[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

EXhibit 10.45

QUALITY AGREEMENT
ON MANUFACTURING AND TESTING
OF BULK DRUG SUBSTANCE

Between

Alder BioPharmaceuticals, Inc.

11804 North Creek Parkway South, Bothell, WA 98011 U.S.A.

as CONTRACT GIVER, subsequently named Alder

And

SANDOZ GmbH

Biochemiestrasse 10, A-6250 Kundl

as contract CONTRACTOR, subsequently named SANDOZ

 

 

 

 

 

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE v2.0

 

TABLE OF CONTENTS

PREAMBLE/PURPOSE5

1.SCOPE of the QUALITY AGREEMENT5

2.General Provisions (Quality assurance)6

 

2.1. Directives and Guidelines

6

 

2.2. Regulatory Activities

7

 

2.3. Validation

7

 

2.4. Manufacturing, packaging and testing instructions and Specifications

8

 

2.5. Alder Audits

8

 

2.6. Regulatory Inspections

10

 

2.7. Person in Plant (Long Term)

11

 

2.8. Product Quality Review

12

 

2.9. Subcontracting

12

 

2.10. Facility, Equipment, and Computer Systems Qualification and Validation

13

 

2.11. Change Management and Approval

14

 

2.12. Changes to Processes and Premises

14

 

2.13. SANDOZ Document Notification, Review, and Approval

16

 

2.14. Influence on Quality by Foreign Materials

16

 

2.15. BSE/TSE-Assessment

16

 

2.16. Deviations, Corrective and Preventative Actions, and Quality Events

17

 

2.17. Non-conforming BDS

19

 

2.18. Recall/Supply Recovery

19

 

2.19 Biological Product Deviation Report (BPDR)

19

3.Raw MaterialS20

 

3.1. Cell Banks

20

 

3.2. Supply of Raw Materials by Alder

21

 

3.3. Procurement of Raw Materials by SANDOZ

21

 

3.4. Sampling

22

 

3.5. Storage

22

4.Manufacturing of Product IN THE cONTRACT mANUFACTURING pHASE22

 

4.1. Cell Banks

22

 

4.2. MPD Document; Batch Manufacturing and Packaging Records

22

 

4.3. Reprocessing and Rework

24

 

4.4. Review of Batch Documentation

24

 

4.5. Warehousing

25

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

2/73CONFIDENTIAL

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE v2.0

 

4.6. Packaging for Dispatch and Transport

25

 

5.

Testing of Products26

 

5.1. Method Transfer, Qualification, and Validation

26

 

5.2. Sampling

27

 

5.3. Testing of Products

27

 

5.4. Out of Specification Results

28

 

5.5. Microbiological Control Program

29

6.ARCHIVING OF Samples and Documentation29

7.Release of Products30

 

7.1. Release for shipment – pre-requisites

30

 

7.2. Shipment under Quarantine

32

8.Product Security32

 

8.1. Waste Material

32

9.Post-Marketing Surveillance and Stability Testing32

 

9.1. Stability Testing

32

 

9.2. Product Complaints

33

 

9.3. Adverse Events

33

10.Terms and Expiration34

11.DEFINITIONS34

12.Version History (Core Document)38

13.APPROVALS (Core Document)39

 

ATTACHMENTS TO THE QUALITY AGREEMENT

 

ATTACHMENT A:

List of QA/QC Liaisons

 

ATTACHMENT B:

Table of Responsibilities

 

ATTACHMENT C:

List of Approved Sub-Contractors

 

ATTACHMENT D:

List of Raw Materials for ALD403 including Critical Raw Materials

 

ATTACHMENT E:

Release Requirements for Cell Banks

 

ATTACHMENT F:

Min/Max doses for change over cleaning calculation for ALD403

 

ATTACHMENT G:

Storage condition / Shelf life

 

ATTACHMENT H:

SANDOZ Release Specifications

 

ATTACHMENT I:

Alder Release Specifications

 

ATTACHMENT J:  

Additional Release Specifications

 

ATTACHMENT K:  

Document Notification/Review/Approval Sheet

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE v2.0

 

ATTACHMENT L:

Critical Reagents and Reference Standards

 

ATTACHMENT M:  

BDS Labeling

 

ATTACHMENT N:

Change Control Notification/Approval Requirements

 

ATTACHMENT O:

SANDOZ biopharmaceutical manufacturing facilities applicable to ALD403

 

ATTACHMENT P:

Sandoz Batch Release Support Information – Detailed Content Requirements

 

ATTACHMENT Q:

Review of Batch Documentation – QC Test Results Documentation to be Provided
with Batch Documentation

 

ATTACHMENT R:

Change history of the Quality Agreement core document

 

 

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

4/73CONFIDENTIAL

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE v2.0

PREAMBLE/PURPOSE

Alder is a company engaged in the development, manufacture, and
commercialization of biopharmaceutical products, including eptinezumab (also
known as ALD403).

SANDOZ holds a manufacturing license issued by FDA and EMA for the facilities in
Kundl, Austria and is obliged to maintain the license.  SANDOZ shall inform
Alder about any change or withdrawal of such authorization without undue delay.

A Contract Manufacturing Agreement dated effective as of 4 May 2015 (executed
12-Jul-2016) has been signed between the parties (CMA), under which SANDOZ
agreed to manufacture for Alder eptinezumab (also known as ALD403) Bulk Drug
Substance (BDS).

This QUALITY AGREEMENT relates to and is the “Quality Agreement” referred to in
the CMA.

The purpose/scope of this QUALITY AGREEMENT is to define the compliance
requirements and responsibilities for the quality and regulatory  operations
between SANDOZ and Alder for the Manufacture by SANDOZ of BDS, for use in
validation and qualification in preparation for regulatory filings and for
commercial human use (or, prior to marketing approval, clinical human use),
according to the applicable Legal Requirements (including without limitation ICH
Guideline Q5, Q7, and Q10, 21 CFR Parts 11, 210, 211, and 600 and 611 et seq.,
EU Guidance on Good Manufacturing Practice Parts I, II and III, and other
regulations as applicable to BDS manufacture), as amended from time to time.
Each party agrees to perform its obligations under this QUALITY AGREEMENT in
accordance with the CMA, this QUALITY AGREEMENT, and the applicable Legal
Requirements.  

1.SCOPE of the QUALITY AGREEMENT

This QUALITY AGREEMENT forms an integrated part of the CMA.  The scope of this
QUALITY AGREEMENT includes the SANDOZ biopharmaceutical manufacturing facilities
at: Biochemiestrasse 10, 6250 Kundl, Austria. Refer to Attachment O for the
buildings applicable to the BDS manufactured by SANDOZ in the Commercial
Facility at the Kundl site.

This QUALITY AGREEMENT shall be reviewed periodically for accuracy and
compliance with the cGMP regulations by both parties according to Alder’s
established review schedule at a minimum. The QA/QC liaisons for quality matters
are defined in Attachment A. The roles and responsibilities of each party are
summarily listed in Attachment B. A list of Alder subcontractors and a list of
SANDOZ approved subcontractors for testing ALD403 is provided in
Attachment C.  The list of Raw Materials, including Critical Raw Materials, for
the Manufacture of ALD403 is provided in Attachment D.  The SANDOZ release
requirements for Cell Banks and a listing of released cell banks are provided in
Attachment E. The dosages to be used for SANDOZ changeover cleaning calculations
is provided in Attachment F.  The storage condition and shelf life for ALD403 is
provided in Attachment G.  The SANDOZ Release Specifications for BDS Product are
listed in Attachment H.  The Alder Release Specifications for BDS

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE v2.0

Product are listed in Attachment I.  The Additional Release Specifications for
BDS are listed in Attachment J.  The form for document approval/notification is
provided in Attachment K.  Critical Reagents and Reference Standards are listed
in Attachment L. Required elements for BDS Labeling are described in Attachment
M. Change Control notification/approval requirements are described in Attachment
N.  Buildings applicable to the BDS manufactured by SANDOZ in the Commercial
Facility at the Kundl site are listed in Attachment O. Detailed content
requirements associated with SANDOZ Batch Release Support Information are listed
in Attachment P.  The QC in-process samples and BDS test results documentation
(including raw data) to be provided as part of the Batch documentation are
defined in Attachment Q. Change history of the Quality Agreement core document
is summarized in Attachment R.

This QUALITY AGREEMENT is comprised of this core document and the
Attachments.  The Attachments are subject to this core document, but are
separately approved, by the quality responsible persons only, and may be
periodically updated. This core document and each of the Attachments has its own
Version History to document changes and the rationales for their acceptability.

This QUALITY AGREEMENT initially spanned the [***] and [***] phases per the
definitions in the CMA, and, as amended, it now also covers the [***] the
[***].  

The effective date of the Quality Agreement core document and the initial
version of the Attachments will be the date of the last approval signatures. The
effective dates of any subsequent versions of each of the Attachments will be
the date of the last approval signature.

In the event of a conflict between this QUALITY AGREEMENT and the CMA, the CMA
shall control and prevail (Reference CMA Clause 37(10).)

2.General Provisions (Quality assurance)

2.1. Directives and Guidelines

Alder is responsible to provide the current information regarding
filing/registration documentation.

SANDOZ has the responsibility to Manufacture BDS and make BDS available for
shipping to Alder according to the registration documentation (e.g., IND, BLA)
and cGMP in accordance with the CMA, this QUALITY AGREEMENT, and applicable
Legal Requirements, including US FDA 21 CFR Parts 11 / 210 / 211 / 600, ICH
Guideline Q7 and EU Guidance on Good Manufacturing Practice Parts I, II and III
and other agency regulations as applicable to BDS Manufacture.

If not otherwise defined in this QUALITY AGREEMENT, the CMA or applicable Legal
Requirements, the provisions of SANDOZ quality management system and standard
operating procedures shall be applied to SANDOZ’S operations.

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE v2.0

Each party will participate in the Technical Committee and Joint Steering
Committee (JSC) activities. (Reference CMA Clause 2.)  Meetings shall be
attended, in person or through telecommunications (telephone, video conference,
etc.), by senior management in the quality and manufacturing departments of both
parties.  SANDOZ and Alder shall mutually agree to the quality metrics (in
accordance to ICH Q10 expectations) to be monitored, tracked and presented at
the meeting.  

