Quality Agreement: Definition & Sample
A quality agreement is a contract that outlines specific quality parameters for a project and which party is responsible for the execution of those parameters. The agreement should cover all aspects of the project that affect the identity, quality, safety, potency, and purity of a product.
There are four types of quality agreements: manufacturing, supplier, vendor, and service quality agreements. Manufacturing quality agreements establish each party’s manufacturing activities. Supplier and vendor quality agreements define the quality of materials or services used in the production process. Service quality agreements establish the quality of services supplied to a manufacturing facility.
Below is a list of common sections included in Quality Agreements. These sections are linked to the below sample agreement for you to explore.
Exhibit 10.17
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FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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QUALITY AGREEMENT
By and between
Contract Vendor Name:
PYRAMID Laboratories, Inc. (PYRAMID)
Address:
3598 Cadillac Avenue, Costa Mesa, CA 92626
(“PYRAMID”)
and
Company:
Xeris Pharmaceuticals Inc.
Address:
3208 Red River, Suite 300
Austin, TX 78705
(“Xeris”)
XERIS and PYRAMID may each be referred to herein individually as a “Party” and collectively
as the “Parties.”
for
See Appendix 1
(“Product” or “Service”)
The Parties wish to further define their individual and collective responsibilities as to the quality aspects of the Product or Service to ensure compliance
with applicable current Good Manufacturing Practices (cGMPs), applicable regulatory submissions for the Product, applicable regulatory submissions for the Services, other applicable regulatory requirements, and XERIS s requirements as specified by
XERIS (the “XERlS Requirements”).
In order to achieve this purpose, this Quality Agreement includes a detailed listing of the activities and
corresponding responsibilities associated with the Product or Service. Unless otherwise indicated, responsibility for each specified activity is assigned to either XERIS or PYRAMID, or to both Parties.
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Agreement by the Parties to perform the activities detailed in this Quality Agreement is Indicated by each
authorized representatives’ signature below:
PYRAMID Laboratories, Inc.
XERIS Pharmaceuticals Inc.
/s/ Sally Dietrick
/s/ Leslie Osmera
Signature
Signature
Name: Sally Dietrick
Name: Leslie Osmera
Title: Quality Assurance Manager
Title VP, Quality Assurance
November 16, 2016
November 16, 2016
Date of Signature
Date of Signature
CONFIDENTIAL
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TABLE OF CONTENTS
Appendices:
Appendix 1:
Contacts and Responsibilities
Appendix 2:
Significant Deviations Requiring Notification
Appendix 3:
Documentation to be Supplied by PYRAMID
Appendix 4:
Authorized Subcontractors
CONFIDENTIAL
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1.
QUALITY AGREEMENT
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1.1
Effective Date
This Quality Agreement shall become effective as of the latest
signature date that appears on page 2 (“Effective Date”).
1.2
Scope
This Quality Agreement outlines the obligations and responsibilities of PYRAMID
Laboratories, Inc. (hereinafter referred to as “PYRAMID”) and XERIS PHARMACEUTICALS (herein referred to as “XERIS”) with respect to the quality assurance of the Product or Service, as defined in Appendix 1 (Definition of Product
or Service), by PYRAMID for XERIS.
1.3
Other Agreements
This Quality Agreement shall complement and is without prejudice to
all other agreements containing logistical, commercial, legal or other terms, which have been entered into between the Parties regarding the Product or Service covered by this Quality Agreement, including, without limitation, that a certain Master
GMP Manufacture Contract between XERIS and PYRAMID Laboratories, Inc dated November 1, 2016 (the “Master Services Agreement”). If there are any direct conflicts between the terms of this Quality Agreement and the
terms of the Master Services Agreement, then (a) this Quality Agreement shall govern with respect to issues directly related to Product specifications or Service quality matters, and (b) the Master Services Agreement shall govern with
respect to all other matters.
1.4
Amendments to Quality Agreement
Amendments to this Quality Agreement must be in
writing and signed by the appropriate representatives of each Party before they are deemed effective.
The Parties agree to amend terms of
this Quality Agreement that need to be amended in order to ensure the Product or Service continues to meet all (a) regulatory requirements of applicable jurisdictions and (b) XERIS requirements.
If an amendment to this Quality Agreement is proposed, the proposing Party will communicate the proposed amendment to the appropriate contact
person at the other Party for review and approval. The appropriate contact person for each Party is listed in Appendix 1 (Contacts and Responsibilities).
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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1.5
Termination of Quality Agreement
Term. This Quality Agreement shall
become effective as of the Effective Date and shall terminate upon the later of (a) expiration or termination of the Master Services Agreement and (b) the final date on which PYRAMID provides Products or Services to XERIS. Notwithstanding
the foregoing, if the Products or Services cease to be provided by PYRAMID to XERIS, this Quality Agreement may be terminated by either Party on providing [***] advance written notice of termination to the other Party. The review date of this
quality agreement is two years from the Effective Date.
Survival. All regulatory obligations required of XERIS or PYRAMID
by any applicable regulatory authorities and all obligations of the Parties under effective regulations shall survive expiration or termination of this Quality Agreement. Examples of such requirements include, but are not limited to: Records
Keeping, Recalls, Complaint and Adverse Event handling and reporting, deviations and investigations, completion of stability studies, provision of information to XERIS which is necessary to maintain compliance with regulatory filings. Also, those
provisions of the Master Services Agreement between the Parties shall not be affected by expiration or termination of this Quality Agreement, including, without limitation, any duties regarding confidentiality or
non-disclosure.
1.6
Debarment
PYRAMID warrants and represents that it is not debarred under the Generic
Drug Enforcement Act of 1992, 21 U.S.C. 335[a] (the “Generic Drug Enforcement Act”), and that it has not been convicted of a crime for which it could be debarred under the Generic Drug Enforcement Act. In connection with the Product (or
provision of Services), PYRAMID further warrants, represents, and covenants that it shall not use in any capacity the services of any person debarred under the Generic Drug Enforcement Act, or convicted of a crime for which a person can be debarred
under the Generic Drug Enforcement Act.
1.7
Use of Third-Parties
PYRAMID may not subcontract or delegate any of its obligations
under this Quality Agreement to any third-party (including, without limitation, any affiliate of PYRAMID) unless XERIS provides prior written consent to PYRAMID for such subcontracting or delegation. Before XERIS grants any such written consent,
XERIS may be required to enter into a written agreement with the third-party (“Third-Party Agreement”). Notwithstanding any subcontracting or delegation hereunder, PYRAMID shall nevertheless remain liable to XERIS for all obligations and
liabilities hereunder.
CONFIDENTIAL
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REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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XERIS shall remain responsible for the acts and omissions of any permitted subcontractors
and will enter into an appropriate written contract with such subcontractors to ensure the qualification and auditing of such subcontractors.
1.8
Assignment
PYRAMID shall not assign any or all of its rights or obligations under this
Quality Agreement without Xeris’ prior written consent, which consent may be granted or withheld in Xeris’ sole discretion. XERIS shall have the right to assign any or all of its rights or to delegate its obligations under this Quality
Agreement without the consent of PYRAMID. In the event of a permitted assignment under this Quality Agreement, the assigning Party shall continue to be bound by all pre-existing obligations under this Quality
Agreement including all obligations of confidentiality and non-disclosure.
2.
PRODUCT
The Product or Service for XERIS by PYRAMID is described in the Master Services
Agreement.
3.
ADMINISTRATIVE INFORMATION
A XERIS and PYRAMID contact list for each project will be
maintained and updated as necessary by XERIS QA and PYRAMID QA. The contact list will be in an agreed upon location and notification of changes to the list will be communicated by XERIS QA and PYRAMID QA.
4.
DEFINITIONS
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NOTE: All capitalized terms used in the Quality Agreement, but not herein
defined, will have the meaning set forth in the Master Services Agreement.
4.1
Batch Production Records
Batch Production Records are a compilation of master
documents and records that contain the procedures and specifications for the Product. These master documents and records are prepared for each stage of Production for a Batch of Product, and include information relating to Production and control of
the Batch.
CONFIDENTIAL
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4.2
Batch Record Package
Batch Record Package is a compilation of records
containing the Production history and control of a Product. These records are generated by Manufacturing and Quality Control (“QC”) and reviewed and approved by Quality Assurance (“QA”). The Batch Record Package consists of Batch
Production Records that contain bill of materials, manufacturing instructions, formulas, appropriate packaging instructions, and deviation documentation and additional documentation which may have been processed as part of the production record of
the Batch. Attachments to the Batch Record Package may include environmental monitoring reports and copies of in-process test records, as required by the Project Plan. Ancillary documents such as raw material
CoAs and their incoming test results are generally not part of the Batch Record Package, but are kept under Good Documentation Practices on site at Pyramid.
4.3
Certificate of Analysis (CPA)
Certificate of Analysis shall have the meaning
assigned in the Master Services Agreement.
4.4
Certificate of Compliance (COC)
Certificate of Compliance or COC means the
certificate to be issued by PYRAMID stating that the Product was produced and tested in compliance with: (i) applicable cGMP guidelines, (ii) terms of this Quality Agreement, (iii) PYRAMID’S internal policies and procedures, and
(iv) the “XERIS” written requirements.
4.5
Components
Any ingredient intended for use in the manufacture of a drug
product, including those that may not appear in such drug. This includes such items as filters, containers, closures and tubing.
4.6
Expiration Date
The date designating the time during which the Product is
expected to remain within established shelf life specifications if stored under defined conditions.
4.7
Lot Number
Lot Number is a unique designator that is used to identify a
specific lot or Batch of Product. Pyramid Lot Numbers contain, at minimum, the year of Production,
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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4.8
Material Specifications
A composite of the specifications and testing performed
on Raw Materials, Process Consumables, Components, and Bulk Drug Substance used to evaluate identity, purity, quality and safety, as appropriate for its intended use. It describes the chemical, physical, microbiological/biological test requirements,
storage conditions, and handling requirements of the material. It also may contain the testing that is performed by the vendor on the Process Consumables, Components and Drug Substance as well as other requirements of the vendor’s certificate
of analysis/certificate of compliance.
4.9
Non-Conformance Report (NCR)
Any
deviation which may potentially impact the safety, identity, strength, purity, or quality of the Product is investigated. These written reports detail the specifics of an investigation resulting from a deviation to approved procedures or
specifications (e.g., deviations, OOS). The investigation includes a description of the incident, investigation, root cause, conclusions and corrective action or action plan, if applicable.
