1018-00006 · Penterra Pharmaceuticals Corp · Transaction Documents

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QUALITY AGREEMENT

Between

PENTERRA PHARMACEUTICALS CORP.

and

MERIDIAN BIO THERAPEUTICS LIMITED

Entered into pursuant to that certain Exclusive License Agreement dated October 2, 2023 (Effective Date: October 20, 2023) between Penterra Pharmaceuticals Corp. and Meridian Bio Therapeutics Limited (the "License Agreement")

Form attached as Exhibit F to the License Agreement

To be executed within sixty (60) days of the Effective Date (on or before December 19, 2023)

Compound: PPC-4187 (Penteracitinib)

FORM — FOR EXECUTION

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ARTICLE 1 — DEFINITIONS

As used in this Quality Agreement (this "Agreement"), the following terms shall have the meanings set forth below. Capitalized terms used but not otherwise defined in this Agreement shall have the meanings ascribed to them in the License Agreement.

1.1 "Active Pharmaceutical Ingredient" or "API" shall mean the active pharmaceutical ingredient for PPC-4187 (Penteracitinib), a selective Janus kinase 1 (JAK1) inhibitor, as manufactured at the facility of Alkerra Manufacturing Inc., located at 5200 Meridian Parkway, Research Triangle Park, North Carolina 27713, United States, or such other facility as may be designated in writing by Penterra and approved by Meridian in accordance with Article 7 (Change Control) of this Agreement.

1.2 "Applicable Laws" shall mean all federal, state, provincial, national, and local laws, statutes, regulations, rules, orders, guidelines, guidances, and standards applicable to the manufacture, testing, packaging, labeling, storage, distribution, and supply of the API and Licensed Products, including without limitation current Good Manufacturing Practice (cGMP), International Council for Harmonisation (ICH) guidelines, and all applicable regulations, requirements, and guidances of relevant Regulatory Authorities, including the United States Food and Drug Administration (FDA), the National Medical Products Administration of the People's Republic of China (NMPA), the Pharmaceuticals and Medical Devices Agency of Japan (PMDA), the Ministry of Food and Drug Safety of the Republic of Korea (MFDS), the Therapeutic Goods Administration of Australia (TGA), and all other Regulatory Authorities having jurisdiction within the Territory.

1.3 "Certificate of Analysis" or "CoA" shall mean a document issued by the supplying Party certifying that a specific batch of API or Licensed Product has been tested and conforms to the applicable Specifications set forth in Appendix 1 hereto, including a summary of all test results, methods used, and acceptance criteria.

1.4 "Certificate of Compliance" or "CoC" shall mean a document issued by the supplying Party certifying that a specific batch of API or Licensed Product was manufactured in compliance with cGMP and the approved manufacturing process, including confirmation that all critical process parameters were within established ranges and that all manufacturing operations were performed in accordance with the approved batch production record.

1.5 "cGMP" shall mean current Good Manufacturing Practice as defined under applicable regulatory frameworks, including without limitation Title 21 of the United States Code of Federal Regulations, Parts 210 and 211 (21 CFR Parts 210 and 211), ICH Q7 (Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients), the European Union Guidelines to Good Manufacturing Practice (EU GMP), and comparable regulations, guidelines, and standards applicable in the Territory, as each may be amended, updated, or superseded from time to time.

1.6 "Contract Manufacturing Organization" or "CMO" shall mean Alkerra Manufacturing Inc. or any successor, substitute, or additional manufacturer engaged by Penterra or Meridian for the manufacture, testing, packaging, or labeling of API or finished Licensed Products, as applicable, and as approved in accordance with the terms of this Agreement and the License Agreement.

1.7 "Deviation" shall mean any departure from approved processes, procedures, specifications, quality standards, or other documented requirements, whether planned or unplanned, including without limitation out-of-specification (OOS) results, out-of-trend (OOT) results, process excursions, equipment malfunctions, and deviations from approved batch production records or standard operating procedures.

1.8 "Effective Date" shall mean October 20, 2023, being the Effective Date of the License Agreement.