2.2. Regulatory Activities

Alder will be responsible for filing of regulatory submissions related to the
Product or the BDS in EU, USA and other countries.  All updates to regulatory
applications related to Product are the responsibility of Alder.

SANDOZ will provide Regulatory Support Services, including providing to Alder
all necessary information which it may possess pertinent to BDS to ensure global
regulatory filings are current and up-to-date.  (Reference CMA Clause 8.)

In connection with Regulatory Authority requests or submission preparation or
other regulatory activities, Alder will provide a written request via Attachment
K to SANDOZ for Manufacturing-related documents, as applicable. SANDOZ shall
provide to Alder upon request verified data that is used for BDS- or
Product-specific documents.

Prior to regulatory submissions, Alder will provide copies of the draft relevant
[***] to SANDOZ for review and an opportunity to comment to support compliance
with regulatory requirements. SANDOZ will provide comments within [***], unless
different timing is mutually agreed.

Alder will within [***] provide copies to SANDOZ of [***].  SANDOZ will within
[***] notify Alder of any changes in SANDOZ’s regulatory status or changes in
its filings that relate to or would potentially affect the ability of SANDOZ to
perform its obligations under this QUALITY AGREEMENT or the CMA, or which would
potentially affect the status of any regulatory filing of Alder.

2.3. Validation

Alder and SANDOZ jointly completed the BDS-related validation activities
(including testing supporting process validation) as set forth in Attachments B
and C. Process validation documentation for the BDS were approved by both SANDOZ
and Alder as part of the Validation Lot Campaign (VLC). Transport Validation
remains the responsibility of Alder.

2.3.1 ALD403 Process Additional Validation

The Process may be amended in writing from time to time by agreement of the
Parties in accordance with the change control process set forth in this QUALITY
AGREEMENT.  SANDOZ shall not change the Process except at the request of or with
permission from Alder. (Reference CMA 1 Clause 1 – “Process” definition)

2.3.2 Ongoing Process Verification (aka. Continued Process Verification)

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE v2.0

Alder and SANDOZ will jointly agree on the OPV Monitoring Plan/OPV Assessment
documents before the start of OPV.  Any subsequent Changes to these documents
will be subject to change control or document revision lifecycle requiring joint
approval prior to implementation.  Investigations and CAPAs resulting from the
OPV Assessment will be jointly reviewed and approved.

2.4. Manufacturing, packaging and testing instructions and Specifications

SANDOZ shall be responsible for ensuring the safe operation of the Manufacture
of the BDS in its premises.

SANDOZ shall apply the agreed control procedures (comprising specifications as
well as methods) for the BDS. The testing control procedures, BDS specifications
and methods will be issued by SANDOZ in their system.  SANDOZ will assure that
the conversion of the BDS specification into SANDOZ’S documentation is accurate,
updated as appropriate and that a cross-reference to the appropriate Alder
specification(s) is referenced in the source document.

SANDOZ must ensure that each person engaged in the Manufacturing, processing,
analytical testing, or handling of the BDS, shall be trained according to SANDOZ
local procedures. SANDOZ training shall be in current Good Manufacturing
Practices and the particular operations that the person performs.  Training in
applicable manufacturing regulations shall be conducted by SANDOZ qualified
individuals on a continuing basis and with sufficient frequency to assure that
each person employed or retained by SANDOZ remains familiar with requirements
applicable to them. This training must be documented in a training record for
each person employed or retained by SANDOZ and training records must be
maintained. (Reference CMA Clause 27(1) and 27(2).)

2.5. Alder Audits

Upon SANDOZ receipt of [***] notice from Alder, SANDOZ will permit employees or
authorized representatives of Alder [***] to conduct routine compliance audits
and inspection of all documents, processes, equipment, operations, quality
systems and facilities of SANDOZ applicable to the Manufacture of the BDS in the
biopharmaceutical facilities at Kundl, Austria (hereinafter an “Audit”).
(Reference CMA Clause 21.)  The scope and manner of each Audit shall be
determined [***] provided, however, that Alder shall conduct such Audits only
(a) during regular business hours, or at the time that SANDOZ is Manufacturing
the BDS, or when the plant is idle or at such other times when Alder can conduct
such Audits without adversely affecting the confidentiality obligations that
SANDOZ owes to its other customers, and (b) for the purpose of making quality
control inspections, which may include inspection of the facilities, etc., used
in the Manufacture, warehousing and shipping of Product, to ensure compliance
with the CMA, this QUALITY AGREEMENT and applicable Legal Requirements. Without
limitation to the foregoing, Alder shall be entitled (a) to conduct [***], and
(b) to conduct [***], each of which shall be conducted in the manner to be
determined by Alder in consultation with SANDOZ. For the [***], SANDOZ will
permit up to [***] For the [***] to conduct the audit.

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE v2.0

Additionally, Alder shall be entitled to conduct “For Cause” audits as required
in connection with critical issues such those presenting a high risk to product
quality [***].  For Cause audits do not require [***] advance notice, but the
timing of a For Cause audit [***]

Alder will provide a written report to SANDOZ within [***].  SANDOZ will provide
Alder with a written response within [***] to any written Audit observations
made by Alder. SANDOZ’s written response shall include expected timelines for
corrective and preventative actions to address Alder’ written observations as
necessary. Upon request, SANDOZ shall complete, and shall provide periodic
updates for the status of completion of, these corrective and/or preventive
actions.  Alder reserves the right to conduct a For Cause audit for any critical
observations that are not satisfactorily addressed through the audit responses.

[***]

2.6. Regulatory Inspections

SANDOZ shall allow Regulatory Authorities to inspect facilities, operations and
quality systems, as necessary to facilitate, obtain or maintain the Regulatory
Approvals, regulatory filings or registrations. SANDOZ will within [***] notify
Alder of general cGMP inspections and/or legal actions relating to the SANDOZ
biopharmaceutical facilities, operations or quality systems that are utilized
for BDS Manufacture, or which otherwise might adversely impact SANDOZ’s ability
to Manufacture BDS, and the proposed corrective actions.

For Product pre-approval inspections, Alder shall have the right to have [***]
if allowed by the Regulatory Authorities; other Alder representatives may be
present in the ancillary areas of SANDOZ facilities to provide support to
Product-related aspects of the inspection; and SANDOZ will provide an update to
Alder at the end of each day regarding inspection progress and potential
issues.  SANDOZ Quality team will coordinate with SANDOZ Manufacturing team to
synchronize the BDS Manufacturing schedule with the PAI regulatory inspection.

For general cGMP inspections, Alder shall have the right to have [***] if
allowed by the Regulatory Authorities; and other Alder representatives may be
present in the ancillary areas of SANDOZ facilities to provide support to
Product-related aspects of the inspection.  

For general cGMP inspections that include ALD403 BDS or Process, SANDOZ will
provide an update to Alder at the end of each day regarding inspection progress
and potential issues related to ALD403 BDS or Process.

For general inspections that involve the production facilities and systems
supporting ALD403 BDS Manufacture, SANDOZ will notify Alder of inspection
outcomes (to include at a minimum[***]) within [***] of the end of the
inspection.  

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

9/73CONFIDENTIAL

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE v2.0

SANDOZ must within [***] notify Alder about critical issues encountered during
regulatory inspections that may have the potential to adversely affect the
SANDOZ premises or facilities, the quality of Product or Process, or the quality
system.  Critical issues are those for which a high risk related to product
quality, safety, product recall, or regulatory enforcement action has been
identified.

SANDOZ shall provide to Alder, within [***] after receipt by SANDOZ, a written
copy of any inspection reports, inspection observations and/or legal actions
with or by Regulatory Authorities relating to: Product pre-approval inspections
(PAI’s), or general cGMP inspections if ALD403 BDS or Process is addressed
within the conduct of the inspection. The reports may be redacted if needed to
ensure client confidentiality of other SANDOZ clients as well as SANDOZ
products.

SANDOZ shall provide Alder with any and all draft responses to regulatory
observations or replies to regulatory inquiries that relate to the Product or
Process.  Alder shall review draft responses and

provide written feedback within [***]. SANDOZ and Alder will work cooperatively
on the responses related to the Product or Process.

For pre-approval and general cGMP inspection observations, SANDOZ shall provide
notification to Alder within [***] of the knowledge that closure of such
observation would impact the Product approval, timing of Product approval, the
Manufacture of BDS, Process, or the timing of the Manufacture of BDS. The
parties will discuss and develop mutually agreed solutions to stay on track with
the Product approval and BDS Manufacture.

If SANDOZ is required by any governmental authority or Regulatory Authority to
have inspected or approved the site of Manufacturing or storing the Product or
any Raw Materials, SANDOZ shall permit and cooperate with officials of the
Regulatory Authority to inspect such sites.

SANDOZ shall secure Alder’s written agreement prior to making any commitments to
any Regulatory Authority observations relevant to Product.

Alder will not provide any official information related to SANDOZ premises and
facilities to a Regulatory Authority without written consent of SANDOZ.

2.7. Person in Plant (Long Term)

Alder shall have the right to provide Alder employees on SANDOZ premises for the
purpose of information exchange and coordinating reviews, approvals, or other
actions required by this QUALITY AGREEMENT, including person-in-plant rights
during production under the CMA, and as otherwise agreed to by Alder and SANDOZ
in writing. (Reference CMA Clause 21(1) and Clause 21(4).)

Upon SANDOZ’s receipt of [***] prior notice from Alder (or as mutually agreed),
Alder may, [***], place [***] at SANDOZ’s manufacturing facility. Alder’s
representatives at SANDOZ shall accept SANDOZ’s procedures regulating external
customer relationships (including cGMP training, hygiene, confidentiality and

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE v2.0

controlled access to facilities and documents) and will obtain SANDOZ’s
agreement prior to any active participation in the Process or analytical
testing.  (Reference CMA Clause 21(1).)  SANDOZ’s obligation to allow visitors
who are [***] is on condition that: (a) such visitors agree in writing to
observe the reasonable customary requirements of SANDOZ regarding security,
health and safety, confidentiality or any other applicable regulations at the
relevant premises (provided, however, that Alder employees shall not be required
to sign a separate confidentiality agreement); (b) any visit shall be under the
specific supervision of SANDOZ (without relieving any visitors of any
obligations with respect to any damage or injury caused by them); and (c) Alder
uses reasonable endeavors to ensure that any visit and the number of visits is
of minimal disruption to SANDOZ day-to-day business. Alder shall provide SANDOZ
with reasonable notice prior to each such visit, communicate to SANDOZ the
reason for each such visit and ensure that such visits are made by relevant
personnel only. Alder, in consultation with SANDOZ, will develop an agenda for
each such visit. (Reference CMA Clause 21(4).)

