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Quality Agreement Technical (Contract Manufacturing)

Quality Agreement means comprehensive written agreement that defines and establishes the obligations and responsibilities of the Quality Units of each of the parties involved in contract manufacturing of drugs subject to cGMP.

Technical Quality Agreement for Contract Manufacturing

This “Quality Agreement” is made by and between

  • Contract Giver a Company incorporated under the Companies Act, 1956, and having its Office_________.  (hereinafter referred to as ________ . which expression shall unless repugnant to the context or meaning thereof be deemed to include its successors, assigns and affiliated companies) and affiliated companies and
  • M/s. ……………………………………………….. (Contract Accepter) having its Corporate office at ……………………………………………………………………………………………………………(“Contract Manufacturer”) (Hereinafter referred to as “Contract Manufacturer” . which expression shall unless repugnant to the context or meaning thereof be deemed to include its successors, assigns and affiliated companies) (Refer Appendix 4 for manufacturing site address)

For contract manufacturing/packaging of finished Product

SIGNED

For and behalf of _______________ For and behalf of M/s._________
Signature & Date Signature & Date
Name :    —————————————  

Name :    —————————————
Title:    ————————————— Title:      —————————————
Department:      ————————————— Department:     —————————————
  • This Quality Agreement is made effective on the date the last Party has executed (signed) this Quality Agreement.

 TABLE OF CONTENTS

1 Definitions
2 Purpose
3 Term and Quality Agreement Review.
4 General
5 Regulatory Submissions
6 Manufacturing
7 Quality Assurance and Quality Control
8 Batch Release
9 Documentation
10 Change Control
11 Stability Studies
12 Periodic Product Review
13 Inspection and Audit
14 Quality Events and Investigations
15 Product Recall
16 Qualification and Validation
17 Data Integrity
18 Storage and Shipping
19 Affiliates
20 Governing Law and Dispute Resolution
    • Appendix 1:         Responsibility Matrix
    • Appendix 2:         QA Contacts
    • Appendix 3:         Quality Events
    • Appendix 4:         Product Details

QUALITY AGREEMENT

By and between Contract Giver and Contract Manufacturer

Recitals

  • WHEREAS, the Parties (as defined herein) have entered into the Commercial Agreement (as defined herein) pursuant to which Contract Manufacturer has agreed to Manufacture (as defined herein) and provide other services related to, each Product (as defined herein) for Contract giver and,
  • WHEREAS, the Parties wish to set forth the terms and conditions on which they will assure the quality of the Products to be Manufactured by the Contract Manufacturer.

NOW, THEREFORE, the Parties agree as follows:

Agreement

Technical Quality Agreement

  • Definitions
    • Unless otherwise specifically provided in this Quality Agreement, the following terms shall have the following meanings:
    • “Affiliates” means, with respect to a company, any company that controls, is controlled by, or is under common control with such first company. For purposes of this definition only, “control” means (a) to possess, directly or indirectly, the power to direct the management or policies of a company, whether through ownership of voting securities, or otherwise, or (b) to own, directly or indirectly, more than fifty percent (50%) of the outstanding voting securities or other ownership interest of such company.
    • “Active Pharmaceutical Ingredient” or “API” means the substance or mixture of substances to be used in the Manufacture of a Finished Product which substance(s) is the active ingredient of such Finished Product.

    • “Regulatory Authority” means respective regulatory Agency.

    • “Applicable Laws and Regulations” with respect to each Product [and each country in the Market], means all national, state, and local laws and the rules, regulations, guidance, guidelines, and requirements of all Regulatory Authorities and pharmacopeias in effect from time to time applicable to the handling, Processing, Packaging and quality control of such Product in such country, including applicable cGMPs.
    • “Batch” means a defined quantity of Product manufactured in one process or series of processes so that the defined quantity can be expected to be homogenous [alternative for Packaging: uniform and consistent].
    • “Bulk Product,” with respect to each Finished Product, means the semi-finished form thereof specified in the Product Requirement Schedule for such Finished Product ready for Packaging into primary and secondary packaging and final labeling.
    • “Certificate of Analysis,” with respect to each Product, means a certificate containing the information and signatures set forth in the “Documentation Requirements” section of the Product Requirement Schedule for such Product.
    • “Certificate of Manufacture/GMP Compliance,” with respect to each Product, means a certificate containing the information and signatures set forth in the “Documentation Requirements” section of the Product Requirement Schedule for such Product.
    • “Commercial Agreement” means the Supply Agreement, between the Parties.
    • “Current Good Manufacturing Practices” or “cGMP” means the laws, regulations, practices, guidelines, guidance, pharmaceutical industry standards, and requirements in force from time to time during the term of this Quality Agreement that applies to the Manufacture of each Product in the Market.
    • “Quality Events”, “Deviation”, “Minor Deviation”, and “Major Deviation” have the meanings set forth in Appendix 3
    • “Effective Date” means the date of execution of this Quality Agreement by the last Party to execute and sign this Quality Agreement.
    • “Emergency Product Complaint” means any Product Complaint with the potential to present significant patient issues, including mislabeling of product mix-up, extraneous material in a Product, possible microbial contamination in a Product, and alleged tampering or counterfeiting.
    • “Excipients” means the excipient substances used in the Processing of each Product as specified in the Product Requirement Schedule for such Product.