1.9 "Licensed Product" shall mean the finished pharmaceutical product containing PPC-4187 (Penteracitinib) as the active ingredient, in 25 mg and 50 mg film-coated tablet formulations, as further described in the Specifications set forth in Appendix 1B hereto, and any additional dosage forms or strengths that the Parties may agree to add by written amendment to this Agreement.

1.10 "License Agreement" shall mean the Exclusive License Agreement dated October 2, 2023, effective October 20, 2023, between Penterra Pharmaceuticals Corp. and Meridian Bio Therapeutics Limited, as the same may be amended, restated, supplemented, or otherwise modified from time to time in accordance with its terms.

1.11 "Penterra" shall mean Penterra Pharmaceuticals Corp., a corporation organized and existing under the laws of the State of Delaware, United States of America, with its principal place of business and headquarters located at 400 Pharma Drive, Suite 800, Princeton, New Jersey 08540, United States.

1.12 "Meridian" shall mean Meridian Bio Therapeutics Limited, a limited company incorporated and existing under the laws of Hong Kong SAR (Company Registration No. 2847631), with its principal place of business and headquarters located at 18/F, Blossom Tower, 88 Queen's Road Central, Hong Kong SAR.

1.13 "Quality Contact" shall mean the designated quality representative from each Party responsible for day-to-day communication under this Agreement, as identified in Appendix 3 hereto, or such replacement designee as may be notified in writing to the other Party from time to time.

1.14 "Recall" shall mean any corrective action resulting in the return, withdrawal, retrieval, or market correction of any API or Licensed Product from the market, clinical supply chain, or distribution channels, whether voluntary or mandated by a Regulatory Authority, including without limitation field safety corrective actions.

1.15 "Reference Standard" shall mean the analytical reference standards for PPC-4187 (Penteracitinib) supplied by Penterra for use by Meridian in quality control testing, method validation, and analytical method transfer, together with all associated characterization data, certificates of analysis, and stability information.

1.16 "Regulatory Authority" shall mean any governmental, quasi-governmental, or regulatory authority, body, agency, department, bureau, commission, council, or instrumentality having jurisdiction over the research, development, manufacture, testing, distribution, marketing, or sale of pharmaceutical products in any jurisdiction, including without limitation the FDA, NMPA, PMDA, MFDS, TGA, Health Sciences Authority of Singapore (HSA), Thai Food and Drug Administration (Thai FDA), National Pharmaceutical Regulatory Agency of Malaysia (NPRA), Badan Pengawas Obat dan Makanan of Indonesia (BPOM), Food and Drug Administration of the Philippines (Philippines FDA), Drug Administration of Vietnam (DAV), and the Taiwan Food and Drug Administration (TFDA).

1.17 "Specifications" shall mean the analytical, chemical, physical, and microbiological specifications for the API and Licensed Products, including all test parameters, analytical methods, and acceptance criteria, as set forth in Appendix 1 hereto (including Appendix 1A for API, Appendix 1B for Finished Products, and Appendix 1C for Reference Standards), as the same may be amended from time to time in accordance with the change control procedures set forth in Article 7 of this Agreement.

1.18 "Supply Agreement" shall mean the API Supply Agreement between Penterra and Meridian for the supply of clinical and commercial API at a transfer price of Penterra's fully-burdened manufacturing cost plus a fifteen percent (15%) markup, for an initial term of three (3) years following the Effective Date, as contemplated by the License Agreement and as may be extended or amended in accordance with its terms.

1.19 "Technology Transfer Agreement" shall mean the Technology Transfer Agreement between Penterra and Meridian governing the transfer of PPC-4187 (Penteracitinib) manufacturing process know-how, analytical methods, Chemistry, Manufacturing, and Controls (CMC) documentation, and related intellectual property, to be completed within twenty-four (24) months of the Effective Date (i.e., by October 20, 2025), as contemplated by the License Agreement.