[***], SANDOZ and Alder will work collaboratively to assure BDS quality, and, as
part of Alder’s quality oversight obligations, Alder will be permitted to be
onsite at the Commercial Facility, in collaboration with SANDOZ, for on-going
discussions, document exchanges, and review of quality topics between their
respective quality units.  With [***] advance notice and mutual agreement on the
timing of the visits, SANDOZ shall provide Alder with on-site access to staff,
and on-site [***] access to documentation, data ([***]), and records that are
relevant to Alder’s quality oversight obligations.

2.8. Product Quality Review

Alder is responsible for submitting the Annual Product Review (APR) to the
authority as the Product license holder. SANDOZ will issue a product quality
review report, which will serve as an input to Alder’s APR per SANDOZ internal
procedures. The review report shall comply with the current requirement of
21CFR211.180(e). Timelines associated with the product quality review report and
the APR deliverables will be agreed jointly.

2.9. Subcontracting

SANDOZ is entitled to subcontract the work or part of the work entrusted by
Alder to the sub-contractors listed in Attachment C, subject to compliance with
the CMA, this QUALITY AGREEMENT, and change control management. If SANDOZ wishes
to retain any new subcontractors, SANDOZ shall obtain the written approval of
Alder before using any such subcontractor (through revision of Attachment
C).  (Reference CMA Clause 37(7).) SANDOZ shall establish written service
agreements and written technical/quality agreements with its sub-contractors
prior to commencement of the subcontracted work.  Any change of the
subcontracting service level or new sub-contractors requires Alder’s prior
written approval and will be subject to change control management. SANDOZ shall
remain solely and fully responsible for the performance of the work by
sub-contractors in accordance with the requirements set forth in the CMA and

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE v2.0

this QUALITY AGREEMENT. (Reference CMA Clause 37(7).) SANDOZ shall oblige its
sub-contractors to comply with the applicable terms of the CMA and this QUALITY
AGREEMENT, including informing SANDOZ on changes relevant to the registration of
Product, such as to the manufacturing location and procedures and to the
equipment and materials used. SANDOZ must ensure that such sub-contractors will
accept foreign and local governmental authorities to inspect facilities,
operations and quality systems, as it is necessary to facilitate, obtain or
maintain the Product approvals of the Regulatory Authorities, including the
investigational new drug application and the registration of Product.

SANDOZ shall audit each sub-contractor prior to using that sub-contractor
according the respective SANDOZ SOP.  Alder shall have the right to review the
SANDOZ annual audit summary of sub-contractors and the evidence of
technical/quality agreements relating to the sub-contractors used for the
Manufacture of BDS during the annual audit.  

SANDOZ must qualify their contracted testing laboratories to ensure that there
is appropriate and required equipment, qualification and training to perform the
necessary testing. (Reference CMA Clause 6(6).)

2.10. Facility, Equipment, and Computer Systems Qualification and Validation

SANDOZ shall ensure that Alder may review at the Kundl facility the records
relating to the Assets and the Facility Modifications (Reference CMA, Clause 1
(1) and Clause 4 (1)) including the applicable change control/summary detailing
the outcomes and validation of the Facility Modifications.

SANDOZ shall maintain a system to ensure that premises, environment,
laboratories, utilities, equipment, computerized systems and other systems that
support the manufacturing operations, including the Assets and Facility
Modifications, are properly designed, validated and maintained in accordance
with cGMP.  SANDOZ shall perform required process equipment, facility and
utility maintenance at periodic and predefined frequencies (as defined in SANDOZ
procedures) to ensure that appropriate maintenance and upkeep is performed on
premises, environment, laboratories, utilities, equipment, computerized systems,
and other systems that support the manufacturing operations, including the
Assets and Facility Modifications.

SANDOZ will ensure appropriate separation and controls are in place for
operation for multi‑product facility.

Approved validation protocols, reports, testing protocols, raw data and system
operation procedures relating to the Product shall be available for consultation
by Alder while on-site or during audits.

2.11. Change Management and Approval

Changes to this QUALITY AGREEMENT and its relevant Attachments shall only be
made by mutual agreement between the parties, and must be in writing and
recorded on the Version History of this QUALITY AGREEMENT core document and the
individual Attachments.

Change control is an integral part of cGMP and requires a mutually agreed change
control process to ensure both Alder and SANDOZ adequately assess any proposed
change to the Manufacture of the BDS.

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE v2.0

Changes that are subject to this Section include without limitation changes to
this QUALITY AGREEMENT itself, changes to the Manufacturing of the BDS, changes
to the BDS Specifications (Attachment H, Attachment I and Attachment J)
(Reference CMA Clause 19), and changes relevant to the registration of the
Product, such as to the Manufacturing location and Manufacturing procedures,
automation controls, process controls, or to the equipment, utilities, and Raw
Materials used. Furthermore, changes that could potentially interfere with the
quality of the Product, such as to the testing or release procedures,
instructions and specifications, must be evaluated as part of and are subject to
Change Control management and approval.  Refer to Attachment N for approval
requirements relating to Change Control.

2.12. Changes to Processes and Premises

SANDOZ or Alder shall prepare a change control request in writing, in advance
and in English, using a mutually agreed process, including changes relevant to
Product-related regulatory submissions or the registration status of Product and
on changes that could potentially impact the quality, safety, efficacy and/or
supply of Product.  Refer to Attachment N for examples of changes.

 

•

SANDOZ or Alder, as applicable, shall prepare a change request in writing. In
this document the following items shall be defined: [***]

Alder is responsible to review and evaluate the regulatory impact of any
proposed change on the product license.  SANDOZ is responsible to review the
regulatory impact of any proposed change on the facility license.  

In general, Alder shall without delay evaluate each change request from SANDOZ
and respond to SANDOZ within [***] with comments/approval/denial, as
applicable.  Similarly, SANDOZ shall without delay evaluate each change request
from Alder and respond to Alder within [***] or per timelines mutually agreed
(e.g. changes linked to regulatory commitments).  If the period cannot be met,
the receiving party will notify the change initiating party about the current
status of the evaluation and endeavor to fully respond to the initiating party
as soon as possible under the circumstances. SANDOZ shall implement the change
per agreed timing after Alder and SANDOZ approval. SANDOZ shall provide actual
timing and listing of initial Batch(es) associated with change to Alder.

For the avoidance of doubt, SANDOZ may, at any time, [***] notification to Alder
and in accordance with any applicable provisions of this QUALITY AGREEMENT,
undertake any change (including routine maintenance and repair work) to any of
its premises or facilities or equipment directly used in the Manufacture of BDS;
provided that any such change shall not impact nor have the potential to impact
the safety, efficacy, quality, identity, strength, purity, registration, and/or
supply of the Product.

Emergency corrective action shall be taken by SANDOZ if necessary to resolve
urgent unacceptable situations related to quality and safety during the ongoing
Process. Such emergency changes can be implemented prior to evaluation and
approval by SANDOZ QA department if permitted under SANDOZ

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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procedure, but the SANDOZ QA department must be notified within [***] after
implementation. SANDOZ shall inform the person-in-plant prior to implementation,
if feasible.  SANDOZ has the right to implement such emergency changes without
prior written approval of Alder, but will notify Alder in writing within [***]
after implementation. Alder will provide an impact assessment [***] after
notification.

Registration relevant change proposals that have been approved by Alder can only
be implemented permanently after obtaining approval from the competent
Regulatory Authorities.   Alder will duly inform SANDOZ after having received
such approvals and the expected deadline for implementation by SANDOZ.

Requirements relating to Raw Material changes are described in section 3.3 and
Attachment N.

SANDOZ will use [***] to implement changes required by a Regulatory Authority,
and will use [***] to implement changes requested by Alder.  

2.13. SANDOZ Document Notification, Review, and Approval

All GMP Documentation, changes and activities subject to ALDER approval or
notification will be handled according to Attachment K of this QUALITY
AGREEMENT. Confidential documents will be exchanged with ALDER via secure e-mail
or an appropriate exchange platform ([***]).

If acceptable, SANDOZ will document such changes according to SANDOZ change
control SOP (Reference CMA Clauses 4, 7, 18, 19 and 20).

2.14. Influence on Quality by Foreign Materials

SANDOZ must refrain from any activity which could adversely affect the safety,
efficacy, identity, strength, purity, or quality of Product.

SANDOZ will not introduce, use or conduct any production activities with
herbicides, pesticides or any known toxins, penicillin, cephalosporin, beta
lactams, cytotoxic products, live vaccines or any other material, product or
process that could reasonably present a potential hazard to Product in the
biopharmaceutical facility or equipment used for Manufacture of BDS.  

Prior to introduction of a new product into the SANDOZ biopharmaceutical
facility, SANDOZ shall maintain the necessary engineering and procedural
controls to minimize the cross-contamination potential of the Product with
cytotoxic or pharmacologically active starting materials at the SANDOZ
facility.  SANDOZ shall immediately provide written notification to Alder in
advance of the use or the planned use of a human cell line to be manufactured at
SANDOZ facility in which the Product is manufactured.  

SANDOZ shall maintain a policy for product changeover for multi-use equipment
used for Manufacture of Product.  [***] as per approved procedures prior to
Manufacture of BDS. SANDOZ shall confirm that all product changeover test
results meet acceptance criteria prior to Release of BDS. SANDOZ shall supply to
Alder upon request product changeover reports that demonstrate acceptability of
changeover results.

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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SUBSTANCE v2.0

SANDOZ shall [***] as defined in SANDOZ procedures between Batches of BDS.

2.15. BSE/TSE-Assessment

All Raw Materials obtained by SANDOZ from a third party and employed in the
Manufacture of the Product will conform with the Note for Guidance on Minimizing
the Risk of Transmitting Animal Spongiform Encephalopathy Agents via Human and
Veterinary Medical Products (EMA-Guidance EMA/410/01 Rev. 3, or applicable
current version).  

