitments of the marketing authorization made to the regulatory authorities by
the Client for the Products.




 









 












	 	 	Following validation of a process change, Patheon will deliver a copy of the related
validation report to the Client and the associated stability data, if applicable, as it
becomes available.





4.11 Documentation





	4.11.1	 	Record Retention
	 
	 	 	Patheon will maintain all batch records for a minimum of [***] past Product
expiry date and supply all these records to the Client upon request.
	 
	 	 	Patheon will maintain records and evidence on the testing of raw materials and
packaging/labeling materials for [***] after the materials were last used in the
manufacture or packaging/labeling of the Product.
	 
	 	 	At the end of the above noted retention period, the Client will be contacted concerning the
future storage or destruction of the documents.
	 
	4.11.2	 	Batch Document Requisition
	 
	 	 	At the request of the Client, Patheon will provide a copy of any of the executed batch
documents relating to Products to the Client within [***] of such request.





4.12 Laboratory Controls





	4.12.1	 	Specifications and Test Methods
	 
	 	 	Patheon will test and approve starting material, intermediate, and the finished Product in
accordance with the approved Specifications, analytical methods, and Patheon’s SOP’s.
	 
	 	 	The Client will provide to Patheon the Active Material Specifications including a
certificate of analysis
	 
	 	 	The Client will provide to Patheon test methods for Active Material and excipients (if
non-compendial). The Client is responsible for validating non-compendial testing methods.
If these methods are not validated by the Client, then Patheon may assist in validation
development with the costs being borne by the Client.
	 
	4.12.2	 	Out of Specifications (OOS) / Out of Trend (OOT)
	 
	 	 	Patheon will notify Client of confirmed out-of-Specification (“OOS”) or out-of-trend
(“OOT”) results within [***]. Patheon will generate a DR type deviation as per Patheon SOP’s and obtain approval of the DR from the Client’s responsible
person within their quality unit. This Client approval will not be unreasonably withheld.




 









 











4.13 Stability





	4.13.1	 	Sample Storage
	 
	 	 	Patheon will store stability samples as required.
	 
	4.13.2	 	Stability Studies and Protocol
	 
	 	 	The Client will develop and validate stability indicating assay(s) prior to process
validation. If required, Patheon may assist with the cost being borne by the Client.
	 
	 	 	If applicable, Patheon will conduct stability studies in accordance with the agreed and
validated stability testing analytical methods at the agreed upon testing points in
accordance with the approved stability protocol.
	 
	 	 	Patheon will perform the stability testing described in a stability protocol agreed to by
both Patheon and the Client. Stability data will be provided by Patheon to the Client on
an ongoing basis as agreed to by both parties.
	 
	4.13.3	 	Stability Failures
	 
	 	 	Patheon will notify the Client of any stability failure for Product supplied to the Client.
If a result indicates that a Product has failed to remain within stability Specifications,
Patheon will notify the Client within [***].
	 
	4.13.4	 	Termination of MSA
	 
	 	 	If the MSA is terminated, Patheon will continue to provide the Client with stability data
supporting the acceptability of the Product until all Product distributed by the Client has
reached the end of its shelf-life.





4.14 Annual Product Review





	4.14.1	 	General
	 
	 	 	The Client will complete the annual product review in accordance with regulatory
requirements of the Product marketed authorization. Patheon will provide copies of all
information and correspondence necessary to support the annual product reviews when
requested by the Client.





4.15
Storage and Distribution



	 
	4.15.1	 	General
	 
	 	 	Patheon will ship Product in accordance with the agreed qualified transportation
requirements provided by the Client to Patheon.




 









 












	4.15.2	 	Product Storage and Shipment Changes
	 
	 	 	Patheon will communicate any proposed changes in storage or shipping to the Client for
review and approval. The Client approval will not be unreasonably withheld.
	 
	4.15.3	 	Product Quarantine
	 
	 	 	Patheon will have a system in place for assuring that unreleased Product is not shipped
unless authorized by the Client’s representative.





4.16 Product Complaints





	4.16.1	 	Complaint Investigation
	 
	 	 	The Client will investigate and resolve all medical and non-medical Product complaints.
Patheon will investigate all Patheon manufacturing and packaging type Product complaints
related to the Manufacturing Services provided. The Client will retrieve complaint
sample(s) and forward them to Patheon in a timely manner to facilitate a complete and
comprehensive investigation.





4.17 Product Recall 





	4.17.1	 	Product Recall Notification
	 
	 	 	The Client will notify Patheon about a Product recall or other regulatory type product
notification (e.g. field alert) as soon as possible, but, in any event, prior to informing
the appropriate regulatory authorities. The Client will be responsible for all related
recall activities.
	 
	4.17.2	 	Government Agency Notification
	 
	 	 	The Client will perform the Product recall and will inform the appropriate regulatory
authorities. Where legislated, Patheon reserves the right to notify regulatory authorities
of Product quality issues. Patheon will inform the Client prior to any notification to the
regulatory authorities.





4.18 Reference and retention Samples





	4.18.1	 	Excipient and Active Ingredient Reference Sample
	 
	 	 	Patheon will keep a reference sample of each material received by Patheon and used to
manufacture the Product. The reference sample will consist of at least [***] the
necessary quantity for all Quality Control tests required to determine whether the
materials meet required Specifications.
	 