4.10
Planned Deviation Report
A Level I Deviation Report is the document which is
used to obtain approvals of either planned changes to temporarily modify approved operating, manufacturing, testing instructions, or procedures; or to intentional document excursions from approved operating, manufacturing, testing instructions,
target/informational test results, or procedures. The deviation does not permanently change existing instructions, batch records, or procedures; it is intended to be a specific/one time use document.
4.11
Product Specifications
Product Specifications shall have the meaning assigned
to it in the Master Services Agreement.
For added clarity, in-process Product
Specifications/requirements are documented within the Batch Production Record and final Product Specifications/requirements are documented within Material Specifications. Product Specifications are a composite of the specifications, PYRAMID
instructions, and Test Methods for a drug or material and is used to evaluate its identity, purity, quality and safety, as appropriate. It describes the chemical, physical, microbiological and biological requirements for testing of the drug and
storage conditions.
4.12
Process Consumables
One time use items such as tubings, filters, etc. These
items are very specific to a batch and will be disposed of following production of the batch.
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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4.13
Raw Materials
Raw Materials means the materials used in the Production of the
Product that may become part of the finished Product such as Active Pharmaceutical Ingredient (API), excipients, and buffer components.
4.14
Redress
The repackaging or placement of additional labeling (stickering)
operation. Repackaging – A repetition of a packaging step which requires a depackaging operation such as exchange of folding box, exchange of leaflet or insert, or delabeling/relabeling. Stickering – An operation by which the information content of
an existing packaging material is altered (changed or added). This alteration is accomplished by the addition of another label(s) or printing of additional information on the existing packaging materials.
4.15
Reinspection
A visual or mechanical/physical evaluation performed to
remove/correct defective units for which the process is not expected to have an adverse effect on Product quality.
4.16
Reprocessing
Duplication of a step or steps currently in the Production process
in order to bring the Product into conformance with Product Specifications and which will not alter the safety, identity, strength, quality, or purity of the Product beyond the established Product Requirements. In addition, an extension of an
approved process step is also regarded as reprocessing.
4.17
Retest Date
The date when a material should be reexamined to ensure that it is
still suitable for use.
4.18
Rework
Subjecting a material or product that does not conform to a standard or
specification to a repeat of one or more manufacturing steps that are different from the manufacturing process described in the application to obtain acceptable material or product.
4.19
Test Method
A Test Method describes chemical, microbiological, or biological
testing procedures and equipment, reagents, calculations, analysis and data interpretation documentation requirements within the QC Analytical Chemistry and Microbiological laboratories.
CONFIDENTIAL
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5.
cGMP COMPLIANCE WITH REGULATIONS
5.1
The principles detailed in the US current Good Manufacturing Practices (21 CFR 210 and 211) and the Rules Governing Medicinal Product in the European Community-Volume IV Good Manufacturing Practice for Medicinal
Products will cover the standards of Production of the Product. The cGMP guidelines will also cover the standards of quality assurance and quality control for the Product, including any Product license requirements only as communicated to PYRAMID by
XERIS.
5.2
PYRAMID and XERIS are responsible for following all Applicable Laws including cGMP, including local, state, and federal laws, as well as applicable terms of both the Master Services Agreement and this Quality Agreement.
6.
PRODUCTION
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6.1
General
6.1.1
The Production operations for the Product to be performed by PYRAMID, as well as the meaning of these two terms, are defined in the Master Services Agreement and associated Project Plans.
6.2
Facility
6.2.1
PYRAMID will Produce the Product at the Facility as specified in the Master Services Agreement. The floor plan of the Production area and corresponding room classifications are available for review during annual audits
of the Facility.
6.2.2
PYRAMID will ensure the Facility and equipment used to Produce the Product will be maintained according to current regulatory requirements and in accordance with the Master Batch Records used to Produce the Product. The
Production of the Product will be conducted in a suitably controlled environment and such Facilities will be regularly monitored for parameters critical to the process to demonstrate compliance with cGMP guidelines and the Batch Production Records.
6.2.3
PYRAMID will maintain controlled access to the premises as a whole including the Facility. PYRAMID will maintain all XERIS Confidential Information as defined in the Master Services Agreement.
CONFIDENTIAL
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6.3
Personnel
6.3.1
PYRAMID will provide adequate personnel with the appropriate education, training and experience to execute responsibilities defined in this Quality Agreement.
6.3.2
XERIS is responsible for providing personnel qualified to train PYRAMID personnel during technology transfer of Production processes and analytical methods.
6.3.3
PYRAMID will maintain adequate training and records for personnel associated with Xeris production processes and analytical methods for its products.
6.4
Materials
6.4.1
PYRAMID will use only Raw Materials, Process Consumables and Components approved by XERIS and sampled, tested and stored in accordance with the Materials Specifications.
6.5
Supplier Qualification
6.5.1
Xeris shall certify (qualify) and audit all critical Product related vendors and suppliers of PYRAMID Supplied Components, Raw Materials, and Process Consumables. XERIS shall certify (qualify) and audit all critical
vendors and suppliers of materials sourced by XERIS, such as API (drug substance). Supplier audits by XERIS shall be furnished to PYRAMID upon request.
6.5.2
Materials Procured by PYRAMID
6.5.2.1
PYRAMID is responsible for ensuring all Raw Materials, Process Consumables and Components procured by PYRAMID for use in the Production of Product comply with the specifications approved by XERIS. PYRAMID is responsible
for ensuring all Raw Materials, Process Consumables and Components are appropriately tested upon receipt, as well as for holding the relevant Certificates of Analysis for the Raw Materials, Process Consumables and Components. PYRAMID is responsible
for ensuring Raw Materials, Process Consumables and Components are released prior to use. PYRAMID is responsible for notifying XERIS of any issues or change requests.
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
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6.5.2.2
PYRAMID will ensure PYRAMID suppliers are qualified per PYRAMID SOPs.
6.5.2.3
For PYRAMID sourced items, PYRAMID is responsible for maintaining a program to evaluate animal derived material and control the risk of Bovine Spongiform Encephalopathy (BSE) and Transmissible Spongiform Encephalopathy
(TSE) and other potential infectious agents.
6.5.3
Materials Sourced by XERIS
6.5.3.1
XERIS is responsible for ensuring all materials sourced by XERIS for use in the Production of Product comply with the specifications registered. XERIS will provide PYRAMID a Certificate of Analysis for all materials
sourced by XERIS. If there is any change to the formulation, manufacture, testing, or specifications of any materials sourced by XERIS, XERIS will notify PYRAMID within [***] of any such changes in reasonable detail including any additional hazards
that result therefrom or storage parameters that are required therefore prior to sending such materials sourced by XERIS to the Facility.
6.5.3.2
XERIS will communicate within [***] any problem confirmed by XERIS that is a change in acceptability of all materials sourced by XERIS. PYRAMID will evaluate the status change for its impact to PYRAMID systems.
6.5.3.3
For XERIS sourced items, XERIS is responsible for maintaining a program to evaluate animal derived material and control the risk of Bovine Spongiform Encephalopathy (BSE) and Transmissible Spongiform Encephalopathy
(TSE) and other potential infectious agents.
6.6
Batch Production Records
6.6.1
PYRAMID shall transcribe the Production information into its own format and will obtain written approval from XERIS for each document version before Production. However, agreed upon changes to documentation will be
handled as outlined by Change Policy (see Article 11).
CONFIDENTIAL
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6.7
Standard Operating Procedures
6.7.1
PYRAMID is responsible for maintaining any Standard Operating Procedures required to Produce, test, and store the Product at PYRAMID and to support cGMPs.
6.8
Dates of Production and Expiration/Retest of Product
6.8.1
Date of Production- PYRAMID will assign the date of Production based on the date that liquid is added to the API to initiate the formulation (compounding) steps.
6.8.2
Expiration/Retest Date – XERIS will calculate the Expiration/Retest Date from the date of Production (see Section 6.8.1) using the shelf life accepted by the FDA or other regulatory agency as appropriate and
as communicated by XERIS to PYRAMID. The Expiration/Retest Date will be the last day of the month computed above.
6.9
Production and Equipment Data
6.9.1
PYRAMID is responsible for keeping records of equipment usage (previous product produced in non-dedicated equipment), cleaning, and any maintenance and calibration performed.
6.9.2
PYRAMID is responsible for maintaining calibration and preventive maintenance procedures and schedules for equipment/instruments used in the Production, packaging, testing and validation/qualification of the Product.
6.9.3
PYRAMID, as a multi-product facility, will have specific written procedures in place to control cross contamination of products.
6.9.4
PYRAMID is responsible for labeling all Product dedicated equipment and storing this equipment appropriately to prevent its use for other products.
6.9.5
PYRAMID will notify XERIS per PYRAMID procedure when introducing new product into the area of the Facility used for the Production of Product.
6.10
Reinspection, Redress, Reprocessing, and Rework
6.10.1
Redress, Reprocessing or Rework of Product shall not be performed without prior approval by PYRAMID QA and XERIS. Documentation for Redress, Reprocessing or Rework will be per approved protocol or Batch Production
Record and execution records will be included in the batch documentation submitted to XERIS upon completion.
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
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6.10.2
Reinspection, Reprocessing, or Rework will require a deviation investigation except where a standard procedure or Batch Production Record allows for such routine activity in the course of normal processing.
6.11
Storage and Shipment
6.11.1
Storage – PYRAMID will store the Product as per the Product Specifications approved by XERIS. PYRAMID will ensure there is no possibility of interference, theft, product contamination, or admixture with any other
materials during storage before shipping of the Product. XERIS will provide details of any labeling and container requirements including container sealing and integrity.
6.11.2
Packaging and Labeling for Transit – The Product will be suitably packaged and labeled for transit. The configuration and labeling of the shipping containers shall be specified by or approved by XERIS. Product
designated for shipment outside of the United States shall be labeled in accordance with applicable laws.
6.11.3
Shipment of Product – XERIS will authorize PYRAMID to ship Product upon submission of a formal Xeris QA request in writing. Released Product will be shipped by PYRAMID to a location designated by XERIS. Quarantined
Product may only be shipped with approval of XERIS and PYRAMID Quality. Product samples required for testing or further processing may be shipped prior to release of the Product. XERIS is responsible for ensuring that shipping configurations and
containers are validated. XERIS is responsible for ensuring that shipping configurations meet all applicable transportation legal requirements (e.g. Department of Transportation (DOT), etc.).