SANDOZ shall supply to Alder a signed BSE/TSE-Risk statement for the BDS that
declares if raw materials of animal origin are used, and for those raw materials
that are of animal origin, an evaluation of the animal origin and an assessment
on whether the materials are in compliance with EMA-Guidance EMA/410/01 Rev. 3
or applicable current version.  SANDOZ shall update the BSE/TSE-Risk statement
[***], and as required due to changes in sourcing of raw materials.  

Upon Alder request, SANDOZ shall provide Alder with the necessary BSE/TSE
Certificates of Compliance for each Raw Material where applicable (e.g.., as
part of Audit or regulatory submission).  Under no circumstance shall SANDOZ use
any bovine-derived material from any country at-risk for the transmission of BSE
(relevant for Product).

2.16. Deviations, Corrective and Preventative Actions, and Quality Events

SANDOZ categorizes unplanned events into either Quality Events, Minor, Major or
Critical deviations (see Section 11 for definitions).

Deviation/OOS/OOE must be handled according to the corresponding SANDOZ standard
operation procedure. Deviations related to Manufacturing (including those
originating from an OOS or OOE) must be reported to Alder in writing where
possible within the timelines defined below. Major and Critical Deviations
related to Manufacturing (including confirmed OOS and OOE) shall be provided by
SANDOZ to Alder as a draft report for Alder review within [***] from the date of
initial discovery. In the instance that an Alder deviation confirms an issue
with the Product or Process and identifies the need for a CAPA, Alder will
notify SANDOZ within [***] of the need of CAPA and jointly agree on the plan.

 

Event Type

(See section 11 – Definitions)

Timelines for written notification after date of discovery by SANDOZ

Quality record submitted to Alder for:

Closed record provided

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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SUBSTANCE v2.0

Event Type

(See section 11 – Definitions)

Timelines for written notification after date of discovery by SANDOZ

Quality record submitted to Alder for:

Closed record provided

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

 

SANDOZ deviations shall include root cause determination, product impact
assessment, and identification of CAPA (corrective action / preventive action)
as appropriate.  

Alder will respond in writing [***] with comments related to the major or
Critical Deviation or that the deviation is acceptable as written.  SANDOZ shall
provide a written response to the Alder comments indicating changes to the
deviation report and justification for Alder comments that are not included with
the revised deviation report.  Alder shall review SANDOZ response and
communicate any additional comments to SANDOZ.  SANDOZ will work cooperatively
with Alder to address comments prior to final closure.

Product related Quality Events as unplanned events that are relevant to Product
disposition and Minor deviations will be provided to Alder upon SANDOZ approval
and prior to or at SANDOZ Product disposition.

[***] The target for approval of final deviation reports is [***]

SANDOZ shall maintain a system to ensure the timely completion of
corrective/preventive actions (CAPA) identified from deviations related to the
Product.  SANDOZ shall provide to Alder a listing of Product-related CAPAs, and
their due dates [***] and, as applicable, CAPA effectiveness verifications.  On
a case by case basis, SANDOZ will provide closed Product-related CAPAs resulting
from deviations [***]

2.17. Non-conforming BDS

Non-conforming BDS is handled according to the CMA. (Reference CMA Clauses 15,
18 and 20, and also reference Section 7 of this Agreement.). Any complaints by
Alder  that a Batch, or one or more samples in a Batch, is not conforming with
the requirements under CMA Clause 18(1) (such BDS being referred to as
“Non-conforming” BDS, and such non-conformity referred to as “Non-conformity”)
shall be delivered to SANDOZ in writing [***] with such complaint being
accompanied by supporting data for purposes of consideration and verification by
SANDOZ. Attachment K will be used for notification of the Nonconformity as a
“Nonconformity Customer Complaint.”

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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2.18. Recall/Supply Recovery

Alder, through the designated group that manages Product recalls, is responsible
for the final recall decision according to the CMA. (Reference CMA Clause 29.)
In the event Alder commences a recall of Product, Alder shall provide SANDOZ
with a written request of any and all data and information needed for an orderly
recall.  SANDOZ shall respond to Alder’s written request [***]   SANDOZ will
fully cooperate with Alder in providing any data requested to support a recall
decision and give reasonable assistance in conducting any such recall or
disposal.  Such data should be provided as a matter of urgency but, in any case,
[***]

Alder may undertake and SANDOZ will provide information to Alder in connection
with mock recalls, and Alder will notify Project Management and Site Quality
Head [***] in advance of any mock recall for administrative purposes
only.  SANDOZ will not notify its staff prior to a mock recall.  

2.19 Biological Product Deviation Report (BPDR)

Upon identification by ALDER that an event requires reporting to the FDA, for
product that was manufactured at SANDOZ, SANDOZ will be notified [***]
(Attachment K). A reportable BPDR is associated with an unexpected event or an
event related to the manufacturing of a licensed and commercially distributed
biological product that represents a deviation from cGMP, regulations,
standards, or specifications, that may affect a distributed product's safety,
purity and potency. SANDOZ shall complete the investigation for the significant
deviation and provide the results of the investigation to ALDER as soon as
reasonably possible and [***] after SANDOZ acquires information reasonably
suggesting a reportable event under cGMP regulations. ALDER shall write the BPDR
and submit to SANDOZ as a draft for review and comment prior to ALDER submission
of BPDR to FDA. ALDER must submit the BPDR to FDA within FDA required timelines
from the date SANDOZ acquires information reasonably suggesting a reportable
event under cGMP regulations. Alder shall provide a copy of the filed BPDR to
SANDOZ.

3.Raw MaterialS

3.1. Cell Banks

[***] (may be referred to as WCB or MWCB) and [***]. Alder is responsible for
ensuring testing of the cell banks is performed prior to shipment of cell banks
to SANDOZ according to Attachment E. The parties shall jointly agree if there
are additional testing requirements. SANDOZ will release the cell banks for
production according to local procedures. Only SANDOZ- and Alder QA-released
cell banks will be used for cGMP Manufacturing at SANDOZ.

Alder will provide the C of A, C of C (if applicable), and cell line
characterization data summary for each Working Cell Bank shipped to SANDOZ (see
Attachment E).  SANDOZ will review the cell line characterization data, storage
conditions and SANDOZ’s cell bank storage procedures prior to release into

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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SUBSTANCE v2.0

SANDOZ’s facility. SANDOZ may perform cell bank testing upon review and
agreement by Alder (according to approved internal procedures) to ensure that
the cell bank is free of adventitious agents.  

[***] shall store Alder cell banks under appropriate conditions and with
appropriate segregation of Alder cell banks from other cell banks, as per [***]
approved procedures. [***]

Alder will be responsible for cell bank shipping. SANDOZ shall send the cell
bank shipper temperature recording device to Alder for review after each
shipment.  Alder shall send to SANDOZ documentation to indicate the
acceptability of the cell bank shipment temperature.  SANDOZ shall review the
cell bank documentation according to local SOPs prior to release of the Working
Cell Bank for cGMP Manufacture (refer to Attachment E).  SANDOZ shall notify
Alder of SANDOZ disposition/release [***] of SANDOZ disposition via Attachment K
(including the SANDOZ batch number and corresponding Alder batch number).

SANDOZ shall utilize Working Cell Banks [***] Alder is responsible for providing
reassessment dates and supplying necessary documentation including updated CoA
based on performed reassessment to SANDOZ, unless otherwise agreed.

Alder may order the preparation of a new master and working cell
bank.  (Reference CMA Clause 3(2).)  [***].

3.2. Supply of Raw Materials by Alder

[***]. In the event that Alder needs to deliver specific Raw Materials required
for cGMP Manufacture of BDS, an agreement would be required by both parties,
and, if both parties agreed thereto, then Attachment D would be annotated
accordingly. In this respect Alder (or its supplier) would need to be qualified
as a raw material supplier for those respective Raw Materials according to
SANDOZ procedures.

3.3. Procurement of Raw Materials by SANDOZ

Refer to Attachment D to this QUALITY AGREEMENT for the required list of Raw
Materials (including those designated as “Critical Raw Materials”), including
the supplier, grade and other required quality parameters and specifications
agreed by both parties for the Manufacture of Product.

SANDOZ is responsible for sourcing all Raw Materials required for Manufacture of
Product. Alder has reviewed the SANDOZ Raw Material specifications referenced in
Attachment D as part of the technical transfer and in support of the [***]
manufacturing campaign, and subsequently has reviewed in support of the Contract
Manufacturing Phase.  For Critical Raw Materials for which the supplier and
supplier’s item number are identified in Attachment D, only the identified item
number from that supplier is allowed for use in production.  For non-critical
Raw Materials, multiple suppliers may be used if the supplied Raw Material is of
the same or higher grade, and the material passes pre-determined specifications,
and is a SANDOZ-approved supplier. Raw Material changes will be managed
according to Attachment N.

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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Refer to Attachment N for classification of Raw Material /Consumable Changes and
related level of customer (Alder) approval required.

SANDOZ must procure Raw Materials from the SANDOZ approved suppliers. Procured
Raw Materials have to be qualified, inspected and tested for compliance by
SANDOZ with the approved specifications as defined. SANDOZ shall inform Alder
[***]on recalls or call-back of material by suppliers and brokers, for quality
or safety reasons if the material was used for the Manufacture of Product.  Only
SANDOZ released Raw Materials and consumable items shall be used for Manufacture
of Product.

3.4. Sampling

SANDOZ must take samples of all Raw Materials and Auxiliary Materials according
to local procedures. Unless otherwise agreed in writing, sampling for testing
(at least identity) of the Raw Materials must be performed. Reserve samples of
Raw Material must be kept according to local procedures.

3.5. Storage

Storage containers and storage/transport conditions must ensure that the
specified quality of Raw Material is not compromised; SANDOZ will store Raw
Materials under appropriate storage conditions according to SANDOZ SOPs and
information from the supplier.

4.

Manufacturing of Product IN THE cONTRACT mANUFACTURING pHASE

4.1. Cell Banks

Under the CMA, [***].  

4.2. MPD Document; Batch Manufacturing and Packaging Records

The MPD Document (Reference CMA Clause 18(5)) consists of ALD403-specific
manufacturing SOPs and ALD403-specific master batch records, describing the
Process and covering all steps, [***].  For Batches Manufactured in the Contract
Manufacturing Phase, BDS shall be Manufactured in accordance with the validated
Process, reflected in the MPD Document and all process parameters and in-process
control results for each successful Batch will be reviewed against the Process
described in the MPD Document.  (Reference CMA Clause 18(5).)