    • “Facilities” means the facilities used by Contract Manufacturers to Manufacture Products.

    • “FDA” means the Food and Drug Administration or National Authority or drug controller cum licensing authority.
    • “Finished Product” means the final presentation of the pharmaceutical product in formulated packaged and labeled form for sale to Contract Giver’s customers.
    • “Foreign Counterpart” means any foreign counterpart to the corresponding Regulatory Authority, filing, law, rule, regulation, or other requirement or item that is applicable to the Contract Manufacturer’s Processing and Packaging of the Products for Contract giver under the Commercial Agreement.
    • “Manufacture” means any of the following activities: receipt of materials, production, Processing, Packaging, labeling, quality control, release, storage and distribution, and related controls involved in the supply of the Product
    • “Market” means the territory wherein the finished products are to be sold.
    • “Materials” means the component materials used to manufacture each Product.
    • “OOS” means out-of-specification.
    • “Package” or “Packaging,” with respect to each Product, means the action of packaging, labeling, testing, inspecting, or any activity of a nature similar to the foregoing that does not change the physical characteristics of such Product, in preparation for storage, distribution or further conversion of Product to Finished Product, [including conversion of the relevant Bulk Product into Finished Product].
    • “Parties” means Contract Giver and Contract Manufacturer.
    • “Party” means either Contract Giver or Contract Manufacturer.
    • “Periodic Product Review” means the w1’itten review of Manufacturing and quality assurance activities for a Product in a defined time period according to the requirements of Appendix 3.

    • “Potential Recall” has the meaning set forth in Appendix 4 hereto.

    • “Process” or “Processing,” with respect to each Product, means the processing steps for conversion of the relevant Materials into, Bulk Product or Finished Product and the testing thereof.
    • “Product” means each Finished Product with respect to which the Parties execute and deliver a Product Requirement Schedule.
    • “Product Complaint” means any complaint that questions the purity, identity, potency Of quality of any Product, its packaging or labeling, or any complaint that concerns any incident that causes any Product or its labeling to be mistaken for or applied to another article, or any bacteriological contamination, or any significant chemical, physical or other change or deterioration in the distributed drug product, or any failure of one or more distributed batches of the Product to meet the Specifications, therefore.
    • “Quality Agreement” means a comprehensive written agreement that defines and establishes the obligations and responsibilities of the Quality Units of each of the parties involved in contract manufacturing of drugs subject to cGMP.
    • “Traceability” means the ability to follow data and records logically within and between Parties to allow the reconstruction of events.
    • “Contract Manufacturer Procedures” means Contract Manufacturer’s written standard operating procedures.

  • Purpose of Quality Agreement

    • The purpose of this Quality Agreement is to define the obligations and responsibilities of Contract Giver and Contract Manufacturer relating to the quality assurance requirements of the Manufacture and the supply to Contract Giver of each Product in accordance with Applicable Laws and Regulations, other requirements agreed by Contract Giver and Contract Manufacturer for the supply of Product under the Commercial Agreement.
    • Contract Giver and Contract Manufacturer are responsible as defined in this Quality Agreement and for convenience purposes in the responsibilities matrix set forth in Appendix 1 hereto for the steps involved in the Manufacture of each Product. If there is any conflict or inconsistency between this Quality Agreement and the responsibilities matrix set forth in Appendix 1, this Quality Agreement shall prevail.

  • Term and Quality Review of Quality Agreement

    • This Quality Agreement shall come into effect on the Effective Date and shall remain in force until the Commercial Agreement is terminated and any and all requirements according to Applicable Law and Regulations have expired relating to all Products. The Parties may agree in writing that this Quality Agreement shall survive termination of the Commercial Agreement. Upon request, the Contract Giver may take the responsibility for the remaining requirements according to Applicable Law and Regulations upon the termination of the Quality Agreement.
    • The Quality Agreement is reviewed every 3 years from the last party that has executed (Signed) this quality Agreement. Contract Giver is responsible for ensuring that this Quality Agreement is reviewed and if applicable updated. Extension of Quality Agreement may be done a maximum of 2 times.
    • Updates of this Quality Agreement shall be made following mutual agreement of the Parties.
    • This Quality Agreement shall be version-controlled, i.e. any update shall be marked as a revised version and the date of such version shall be stated and any such version shall be recorded.

  • General

    • This Quality Agreement shall be accessible to Regulatory Agencies as required by law or as determined by Contract Giver.
    • Contract Manufacturer shall ensure that it registers with all necessary Regulatory Authorities in accordance with Applicable Laws and Regulations and Contract Manufacturer shall obtain and maintain all licenses, authorizations, and approvals required by Applicable Laws and Regulations in order to manufacture each Product in accordance with this Quality Agreement and the Commercial Agreement.
    • The quality assurance contacts of each of the Parties including the addressees are specified in Appendix 2. Any changes in such quality assurance contacts set forth in Appendix 2 shall be informed in writing and updated.
    • Any other provision of this Quality Agreement may be amended by mutual agreement of the Parties expressed in writing.
    • Contract Manufacturer shall ensure that all activities at all Facilities and locations, including activities of Contract Manufacturer’s approved Contract Manufacturers, associated with Manufacture and supply of Product are carried out in compliance with the Applicable Laws and Regulations and the Product Requirement.