6.11.4
PYRAMID will ship Product to designated sites following procedures approved by XERIS which conform to the Master Services Agreement and the regulatory submission for the Product using shipping containers, temperature
controls, and recorders authorized by XERIS.
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
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6.12
Product and Process Development
6.12.1
XERIS is responsible for all product and process development and process validation unless specifically contracted to PYRAMID. PYRAMID will comply with the relevant requirements of this Agreement to support the
realization of XERIS product development. XERIS will provide the necessary information to allow PYRAMID to manufacture and ship XERIS Products meeting the specifications set forth in this Agreement. Specifically,
6.12.1.1
Product and Process Design are Xeris’ responsibility. At Xeris’ request, PYRAMID will collaborate on design of development and scale up studies and process assessments designed to evaluate sources of process
variability and how to control them. PYRAMID may also perform these studies at Xeris’ direction. It is Xeris’ responsibility to work with PYRAMID to define the process controls and operational ranges for the manufacturing process.
6.13
Risk Management
6.13.1
XERIS is responsible for overall product risk management. PYRAMID will collaborate with XERIS, when requested, on individual risk assessments. PYRAMID is responsible for the assessment, control, and mitigation of risks
related to the manufacturing processes for the Product. PYRAMID will provide information to XERIS on all deviations, changes, test results, etc., which affect the Product and may impact Product risk assessments.
7.
QUALITY CONTROL
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7.1
General
7.1.1
The testing activities for the Product which are to be performed by PYRAMID, shall be determined by XERIS and specified in the Product Specifications.
7.1.2
XERIS is responsible for qualification and supply of all non-compendial reference standards.
7.2
Subcontracting
7.2.1
PYRAMID will notify XERIS of outsourcing of analytical testing within [***].
7.3
PYRAMID Supplied Raw Materials, Process Consumables, and Components
7.3.1
Quality control of Raw Materials, Process Consumables, and Components supplied by PYRAMID will be undertaken by PYRAMID unless otherwise specified in writing by XERIS. PYRAMID will notify XERIS of any investigations
related to the storage and handling of any Raw Materials, Process Consumables, and Components supplied by PYRAMID that have been used to produce Product.
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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7.4
In-Process and Finished Product Testing
7.4.1
PYRAMID will perform in-process and finished Product testing as directed by XERIS using approved XERIS Product Specifications and validated, or otherwise verified, Test Methods.
7.4.2
A Certificate of Analysis, confirming that the Product has been Produced and tested in accordance with the Product Specifications, will be issued by XERIS or XERIS designated laboratory.
7.4.3
XERIS may perform testing at its cost to confirm or supplement the PYRAMID testing. XERIS may perform confirmatory testing during the initial term of the Master Services Agreement to validate the PYRAMID testing.
Periodically thereafter, XERIS may test material to confirm the PYRAMID testing. Dispute resolutions of conflicting test data will be handled per Article 10.
7.4.4
Shipping of samples to XERIS or a third party contract laboratory will be per a validated or otherwise qualified shipping method provided by or approved by XERIS.
7.5
Retain Samples
7.5.1
XERIS is responsible for storing retain samples of Product per 21 CFR 211.170.
7.5.2
Retain samples shall consist of at least enough material to perform full testing in duplicate.
7.5.3
PYRAMID and / or XERIS is responsible for storing appropriate quantities of retain samples of (a) primary packaging materials, (b) Raw Materials, except water, compressed gases, highly volatile compounds and
those that are not stable, and (c) Bulk Drug Substance used in the formulation of the Product for [***] past Product Expiration Date assigned by XERIS, or for [***] after distribution of the Batch, whichever is longer. Destruction of
Xeris materials may be done at a timing by Xeris, not to exceed regulatory requirements.
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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7.6
Stability Program
7.6.1
XERIS is responsible for maintaining a routine stability-testing program for the Product and reference standards. PYRAMID will provide samples of Product to XERIS or Xeris’ designated Testing facility for placement
on a stability program as directed by XERIS in this Quality Agreement. XERIS is responsible for identifying the Batch number and quantity of Product for each lot to be tested.
7.7
Out-of-Specification (OOS) Investigations
7.7.1
PYRAMID is responsible for investigating any testing performed by PYRAMID that fails to meet Product Specifications and notifying XERIS within [***] of the initiation of any investigation. XERIS retains the right to
review investigation data and reports to provide technical comments and assist with corrective action. Each investigation will be reviewed by PYRAMID’S designated Quality representative, and will follow the procedures recommended by regulatory
agencies and as defined in appropriate PYRAMID Standard Operating Procedures for OOS investigations. All completed investigation reports will be included in the released, executed Batch Record Package that will be provided to XERIS.
7.7.2
PYRAMID must obtain XERIS quality assurance approval for retesting and/or resampling prior to the initiation of testing for any OOS not determined to be the cause of a laboratory error.
8.
QUALITY ASSURANCE
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8.1
Documentation
8.1.1
XERIS shall have the right to review and approve (such approval not to be unreasonably withheld) the following documents associated with their Product prior to implementation: (i) Product Specifications,
(it) Product specific Test Methods, (iii) Master Batch Records and (iv) Raw Material, Process Consumables, Components and in-process specifications as part of the Master Batch Record approval,
(v) Product specific Standard Operating Procedures (vi) stability, process validation, laboratory method validation/qualification, equipment qualification, and cleaning validation protocols and summary reports specific to their Product or
XERIS dedicated-equipment.
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[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
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8.1.2
Master Batch Record – PYRAMID is responsible for creating the Product specific Master Batch Record. XERIS will approve each revision of the Master Batch Record prior to its use for cGMP Production. Original executed
Batch Record Packages with Lot Numbers issued by PYRAMID will be maintained on-site by PYRAMID’S Document Management department.
8.1.3
Product Specific Standard Operating Procedures – PYRAMID is responsible for creating and maintaining the Product specific Standard Operating Procedures based on XERIS supplied information. XERIS will review such
Standard Operating Procedures and provide approval via PYRAMID Document Control procedures.
8.1.4
General Standard Operating Procedures – PYRAMID is responsible for creating and maintaining all Standard Operating Procedures and other documentation required to support cGMP operations at PYRAMID. XERIS will be allowed
to review such Standard Operating Procedures during on-site audits.
8.1.5
Labels-PYRAMID or XERIS may generate a label proof for review. Approval will be by XERIS and PYRAMID prior to generation and use of labels for Product.
8.2
Deviations
8.2.1
Deviations – Any deviation from the process during Production, including, but not limited to, Batch Production Record execution, environmental monitoring excursions or processing procedures, will be carefully explained
and documented in an investigation and referenced in the Batch Production Records per PYRAMID procedures. All temporary changes to Batch Production Records or Xeris product related Standard Operating Procedures are reviewed and approved by PYRAMID
QA AND XERIS QA prior to implementation. Deviations must be justified and approved by PYRAMID’S designated quality representative as well as on site or off site Xeris QA representative and the affected area management, and be included in the
released, executed Batch Record Package.
8.2.1.1
XERIS Product Related Deviations – Deviations will be communicated to XERIS within [***] of the recognition of
the deviation. All investigations related to Product must be completed
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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and will be forwarded to XERIS for review as part of the released, executed Batch Record Package. Each investigation will be reviewed and approved by PYRAMID’S designated quality
representative. XERIS may review and approve, such approval not to be unreasonably withheld, Deviation reports. XERIS review and approval process shall not exceed [***]. If XERIS approval exceeds ten [***], PYRAMID reserves the right to approve
Deviations at its sole discretion. XERIS retains final disposition of any Batch of Product. PYRAMID is responsible for investigating any test result or in-process test which fails to meet Product
Specifications (see 7.7.7 OOS above). XERIS, as Product experts, may, at its cost, conduct its own independent failure investigation, and may participate in the PYRAMID failure investigation, as applicable.
8.2.2
XERIS will authorize the disposition of any Batch of Product aborted or rejected by PYRAMID.
8.2.3
PYRAMID will provide notification to XERIS if any problems are discovered that may impact Product previously shipped to XERIS or its distributor(s) or licensee(s) within [***] of initiation of the investigation.
8.3
Batch Disposition
8.3.1
For each Batch, PYRAMID will provide to XERIS the released Batch Record Package for review.
8.3.2
PYRAMID is responsible for ensuring the Product has been Produced according to the Product Specifications, procedures documented in the Batch Production Records, and this Quality Agreement. PYRAMID will provide to XERIS
a Certificate of Compliance.
8.4
Product Release
8.4.1
Release of the Product is the ultimate responsibility of XERIS and will be undertaken by XERIS QA based on XERIS’ internal procedures, the Batch Record Package documentation provided by PYRAMID, and completion of
any release testing required by XERIS.
8.4.2
Any problem discovered by XERIS likely to cause rejection of the Product will be communicated to PYRAMID within [***] upon discovery of the problem.
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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8.5
Records Retention
8.5.1
PYRAMID will retain Batch Production Records for the Product for a minimum of [***] beyond the Expiration Date of Product.
8.5.2
PYRAMID will return any Batch Production Records past the date in 8.5.1 above after first notifying XERIS in writing no less than [***] in advance.
8.6
Production and Quality Presence in the Production Facility
8.6.1
PYRAMID will permit no more than [***] XERIS representatives (such representatives to be reasonably acceptable to PYRAMID) to be present at the site in the Facility where Product is being Produced (during the Production
and testing of the Product) for observational purposes only and such representatives while at the Facility shall at all times be subject to obligations of confidentiality set forth in Article 14 of the Master Services Agreement and all of
PYRAMID’S rules and procedures.
8.7
Self-Inspection
8.7.1
PYRAMID will operate an annual internal auditing program to drive continuous improvement of cGMP operations, as per Pyramid’s own Quality Management System.
8.8
Product Complaints
8.8.1
XERIS is responsible for receiving and initially investigating any Product complaints. XERIS will notify PYRAMID within [***] of discovery of any problems thought to be due to Production, which are found during the
distribution of the Product and provide Product samples, if applicable, representative of the complaint. PYRAMID will perform investigations for any issue thought to be due to Production of Product. Investigation reports will be forwarded to XERIS
within [***] of initiation of the investigation or PYRAMID will notify XERIS and the Parties will agree, through good faith discussions, on a new target date for completion.