SANDOZ shall assure that all BDS is Manufactured in accordance with the Process,
the BDS Specifications, cGMP and (as applicable) the requirements of the FDA and
the EMA, including corresponding manufacturing procedures and packaging
instructions, and that all process parameters and in-process control results for
each successful Batch are reviewed against the Process described in the MPD
Document. (Reference CMA Clause 18(1).)  

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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When a change is approved through change control (refer to Sections 2.11-2.12),
SANDOZ will submit proposed BDS specific master batch records to Alder for
approval before the change can be implemented.  SANDOZ will supply the proposed
records to Alder [***] to allow [***]. Master batch documentation is written in
[***]. SANDOZ shall provide deviation reports (including Reportable Deviations,
OOS and OOE / Out of Trend (OOT) reports), change controls, development and
technical reports related to the Product, and process validation reports as
applicable to Alder written in [***]. Revision of Product-specific documents
including but not limited to the most current versions of [***] process
validation protocols and reports, manufacturing process descriptions,
specifications for non-compendial raw materials (at commercial stage),
analytical methods, analytical method validations (except compendial methods),
BDS specifications, and packaging specifications at SANDOZ shall be coordinated
between SANDOZ and Alder.  For each draft revised document, SANDOZ shall also
provide a red-lined version or detailed listing of the proposed changes, along
with rationale for the changes according to Section 2.11. Alder shall [***]
review and provide comments in writing to SANDOZ [***]  SANDOZ will work
cooperatively with Alder to address the Alder comments and update the draft
document accordingly.  The final revised record shall be submitted to Alder for
Alder translation and approval prior to the final SANDOZ approval and
implementation.

SANDOZ will ensure that the BDS final containers have met requirements for
container sterilization from review of the final container certificates provided
by the vendor and that the processes are in place to ensure container closure
integrity of the BDS filled final containers upon BDS storage by SANDOZ.

SANDOZ agrees to provide copies of original batch documents (Manufacturing
Records) as well as facility, Process, or utility documentation (excluding
proprietary documentation) and Standard Operating Procedures (SOPs) related to
Manufacture of the BDS, when requested by Alder, [***]  Alder shall be
responsible for document translation. (Reference CMA Clause 18(1).)

SANDOZ shall compile and archive clear structured Batch documentation for each
Batch of BDS. The Batch Manufacturing Records as well as testing documentation
kept by SANDOZ must comply with the GMP guidelines, and be retained for [***]or
such longer period as is required under applicable Legal Requirements.
Electronic archiving is possible instead of retaining paper records as defined
in SANDOZ approved procedures. SANDOZ shall not destroy Batch Manufacturing
Records or testing documentation without first notifying Alder and providing to
Alder the option of shipping Batch Manufacturing Records and testing
documentation from SANDOZ to Alder prior to destruction of any documentation.

SANDOZ shall have written procedures to ensure that in-process and release test
data recorded into Product-specific documents (e.g. deviation reports, Product
quality review, validation reports, and technical reports) has been verified by
SANDOZ for transcriptional accuracy from source documentation.  For all executed
MPD documents, SANDOZ shall emphasize data integrity, ensuring that data are
complete, consistent and accurate (attributable, legible, contemporaneously
recorded, an original or true copy, and accurate), and shall be responsible for
restricting access to cGMP computer systems, validating workflow on computer
systems,

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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controlling blank forms, reviewing audit trails, training personnel in detecting
data integrity issues, in accordance with regulatory authority recommendations
regarding data integrity.  SANDOZ shall validate all automated calculations for
in-process and release test data or verify with second person the accuracy of
calculations in the absence of validation.  

SANDOZ shall perform tech transfer for process and development activities within
SANDOZ facilities according to approved SANDOZ procedures.  

4.3. Reprocessing and Rework

Any use of Product not meeting the release specifications after testing is not
allowed unless authorized by Alder.

Reprocessing in the sense of repeating process steps that are part of the
validated Manufacturing Process are only allowed in exceptional cases for a
validated process, and require prior written approval from Alder.  Any
Reprocessing of Product is prohibited without prior change control review and
approvals, as described in Section 2.  

Rework of Product or its intermediates in the sense of performing process steps
that are different from the agreed Manufacturing Process is not allowed.

4.4. Review of Batch Documentation

After detailed review of the Batch documentation of each Batch by SANDOZ, SANDOZ
is responsible to ensure that a statement of compliance with GMP (Certificate of
Conformity/Compliance, confirmation statement) signed by [***] is included or
attached to the certificate of analysis (CoA) that is signed by the [***] and
[***]. SANDOZ shall also provide the following Certificates and Manufacturing
Records (also known as Batch Release Support Information), to Alder for each
Batch, to enable Alder to perform Batch review and disposition. Refer to
Attachment P for detailed content elements of the SANDOZ Batch Release Support
Information.  

 

•

Copies of SANDOZ-executed Batch records (to include [***], and as applicable,
[***]) that have been reviewed by SANDOZ manufacturing and SANDOZ QA

 

•

SANDOZ-Certificate of Analysis

 

•

SANDOZ-Certificate of Conformity for each Batch. Alder will provide instructions
on the required derivation and formatting for the Retest date. The Certificate
of Compliance will contain a statement attesting that the Batch was prepared in
conformance with cGMP; including reference to relevant governing regulation(s).

 

•

SANDOZ material report(s) summarizing starting materials and raw materials used
(material number, batch number, material status, expiry date, quantity)

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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•

Copy of SANDOZ Batch disposition checklist

 

•

Copies of approved QC data records (in-process) including raw data (See
Attachment Q)

 

•

Copies of approved QC data records (BDS) including raw data (See Attachment Q)

 

•

All deviations reports, including process and product related Deviations, Out of
Specification (OOS) and Out of Expectation (OOE) reports associated with the
Batch.

Any additional requests under the terms stated below shall be approved by both
parties.

4.5. Warehousing

SANDOZ is responsible to ensure that BDS is stored under appropriate conditions
of temperature and, light, and cleanliness so that identity, strength, quality
and purity of the BDS are not affected. Reference Attachment G for Product
storage conditions.  Alder shall transfer any known light exposure requirements
of the Product to SANDOZ, and SANDOZ has the responsibility to provide the
necessary light protection for the BDS as defined in SANDOZ batch records and
SOP’s.  In the event that the identity, strength or quality of the Product in
the warehouse could be adversely affected for any reason, SANDOZ shall take
immediate action to prevent any potential damage to the Product. In any case
SANDOZ shall inform Alder in writing where possible [***] of such adverse event.

SANDOZ will not use wood pallets in classified manufacturing areas or for
storage and shipment of Product.

4.6. Packaging for Dispatch and Transport

SANDOZ is responsible to ensure that the requirements regarding the packaging
for dispatch and transport to the agreed hand-over point of Product is met.

Shipments of Product is performed under [***] (Incoterms 2010) and in accordance
with the specific delivery provisions set out in Schedule 1 of the CMA.
(Reference CMA Clause 15(1).)

SANDOZ will apply a tamper-evident seal to the shipping container used to ship
BDS to Alder (or an independent facility under contract to Alder) in a manner
such that, if the seal is breached or missing, Alder will be alerted to the
possibility that the contents may have been altered.  The tamper-evident seal to
be used shall be mutually agreed by SANDOZ and Alder. SANDOZ will ensure that
Product is stored up until the time of shipment within the material’s labeled
storage range. SANDOZ will package the Product containers for shipment according
to agreed packaging specifications and with temperature monitoring devices.

[***].

SANDOZ shall ensure that each BDS container has an attached sample suitable for
the receiving site to perform ID testing.  [***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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SUBSTANCE v2.0

Alder (or an independent facility under contract to Alder) will inspect the
shipping container packaging and seal, and each BDS Product container upon
receipt after shipment.    If a discrepancy is observed which may relate to the
SANDOZ operations, Alder shall issue a written request for SANDOZ to initiate a
deviation. SANDOZ shall investigate and provide to Alder a copy of the completed
deviation report. SANDOZ shall implement any agreed actions arising out of the
completed investigation report in order to avoid the reoccurrence of similar
issues in the future.

The container-labels for the Product are defined per Attachment M.

5.Testing of Products

5.1. Method Transfer, Qualification, and Validation

When test methods are to be transferred to SANDOZ, Alder or its designee will
conduct a formal method transfer according to mutually agreed upon
procedures.  The format of the test method transfer protocol and test method
report will be mutually agreed upon by Alder and SANDOZ.  Each test method
transfer protocol and report will be reviewed and approved by SANDOZ and
Alder.  SANDOZ test method SOPs resulting from a successful analytical transfer
(and subsequent revisions) will be reviewed and approved by Alder and SANDOZ.
Any changes to agreed upon test method SOPs will be handled via SANDOZ Change
Control Management (reference section 2.12).  Raw data from the analytical
transfer will be maintained at SANDOZ and available to Alder, upon request.
Compendial test methods do not require transfer, however the SANDOZ test method
SOPs for compendial methods are to be made available to Alder, upon request,
during audits.  Compendial methods require verification at the labs used by
SANDOZ.

SANDOZ and Alder shall ensure that analytical methods, in-process, and Product
release testing at SANDOZ are qualified (SANDOZ “early stage validation”) for
clinical manufacture and validated prior to Process Validation and commercial
manufacture.  Protocols and reports shall be jointly approved.  SANDOZ test
method SOPs resulting from a successful qualification or validation (and
subsequent revisions) will be reviewed and approved by Alder and SANDOZ.  [***]

SANDOZ shall perform analytical methods within SANDOZ labs according to approved
SANDOZ procedures.  

5.2. Sampling

SANDOZ shall take samples of BDS and its intermediates according to the current
SOPs and batch records. [***]

SANDOZ shall deliver to Alder or Alder’s designated testing laboratory samples
of each Batch of the BDS, as and when Batches are Manufactured, and [***] in
accordance with a mutually approved sampling plan. [***].

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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For special or investigational testing not included in the sampling plan, Alder
may request that SANDOZ ship in-process or release testing samples (including
reserve samples) to Alder or a designated testing laboratory specified by
Alder.  Transportation of samples for testing will be performed according to
SANDOZ shipment procedures (temperature monitored).