  • Regulatory Submissions

    • Contract Giver / Contract Manufacturer shall be responsible for regulatory submissions for Product as applicable.
    • Contract Giver shall provide support and any necessary documentation related to the Manufacture of Product to assist Contract Manufacturer in the completion of regulatory submissions for Product.
    • Party (Contract Giver) shall also provide Contract Manufacturer with any data or documentation required to maintain compliance with Contract Manufacturer’s regulatory submission.
    • Contract Giver shall notify Contract Manufacturer ninety (90) days prior to any significant regulatory submission due date to which it is committed and where support from Contract Manufacturer is required to meet the obligation.
    • Party (Contract Manufacturer) shall provide Contract Giver with a copy of any new regulatory submission relating to the Processing and Packaging of Product by Contract Manufacturer for comment prior to submission to Regulatory Authorities. Contract Giver shall be responsible for the final content, formatting, and wording of such regulatory submissions.
    • Contract Manufacturer shall be solely responsible for all correspondence, communications/dealings with Regulatory [Governmental] Authority unless otherwise required. by Contract Giver. Contract Manufacturer shall, on receipt of any notice, query, investigation, or letter from Regulatory [Governmental] Authorities, notify Contract Giver promptly of the same along with all information pertinent thereto. Contract Manufacturer shall finalize its reply or report or provide information to Regulatory [Governmental] Authority in consultation with Contract Giver. Contract Manufacturers shall ensure that no such response shall include any false or misleading information.
    • If any notice, report, query, or letter is received by Contract Giver from Regulatory [Governmental] Authority, in respect of or directly/indirectly pertaining to this Agreement, Contract Manufacturer shall upon request by Contract Giver promptly provide all information, records, and documents, as may be required, for responding to the same. Contract Giver, may, if it deems necessary, require Contract Manufacturer to respond to such notice, report or query, or letter, as the case be, and Contract Manufacturer shall within a reasonable time, reply or report or provide information to the Regulatory [Governmental] Authority, in consultation with Contract Giver.

  • Manufacturing

    • Each Product supplied by CONTRACT MANUFACTURER hereunder shall be manufactured (including, without limitation, all testing and packaging) in the Production Facility, which shall have been approved for the manufacture of each Product by the FDA or National Authority or drug controller cum licensing authority., in accordance with the following (collectively, the “Product Manufacturing Requirements”): (i) the Specifications for the Product, including purity, potency and physical and chemical properties, and stability and formulation specifications, (ii) cGMP, ICH Guidelines (iii) the standards and manufacturing processes set forth in the approved MFC and (iv) all Applicable Laws and all other applicable rules, regulations, and requirements of the FDA or National Authority or drug controller cum licensing authority relative to the manufacture, testing, packaging and shipment of the Product.
    • Contract Manufacturer shall not subcontract any works related to the manufacturing operations of the products to any other party without the prior written approval of the Contract giver.
    • Party ( Contract giver) shall not permit any recovery, reworking, or reprocessing of Products.
    • Contract Manufacturer shall have a documented and defined process for the destruction of excess, obsolete, or rejected materials. Contract Manufacturer shall notify and obtain agreement from Contract giver prior to destruction or other use of any Materials or Products.
    • Contract Manufacturer shall manufacture each Product in accordance with written master batch records that have been agreed by the Contract giver prior to initial implementation, and the same may be amended from time to time in accordance with the change control procedures.

  • Quality Assurance and Quality Control

    • The contract manufacturer is responsible for the quality control and quality assurance of each Product, including testing, documentation review, and retention according to the defined and approved procedures/regulations.
    • Contract Manufacturer shall retain reference samples from each batch of each Product and materials.

  • Batch Release

    • Contract Manufacturer’s QA shall release each Batch of each Product to the Contract giver in accordance with Approved Procedures. Contract Manufacturer QA shall ensure the batches release of each product to the Contract giver as per the procedure. In the event of a Major Deviation, the Contract Manufacturer shall inform the Contract giver prior to batch release
    • Party (Contract Manufacturer) shall perform the final release of each Batch of Product to the Contract giver in accordance with Contract Manufacturer Procedures. In the event of a Major Deviation, the Contract Manufacturer shall inform the Contract giver prior to batch release
    • Contract giver shall be responsible to release the product to market.

  • Documentation

    • A Certificate of Analysis or Certificate of Manufacturing/cGMP Conformance shall accompany all Materials supplied by a Party to the other Party.
    • A Certificate of Analysis and/or Certificate of Manufacturing/cGMP Conformance shall accompany all Products supplied by a Party to the other Party.
    • Contract Manufacturer shall provide Contract giver with any additional documentation as requested in writing by the Contract giver.
    • Party (Contract Manufacturer) shall retain all documentation for the Product as per the document retention procedure.
    • Contract Manufacturer shall provide copies of retained documentation to Contract giver within twenty-four (24) hours of receiving a request unless otherwise agreed with Contract giver.