8.9
Product Recalls
8.9.1
Each Party will notify the other Party within [***] of (a) receipt of written notice if any Batch of
Product is alleged or proven to be the subject of a recall, market withdrawal or correction or (b) either Party’s determination that a recall is necessary. XERIS is responsible for instituting a Product
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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recall, market withdrawal or correction. XERIS will notify PYRAMID of any recall within [***] of initiation, which may be due to the Production of Product. Investigation reports regarding the
defect or cause of the recall or withdrawal will be forwarded to XERIS within [***] after receipt of request. In the event that the investigation requires additional time to complete, PYRAMID will notify XERIS and the Parties will agree, through
good faith discussions, on a new target date for completion.
8.10
Adverse Events
8.10.1
As per US FDA regulations (21CFR312.32a), an “adverse event” shall mean any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, and a
“suspected adverse reaction” shall mean any adverse event for which there is a reasonable possibility that the drug caused the adverse event.
8.10.2
PYRAMID shall notify XERIS within [***] of any adverse event report it receives related to Product. XERIS shall advise PYRAMID of any suspected adverse reaction within [***] of XERIS’ determination that the adverse
reaction is thought to be due to Production of Product. PYRAMID will perform investigations for any issue thought to be due to Production of Product. Investigation reports will be forwarded to XERIS within [***] of initiation of the investigation or
PYRAMID will notify XERIS and the Parties will agree, through good faith discussions, on a new target date for completion.
9.
REGULATORY COMPLIANCE
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9.1
Regulatory Inspections
9.1.1
PYRAMID will permit access by regulatory agencies with review authority over Product to PYRAMID’S premises. PYRAMID will inform XERIS of any announced regulatory inspections that directly involve the Product within
[***] of the notification to PYRAMID of such an inspection. PYRAMID will immediately inform XERIS of any unannounced regulatory inspections that directly involve the Product. PYRAMID will permit XERIS representatives (such representatives to be
reasonably acceptable to PYRAMID) to be present at the Facility for a pre-approval inspection or any subsequent inspection that directly involves Product. XERIS personnel may be allowed to participate directly
in the inspection.
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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9.1.2
PYRAMID will secure the agreement of XERIS prior to making any commitment to a regulatory agency specifically regarding XERIS Product. XERIS shall be provided with draft responses to regulatory observations that
directly involve the Product and its Production in a timely manner prior to submission to the regulatory authorities. XERIS shall have right to provide comments to the responses and corrective actions and approve final responses that pertain
directly to the Product. PYRAMID shall retain the final authority for corrective actions and content of the responses to the regulatory authority for all non-product related items.
9.1.3
PYRAMID will forward to XERIS any observations and responses from a routine regulatory inspection relating to the Facility where Xeris’ Product is Produced.
9.1.4
XERIS will inform PYRAMID in writing of any regulatory issue that impacts PYRAMID’S ability to Produce the Product promptly upon the discovery or receipt thereof and in any event within [***].
9.2
Regulatory Actions
9.2.1
XERIS will provide PYRAMID as appropriate, a copy of the relevant Product sections of the Chemistry, Manufacturing, and Controls (CMC) section of their regulatory filings prior to NDA submission for review and comment
by PYRAMID’S Regulatory Affairs department. Upon submission to the regulatory agency, XERIS will provide PYRAMID appropriate sections of the final copy of the CMC section for Product.
9.2.2
XERIS will notify PYRAMID of any regulatory actions related to the Product that may impact PYRAMID promptly upon the discovery or receipt thereof and in any event within [***].
9.2.3
Each Party agrees to supply the other Party with any Production, testing, or storage data within [***], if requested, as the result of a regulatory inspection, or a potential regulatory exposure such as a recall or
significant Product complaint.
9.3
Right to Audit
9.3.1
PYRAMID will allow representatives from XERIS (such representatives to be reasonably acceptable to PYRAMID), or Qualified Person for EU, to have access to PYRAMID’S Production, warehousing, laboratory premises,
records, regulatory filings (i.e., DMF) and communications (i.e., FDA 483s) solely for audit purposes listed below in Sections 9.3.2 through 9.3.4; and subject at all times to PYRAMID’S obligation to protect the confidential information of its
clients.
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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9.3.2
PYRAMID will permit XERIS to conduct a preparatory audit of cGMP Production of the Product for the pre-approval inspection for Product.
9.3.3
PYRAMID will permit XERIS to conduct ‘for cause’ audits to address Product quality or safety problems as discovered through Product failures or complaints related to PYRAMID’S Production of the Product,
for so long as such problems exist and are persisting or directly after the occurrence of such problem.
9.3.4
PYRAMID will permit XERIS to perform [***],[***], cGMP compliance audit per year.
9.3.5
PYRAMID will use reasonable efforts with its critical vendors, contractors or subcontractors used in the Production of Product to facilitate audits by XERIS.
9.3.6
While at PYRAMID’S premises, XERIS agrees to follow (and shall cause its representatives to follow) all of PYRAMID’S rules and procedures and shall use its best efforts not to interfere with or interrupt other
PYRAMID projects or PYRAMID personnel.
9.4
Audit Closeout
9.4.1
An exit meeting will be held with representatives from PYRAMID and XERIS to discuss significant audit observations.
9.4.2
XERIS will provide a written report of all observations within [***] days to PYRAMID. Within [***] of the audit report receipt, PYRAMID will provide a written response to all findings that details corrective action to
be implemented. PYRAMID will follow up to ensure all corrective actions are implemented.
10.
DISPUTE RESOLUTION
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10.1
Non-conformity Dispute – In the event that a dispute arises between
PYRAMID and XERIS regarding the conformity of a Batch of Product, the resolution will proceed in stages. The first stage requires direct communication between the Quality units from both Parties (Appendix 2), who will in good faith promptly
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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attempt to reach an agreement. If these actions fail to achieve resolution, the second stage will employ a qualified third party consultant to review the Batch Record Package and related
documentation. This third party consultant must be agreeable to both Parties prior to use. The results from this referee consultant will be used as final authority regarding the conformity or non-conformity of
the Batch of Product and the responsibility therefore if non-conforming. Financial liability is determined in the Master Services Agreement.
10.2
Test Result Dispute – Notwithstanding the requirements outlined in the MSA, in the event that a dispute arises between PYRAMID and XERIS in the testing performed by PYRAMID for the Product, the resolution wilt proceed
in stages. The first stage requires direct communication between Quality units from both Parties (Appendix 2) to determine that the methods of analysis are the same and are being executed in the same manner at the applicable sites. Second, carefully
controlled and split samples should be sent from one site to another in an attempt to reach agreement. Should there be a failure to achieve resolution, Quality management from the Parties will be required to meet to work through the analysis of a
mutually agreeable sample. If these actions fail to achieve resolution a qualified referee laboratory will be used to analyze the samples. This laboratory must be agreeable to both Parties prior to use. The results from this referee laboratory will
be used as final authority to determine conformity or nonconformity and the responsibilities therefore if non-conforming. Financial liability is determined in the Master Services Agreement.
11.
CHANGE POLICY
11.1
All changes to approved documents will be managed via PYRAMID’S change control or planned deviation processes.
11.2
All proposed changes go through a technical, regulatory, and cGMP impact assessment by the PYRAMID expert groups per PYRAMID change control procedure. The scope of this change process potentially impacting the Product
(for Phase III, registration, or commercial purposes) includes but is not limited to Raw Materials, Process Consumables, Components, packaging materials, labeling, Production process, XERIS specific validated equipment, Facilities, utilities or
computer systems, Product Specifications, and Test Methods.
11.3
The Product-specific controlled documents for Phase III, registration, or commercial purposes such as Batch Records, Product Specifications, and Product related Standard Operating Procedures or changes that may affect
Xeris’ regulatory submissions will also go through Xeris’ review for regulatory impact, implementation requirements, and Xeris’ approval. Changes must have appropriate documentation to justify the rationale behind the change.
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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11.4
The Parties will assess changes within [***] and those changes marked urgent the Parties will use commercially reasonable efforts to assess within [***].
11.5
Each Party agrees to notify the other of changes in key project personnel to ensure the effectiveness of arrangements and assure the quality of the Product.
11.6
XERIS will notify PYRAMID in writing who is authorized to make and approve changes on their behalf.
12.
PRODUCT AND PROCESS VALIDATION
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12.1
Process Validation- XERIS is responsible for ensuring the PYRAMID Production process is validated. The validation should ensure the process is capable of effectively and reproducibly achieving the Product acceptance
specifications and quality attributes. PYRAMID shall provide adequate resources to execute process validations as per mutually approved protocols. XERIS is responsible for development and validation of the manufacturing process including processing
hold times, formulation and process parameters, and filter validations. The activities may be contracted to PYRAMID, and if so, terms shall be outlined in the Master Services Agreement or in the Project Plan.
12.1.1
PYRAMID will work in conjunction with XERIS to support their process validation or related studies. PYRAMID may perform these studies on behalf of XERIS. XERIS holds final responsibility for the study design and
execution, results, and conclusions.
12.1.2
PYRAMID will provide XERIS with appropriate quality system, material, process, or product data to support Xeris’ continued process verification activities. PYRAMID may also collaborate with XERIS on process
assessments as a means of evaluating process variability. PYRAMID performs routine reviews of quality system, manufacturing, calibration, and maintenance data as part of the [***] management review. Where appropriate, those data may be made
available to XERIS for incorporation into their process verification activities.
12.2
Cleaning Verification/Validation – PYRAMID is responsible for ensuring adequate cleaning of Product contact parts used in the Production of Product is carried out between Batches of different product to prevent
contamination.
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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12.3
Sterilization and Depyrogenation Validation – PYRAMID is responsible for ensuring sterilization processes are validated and adequate sterilization and depyrogenation is carried out on the Components and appropriate
equipment prior to the Production of each Batch of Products.
12.4
Equipment, Computerized Systems, Facility, and Utilities Qualification – PYRAMID is responsible for ensuring any equipment, computer, Facility, utility and support systems used for the Production of Product are
qualified according to applicable regulatory requirements.