1.20 "Territory" shall mean the Asia-Pacific territory as defined in Schedule D to the License Agreement, comprising the following countries, territories, and jurisdictions: the People's Republic of China (including Hong Kong Special Administrative Region and Macau Special Administrative Region), Japan, the Republic of Korea, Australia, New Zealand, Singapore, the Kingdom of Thailand, Malaysia, the Republic of Indonesia, the Republic of the Philippines, the Socialist Republic of Vietnam, and Taiwan.

Any capitalized term used herein that is not defined in this Article 1 shall have the meaning ascribed to such term in the License Agreement. In the event of any inconsistency between a definition set forth in this Agreement and the corresponding definition in the License Agreement, the definition in the License Agreement shall control unless this Agreement expressly provides otherwise. References to any statute, regulation, or guideline shall be deemed to include all amendments, restatements, replacements, and successor provisions thereto.

ARTICLE 2 — PURPOSE AND SCOPE

2.1 Purpose. The purpose of this Quality Agreement is to establish the quality-related responsibilities, obligations, and procedures governing: (a) the supply of API and Reference Standards by Penterra to Meridian; (b) the manufacture, testing, storage, release, and distribution of Licensed Products by Meridian in the Territory; and (c) the quality aspects of the technology transfer activities between the Parties. This Agreement is intended to ensure that all API and Licensed Products are manufactured, tested, stored, released, and distributed in compliance with cGMP, Applicable Laws, and the Specifications, and to define the respective quality obligations of each Party in a manner consistent with ICH Q7, ICH Q10, and applicable Regulatory Authority expectations.

2.2 Scope. This Quality Agreement covers the following quality-related activities and obligations:

(a) the supply of API by Penterra (directly or through Alkerra Manufacturing Inc. as its CMO) to Meridian during the initial three (3)-year supply term under the Supply Agreement, including incoming quality control, testing, acceptance, and rejection procedures;

(b) technology transfer activities governed by the Technology Transfer Agreement, including the transfer of manufacturing process know-how, analytical methods, and CMC documentation, and the quality oversight obligations of each Party during such transfer;

(c) Meridian's manufacture of finished Licensed Products (25 mg and 50 mg film-coated tablets of Penteracitinib) at Meridian's designated Asia-Pacific manufacturing facility, including during the period following completion of technology transfer;

(d) quality control, quality assurance, and release testing obligations of each Party with respect to API and Licensed Products, respectively;

(e) change control procedures applicable to the API, Licensed Products, Specifications, manufacturing processes, testing methods, facilities, equipment, and raw material sources;

(f) deviation management and corrective and preventive action (CAPA) procedures;

(g) product quality complaint handling, investigation, and resolution;

(h) recall and field safety corrective action procedures;

(i) regulatory inspection readiness, audit rights, and cooperation obligations;

(j) annual product quality review requirements;

(k) documentation, record retention, and data integrity standards; and

(l) quality governance, communication, and escalation mechanisms.

2.3 Relationship to Other Agreements. This Quality Agreement supplements, and is subject to the terms and conditions of, the License Agreement, the Supply Agreement, and the Technology Transfer Agreement. Nothing in this Agreement is intended to modify, limit, or supersede any right or obligation of either Party under the License Agreement, the Supply Agreement, or the Technology Transfer Agreement, except as expressly provided herein. In the event of any conflict or inconsistency between the terms of this Quality Agreement and the terms of the Supply Agreement with respect to quality-related matters (including but not limited to Specifications, testing, release, storage, change control, deviation management, CAPA, complaints, recalls, and regulatory inspection cooperation), the terms of this Quality Agreement shall prevail. In the event of any conflict or inconsistency between the terms of this Quality Agreement and the terms of the License Agreement, the terms of the License Agreement shall prevail. The Pharmacovigilance Agreement between the Parties, once executed, shall govern pharmacovigilance-related matters; quality-related aspects of safety reporting shall be coordinated as provided in Section 4.7 and Section 8.5 of this Agreement.