  • Change Control

    • The contract giver and Contract Manufacturer shall maintain change control systems that assure that all Major Changes are appropriately agreed with the other Party. The Major Changes that require pre-approval by the Contract giver such as but are not limited to site or facility of manufacturer/ testing, batch size, specification test procedure, pharmacopeia changes affecting regulatory filling, expiry/product shelf life, and packaging materials. For labeling changes, the Contract Manufacturer shall only be notified after the Contract giver approves the change.
    • If the Contract Manufacturer wishes to initiate a Major Change, the Contract Manufacturer shall submit a change control request in writing. The contract giver shall respond in writing. The contract giver shall notify the Contract Manufacturer of any Major Change impacting the Contract Manufacturer, and the Contract Manufacturer and Contract giver shall agree on how to implement such changes.
    • Contract giver may require Contract Manufacture to provide Contract giver samples of the Product Manufactured using the changed process, equipment, Facilities, or Materials, in sufficient quantity to enable Contract giver to establish the effect of the change. The contract giver shall communicate such requirements in writing to the Contract Manufacturer.
    • Contract Manufacturer shall notify Contract giver of the first Batches and the packaging dates thereof for which the change shall be implemented.
    • A Party shall inform the other Paid in writing of any change in current local or international legislation of which it becomes aware and which may affect the supply of any Product or service to Contract giver.
    • A Party may implement certain emergency changes for example safety changes without following the prospective approval process according to the procedure. Such changes and the arrangements to control the change must be agreed with the other Party as soon as practicable.

  • Stability Studies (Applicable when Stability study is conducted by a contract manufacturer)

    • The contract manufacturer shall be responsible for carrying out and reporting stability testing in accordance with the defined procedures in line with regulatory requirements.
    • From time to time Contract giver may require the Contract Manufacturer to conduct stability studies in addition to those set forth in the applicable Product Requirement Schedules, including in support of changes implemented in accordance with the change control of procedures specified in this procedure, Contract giver shall communicate such requirements in writing to Contract Manufacturer.
    • Contract Manufacturer shall notify any stability failure or adverse trend in results likely to lead to a stability failure during the period of a study to Contract giver as soon as possible and in any event within twenty-four (24) hours of becoming aware of such stability failure or adverse trend. Contract Manufacturer shall evaluate/investigate all OOS stability results or adverse trends in accordance with of this Quality Agreement, provided that Contract Manufacturer shall provide an interim report summarizing the stability OOS investigation progress, in writing, within three (3) days of discovery of the stability failure.
    • In the event the Quality agreement is terminated, the Contract Manufacturer will continue to generate stability data to support the acceptability of Product(s) until all Products distributed by the Contract giver have reached the end of their shelf.

  • Periodic Product Review

    • The Contract Manufacturer will conduct a periodic quality review of the Product in accordance with the defined procedures and regulatory requirements. A copy of the Periodic Product Review shall be provided to the Contract giver.

  • Inspection and Audit

    • Inspections by Regulatory Authorities
    • Contract Manufacturer shall permit all inspections by applicable Regulatory Authorities.
    • Contract Manufacturer shall, immediately on receiving notice, inform Contract giver of any quality system or Regulatory Authority inspection that may impact on Products.
    • Party (contract giver) shall have the option for Contract giver personnel to be present at the Contract Manufacturer during the inspection in order to represent the Contract giver interests related to the Products.
    • Contract Manufacturer shall provide Contract giver with copies of all communication and documentation issued to or by Regulatory Authority as also such other information pertinent thereto, as may be required by Contract giver, from time to time.
    • Contract Manufacturer shall make available to Contract giver at agreed times, during and after the inspection, all the findings of such inspection that may have an impact on Products or their Manufacture.
    • Parties (Manufacturer and Contract giver) shall jointly agree on the response and any improvement plan to any adverse observations relating to the Products or their Manufacture, prior to these being submitted to the Regulatory Authority. Parties shall meet regularly to review progress in the implementation of this plan.

    • Audits by the Contract giver

    • Contract giver shall have the right upon giving at least one (1) week’s notice to Contract Manufacturer to carry out periodic quality and compliance systems audits. Contract giver shall also have the right upon giving at least ‘twenty-four (24) hours’ o1 mutually agreed dates notice to carry out quality and compliance systems audit in order to investigate a Quality Event.
    • Contract Manufacturer shall provide access to personnel, facilities, records, and control documents relevant to the Manufacture of Products. The contract giver shall make the results and recommendations from the audit available to the Contract Manufacturer. Where the Contract giver’s audits identify quality and compliance issues, the Contract Manufacturer and Contract giver shall agree on a quality and compliance improvement plan with timings and shall regularly review progress in the implementation of this plan.
    • Any information made available to the Contract giver during an audit and the Contract giver’s audit results and recommendations on quality and compliance issues shall be confidential and be covered by the confidentiality article in the Commercial Agreement.
    • The contract giver shall audit the contract manufacturing facility every two years and will provide an audit report within thirty (30) calendar days of the audit. The contract manufacturer will respond to the audit within thirty (30) calendar days of receiving the report from the Contract giver.
    • Contract Manufacturer shall have a system for evaluating and maintaining its Supplier/Vendor of any goods or services associated with the Manufacture of each Product. Contract giver shall have the option for Contract giver personnel to be present at Contract Manufacturer’s audits of its Supplier/Vendor used in connection with the supply of the Products to Contract giver.