12.5
Laboratory Qualification – PYRAMID is responsible for ensuring all laboratories are in compliance with cGMPs and are qualified in all of the methodology associated with the Product. If Product specific analytical work
is performed at PYRAMID, then XERIS will provide any relevant analytical documentation to assist in the methods transfer or methods validation. PYRAMID is responsible for third party laboratory qualification unless such laboratory is specified by
XERIS. PYRAMID may be contracted to qualify third party laboratory at Xeris’ expense.
12.6
Shipping Qualification – XERIS is responsible for qualifying the shipping containers and process used for Product. If agreed, this activity may be contracted to PYRAMID. XERIS shall ensure all DOT requirements are met
by shipping configurations.
13.
PERIODIC PRODUCT REVIEW, ANNUAL REPORT AND DRUG LISTING
13.1
Product Review
13.1.1
In accordance with a Project Plan, PYRAMID will perform Product review for the Product and will issue an annual report to XERIS. This report will cover all production and testing activities performed by PYRAMID. It will
consist of a review of any changes at PYRAMID in the production, testing, storage, shipping or validation of the Product in the review period and a summary of the Batches made, released, and rejected. Also, control charting and summarizing of key
Product parameters may be performed. Any abnormalities will be explained in the annual review. PYRAMID will provide the requested information to XERIS annually commencing with the start of commercial Production.
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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13.2
Annual Report
13.2.1
XERIS is responsible for preparing any annual report to regulatory authorities as required by applicable regulations. At least [***] before the annual report due date, XERIS shall request in writing from PYRAMID any
information required for preparation of the annual report. PYRAMID will provide the requested information to XERIS within [***].
13.3
Drug Listing
13.3.1
PYRAMID is responsible for Establishment Registration with the appropriate agency, while XERIS is responsible for drug listing activities including listing PYRAMID as the manufacturer of the Product. PYRAMID will
provide XERIS with applicable information needed for drug listing, including Establishment Registration number and/or Facility Establishment Identifier (FEI) number.
14.
Quality Responsibilities Table
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Note: if inconsistencies exist between the text of the Quality Agreement
and this table, the text of the Quality Agreement takes precedent.
Responsibilities
XERIS
PYRAMID
A
Compliance Requirements
1.01
Follow applicable regulations and current Good Manufacturing Practices, as well as locally imposed requirements.
• 21CFRPart4
• 21CFRPart11
• 21 CFR Parts 210 and
211
• 21 CFR Parts
600, 601 & 610
• Eudralex – Annexes 1 and 13, the Rules Governing Medicinal Products in the European Union,
Volume 4 EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use.
• ICH Q9 – Quality Risk Management
• ICH Q10 –
Pharmaceutical Quality System
• Eudralex – The Rules Governing Medicinal Products in the European Union, Volume 10, Chapter
3
Applicable compendia requirements (e.g. USP, EP), as required by XERIS and
PYRAMID agreed to in writing by the Parties
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
1.02
Manufacture, package, ship, store and test the Product and materials in an environment meeting the applicable cGMP regulations, which is designed, constructed and maintained in a manner that a) permits the operation therein to be
performed under clean, sanitary and orderly conditions; b) permits the effective cleaning of all surfaces; and c) prevents the contamination of the Product and the addition of extraneous material to the Product.
[***]
[***]
1.03
Manufacture the Product in adherence to approved Master Batch Records (MBRs) and product specifications, etc. where applicable.
[***]
[***]
1.04
Refrain from activity that could adversely affect quality of the Product.
[***]
[***]
1.05
Have management controls in place to track and trend investigations and corrective or preventative action commitments.
[***]
[***]
1.06
Maintain a Quality Unit that is independent of production and that fulfills both quality assurance and quality control responsibilities.
[***]
[***]
1.07
Disposition of Product by Quality Unit or Qualified Person (QP) after review of all relevant documents (see Appendix 3) to ensure compliance.
[***]
[***]
1.08
Product failing to meet specifications may not be supplied to XERIS without Xeris’ prior written consent.
[***]
[***]
1.09
Involve the Quality Unit in all Good Manufacturing Practices related matters.
[***]
[***]
1.10
Notify XERIS within [***] of any changes not subject to cGMP change control that would affect documentation within this Quality Assurance Agreement including but not limited to PYRAMID’s “Primary Contacts”,
“Quality Agreement Signatory”, or a company name change due to a merger/acquisition.
[***]
[***]
1.11
Maintain adequate internal and external audit programs per Good Manufacturing Practices.
[***]
[***]
1.12
Maintain effective quality systems that minimize the potential for product quality, regulatory and compliance issues.
[***]
[***]
1.13
Permit a representative of XERIS to be present during any stage manufacture of Product (Person in the Plant).
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
B
Right to Audit
2.01
Have the right to audit PYRAMID’s facilities and systems [***] per year, as they relate to the manufacture of Product, at appropriate times. XERIS retains the right to conduct “for cause” audits as necessary.
[***]
[***]
2.02
Schedule visits and/or audits.
[***]
[***]
2.03
Request product-specific documents for review to ensure continued adherence to the agreed upon manufacturing process, applicable current Good Manufacturing Practices and other applicable requirements during audits.
[***]
[***]
2.04
Provide documents as requested in 2.03.
[***]
[***]
2.05
Issues PYRAMID a confidential audit report summarizing audit observations within [***] of the audit date. If required by XERIS policies and procedures or by any competent authority, XERIS reserves the right to share the audit report
with a third party undertaking QC release activities in relation to Product on behalf of XERIS.
[***]
[***]
2.06
Issue responses to all observations in writing to XERIS within [***] of receipt. Responses are to include timelines and plans for closure of all commitments.
[***]
[***]
2.07
Ensure that deficiencies highlighted during these audits are remediated in accordance with a mutually agreed upon action plan.
[***]
[***]
C
Regulatory Inspections and Exchanges
3.01
Coordinate all activities necessary to ensure readiness prior to regulatory agency Pre-Approval Inspections and maintain inspection readiness throughout the approval process.
[***]
[***]
3.02
Coordinate all activities necessary to ensure and maintain readiness for all announced and unannounced regulatory agency inspections.
[***]
[***]
3.03
Notify XERIS within [***] of receiving a written notification of failures to comply with Good Manufacturing Practices after a general site inspection (i.e. an inspection not directly related to a specific XERIS product or service)
from any regulatory agency.
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
3.04
Notify XERIS within [***] of being notified of any pending or ongoing regulatory authority inspection or communication related to XERIS Products or the facilities, equipment, or process used to produce, test or warehouse the
Product. In the event that the inspection pertains to XERIS Product, PYRAMID shall permit a representative of XERIS to be present during any such inspection. If a XERIS representative cannot be on site for the inspection, then daily updates will be
communicated to XERIS summarizing the inspector’s observations.
[***]
[***]
3.05
Obtain XERIS approval for all documents and correspondence related to XERIS products, prior to providing same to any regulatory agency. Provide a list or copies of all documents directly related to a XERIS Product or operations that
have been shared with a regulatory agency during any inspection. Copies of PYRAMID’s Product related correspondence with regulatory agencies will also be provided to XERIS.
[***]
[***]
3.06
Provide copies to XERIS within [***] of correspondence received from regulatory authorities (Boards of Health, Health Authority, etc.) related to XERIS Product and related operations performed by PYRAMID, other than correspondence
described in item 3.03.
[***]
[***]
3.07
Notify XERIS by telephone, followed by written communication, within [***] of the receipt of a Regulatory Authority inspection report, deficiency letter or regulatory compliance observation, which contains any significant adverse
findings that relate to XERIS Products or the facilities used to produce, test, or warehouse the Product. Significant adverse findings include, but are not limited to, conditions, practices, or processes that adversely affect or may potentially
adversely affect Product or service quality and/or the rights, safety or wellbeing of subjects/patients and/or the quality and integrity of data, documentation, or other materials or information addressed in the inspection.
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
3.08
Provide a copy of the regulatory inspection report, deficiency letter, or regulatory compliance observations, response and related correspondence to XERIS, edited to exclude PYRAMID proprietary information within [***] of receipt,
Allow XERIS to review, comment on the response, and approve the response relevant to Product supplied to XERIS, prior to submission of the response to the regulatory authority.
[***]
[***]
3.09
Notify PYRAMID of any regulatory compliance observation received by XERIS that pertains to operations performed by PYRAMID and requires PYRAMID information or action.
[***]
[***]
3.10
Provide XERIS with information requested to ensure compliance with regulatory requirements within [***] of notification, or as required to meet regulatory obligations.
[***]
[***]
3.11
Upon obtaining permission from XERIS, sample and retain an equal amount of product if samples of XERIS product are taken by the regulatory authority, until given further written instruction from XERIS.
[***]
[***]
3.12
Provide PYRAMID with advance written notification of new or supplemental regulatory submission/application that impacts the operations performed by PYRAMID.
[***]
[***]
D
Regulatory Documentation
4.01
Provide all necessary Letters of Authorization, or other documentation, to permit reference to PYRAMID’s Master File(s) to facilitate the registration of the Product, if applicable.
[***]
[***]
4.02
Maintain annual reports as required in accordance with the regulations of the applicable regulatory authority.
[***]
[***]
4.03
Liaison with Regulatory Authorities for approval, maintenance and updating of regulatory submissions where required.
[***]
[***]
4.04
Notify XERIS of any regulatory application change as applicable before submitting the change to the regulatory authority and prior to implementation.
[***]
[***]
4.05
Upon request, provide assistance in the preparation and review of pertinent sections of new or supplemental regulatory applications where XERIS owns the product registration and submit comments to the proposed application to
XERIS.
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
4.06
Provide appropriate sections of product registration/regulatory submissions relevant to manufacture and quality control of Product to PYRAMID for review prior to submission.
[***]
[***]
4.07
Establish appropriate data verification procedures for data generated that will be provided for submission in regulatory documents by XERIS.
[***]
[***]
4.08
Ensure that XERIS is provided copies of current health authority regulatory licenses, cGMP certificates and related documents.
[***]
[***]
4.09
Secure and maintain all licenses and implement all necessary regulatory compliance procedures (e.g., compliance with DEA Regulations, Schedules 1-5) necessary to (a) receive and process
active pharmaceutical ingredients and drug products relating to Products and Services at PYRAMID’S facilities and (b) distribute Products to Xeris’ designated facilities.