Any additional sampling that is not defined in current SOPs and batch records
must be approved by both parties.  

5.3. Testing of Products

Alder will supply Product-specific reagents and reference standards (including
CoA and expiry/retest date) to SANDOZ. SANDOZ shall store the Process Transfer
Materials (see definition in CMA) at the proper labeled storage condition in
qualified equipment. The introduction of a new lot of critical reagent or
reference standard for qualified or validated assays must go through Change
Control (Section 2.11).

 

•

SANDOZ will be responsible for the compliance of the cGMPs for the BDS
Manufacture in alignment with the BDS Specifications, and will carry out
complete in-process and release testing according to the agreed test
documents.  In-process testing results will be documented in BDS batch records
with comparison to the allowable range, as appropriate.  The Certificate of
Analysis (CoA) for the release testing must comply with internationally
harmonized requirements for Batch certification. including: [***]

A CoA for each individual Batch of Product must be issued and provided to Alder.

[***]

5.4. Out of Specification Results

Out of Specification (OOS) investigations (See OOS definition in Section 11)
must be handled according to the corresponding SANDOZ standard operation
procedure for testing performed under SANDOZ control. For testing performed
under Alder control, Out of Specification (OOS) investigations must be handled
according to the corresponding Alder or designee’s standard operation procedure.
For OOS investigation (Level II investigation) associated with the Alder
Specifications, refer to Section applicable to Customer Complaint (BDS
Non-Conformity) in Section 2.17. Out of Specification investigations are
performed for BDS Specifications that are not met for Product release testing.

SANDOZ will notify Alder of all suspect OOS/OOT (Level I) results [***] of
observation.  SANDOZ shall perform a Level I laboratory investigation to
determine if a laboratory error is responsible for the OOS result. Re-analysis
and Repeat Assays performed under Level I OOS in SANDOZ SOPs do not require
prior approval from Alder.  If Level I investigation does not find a conclusive
root cause for the OOS or OOE result, then SANDOZ must notify Alder [***] after
completion of the Level I investigation. All investigation

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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must be undertaken by Sandoz in close cooperation with Alder. ALDER shall review
alternative Level II re-test plans for ALD403 specific test methods and approve
the final OOS report.

If the OOS result is confirmed, a separate manufacturing investigation must be
initiated in accordance with SANDOZ standard operating procedures, and the Level
II OOS investigation may be closed.  The OOS investigation report must be in
conformance with FDA OOS guidance “Investigating Out-of-Specification (OOS) Test
Results for Pharmaceutical Production” (2006 or if superseded, current version),
and will be approved by Alder.  

SANDOZ shall perform required manufacturing investigations for confirmed OOS
results to determine if there is a Manufacturing root cause for the result, as
well as any corrective action / preventive action.  SANDOZ shall provide OOS
investigation report and any related manufacturing investigation report to Alder
for review and approval in accordance with Section 2.16.  SANDOZ will trend
invalid assays, and providing trending reports upon request from Alder.

5.5. Microbiological Control Program

SANDOZ will maintain an appropriate microbiological monitoring program to ensure
acceptable microbiological quality and compliance with applicable laws and
regulations.  

[***]  

The [***] shall be established as per SANDOZ procedures. SANDOZ shall perform
microbial identification for [***]  SANDOZ shall continually monitor [***]
excursions to determine if there is an upward and/or worsening trend, and to
take corrective and preventive action as appropriate to improve the trend.

SANDOZ shall [***] for the Bulk Drug Substance are indicated in the CMA
(Reference CMA Schedule 2) and in Attachment H.

Alder shall perform an assessment of the impact [***] to the Alder Product as
part of Alder lot disposition procedures.

6.ARCHIVING OF Samples and Documentation

SANDOZ ensures that Reserve Samples (also known as Reference Samples) and
Manufacturing Records related to the Manufacture are archived under defined
conditions as follows:

The Reserve Sample amount to be stored shall be sufficient to perform [***]
according to the testing instructions.

SANDOZ shall notify Alder [***] in the event of any issues concerning the
Reserve Samples according to deviation handling in section 2.16.

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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SANDOZ shall not discard or destroy Bulk Drug Substance Reserve Samples or
Manufacturing Records (including electronic records) once the archive period has
been reached without first contacting Alder in writing and obtaining Alder
written response as to whether samples or documentation may be discarded or if
they are to be shipped to Alder.

The Reserve Samples are only allowed to be used for investigational purpose by
SANDOZ with prior written approval by Alder.   Alder may request Reserve Samples
from SANDOZ by written request.  SANDOZ to ship samples [***], unless otherwise
agreed, after receipt of Alder request.

 

Archive periods

Item

Period

[***]

[***]

[***]

[***]

[***]

[***]

[***]

[***]

Table 1: Storage periods for samples and documentation

7.Release of Products

7.1. Release for shipment – pre-requisites

The final release of a Batch requires BDS Specifications to be met.   [***]  
Alder may perform concurrent review per a mutually agreed upon plan. A SANDOZ
[***] will signify that the Batch is released in compliance with cGMP. SANDOZ
will inform Alder [***] that a Batch has been Released and provide to Alder or
its designee samples of the Batch [***] and the related Manufacturing Records
(including the Certificates) [***] in accordance with CMA Clause 20(1) and
(2).   Confidential documents will be exchanged with ALDER via secure e-mail or
an appropriate exchange platform [***].

SANDOZ shall provide Alder with the related Manufacturing Records (including the
Certificates) for the Batch as soon as possible after the Batch is Manufactured
and [***] (CMA Clause 20(1).)

SANDOZ to respond [***] of receipt of Alder comments.  SANDOZ will work
cooperatively with Alder to address any Alder comments and update the Batch
Release documentation and Manufacturing Records accordingly, as required.  

In accordance with CMA Clause 20(3), [***] whichever occurs last (the
“Start-review Date”), Alder or its representative(s) may, at Alder’s option,
analyze and test each Batch and samples from each Batch and review the related
Certificates and Manufacturing Records.  Any Customer Complaints by Alder that a
Batch, or one of more samples in a Batch, is not conforming with the
requirements under CMA Clause 18(1) (such BDS being referred to as
“Non-conforming” BDS, and such non-conformity referred to as “Non-conformity”)

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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shall be delivered to SANDOZ in writing [***] after the Start-review Date of
such Batch (or , in the case of latent Non-conformity that was not readily
ascertainable by the testing of the BDS and review of the related Certificates,
[***] after discovery of such latent Non-conformity), and such complaint being
accompanied by supporting data for purposes of consideration and verification by
SANDOZ.

The procedures set out in Clause 20 of the CMA will apply to any complaints by
Alder regarding Non-conformity.  The parties acknowledge and agree that the
warranties set out in CMA Clause 18(1) apply to all BDS Manufactured under the
CMA, regardless of whether SANDOZ, Alder or a Third Party test the BDS for
conformity.

For the avoidance of doubt, however, all of the BDS Specifications are required
to be met in order to demonstrate that the BDS conforms to the requirements set
out in CMA Clause 18(1), [***].  See Attachments H, I, and J

[***] For the avoidance of doubt, the date for delivery of BDS Batches to Alder
shall be based on SANDOZ Release and according to the provisions in the CMA.
(Reference CMA Clauses 15(1) and (2).)

7.2. Shipment under Quarantine

Shipment of BDS under quarantine, i.e. without meeting the pre-requisites for
shipment as defined in section 7.1.,[***]  (Reference CMA Clause 15(1).) Alder
will keep BDS under quarantine until SANDOZ and Alder’s formal
disposition.  Alder reserves the right to further process the Batch, as long as
the batch remains under quarantine, meets internal requirements and is under
Alder’s QA control.  Alder will not release the Batch for distribution, sales,
or intended use (e.g., use for human clinical purpose) until [***]  A Batch that
has been shipped under quarantine shall be subject to all testing and quality
assurance review requirements as SANDOZ and Alder normally require to enable
subsequent full release, and for each Batch of BDS being in conformity with the
requirements set forth in CMA Clause 18(1).  (Reference CMA Clause 15(1).)

8.Product Security

8.1. Waste Material

Any waste material or packaging component bearing the Alder name must be defaced
and/or incinerated by SANDOZ.  SANDOZ shall provide a proof of destruction
certificate to Alder on request.

8.2. Counterfeiting

SANDOZ shall have a system in place that set out their counterfeit,
theft,  diversion,  and economically motivated adulteration detection and
avoidance system in relation to as BDS. SANDOZ shall notify Alder immediately in
writing of any known incident or any suspicion of counterfeit, theft, diversion
or adulteration of  BDS and shall help in any necessary investigation requested
by Alder.

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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9.Post-Marketing Surveillance and Stability Testing

9.1. Stability Testing

Alder is responsible for maintaining a follow-up stability program for the
Product under ICH conditions.

[***] and as requested by Alder and defined in a separate approved written
sampling plan, SANDOZ is responsible for collecting samples designated for
stability testing.  Stability samples shall be collected by SANDOZ in
appropriate sample containers and volumes as specified by Alder, and SANDOZ
shall make the samples available for shipment at the earliest date.  SANDOZ
shall include temperature recording device with stability sample
shipment.  Alder shall review shipment temperature at receiving site for
acceptability.  SANDOZ shall make the samples available for shipment prior to
the due date of the first stability test time point.

If a stability result is confirmed by Alder as an Out of Specification (OOS)
result, Alder will notify SANDOZ where possible [***]. In the case of [***],
Alder will notify SANDOZ [***]  SANDOZ shall perform a Manufacturing
investigation for confirmed stability OOS results to determine if there is a
Manufacturing root cause for the result and whether corrective or preventive
actions should be taken to remedy the issue, and submit the investigation report
to Alder in accordance with section 2.16.

9.2. Product Complaints

Alder is responsible for handling Product Complaints that are derived from the
market (for commercial material), from clinical trials (for clinical material)
and adverse drug events and shall reply to inquiries as promptly as possible.
Alder shall provide applicable complaint information to SANDOZ [***]. SANDOZ
shall [***] investigate Product Complaints and report results to Alder [***]
unless reporting requirements dictate an earlier timing. If this time period is
unable to be met, SANDOZ will notify Alder to arrange an agreed upon timeframe
where an interim report can be evaluated to meet reporting requirements to
regulatory authorities. Complaints of a critical nature [***] must be
investigated [***] and interim results reported to Alder [***]

In the event that SANDOZ receives a Product Complaint which potentially impacts
a Batch supplied to Alder, SANDOZ shall forward the complaint to Alder [***]

Alder, with SANDOZ cooperation, shall be responsible for responding to the FDA
or other Regulatory Authority and filing any reports with the FDA or other
Regulatory Authority concerning such reactions (including Drug Experience
Reports) caused by the Product.