  • Quality Event and Investigations (Quality Agreement)

    • Contract Manufacturer shall have documented and defined processes for management of Quality Events including tracking and trending of Quality Events.
    • A Party shall inform the other Party within twenty-four (24) hours and confirm in writing within three (3) days of becoming aware of any Quality Event that is significant enough to require investigation to determine impact on Product quality.
    • Receiving Party shall acknowledge in writing receipt of such Quality Event notification.
    • Contract Manufacturer shall be responsible for the investigation of Quality Events relating to activities at Contract Manufacturer and Contract Manufacturer’s Contract Manufacturers.
    • The contract giver shall be responsible for the investigation of Quality Events relating to activities at the Contract giver and the Contract giver’s Contract Manufacturers/distributors.
    • If a Quality Event could have been caused by activities at either (a) Contract giver, its Contract Manufacturers/distributors, or (b) at the Contract Manufacturer, its Contract Manufacturers, then both Contract giver and Contract Manufacturer shall be responsible for investigating the Quality Event, provided that Contract giver shall retain the right to coordinate the investigations of both Contract Manufacturer and Contract giver.
    • Parties may require further data and samples of Product (As applicable) resulting from Quality Events in sufficient quantities and in a timely manner for the other Party’s investigation of the Quality Event.
    • Both Parties shall communicate such requirements in writing to the other Party.
    • Parties shall acknowledge receipt in writing of a Product sample related to the Quality Event.
    • Based upon the severity of the problem Contract Manufacturer shall provide a copy of the completed Quality Event investigation report to the Contract giver as follows:
      • Major Deviations within twenty-one (21) days or as agreed with Contract giver.
      • Product Complaints within seven (7) days.
    • Emergency Product Complaints, which shall be determined by Contract giver within 48 hours.
    • Notice of Minor Deviations shall be included with Batch documentation or as per Contract Manufacturers Procedure.

  • Product Recall

    • Contract Manufacturer shall notify Contract giver in accordance with Contract Manufacturer Procedures as soon as possible and in any event within twenty-four (24) hours of discovery of a Potential Recall with respect to any Batch of Product delivered to Contract giver
    • Contract Manufacturer shall conduct an immediate investigation to determine the root cause of the Potential Recall and provide Contract giver with a written investigation report as soon as reasonably practicable and, in any case, in time to meet any required regulatory timeline specified by Contract giver.
    • Party (Contract giver) shall make the final decision, after consultation with Contract Manufacturer, of whether to conduct a recall.

    • Contract Manufacturer shall not initiate any recall of any Product.

    • In the event that Contract giver shall be required or shall voluntarily decide to recall any Product Manufactured by Contract Manufacturer, Contract giver shall inform Contract Manufacturer of such recall in accordance with Contract giver’ s customary procedures.
    • Contract giver shall have responsibility for any communication with Regulatory Authorities regarding such recall, provided that Contract Manufacturer shall co-operate with Contract giver in developing such communications.
    • Contract Manufacturer shall provide Contract giver reasonable and prompt assistance to investigate any recall believed to relate to the Products.
    • The coordination and management of any recall situation will be the responsibility of Contract giver. Contract Manufacturer shall cooperate with Contract giver in implementing such recall.
    • In the event of a recall, Parties shall ensure that all recalled Product supplied from Contract Manufacturer’s site, are reconciled and shall provide Contract giver with all requested information regarding the distribution of recalled Product.
    • Contract Manufacturer shall ensure that recalled Product under Contract Manufacturer’s control is secured and is subsequently destroyed if required or otherwise handled in accordance with Contract giver’s instructions.

  • Qualification and Validation (Quality Agreement)

    • Process and analytical qualification and validation

    • Contract Manufacturer shall ensure that the manufacturing process, analytical instrumentation and analytical methodologies are appropriately qualified and/or validated before any routine production can begin. Contract Manufacturer shall review the validation status of each manufacturing process of products on a periodic review preferably during the periodic product review.

    • Cleaning Validation

    • Contract Manufacturer shall perform efficient cleaning between batches of different products to prevent cross contamination.
    • The cleaning process shall be validated before the first batches of product are made for the exclusive distribution to Contract giver, unless otherwise agreed between the parties to perform other methods to prove the effectiveness of the cleaning process.
    • The validation shall be updated to cover any new products made in the same facilities as those facilities used to manufacture product for the exclusive distribution to Contract giver.

    • Facility and Utilities Qualification and Validation

    • Contract Manufacturer shall be responsible for the qualification and/or validation of all relevant utility, equipment, computer system and facilities associated with the Manufacture, storage or testing of the products.

  • Data Integrity

    • Contract Manufacturer shall ensure that all data relevant for the cGxP (current good practices) activities conducted pursuant to this agreement is accurate, controlled and safe from intentional or unintentional manipulation or loss.
    • Contract Manufacturer’s Procedure, automation system and/or management control must ensure complete data integrity and be assessed regularly.
    • Party (Contract Manufacturer) shall ensure that its documentation practices and data handling processes (Paper and electronic) are well defined and they are understood and implemented by all personnel.
    • Contract Manufacturer shall ensure that any breach of data integrity is investigated and immediately reported in whiting to Contract giver if it affects the quality of product.