[***]
[***]
E
Animal Derived Materials
5.01
Have an effective program in place for PYRAMID sourced materials that is aligned with XERIS requirements to evaluate and control the risk of Transmissible Spongiform Encephalopathy for raw materials and components.
[***]
[***]
5.02
Notify XERIS of the use of any animal derived materials. The foregoing requirement includes any animal derived materials used in the Product manufacturing process including: (i) those used as machine lubricants, cleaning agents/aids
and/or processing aids, and; (ii) any animal derived materials that have contact with Product.
[***]
[***]
5.03
Maintain appropriate records for each lot of animal derived material to ensure traceability. Where required by local regulations, the location where animals lived or were slaughtered (if applicable) must be documented.
[***]
[***]
5.04
Provide BSE/TSE certification from vendors of API and primary packaging supplied to PYRAMID by XERIS.
[***]
[***]
F
Buildings and Facilities
6.01
Buildings and facilities used in the manufacture, handling or storage of the Product shall be designed, constructed and maintained to facilitate cleaning, maintenance and operations and to ensure orderly placement of equipment and
materials to prevent mix-up and contamination.
[***]
[***]
6.02
Ventilation systems will be designed and maintained to minimize the risk of contamination.
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
6.03
Dispose of sewage, refuse and other waste in a safe and timely manner following applicable environmental health and safety regulations.
[***]
[***]
6.04
Maintain a set of current drawings for critical utilities including water, electricity, compressed gasses and air handling.
[***]
[***]
6.05
Maintain and document an adequate, effective pest control program.
[***]
[***]
6.06
Notify XERIS prior to the implementation of a change in product category manufactured in the same facility and equipment as XERIS Product (such as veterinary drugs or hazardous, deleterious, potent or sensitizing materials, for
example: Penicillin, beta-lactam, etc.).
[***]
[***]
6.07
Notification to XERIS within [***] of any significant shutdowns or operational interruptions of PYRAMID’s facilities which may impact the XERIS Products.
[***]
[***]
6.08
Notify and receive approval from XERIS prior to use of existing or expanded laboratory or storage facilities that have not been specifically reviewed for their suitability during a XERIS cGMP compliance audit or without prior
written approval by the XERIS.
[***]
[***]
G
Personnel and Training
7.01
Provide sufficient training, including for applicable Good Manufacturing Requirements, to meet obligations of this Quality Agreement.
[***]
[***]
7.02
Provide adequate personnel qualified by appropriate training and experience to perform and supervise the manufacture, testing, packaging and disposition of the Product.
[***]
[***]
7.03
Ensure training is regularly conducted, assessed and documented by qualified individuals.
[***]
[***]
7.04
Have written job descriptions for positions responsible for performing Good Manufacturing Practices related activities.
[***]
[***]
7.05
Ensure that non-employees, including consultants, advising on the manufacture and control of the Product have sufficient education, training, and experience to advise on the subject for which
they are retained. Non-employees will be supervised as required and trained in Good Manufacturing Practices.
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
H
Suppliers Qualification
8.01
Xeris shall certify (qualify) and audit all Product related vendors and suppliers of PYRAMID Supplied Components, Raw Materials, and Process Consumables. XERIS shall certify (qualify) and audit all vendors and suppliers of materials
sourced by XERIS, such as API (drug substance). Supplier audits by the XERIS may be furnished to PYRAMID upon request.
[***]
[***]
I
Sub-Contracting
9.01
XERIS is responsible to identify and qualify any Sub-Contractors that may be required for analytical testing, third party manufacturing, or sterilization. XERIS shall ensure these Sub-Contractors operate in compliance with current Good Manufacturing Practices, compendial requirements and any other applicable regulations.
[***]
[***]
9.02
Not engage any Sub-Contractor without the prior written consent of XERIS.
[***]
[***]
9.03
Maintain Sub-Contractor as a qualified contractor following approved procedures in accordance with XERIS Requirements. Documentation should be supplied to PYRAMID to allow for confirmation by
external auditors when necessary.
[***]
[***]
J
Change Control
10.01
Have approved written procedures for control of changes impacting the Product including, but not limited to, manufacturing components/raw materials or process, packaging materials, labeling, computer hardware/software, product
specifications, and test methods. Ensure any changes are reviewed/approved by Quality Unit. Include in written procedures the process and criteria for customer notification and approval, follow up and closure of changes.
[***]
[***]
10.02
Notify XERIS and XERIS QA as soon as reasonable, but no later than [***] after any emergency, unplanned changes which directly impact a XERIS Product or Service, In the case of emergency changes, PYRAMID and XERIS shall cooperate to
expedite the review and approval process prior to final acceptance of the change,
[***]
[***]
10.03
Notify XERIS and XERIS QA of all significant changes to facility, process, test methods, quality systems and specifications. Significant changes are those that impact Product identity, strength, safety, potency, purity, stability,
manufacturing timelines, regulatory status or validation/qualification.
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
10.04
Issue a change request for each change as soon as possible after the need for change is apparent, allowing [***] for XERIS to comment and approve or reject changes prior to implementation or for PYRAMID to comment on the feasibility
of or timeline for the change.
[***]
[***]
10.05
Provide copies of change control documentation such as supporting data, validation/qualification reports and contractor approved change control forms for changes impacting Product as requested by XERIS,
[***]
[***]
10.06
Implement monograph changes in order to meet new or revised compendial requirements,
[***]
[***]
10.07
Jointly establish a strategy to secure regulatory approvals as necessary and to mutually agree to an implementation timetable.
[***]
[***]
10.08
Specify to PYRAMID who is authorized to make and approve changes (per Section 11 of this Agreement) on behalf of XERIS.
[***]
[***]
K
Validation/Qualification
11.01
Define all process parameters, critical process control points and quality attributes and Specifications.
[***]
[***]
11.02
Have a written master validation/qualification plan for the facilities, equipment/instruments, manufacturing process, cleaning procedures, analytical procedures, in process control tests and computerized systems approved by the
Quality Unit (as appropriate).
[***]
[***]
11.03
Prepare and maintain validation/qualification documentation approved by the Quality Unit, including protocols, reports and associated documentation. Provide such documents to XERIS upon request.
[***]
[***]
11.04
Validate/qualify as necessary all critical systems, utilities and equipment/instruments used for the manufacture and control of Product (through installation Qualification (IQ), Operational Qualification (OQ), and/or Performance
Qualification (PQ)).
[***]
[***]
11.05
Validate/qualify computer systems and associated software used in Good Manufacturing Practices-related activities associated with the Product. Procedures must be in place to ensure the integrity, archiving, retrieval and destruction
of the electronic data that comply with applicable regulations.
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
11.06
Validate/qualify methods and procedures for cleaning of equipment with acceptance criteria for residues defined and justified. Alternative evaluations of cleaning validation/qualification (dedicated equipment, matrix approach, worst
case scenario, etc.) are to be approved by XERIS.
[***]
[***]
11.07
Develop and execute a plan for process and method validation/qualification including definition of roles and responsibilities between PYRAMID and XERIS for performing technology transfers, if applicable.
[***]
[***]
11.08
Where method validation is performed by PYRAMID:
• Write method validation protocol,
[***]
[***]
• Review and approve method validation protocol,
[***]
[***]
• Execute method validation protocol,
[***]
[***]
• Write method validation report, and
[***]
[***]
• Review and approve method validation report.
[***]
[***]
11.09
For process validation:
• Write process validation protocol,
[***]
[***]
• Review and approve process validation protocol,
[***]
[***]
• Execute process validation protocol,
[***]
[***]
• Write process validation report, and
[***]
[***]
• Review and approve process validation report,
[***]
[***]
11.10
Validate/qualify all manufacturing processes, Product formulation, mixing operations and hold times for the formulation process.
[***]
[***]
11.11
Qualify time limitations for each phase of production.
[***]
[***]
11.12
Evaluate protocol deviations encountered during validation/qualification to determine impact on validation/qualification studies, including need to conduct repeat studies.
[***]
[***]
11.13
Evaluate validated/qualified systems and processes periodically to verify they are still operating in a valid manner.
[***]
[***]
11.14
Report all media simulation failures for Product related aseptic manufacturing processes.
[***]
[***]
11.15
Permit a representative of XERIS to be present during process demonstration and validation.
[***]
[***]
11.16
Validate / qualify bioburden and sterility assays.
[***]
[***]
11.17
Qualify suppliers for API (drug substance) and excipients.
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
L
Preventive Maintenance and Calibration
12.01
Maintain calibration and preventive maintenance procedures and schedules for equipment/instruments used in the manufacture, packaging, testing and validation/qualification of the Product. Include calibration tagging where
appropriate.
[***]
[***]
12.02
Inform XERIS within [***] if an instrument used for Services performed for Xeris is found to be out of calibration or out of tolerance and perform investigation.
[***]
[***]
12.03
Document and review (including calibration performed by Sub-Contractor) manufacturing and laboratory equipment/instrumentation calibration data.
[***]
[***]
M
Manufacturing and Laboratory Investigations
13.01
Have appropriate procedures for the identification, investigation, reporting, tracking, trending and closure of deviations as per applicable cGMP requirements. Investigations must include but are not limited to known lab errors,
atypical results and Out-of-Specification (OOS) results that occur during the manufacture and testing of the Product, including stability testing (as applicable).
[***]
[***]
13.02
Document and notify XERIS and Xeris QA within [***] of first knowledge of any significant deviation. Significant deviations include, but are not limited to, those which have the potential to affect the quality, identity, purity
and/or strength of the Product; those which have significant impact on manufacturing timelines; those which impact the cGMP, validation/qualification or regulatory status; any OOS test result which cannot be invalidated within [***] or any deviation
resulting in the Product being outside of filed registration limits (see Appendix 3 for examples). XERIS retains the right to request notification of additional deviations on a case by case basis. All deviations must be resolved prior to release of
Product.
[***]
[***]
13.03
Review and approve any significant deviation prior to Product release.
[***]
[***]
13.04
Notify XERIS and XERIS QA within [***] of first knowledge of all confirmed Out-of-Specification results generated during stability testing of
Product.
[***]
[***]
13.05
Provide investigation/deviation documentation, including original and any retest or resample results to XERIS with the batch record, or upon request.
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
13.06
Assist PYRAMID in investigations when deemed appropriate.
[***]
[***]
13.07
Complete investigations within [***] of commencement.