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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9.3. Adverse Events

Adverse events (Reference CMA 21. (6)) associated with potential product quality
issue shall be assessed as Product Complaints per Section 9.2.

10.Terms and Expiration

This QUALITY AGREEMENT forms an integrated part of the CMA and shall come into
force at sign-off by the parties hereto.

SANDOZ and Alder will periodically review this QUALITY AGREEMENT (including its
Attachments) per review schedule defined per Alder procedures or more often in
the event of a significant change to the process or systems, and the parties
will amend this QUALITY AGREEMENT, in writing, as needed.  Any amendments to
this QUALITY AGREEMENT core document will also be reviewed by SANDOZ and Alder
legal representatives to ensure consistency with the commitments contained in
the CMA and associated orders/scope of works/signed quotes/addenda.

This QUALITY AGREEMENT shall be terminated upon expiration or termination of the
CMA.  Obligations that, by their nature, should survive the expiration or
termination of this QUALITY AGREEMENT, such as ongoing regulatory requirements
(including for example maintaining records and supporting Product Complaint
investigations), shall survive the expiration or termination of this QUALITY
AGREEMENT.

11.DEFINITIONS

The following terms shall have the meanings assigned to them below for purposes
of this QUALITY AGREEMENT.  Capitalized terms used but not defined in this
QUALITY AGREEMENT shall have the meaning given in the CMA.

 

Auxiliary Materials

Any material used for Manufacture, or for maintenance of equipment or buildings,
which is not a raw or packaging material, e.g. lubricants, detergents, silicon
rubber.

Annual Product Review (APR)

A reporting process by which written records required by 21CFR211.180(e)shall be
maintained so that data therein can be used for evaluating, at least annually,
the quality standards of the Product to determine the need for changes in
Product specifications or manufacturing or control procedures. (Alder is
responsible for submitting this report to the FDA).

Annual Product Quality Review (APQR)

A collection of data provided by SANDOZ [***] (to be established in subsequent
quality agreements) presented in a clear format, that makes it possible to
identify quality problems, deviations and trends and/or to substantiate
consistent quality.

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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Assets

Any asset that (i) is permanently affixed to a facility, and/or (ii) is not

capable of being easily moved from the facility and/or which (iii) is part of
the permanent facility. Assets shall comprise the assets listed in Schedule 4 to
this Agreement. (CMA Clause1 (1))

Biological Product Deviation Report (BPDR)

An FDA-reportable event reporting (according to 21 CFR 600.14) that represents a
deviation from cGMP, applicable regulations, applicable standards, or
established specifications that may affect the safety, purity, or potency of a
product, or represents an unexpected or unforeseeable event that may affect the
safety, purity or potency of that product, and occurs in the SANDOZ facility and
involves a distributed biological product.

 

Changes

A planned alteration, replacement, or origination of a new item (e.g., Product,
equipment, facility) or elimination of Specifications, methods, facilities,
utilities, equipment, computer systems, master records or controls that are used
for the manufacture, processing, packaging, or holding of Product.

Continuous Process Verification CPV

Third validation stage as continual assurance that the process remains in a
state of control (the validated state) during commercial manufacture. A system
or systems for detecting unplanned departures from the process as designed is
essential to accomplish this goal.  SANDOZ refers to this as Ongoing Process
Verification.

Critical Deviation

 

 

A deviation having [***].

A critical deviation refers to those deviations that are [***]

Critical Raw Material

A raw material that [***].

Critical Reagent

A reagent used [***]. Critical reagents are [***].

Major deviation

Those deviations have [***]

Those deviations that require [***].  If the deviation identifies [***].

Manufacturing Process Description Document

[***] manufacturing SOPs and [***] master batch records, describing the Process
and covering all steps, from thaw of the cell bank vial to filling and
labeling/packaging the BDS, and includes in-process controls, process
parameters, and all the methods used to test the in-process and BDS respectively
against the in-process controls and SANDOZ Release Specifications, as applicable
(Reference CMA Clause 18(5))

Manufacturing Records

All documents relating to the Manufacture of a Batch, including manufacturing
instructions, deviations, test results, out of specification results,
investigations, bills of materials and Certificates, including Certificates of
Analysis, as described with more particularity in this Quality Agreement.

Minor deviation

Any unplanned [***]

Master Cell Bank (MCB)

An aliquot of a single pool of cells that generally has been prepared from the
selected cell clone under defined conditions, dispensed into multiple
containers, and stored under defined conditions. The MCB is used to derive all
Working Cell Banks.

Master Working Cell Bank (MWCB) –(SANDOZ)
or Working Cell Bank (WCB) (Alder)

A culture of cells derived from the Master Cell Bank and intended for use in the
preparation of production cell cultures.

Nonconformity

With respect to BDS, [***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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Customer Complaint

Any written complaints by Alder that a Batch, or one or more samples in a Batch,
is not conforming with the requirements under CMA Clause 18(1)

Process

CMA Clause 1(1) "Process" means the series of processes, methods, tests and
techniques by which the BDS is Manufactured from the ALD403 Cell Line, as
described in detail in a manufacturing process description document for the
process established at such facility, which shall be agreed by the Parties, and
as defined in the Manufacturing Records, generated for such facility where the
BDS is Manufactured, and “Processed” and “Processing” shall be interpreted
accordingly.

Product

CMA Clause 1(1) "Product" means the proprietary product known as ALD403, which
is a recombinant protein having the amino acid sequence, and encoded by the
nucleic acid constructs, described in

further detail on Schedule 1 to the Specifications Letter. Also known as
eptinezumab.

Product Complaint

Any written, electronic, or oral communication that alleges deficiencies related
to the safety, identity, strength, purity or quality of Product.  

Ongoing Process Verification (OPV)

Refer to CPV

Out of Expectation (OOE)

Out of Expectation results are testing results that, while not Out of
Specification, they are atypical results when compared to expected and/or
historical results and warrant further investigation.

Out of Specification (OOS)

For the purpose of this Quality Agreement, Out of Specification results are
testing results that do not meet the BDS Specification.  

[***]

[***]

Quality Event

Quality Events are distinguished from Deviations or OOS/OOE laboratory tests.
Quality Events are results of the following processes: [***]

Re-analysis

An analysis performed during the [***] which may include testing of stock
solutions, dilutions, vial contents, etc. derived from the preparation of the
suspect sample. Re-analysis is performed as part of hypothesis testing in the
[***]

Reference Sample

EU term synonymous with US term Reserve Sample.

Reference Standard

A substance, used in routine laboratory analysis, which has been shown by an
extensive set of analytical tests to be authentic material of established
quality and purity.

Repeat Assay

An assay which is performed due to an invalidation of the prior assay (e.g. when
an assay or sample result is determined to be invalid the next assay performance
or sample analysis is considered a repeat analysis).

Reprocessing

Repeating process steps that are part of the established manufacturing procedure

Re-sampling

Additional testing on a new sample collected from the batch from a new sampling
of the batch. A re-sample may be collected in the event that the original sample
is suspected to not be representative or is confirmed to not be representative
of the batch, or if none of the original sample remains.  The sampling scheme
for the resample must be documented prior to re-sampling, in the OOS
investigation report.

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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Reserve Sample

US term synonymous with EU term Reference Sample. A sample of a batch of
Starting Material, packaging material or product which is stored

for the purpose of being analyzed should be need arise during the shelf life of
the batch concerned. The sample quantity is an amount [***]

Re-testing

Additional testing from the same sample as originally prepared, tested and from
which the OOS result was obtained.

Retest Date

The date when a material should be re-examined to ensure that it is still
suitable for use.  

Rework

Performance of additional process steps that are different from the agreed
manufacturing process.

Start-review Date

Delivery and Release of Batch and delivery of the related Certificates for the
Batch and the related Manufacturing Records, whichever occurs last.

 

12.Version History (Core Document)

The table below documents the version history for the core document of the
Alder-SANDOZ QUALITY AGREEMENT.  Each of the Attachments referenced in the core
document are individual version controlled, with a version history and approval
signatures.

Ver.

Ver. Date

Changes

Reason for change

1.0

[***]

Initial version

Required by CMA.

2.0

[***]

[***]

[***]

[***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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13.APPROVALS (Core Document)

 

ALDER

 

 

 

SANDOZ

 

[***]

27 JULY 2018

 

 

[***]

20 JUL 2018

Signature

Date

 

 

Signature

Date

[***]

Alder BioPharmaceuticals, Inc.

 

 

 

[***]
Sandoz GmbH

 

 

 

 

 

 

[***]

20 JUL 2018

 

 

 

 

Signature

Date

 

 

 

 

[***]
Sandoz GmbH

 

[***]

26 JUL 2018

 

 

[***]

20 JULI 2018

Signature

Date

 

 

Signature

Date

[***]

Alder BioPharmaceuticals, Inc.

 

 

 

[***]
BTC Sandoz GmbH

 

 

 

 

 

 

 

 

 

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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ATTACHMENT A: List of Liaisons

[***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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Version History (Attachment A)

Version

Version Date

Changes

Reason for change

A-1

[***]

Initial version.

Required by CMA.

A-2

[***]

[***]

[***]

A-3

[***]

[***]

[***]

 

[***]

Approvals (Attachment A)

ALDERSANDOZ

[***]27 JULY 2018

SignatureDate

[***]
Alder BioPharmaceuticals, Inc.

[***]20. JULI 2018

SignatureDate

[***]
Sandoz GmbH

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

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ATTACHMENT B: Table of Responsibilities

S=SANDOZA=Alder [***]

Version History (Attachment B)

Ver.

Ver. Date

Changes

Reason for change

B-1

[***]

Initial version.

Required by CMA.

B-2

[***]

[***]

[***]

B-3

[***]

[***]

[***]

[***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

36/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Approvals (Attachment B)

ALDERSANDOZ

[***]27 JULY 2018

Signature                             Date

[***]
Alder BioPharmaceuticals, Inc.