  • Storage and Shipping

    • If shipment done by Contract Manufacturer, manufacturer will ensure that during Packaging, storage, and shipment of the products that there is no possibility of deterioration, contamination, or mixing with any other materials.
    • If product shipped under controlled condition, Temperature monitoring devices must be included in every shipment.
    • Shipment documentation will indicate the placement location for the monitors.
    • The monitors must be in the center of the top horizontal layer of one pallet inside a clearly marked box (product part box or separate box).
    • lf multiple pallets are used for one lot of finished goods, one representative pallet of the lot may be selected for monitoring.

  • Affiliates

    • If Contract Manufacturer or any Affiliate of Contract giver so desire, such Affiliate of Contract giver and Contract Manufacturer may enter into an agreement on the same terms and conditions as this Quality Agreement excluding the Product Requirement Schedules.
    • Such Affiliate of Contract giver shall first send to Conti act Manufacturer a letter substantially with one or more Product Requirement Schedule, or such agreement can be entered into by separate agreement in writing between such Affiliate and Contract Manufacturer.
    • If Contract Manufacturer and such Contract giver Affiliate reach an agreement in writing all of the terms and conditions of this Quality Agreement will apply between that Affiliate and Contract Manufacturer, except to the extent expressly otherwise agreed between that Affiliate and Contract Manufacturer in writing.

  • Governing Law and Dispute Resolution

    • The interpretation and construction of this Quality Agreement shall be governed by the laws as set out in the Commercial Agreement.
    • Further, the provisions of Arbitration and Equitable Relief, as set out in the Commercial Agreement, shall apply to this Quality Agreement.

APPENDIX OF QUALITY AGREEMENT

THIS AGREEMENT IS EXECUTED by the authorized representatives of the Parties as signed on the front page of this Quality Agreement.

Appendix 1 : Responsibility Matrix

This matrix is for reference purposes. The full wording of each section is contained in the main body of the Quality Agreement and takes precedence over this matrix wording in the event of any conflict.

* if applicant / product technology own by Contract giver.

Responsibility For Contract Manufacturer Contract giver

Term and Agreement Review
Updating the Quality Agreement

Compliance Requirements
Obtaining Regulatory Approvals of products
Follow the applicable Regulatory authority directives, regulations and guidelines
Manufacture the Product in adherence to applicable regulatory submissions or filings Commercial Product c License Applications, Marketing Authorization,(whenever applicable) and Specifications.
Have management controls in place to track and trend investigations and commitments.
Notify each other of key organizational and/or key personnel changes that have direct impact on either party’s ability to abide by the terms of this Quality Agreement.
Compliance at Contract Manufacturer and Contract Manufacturer’s Contract Manufacturers

Regulatory Submissions and Inspections
Regulatory submission for Product
Maintain (including annual reports if required) the regulatory application, as applicable, in accordance with the regulations of the applicable regulatory authority.
Liaison with Regulatory Authorities for communication, approval, and maintenance of the application.
Notify Contract giver within one (1) business day of any pending or ongoing regulatory authority inspection or communication specific to the Product or service provided to the Contract giver
Provide a copy of the regulatory inspection report, deficiency letter, or regulatory compliance observations, and response associated with Applicant Holders product-specific issue, upon request.
Notify Contract giver of any regulatory compliance observation received by Regulatory authority that pertains to operations performed by Contract manufacturer and requires Contract giver information. Contract giver will provide requested information within agreed time frame or as required to meet regulatory obligations.

Manufacturing
Mutually agree on a program to evaluate and control the risk of live virus, mammalian-derived biologics (relevant human or animal viruses), Bovine Spongiform Encephalopathy (BSE), and Transmissible Spongiform Encephalopathy (TSE) for raw materials, components, and processing aids (e.g., product transfer lines, bag liners, storage containers (bags), filters, etc.) where applicable. Avoidance of high-risk substances in same facility of manufacture
Destruction of excess Materials
Monitoring devices with Product shipment If shipment done by manufacturer.
Monitoring devices with Product shipment If shipment done by Contract giver
Development of master Batch records
Review and approve Master Batch Records

Validation/Qualification
Have a written Validation Master Plan (VMP) for Product (including, but not limited to the facilities, equipment/instruments, manufacturing process, cleaning procedures, analytical procedures, in process control tests and computerized systems) approved by the quality unit.
Prepare and maintain validation/qualification documentation approved by the quality unit, including protocols, reports and associated documentation.
Validate/qualify as necessary all critical systems, utilities and equipment/instruments used for the manufacture and control of Product (Installation Qualification (IQ), Operational Qualification (OQ), and/or Performance Qualification (PQ)).
Validate/qualify computer systems and associated software used in Good Manufacturing Practices related activities associated with the Product, according to regulatory requirements including 21CFR Part 11.