[***]
[***]
13.08
Approve in writing any significant deviation from PYRAMID’S internal specifications or standard operating procedures that may affect XERIS Products or services. The decision to approve will not be unreasonably withheld
or delayed.
[***]
[***]
13.09
Complete corrective/preventive action (CAPA) commitments resulting from investigation closure within the planned timeframe. Provide evidence of closure of CAPA items to XERIS for notified deviations.
[***]
[***]
N
Documentation and Records
14.01
Document all required process and testing steps at the time such process or testing step is executed.
[***]
[***]
14.02
Record all changes to process or testing documents in a cGMP compliant fashion (e.g., by initialing and dating all changes).
[***]
[***]
14.03
Have a controlled system to initiate, review, revise, approve, obsolete and archive all Good Manufacturing Practices documentation.
[***]
[***]
14.04
Maintain a document control system for Standard Operating Procedures.
[***]
[***]
14.05
Maintain a document control system for specifications, including: raw materials, Product labeling, packaging materials and other materials that would likely affect Product quality.
[***]
[***]
14.06
Review and approve all Good Manufacturing Practices-related records.
[***]
[***]
14.07
Retain, archive and destroy all Good Manufacturing Practices-related documents and data pertaining to Services performed for XERIS in
accordance with XERIS and regulatory requirements as defined below:
• keep all original analytical records including test results, records, charts, computer
reports and graphs for a minimum period of [***] or if batch-related, one year in excess of expiration date,
• keep all validation/qualification and technical transfer documents in connection with
Service performed for XERIS for [***] after the life of the Product,
• keep original investigation and out-of-specification report documentation in connections with Services performed for XERIS for a minimum of [***] or [***] beyond expiration date of associated batch,
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
• at the end of retention period, notify XERIS prior to destruction of
records identified above, including a specific identification of the records. XERIS retains the right to have transferred and to maintain any such record as it relates to Product at its discretion,
• ensure that original
records are protected from fire and water damage in a limited access area and
• retain Batch Record documentation to meet applicable regulatory requirements and any
special instruction provided by XERIS.
14.08
Write Master Batch (or, as applicable, Packaging) Records.
[***]
[***]
14.09
Review and approve Master Batch Records.
[***]
[***]
14.10
Have all executed batch-related records reviewed and approved by PYRAMID’S Quality Unit prior to submission to XERIS for release. Ensure records have a unique lot identification number.
[***]
[***]
14.11
For laboratory control records, include complete data derived from all tests conducted to ensure compliance with specifications. These records will contain the date and the signature of a second qualified person showing review and
verification of the records.
[***]
[***]
14.12
Provide copies of documents or records needed to ensure compliance with regulatory requirements or filings to XERIS upon request.
[***]
[***]
14.13
Provide copies of documents and records for XERIS disposition of product listed in Appendix 4.
[***]
[***]
14.14
Provide a Certificate of Analysis for the release of each manufactured lot.
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
14.15
Provide a complete Certificate of Analysis (only for tests performed by PYRAMID or subcontracted by PYRAMID) for each shipment of the
Product, containing at minimum the following information:
• XERIS Product number,
• PYRAMID Product
number, (if applicable). PYRAMID lot number,
• Name of Product,
• Batch size,
• Name of the test (if applicable),
• Test method (if
applicable),
• Specification limit (if applicable),
• Expiration date (if
applicable)
• Actual
test result (as a numerical value, unless designated Pass/Fail in the specification limit), including retest results if required (if applicable)
• Date tested for each test (if applicable)
• Quality Assurance
approval and date,
• Manufacturing site (name and address)
• Manufacturing date,
and
• Storage
conditions
[***]
[***]
14.16
Release of the Drug Product.
[***]
[***]
14.17
Provide Certificate of Compliance certifying Product was manufactured in a current Good Manufacturing Practices-compliant facility and was tested in accordance with and meets specifications and was manufactured according to its
approved regulatory dossier.
[***]
[***]
14.18
Keep and make accessible to XERIS upon request all manufacturing, analytical, and distribution records. Where original documentation is in a language other than English, a direct translation to English will be provided by PYRAMID
upon request by XERIS. Care should be taken that any changes made to the English version are also reflected in the original language documentation.
[***]
[***]
O
Production and In-Process Controls
15.01
Have approved written procedures in place for qualification of subcontractors that provide cGMP-materials and services.
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
15.02
Perform and maintain all PYRAMID qualifications in a current state as per applicable procedures and XERIS Requirements.
[***]
[***]
15.03
Provide current Raw Material, API, and Product Specifications to PYRAMID.
[***]
[***]
15.04
Have a system for batch identification including assigning lot numbers.
[***]
[***]
15.05
Implement and document specifications for raw materials, packaging materials, and Product labeling and processing aids that would likely affect Product quality pursuant to specification documentation provided by XERIS.
[***]
[***]
15.06
Have approved written procedures for all required in-process sampling and testing.
[***]
[***]
15.07
Qualify suppliers for API (drug substance) and excipients.
[***]
[***]
15.08
Procure, test (as required), and disposition raw materials, components, packaging and labeling used in manufacture and packaging of Product.
[***]
[***]
15.09
Document actual yields for the Product, and evaluate actual yields versus theoretical in-process yield control limits.
[***]
[***]
15.10
Provide a Xeris-defined Date of Manufacture (DOM) for assigning to Product.
[***]
[***]
15.11
Use a Xeris-defined Date of Manufacture (DOM) in the Master Batch Records (MBRs).
[***]
[***]
15.12
Assign Product expiration (shelf-life) date.
[***]
[***]
15.13
Have appropriate inspection process or device in place to ensure the correct Product is packaged, the correct labeling is utilized, and any inline marking is completely and accurately located and legible.
[***]
[***]
15.14
Include in shipper label, at a minimum:
• name and address of the manufacturer,
• unique identifying
code (ex. lot number),
• batch record or Pyramid project number,
• quantity of
contents,
• storage
and special transport conditions,
• manufacturing date,
• XERIS-assigned expiry
date (if provided), and
• any special requirements (if applicable).
[***]
[***]
15.15
Where appropriate, develop all labeling in accordance with applicable regulations (including for the country intended for distribution) and regulatory submission (as applicable).
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
15.16
Include a representative label in the batch record.
[***]
[***]
15.17
Establish and maintain a program for environmental monitoring including tracking and trending processes.
[***]
[***]
15.18
Retain reserve samples of raw materials, packaging materials and Product label, intermediates (if applicable) in accordance with PYRAMID’s written procedures.
[***]
[***]
15.19
Retain reserve samples of Final Product (Pre-Filled Syringes (PFS)).
[***]
[***]
15.20
Provide certification that all at-risk raw materials/components have been tested for the absence of BSE/TSE contamination for each lot of Product supplied to XERIS.
[***]
[***]
P
Process Equipment
16.01
Process equipment must be uniquely identified, status tagged and managed with an equipment history log or equivalent system. Process lines will be appropriately identified.
[***]
[***]
16.02
Use appropriate food grade machine lubricants and oils that contain no animal derived materials.
[***]
[***]
16.03
Maintain a current set of “as-built” drawings for equipment and facilities.
[***]
[***]
Q
Reprocess (if applicable)
17.01
Where reprocessing is required and permitted, review and approve all reprocessing steps.
[***]
[***]
17.02
Document approval in specific reprocessing protocols or special batch record instructions.
[***]
[***]
17.03
Perform reprocessing only where specified in protocol or specific batch record instructions approved by XERIS.
[***]
[***]
17.04
Review and approve Product requiring reprocessing.
[***]
[***]
R
Rework (if applicable)
18.01
Where rework is required and permitted, have a protocol or procedure that has been approved by both XERIS and PYRAMID, and any regulatory approval that may be required prior to implementation.
[***]
[***]
18.02
Review and approve Product requiring rework.
[***]
[***]
S
Laboratory Controls
19.01
Have written procedures for sample management, identification, testing, disposition and recording, approval, tracking, storage, retention and disposal of laboratory data.
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
19.02
Hold samples and dispose of them as required by specifications and procedures.
[***]
[***]
19.03
Destroy samples and sample packaging in a secure and legal manner that prevents unauthorized use or diversion in accordance with
PYRAMID’s procedures. Maintain destruction records.
Destruction method must render any XERIS owned registrations, logos or trademarks
unidentifiable.
[***]
[***]
19.04
Have approved written procedures for management, preparation and use of reference standards, reference materials, reagents, and solutions including qualification/requalification of use period.
[***]
[***]
19.05
Mutually agree on source, grade and characterization of reference standards/materials, if not XERIS supplied.
[***]
[***]
19.06
Provide PYRAMID with qualified non-compendial standards and corresponding storage conditions, potency/purity information, and expiration/review dating.
[***]
[***]
19.07
Have appropriate specifications and test procedures for the Product, which are consistent with the applicable compendia! monograph, XERIS-approved product monograph and/or Product Specifications.
[***]
[***]
19.08
Test Product in accordance with qualified or validated methods, as appropriate, and with specifications using calibrated, qualified equipment. Shall not perform reduced testing regimen without meeting requirements of an established
program or protocol reviewed and agreed to by XERIS.
[***]
[***]
19.09
Transfer all test methods qualified or validated by XERIS according to protocols (that includes roles & responsibilities) approved by PYRAMID and XERIS.
[***]
[***]
19.10
Ensure method transfers have been completed and approved prior to the generation of any cGMP test data.
[***]
[***]
T
Retest
20.01
Perform retesting, when required and approved, in accordance with approved protocols or procedures.
[***]
[***]
20.02
Approve retest protocols for retesting associated with confirmed OOSs as applicable.
[***]
[***]
U
Stability (if applicable)
21.01
Maintain a documented, ongoing stability program to monitor the stability of the Product using stability indicating procedures.
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
21.02
Store stability samples in containers/closures in accordance with approved protocols which include time stations and storage conditions.
[***]
[***]
21.03
Write stability protocol and reports.
[***]
[***]
21.04
Review and approve stability protocols prior to executing stability studies.
[***]
[***]
21.05
Approve stability reports.
[***]
[***]
21.06
Provide approved stability protocols and stability reports to XERIS.
[***]
[***]
21.07
Assign and approve appropriateness of storage conditions and retest or expiry date base on stability data.
[***]
[***]
21.08
Perform stability testing of reworked/reprocessed batches or those associated with investigations or revalidations/re-qualifications as required by XERIS.