	 	 	The reference samples will be stored by Patheon under controlled conditions in accordance
with GMP storage requirements for [***] beyond the expiration date of the last
batch of the product containing the




 









 






	 	 	     materials. The reference samples will be made available by Patheon to the Client, if requested






	4.18.2	 	Finished Product Retention Sample
	 
	 	 	Retention samples of finished Product will be retained by Patheon for one (1) year past
Product expiry or such longer period as required by law. Where applicable, the legal
sample(s) of finished Product must be retained by the Client.





* * *



IN WITNESS WHEREOF, the parties have caused their duly authorized officer to execute and deliver
this Quality Agreement as of the Effective Date identified on the first page:













	 	 	 	 	 	 	 	 	 

	AVANIR PHARMACEUTICALS, INC	 	 	 	PATHEON, INC
	 
	 	 	 	 	 	 	 	 
	Name:    Randall E.
Kaye
	 	 	 	Name:
   Brian Dale

	 

	 	 
	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 
	Signature:

	 	/s/ Randall E. Kaye	 	 	 	Signature:	 	/s/ Brian Dale
	 

	 	 
	 	 	 	 	 	 
	 
	 	 	 	 	 	 	 	 
	Date:    January 9,
2010
	 	 	 	Date:
   January 19, 2010

	 

	 	 
	 	 	 	 	 	 






 











 




SECTION 5: APPENDES





	 	•	 	Appendix A: Product(s)
	 
	 	•	 	Appendix B: Avanir Contacts
	 
	 	•	 	Appendix C: Patheon Approved Supplier List
	 
	 	•	 	Appendix D: Client Approved Supplier List
	 
	 	•	 	Appendix E: Patheon Approved Contract Laboratories List




 









 
















APPENDIX A: PRODUCT(S)




	 	 	 	 	 
	Products (s)	 	Galenic Form	 	Dosage (Strength)
	[***]

	 	[***]
	 	Dextromethorphan HBr/Quinidine

Sulfate [***]
	 
	 	 	 	 
	[***]

	 	[***]
	 	Dextromethorphan HBr/Quinidine

Sulfate [***]






	 	 	 

	Quality Agreement 

QG01-05-T001-01

	 	






 









 











APPENDIX B: QUALITY CONTACTS




	 	 	 	 	 
	 	 	Patheon	 	Avanir
	Responsibility

	 	Quality Assurance
	 	General
	Name

	 	[***]	 	 
	Title

	 	[***]	 	 
	Phone

	 	[***]	 	 
	Fax
	 	 	 	 
	E-mail

	 	[***]	 	 
	Address
	 	 	 	 
	 
	 	 	 	 
	Responsibility

	 	Regulatory Affairs
	 	Regulatory Affairs
	Name

	 	[***]
	 	[***]
	Title

	 	[***]
	 	[***]
	Phone

	 	[***]
	 	[***]
	Fax
	 	 	 	 
	E-mail

	 	[***]
	 	[***]
	Address
	 	 	 	 
	 
	 	 	 	 
	Responsibility

	 	Product Complaints
	 	Audits
	Name

	 	[***]	 	 
	 
	 	 	 	 
	 
	 	 	 	 
	 
	 	 	 	 
	 
	 	 	 	 
	Address
	 	 	 	 
	 
	 	 	 	 
	Responsibility

	 	Product Release	 	 
	Name

	 	[***]	 	 
	Title
	 	 	 	 
	Phone
	 	 	 	 
	Fax
	 	 	 	 
	E-mail
	 	 	 	 
	Address
	 	 	 	 
	 
	 	 	 	 
	Responsibility

	 	Account Manager	 	 
	Name
	 	 	 	 
	Title
	 	 	 	 
	Phone
	 	 	 	 
	Fax
	 	 	 	 
	E-mail
	 	 	 	 
	Address
	 	 	 	 






	 	 	 

	Quality Agreement 

QG01-05-T001-01

	 	






 









 











APPENDIX C: PATHEON APPROVED VENDOR LIST




	 	 	 	 	 
	SAP Code	 	Material Description	 	Manufacturer
	[***]

	 	[***]
	 	[***]
	[***]

	 	[***]
	 	[***]
	[***]

	 	[***]
	 	[***]
	[***]

	 	[***]
	 	[***]
	[***]

	 	[***]
	 	[***]
	[***]

	 	[***]
	 	[***]
	[***]

	 	[***]
	 	[***]
	[***]
	 	[***]
	 	[***]
	[***]

	 	[***]
	 	[***]
	[***]

	 	[***]
	 	[***]
	[***]

	 	[***]
	 	[***]
	[***]

	 	[***]
	 	[***]
	[***]

	 	[***]
	 	[***]
	[***]

	 	[***]
	 	[***]






	 	 	 

	Quality Agreement 

QG01-05-T001-01

	 	






 









 











APPENDIX D: CLIENT APPROVED VENDOR LIST




	 	 	 	 	 
	SAP Code	 	Material Description	 	Supplier/Manufacturer
	[***]

	 	[***]
	 	[***]
	 

	 	 	 	[***]
	 
	 	 	 	 
	[***]

	 	[***]
	 	[***]
	 

	 	 	 	[***]






	 	 	 

	Quality Agreement 

QG01-05-T001-01

	 	






 









 











APPENDIX E: PATHEON APPROVED CONTRACT LABORATORIES LIST




	 	 	 
	Contract Laboratory	 	Location
	[***]

	 	[***]
	[***]

	 	[***]
	[***]

	 	[***]
	[***]

	 	[***]
	[***]

	 	[***]
	[***]

	 	[***]
	[***]

	 	[***]
	[***]

	 	[***]
	[***]

	 	[***]






	 	 	 

	Quality Agreement 

QG01-05-T001-01