Procedures must be in place to assure the integrity, archival, retrieval and destruction of the electronic data that comply with applicable regulations.
Validate/qualify methods and procedures for cleaning of equipment with acceptance criteria for residues defined and justified.
Write, review and approve method validation/ qualification/verification/transfer protocols and reports.
Review and approve method validation / qualification verification / transfer protocols.
Validate/qualify all manufacturing processes as mutually agreed.

Quality Assurance and Quality Control
Quality assurance and control of all Materials
Quality assurance and control of Product
Retention of reference samples
Internal control Limits

Batch Release
Release of Product to Contract giver
Release of Finished Product to Market

Sub-Contracting / Vendor Management
Approve vendors and Supplier of raw materials in accordance with Contract giver ‘s vendor‘ management program requirements. If the Contract Manufacturer agrees to use raw materials originally sourced and approved by Contract giver, it is the Contract giver as well as Contract Manufacturer’s responsibility to maintain the vendor / material according to the requirements of the vendor management program. It is the Applicant Holders responsibility to manage the API Contract Manufacturer according to their approved Vendor Management program procedures.
Contract Manufacturer will not sub-contract any laboratory testing or manufacturing work (or like) to a third-party contract laboratory or third-party manufacturer (or the like) (a “Sub-Contractor”) unless instructed to do so by Contract giver. lf -instructed, Contract giver shall require to ensure the Sub-contractor to operate in compliance with current Good Manufacturing Practices, compendia requirements, and any other applicable regulations.
Qualify and maintain Sub-Contactor as qualified following approved procedures according to a schedule and provide documentation to Contract giver for this qualification.
Contract Manufacturer shall retain a copy vendor’s document for reference and record purpose.

Change Control
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.
Notify Applicant Holder of all changes to facilities, critical utilities, equipment, processes (e.g,. manufacturing, cleaning, analytical testing, etc.), specifications, test procedures, master batch records, raw materials, processing aids (e.g., filters), components, container, closure, packaging, and labeling, specific to the Product that may impact on the quality and safety
of the Product including, but not limited to stability, regulatory filing status, overall qualification or validation status of a manufacturing or analytical test method, primary labeling, container / closure, packaging or specification. Contract Manufacturer will not initiate or implement changes without documented approval from the Contract giver.
For changes that have a regulatory impact, Contract Manufacturer and Contract giver shall mutually agree to a strategy to secure regulatory approvals as necessary, and shall mutually agree on an implementation timeline.
To notify Contract giver with respect to the implementation of changes.
Notification of changes in legislation affecting Product

Stability Studies

 @: If stability performed by Contract giver
Conducting stability studies and reporting results
Notification to Contract giver of stability failures or adverse trend
Provision of samples to support Contract giver stability
Annual Product Review
Contract Manufacturers prepare an annual review of quality information and data that includes at a minimum;

  • Documentation of trends (Water and Environment Monitoring),
  • Corrective action (if any),
  • Date of review,
  • Signatures/title of the reviewers,
  • Product identification,
  • Review period,
  • Batch records (including reworks),
  • Applicable change control records,
  • Returned or salvaged Product records,
  • Product investigation records,
  • Non-conforming materials’ reports,
  • Batch record deviations,
  • Reconciliation of Product complaints investigated versus total product complaints registered with contract giver
  • Specifications and test results,
  • Applicable Out of Specification and Out of Trends pertaining to the product under review
  • Applicable validation/qualification of methods, manufacturing equipment and process
  • Stability data,
  • Review of reserve samples,
  • Review of regulatory agency compliance commitments, and review of technical/quality agreements

In case of any adverse trend, contract manufacturer and Contract giver shall discuss the issue either in person or over phone.
It is the Applicant Holders responsibility to file the Appropriate Annual Reports as required by regulations to keep the file current and approved.

Audit And Inspection
Response to Regulatory Authority impacting Product
Right to Audit of Contract Manufacturers facility with respect to Applicable GMP practice.
During the audit, Contract Manufacturer will make accessible all AMP records and documents applicable to services rendered to Contract giver.

Contract Manufacturer will issue responses to observations in writing to Contract giver or approved designee within thirty (30) days of receipt.

Responses are to include timelines and plans for closure of all commitments by Contract Manufacturer

Quality Events and Investigation
Have appropriate procedures for the identification, investigation, reporting, tracking, trending and closure of deviations. Deviations include but are not limited to OOS results that occur during the manufacture and testing of the Product, including stability testing (as applicable). All OOS results will be investigated in accordance with cGMP.
Document and obtain approval from the Contract giver Quality of Critical / Major Product specific deviations, defined as affecting the result generated or service provided or any deviation outside of Product registration or Product safety and quality, if applicable:(i) client notification within one (1) business day, and (ii) prior to release of product.
Notify the Contract giver within one (I) business day of the determination of a potential Product related Out-of- Specification result.
Investigation of Quality Event
Systems for management of Quality Events at Contract Manufacturer
Complete investigations within a target of thirty (30) calendar days of commencement. Contract Manufacturer shall notify the Contract giver if investigations will extend beyond the original target of thirty (30) days.
Provide investigation documentation to Contract giver
Support of other Party’s investigation
Complete corrective and preventative action commitments resulting from investigation closure within the planned timeframe by Contract Manufacturer.