[***]20. JULI 2018

Signature                        Date

[***]
Sandoz GmbH

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

37/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

ATTACHMENT C: List of Approved Sub-Contractors

List of contract labs of Alder [***]

List of contract labs of SANDOZ [***]

Contract Lab codes [***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

38/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Version History (Attachment C)

Ver.

Ver. Date

Changes

Reason for change

C-1

[***]

Initial version.

Required by CMA.

C-2

[***]

[***]

[***]

 

[***]

Approvals (Attachment C)

ALDERSANDOZ

[***]27 JULY 2018

SignatureDate

[***]
Alder BioPharmaceuticals, Inc.

[***]20. JULI 2018

SignatureDate

[***]
Sandoz GmbH

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

39/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

ATTACHMENT D: ALD403 raw materials for use at [***] production scale[***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

40/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Version History (Attachment D)

Version

Version Date

Changes

Reason for change

D-1

[***]

Initial version.

Required by CMA.

D-2

[***]

[***]

[***]

D-3

[***]

[***]

[***]

[***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

41/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Approvals (Attachment D)

ALDERSANDOZ

[***]27 JULY 2018

SignatureDate

[***]
Alder BioPharmaceuticals, Inc.

[***]20. JULI 2018

SignatureDate

[***]
Sandoz GmbH

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

42/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

ATTACHMENT E: Release Requirements for [***]

SANDOZ Release Requirements for [***]

Minimum requirements for
Certificate of Analysis for
[***]

[***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

43/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Listing of ALD403 [***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

44/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Version History (Attachment E)

Ver.

Ver. Date

Changes

Reason for change

E-1

[***]

Initial version

Required by CMA

E-2

[***]

[***]

[***]

E-3

[***]

[***]

[***]

[***]

Approvals (Attachment E)

ALDERSANDOZ

[***]27 JULY 2018

SignatureDate

[***]
Alder BioPharmaceuticals, Inc.

[***]20. JULI 2018

SignatureDate

[***]
Sandoz GmbH

 

 

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

45/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

ATTACHMENT F: Min/Max doses for [***] ALD403

[g0baqefjxjkx000001.jpg]

MEMORANDUM

Date:[***]

To[***]

From:[***]

Subject:AI.D403 Minimum & Maximum [***] Dosage for [***]

This memo documents the minimum & maximum [***] dosage of ALD403 that [***]

The minimum & maximum [***] dosages for ALD403 [***]

[***]

[***]

Cc.

[***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

46/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Version History (Attachment F)

Ver.

Ver. Date

Changes

Reason for change

F-1

[***]

Initial version.

Required by CMA.

F-2

[***]

[***]

[***]

 

[***]

Approvals (Attachment F)

ALDERSANDOZ

[***]27 JULY 2018

SignatureDate

[***]
Alder BioPharmaceuticals, Inc.

[***]20. JULI 2018

SignatureDate

[***]
Sandoz GmbH

 

 

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

47/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

ATTACHMENT G: Storage condition / Shelf life [***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

48/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Version History (Attachment G)

Version

Version Date

Changes

Reason for change

G-1

[***]

Initial version.

Required by CMA.

G-2

[***]

[***]

[***]

G-3

[***]

[***]

[***]

 

Approvals (Attachment G)

ALDERSANDOZ

[***]27 JULY 2018

SignatureDate

[***]
Alder BioPharmaceuticals, Inc.

[***]20. JULI 2018

SignatureDate

[***]
Sandoz GmbH

 

 

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

49/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

ATTACHMENT H: SANDOZ Release Specifications * [***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

50/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Version History (Attachment H)

Ver.

Ver. Date

Changes

Reason for change

H-1

[***]

Initial version.

Required by CMA.

H-2

[***]

[***]

[***]

H-3

[***]

[***]

[***]

 

[***]

Approvals (Attachment H)

ALDERSANDOZ

[***]27 JULY 2018

SignatureDate

[***]
Alder BioPharmaceuticals, Inc.

[***]20. JULI 2018

SignatureDate

[***]
Sandoz GmbH

 

 

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

51/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

ATTACHMENT I: Alder Release Specifications *[***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

52/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Version History (Attachment I)

Ver.

Ver. Date

Changes

Reason for change

I-1

[***]

Initial version.

Required by CMA.

I-2

[***]

[***]

[***]

1-3

[***]

[***]

[***]

 

[***]

Approvals (Attachment I)

ALDERSANDOZ

[***]27 JULY 2018

SignatureDate

[***]
Alder BioPharmaceuticals, Inc.

[***]20. JULI 2018

SignatureDate

[***]
Sandoz GmbH

 

 

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

53/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

ATTACHMENT J: Additional Release Specifications *[***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

54/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Version History (Attachment J)

Ver.

Ver. Date

Changes

Reason for change

J-1

[***]

Initial version.

Required by CMA.

J-2

[***]

[***]

[***]

J-3

[***]

[***]

[***]

 

[***]

Approvals (Attachment J)

ALDERSANDOZ

[***]27 JULY 2018

SignatureDate

[***]
Alder BioPharmaceuticals, Inc.

[***]20. JULI 2018

SignatureDate

[***]
Sandoz GmbH

 

 

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

55/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

ATTACHMENT K: Document Notification/Review/Approval Sheet

[***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

56/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Version History (Attachment K)

Ver.

Ver. Date

Changes

Reason for change

K-1

[***]

Initial version

Required by CMA

K-2

[***]

[***]

[***]

K-3

[***]

[***]

[***]

 

[***]

Approvals (Attachment K)

ALDERSANDOZ

[***]27 JULY 2018

SignatureDate

[***]
Alder BioPharmaceuticals, Inc.

[***]20. JULI 2018

SignatureDate

[***]
Sandoz GmbH

 

 

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

57/73CONFIDENTIAL

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

ATTACHMENT L: Critical Reagents and Reference Standards [***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

58/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Version History (Attachment L)

Version

Version Date

Changes

Reason for change

L-1

[***]

Initial version.

Required by CMA.

L-2

[***]

[***]

[***]

L-3

[***]

[***]

[***]

 

[***]

Approvals (Attachment L)

ALDERSANDOZ

[***]27 JULY 2018

SignatureDate

[***]
Alder BioPharmaceuticals, Inc.

[***]20. JULI 2018

SignatureDate

[***]
Sandoz GmbH

 

 

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

59/73CONFIDENTIAL

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

ATTACHMENT M: BDS Labeling

[***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

60/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Version History (Attachment M)

Ver.

Ver. Date

Changes

Reason for change

M-1

[***]

Initial version.

Required by CMA.

M-2

[***]

[***]

[***]

M-3

[***]

[***]

[***]

 

[***]

Approvals (Attachment M)

ALDERSANDOZ

[***]27 JULY 2018

SignatureDate

[***]
Alder BioPharmaceuticals, Inc.

[***]20. JULI 2018

SignatureDate

[***]
Sandoz GmbH

 

 

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

61/73CONFIDENTIAL

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

ATTACHMENT N: Change Control Notification/Approval Requirement

[***]

Table 1: [***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

62/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Table 2: [***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

63/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Table 3:[***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

64/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Version History (Attachment N)

Version

Version Date

Changes

Reason for change

N-1

[***]

[***]

[***]

 

[***]

Approvals (Attachment N)

ALDERSANDOZ

[***]27 JULY 2018

SignatureDate

[***]
Alder BioPharmaceuticals, Inc.

[***]20. JULI 2018

SignatureDate

[***]
Sandoz GmbH

 

 

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

65/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

ATTACHMENT O: SANDOZ biopharmaceutical manufacturing facilities applicable to
ALD403

[***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

66/73CONFIDENTIAL

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Version History (Attachment O)

 

Version

Version Date

Changes

Reason for change

O-1

[***]

[***]

[***]

 

[***]

Approvals (Attachment O)

ALDERSANDOZ

[***]27 JULY 2018

SignatureDate

[***]
Alder BioPharmaceuticals, Inc.

[***]20. JULI 2018

SignatureDate

[***]
Sandoz GmbH

 

 

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

67/73CONFIDENTIAL

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

ATTACHMENT P: Sandoz Batch Release Support Information - Detailed Content
Requirements

This Attachment specifies detailed content requirements to include as part of
records of the Sandoz Batch Release Support Information. Refer to the core
Quality Agreement for the complete list of records. [***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

68/73CONFIDENTIAL

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Version History (Attachment P)

Version

Version Date

Changes

Reason for change

P-1

[***]

[***]

[***]

 

[***]

Approvals (Attachment P)

ALDERSANDOZ

[***]27 JULY 2018

SignatureDate

[***]
Alder BioPharmaceuticals, Inc.

[***]20. JULI 2018

SignatureDate

[***]
Sandoz GmbH

 

 

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

69/73CONFIDENTIAL

--------------------------------------------------------------------------------

ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

ATTACHMENT Q: Review of Batch Documentation - QC Test Results Documentation to
be Provided with Batch Documentation [***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

70/73CONFIDENTIAL

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Version History (Attachment Q)

Version

Version Date

Changes

Reason for change

Q-1

[***]

[***]

[***]

 

[***]

Approvals (Attachment Q)

ALDERSANDOZ

[***]27 JULY 2018

SignatureDate

[***]
Alder BioPharmaceuticals, Inc.

[***]20. JULI 2018

SignatureDate

[***]
Sandoz GmbH

 

 

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

71/73CONFIDENTIAL

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

ATTACHMENT R: Quality Agreement Core Document Change History [***]

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

72/73CONFIDENTIAL

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ALDER-SANDOZ QUALITY AGREEMENT ON MANUFACTURING AND TESTING OF BULK DRUG
SUBSTANCE (VERSION 2.0)

Version History (Attachment R)

Ver.

Ver. Date

Changes

Reason for change

R-1

[***]

[***]

[***]

 

[***]

Approvals (Attachment R)

ALDERSANDOZ

[***]27 JULY 2018

SignatureDate

[***]
Alder BioPharmaceuticals, Inc.

[***]20. JULI 2018

SignatureDate

[***]
Sandoz GmbH

 

 

 

[***] = Certain confidential information contained in this document, marked by
brackets, is filed with the Securities and Exchange Commission pursuant to Rule
24b-2 of the Securities Exchange Act of 1934, as amended.

73/73CONFIDENTIAL