[***]
[***]
21.09
Document and notify XERIS and Xeris QA within [***] of first knowledge of any OOS (out of specification) results obtained during stability testing that cannot be invalidated within [***].
[***]
[***]
21.10
Confirmed OOS must be reported to Xeris in [***].
[***]
[***]
V
Storage and Distribution
22.01
Validate/qualify and maintain storage facilities appropriate for conditions specified on the Product label. Maintain records of any critical parameters.
[***]
[***]
22.02
Establish and maintain an environmental monitoring program including trending activities to ensure adherence to specified product, raw material, packaging material and component storage conditions {such as temperature and
humidity).
[***]
[***]
22.03
Upon PYRAMID’s receipt of sample(s) from XERIS, when samples are provided with temperature recorders, read recorder and report results to XERIS, noting temperature excursions.
[***]
[***]
22.04
Provide any special precautions to be taken during sample storage, handling, testing and disposal.
[***]
[***]
22.05
Provide PYRAMID with corresponding storage conditions.
[***]
[***]
22.06
Receive, handle and store the XERIS reference standards as defined in writing by XERIS. PYRAMID will maintain a use log (or equivalent) for all XERIS reference standards.
[***]
[***]
22.07
Have validated/qualified systems for controlling quarantined, rejected or recalled materials and segregate rejected or recalled materials.
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
22.08
Storage of bulk material up to packaging and shipment to XERIS.
[***]
[***]
22.09
Storage of Finished Product.
[***]
[***]
22.10
Provide Product Material Safety Data Sheet or equivalent.
[***]
[***]
22.11
Ship Product in accordance with qualified transportation requirements.
[***]
[***]
22.12
In the event of an environmental excursion affecting Product, notify XERIS within [***] and make subsequent investigation available to XERIS upon request.
[***]
[***]
22.13
Have a system in place for ensuring unreleased Product is not shipped unless authorized by XERIS Quality Assurance unit; Shipment pending Acceptable Sterility test results.
[***]
[***]
22.14
Have validated/qualified systems for tracking Product inventory and shipments and maintain appropriate records for such activities.
[***]
[***]
W
Control, Disposal and Destruction of Production Materials
23.01
Have a procedure for the access, control, reconciliation, disposition, disposal, and destruction of obsolete or rejected production materials
proprietary to XERIS or bearing XERIS proprietary information used in the Product manufacture, packaging and labeling that include but is not limited to:
• Active Pharmaceutical Ingredient/ Biological Drug Substance
• Excipient Raw
Materials
• Tooling,
dies, printing rolls, plates and associated drawings used in the manufacturing of Product.
• XERIS printed components and materials used to print such component, including but not
limited to: printed components, containers, closures, tools, dies, plates, drawings and artwork including all electronic files.
[***]
[***]
23.02
Dispose and destroy obsolete or rejected production materials in a secure and compliant manner that prevents unauthorized use or diversion in compliance with environmental regulations. Maintain destruction records and provide to
XERIS upon request. Destruction method must render all XERIS owned trademarks, logos, or registration marks as unidentifiable.
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
X
Complaints
24.01
Have written procedures in place to document, investigate, issue reports, follow up, respond to XERIS and manage all Product quality related complaints.
[***]
[***]
24.02
Where XERIS is the regulatory submission holder:
• Notify PYRAMID within [***] of product complaints received by XERIS
that potentially impact quality, purity, safety and effectiveness of distributed Product and could result in a product recall.
[***]
[***]
• Manage complaint investigations and any required regulatory
reporting.
[***]
[***]
• Assist in investigations of Product-related complaints, as requested by
XERIS and report progress of investigation to XERIS in a timely manner.
[***]
[***]
• Retain complaint investigation records.
[***]
[***]
• Evaluate trends and severity of complaint.
[***]
[***]
• Implement corrective actions associated with manufacture of
Product.
[***]
[***]
24.03
Where PYRAMID is the regulatory submission holder;
• Notify each other within [***] of product complaints that impact
quality, purity, safety and effectiveness of distributed Product that are likely to result in a field alert, BPDR and/or recall.
[***]
[***]
• Conduct and complete complaint investigation and any required
regulatory reporting within [***].
[***]
[***]
• Assist in investigations of Product related complaints, when
required.
[***]
[***]
• Retain complaint investigation records.
[***]
[***]
• Evaluate trends and severity of complaint.
[***]
[***]
• Implement corrective actions as necessary.
[***]
[***]
24.04
Significant complaints (e.g. those alleging product contaminations, tampering, counterfeiting, etc. or which have been reported to a regulatory authority) require preliminary investigation and response to the other party within
[***].
[***]
[***]
24.05
Should a complete investigation report not be able to be completed within [***], interim reports communicated to XERIS is required.
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
Y
Recalls
25.01
Where XERIS is the regulatory submission holder:
• Notify XERIS in writing within [***] of discovery of any product
defects that could result in a product recall or abnormal restriction on the supply of Product.
[***]
[***]
• Sole responsibility for determining the need for recall of XERIS
Product. There shall be approved procedures for issuing field alerts, Biological Product Deviation Reports (as applicable), Product Defect Reports and recall that address the decision making process, correspondence with regulatory agencies,
management of recalls, and reconciliation of returned Product.
[***]
[***]
• Cooperate and participate in the investigation to make the decision to
issue field alerts, Biological Product Deviation Reports, Product Defect Reports or recalls.
[***]
[***]
• Review and ensure the accuracy of correspondence for submission to
regulatory agency, as requested by XERIS.
[***]
[***]
• Issue correspondence to regulatory agencies.
[***]
[***]
• Manage recall and reconciliation of returned Product.
[***]
[***]
25.02
Where PYRAMID is the Product regulatory submission holder:
• Notify each other in writing within [***] of any product defects that
could result in a Product recall or abnormal restriction on the supply of Product.
[***]
[***]
• Have approved procedures for issuing field alerts,
• Biological Product
Deviation Reports (as applicable) and recall that address the decision making process, correspondence with regulatory agencies, management of recalls, and reconciliation of returned Product.
[***]
[***]
• Facilitate the process for determining the need to issue field alerts
or recalls.
[***]
[***]
• Cooperate and participate in the investigation to make the decision to
issue field alerts, Biological Product Deviation Reports or recalls.
[***]
[***]
• Make final decision to issue recalls.
[***]
[***]
• Review and ensure accuracy of correspondence for submission to
regulatory agency.
[***]
[***]
• Issue correspondence to regulatory agencies.
[***]
[***]
• Manage recall and reconciliation of returned Product.
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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Responsibilities
XERIS
PYRAMID
Z
Adverse Experiences
26.01
XERIS shall be responsible for adverse drug reaction reporting for the Product to regulatory authorities.
[***]
[***]
26.02
In the event XERIS has or receives any information regarding any adverse experience which may be related to the use of the Product, XERIS shall immediately, and in no event later than within [***] of receipt by XERIS, provide
PYRAMID with all pertinent information to facilitate investigation.
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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APPENDIX 1: Contacts and Responsibilities
Position
XERIS Pharmaceuticals
PYRAMID Laboratories, Inc.
Contract Manager
[***]
[***]
Analytical
[***]
[***]
Quality Assurance
[***]
[***]
Pharmaceutical Development
[***]
[***]
Project Manager
[***]
[***]
Regulatory
[***]
[***]
Contact Information
PYRAMID Laboratories, Inc.
Phone Number: [***]
XERIS Pharmaceuticals
[***]
Phone Number: [***]
NOTE:
1)
A designee may be assigned to specific projects by the responsible personnel.
2)
The designated representatives of each company will be responsible for the supply or receipt of information and controlled documents.
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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APPENDIX 2: Significant Deviations Requiring Notification to XERIS
Significant Deviations that require notification to XERIS (minimum
expectations)
[***]
Significant deviations
List of specific examples (but not limited
to)
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
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APPENDIX 3: Documentation to be Supplied by PYRAMID
The following documents/records will be supplied to XERIS:
•
Master Batch Records for XERIS review and approval
•
Executed batch records
•
Environmental monitoring and personnel monitoring results are part of the executed batch record.
•
Any in-process testing results documented in the executed batch record
•
List of all in-going materials by lot number, including the XERIS lot numbers where applicable
•
All completed and approved deviations and investigations (including those approved by XERIS)
•
BSE/TSE Statement for the components of the lot manufactured
•
Any analytical results applicable to the release of the lot as tested by PYRAMID
•
Certificate of Compliance from PYRAMID including cGMP statement
CONFIDENTIAL
[***] INDICATES MATERIAL THAT HAS BEEN OMITTED AND FOR WHICH CONFIDENTIAL TREATMENT HAS BEEN
REQUESTED. ALL SUCH OMITTED MATERIAL HAS BEEN FILED WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE 406 PROMULGATED UNDER THE SECURITIES ACT OF 1933, AS AMENDED
Document No:
Revision:
Revision Date:
Replaces:
Page:
QA-Xeris
00
11/10/16
NA
Page
52
of 52
APPENDIX 4: Authorized Subcontractors
PYRAMID may not subcontract any of its obligations under this Quality Agreement except pursuant to the provisions of Section 7.2 of the Quality
Agreement. The Parties acknowledge and agree that the subcontractor(s) listed below have satisfied the requirements set forth in Section 8 of the Quality Agreement, have been approved by XERIS, and may perform activities on behalf of PYRAMID
under the Quality Agreement, subject to PYRAMID’s and such subcontractor’s continuing obligations under the Quality Agreement, including, without limitation, their respective obligations under Section 8.
SUBCONTRACTOR NAME:
[***]
ADDRESS
[***]
[***]
TYPE OF SERVICE
MICROBIOLOGY TESTING LABORATORY
SUBCONTRACTOR NAME:
[***]
ADDRESS
[***]
[***]
TYPE OF SERVICE
ANALYTICAL TESTING LABORATORY
[NOTE TO AUTHOR: If no subcontractors are qualified and approved by XERIS prior to signing, the chart in this Appendix 4
should read “None.” If more than one subcontractor is qualified and approved by XERIS prior to signing, add additional sections as needed]
CONFIDENTIAL
Reference:
Security Exchange Commission – Edgar Database, EX-10.17 17 d547651dex1017.htm EX-10.17, Viewed October 23, 2021, View Source on SEC.