Product Recall
Inform Contract giver of Potential Recall
Investigation of Potential Recall at Contract Manufacturer
Decision to recall; notify Contract Manufacturer of recall; response to Regulatory Authorities regarding recalls
Assistance to Contract giver to investigate recall
Coordination and management of recall
Recall related Product reconciliation

Documentation and Records
Document all required process and testing steps at the time such process or testing step is executed.
Have a document control system to initiate, review, revise, approve, store, obsolete and archive all Good Manufacturing Practices documentation. The system will ensure all necessary GMP documentation is readily retrievable.
Retain, archive and destroy all GMP documents and data pertaining to Product as defined below:

  • Keep all original batch record documentation for ‹ duration in accordance with good documentation practices
  • Notify Contract giver prior to destruction of records and/or transfer of documents
  • Ensure that records are properly secured and/or protected from fire damage in a limited access area.
For laboratory control records, include complete data derived from all tests conducted to ensure compliance with specifications. These records will contain the dat and the signature of a second qualified person showing review and verification of the records.

Appendix 2 : QA Contacts (Quality Agreement)

Contract giver

Primary Contact Alternate
Name :

Designation :

Contact Details :

E-mail :

Signature :

Date :

 Name :

Designation :

Contact Details :

E-mail :

Signature :

Date :

Contract Manufacturer

Primary Contact Alternate
Name :

Designation :

Contact Details :

E-mail :

Signature :

Date :

 Name :

Designation :

Contact Details :

E-mail :

Signature :

Date :

Appendix 3 : Quality Events (Quality Agreement)

Any non-conformance with an established procedure or process or Product Requirement Schedule or the Applicable Laws and Regulations is a Deviation except where such non-conformance is planned and controlled within Party’s change control systems (such ‘non-conformances’ are considered to be planned changes).

Deviations can be major or minor according to their impact on Product quality, safety or efficacy. Any significant Deviation requiring an investigation to determine the impact on Product quality, safety or efficacy] is classified as a Major Deviation. Other Deviations that have no obvious Product quality, safety or efficacy implication and that do not require investigations are classified as Minor Deviations.

Any Major Deviation or Product Complaint with a Product quality implication is a Quality Event. Any Quality Event that has the potential to lead to Product recall is a Potential Recall.

Examples of Quality Events include the following:

  1. Product Complaint with Product quality implication
  2. Rejection of a Batch.
  3. Out of Specification (OOS) investigation (quarantine or rejection of a Batch or any part of a Batch due to failure to meet established release specification. or in-process specifications established in the applicable Product Requirement Schedules).
  4. Stability failure or significant adverse change in trend compared to expected results.
  5. Product, Packaging or labeling mix-up involving the Batch.
  6. Probable or known cross contamination of a Product with another product, extraneous foreign material or microorganisms.
  7. In-process or finished Product testing trends that indicate that a Batch performs outside established action or alert limits.
  8. Batches subject to rework or reprocessing where these are not registered.
  9. Batches associated with an equipment malfunction where registered process parameters are impacted.
  10. Batches subject to a malfunction of a facility utility system including HVAC, water, sprinkler, plumbing, fire protection, and electrical.
  11. Batches subject to natural disasters or acts of God such as flooding, fire, earthquake, lightning strike.
  12. Batches requiring a formal investigation for the following: reconciliation discrepancy; line clearance failure, sterility failure, environmental monitoring failure or alert.
  13. Bulk or packaged Product that exceeded the established Product hold times in bulk containers.
  14. Product stored outside the established environmental conditions.
  15. Media fill failure.
  16. Bio burden failure.
  17. Deviations from established time limits for the completion of production steps.
  18. Deviations from normal goods receipt process; e.g. damaged, tampered, missing documentation.
  19. Calibration failure.

Quality Event Report Requirements

When Contract Manufacturer is required to submit a Quality Event report to Contract giver, the format of the report shall at least contain the following information as appropriate to the deviation:

  • Name of Contract Manufacturer and Site where applicable:-
  • Unique deviation number
  • Product(s) affected (with material codes)
  • Batch affected (including assessment if other may be affected)
  • Delivery site(s)
  • Description of normal procedure
  • Description of deviation from normal procedure
  • Identified root cause of deviation
  • Conclusion and decision on deviation
  • Any changes to procedures or documentation which will be needed as, a result of this deviation (corrective and preventive, as applicable)
  • QA Signature on behalf of Contract Manufacturer

Product Quality Complaint Requirements

Contract Manufacturer should minimally provide the following information:

  1. Name of Product
  2. Contract Manufacturer’s reference number
  3. Contract giver Product code
  4. Batch Number
  5. Expiry or retest date
  6. Details of Complaint including any investigation by Contract Manufacturer
  7. Origin of Complaint
  8. Photographs, if appropriate

Appendix 4 : Product Details

Sr. No. Product Name Strength Pack Size Shelf Life Market Manufacturing Site Address
1.     
2.     
3.     
4.     
5.     
6.     
7.     
8.     

 

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pharmabeginers

Janki Singh is experienced in Pharmaceuticals, author and founder of Pharma Beginners, an ultimate pharmaceutical blogging platform. Email: [email protected]

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