2.4 Regulatory Context. This Quality Agreement has been drafted in compliance with, and the Parties' obligations hereunder shall be performed in accordance with, the following regulatory frameworks and guidelines, as applicable:

(a) ICH Q7 — Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients;

(b) ICH Q10 — Pharmaceutical Quality System;

(d) 21 CFR Parts 210 and 211 — Current Good Manufacturing Practice for Finished Pharmaceuticals (U.S.);

(e) 21 CFR Part 211 Subpart J — Records and Reports;

(f) applicable regulations, guidelines, and guidances of the FDA, NMPA, PMDA, MFDS, TGA, and other Regulatory Authorities having jurisdiction within the Territory; and

(g) ICH Q1A(R2), ICH Q1B, ICH Q2(R1), ICH Q3A(R2), ICH Q3B(R2), ICH Q3C(R8), ICH Q3D(R1), ICH Q6A, and other applicable ICH guidelines.

Each Party shall remain responsible for monitoring changes to Applicable Laws and regulatory expectations within its respective jurisdictions and for promptly notifying the other Party of any such changes that may materially affect the quality obligations set forth herein.

ARTICLE 3 — QUALITY RESPONSIBILITIES OF PENTERRA (SUPPLIER)

3.1 Manufacturing and Supply of API. Penterra shall ensure that the API is manufactured at Alkerra Manufacturing Inc. (located at 5200 Meridian Parkway, Research Triangle Park, NC 27713), or at such other approved substitute facility as may be designated in accordance with Article 7 (Change Control), in compliance with cGMP, Applicable Laws, and all relevant regulatory commitments. Penterra shall ensure that each batch of API supplied to Meridian conforms to the Specifications set forth in Appendix 1A. Penterra shall maintain oversight of Alkerra Manufacturing Inc.'s manufacturing operations through a quality agreement between Penterra and Alkerra Manufacturing Inc., and shall be responsible for ensuring that Alkerra Manufacturing Inc. operates in compliance with cGMP and the requirements of this Agreement. API shall be supplied to Meridian at Penterra's fully-burdened manufacturing cost plus a fifteen percent (15%) markup, as provided in the Supply Agreement. Penterra shall be responsible for ensuring that each batch of API is manufactured using the approved manufacturing process, validated analytical methods, and qualified equipment, and that all critical process parameters and in-process controls are within established ranges.

3.2 Certificate of Analysis and Certificate of Compliance. Penterra shall provide a Certificate of Analysis (CoA) and a Certificate of Compliance (CoC) with each batch of API shipped to Meridian. The CoA shall set forth the test results for all parameters specified in Appendix 1A, including the analytical methods used, acceptance criteria, and actual results obtained. The CoC shall certify that the batch was manufactured in compliance with cGMP and the approved manufacturing process, that all critical process parameters were within established ranges, and that no unresolved Deviations impacting product quality are outstanding for such batch. Each CoA and CoC shall be signed by an authorized quality representative of Penterra or its CMO.

3.3 Reference Standards. Penterra shall supply Reference Standards for PPC-4187 (Penteracitinib), including the primary Reference Standard and any working standards, to Meridian for use in quality control testing, analytical method validation, and analytical method transfer activities. Each lot of Reference Standard shall be accompanied by comprehensive characterization data, including purity determination, spectroscopic characterization, and a certificate of analysis. Penterra shall notify Meridian in advance of any change in Reference Standard lot designation and shall provide sufficient lead time for Meridian to qualify replacement lots. Penterra shall bear the cost of supplying Reference Standards during the term of the Supply Agreement; thereafter, the Parties shall negotiate in good faith regarding cost allocation for ongoing Reference Standard supply.

3.4 Batch Records and Documentation. Penterra shall maintain complete and accurate executed batch production records, packaging records, and testing records for each batch of API manufactured and supplied to Meridian, for a minimum of ten (10) years from the date of batch release or such longer period as may be required by Applicable Laws. Penterra shall provide copies of executed batch production records (including in-process testing data, environmental monitoring data, and equipment use logs) to Meridian upon Meridian's reasonable written request, within thirty (30) days of such request. Such records shall be provided in English or accompanied by a certified English translation.

3.5 Stability Program. Penterra shall establish and maintain an ongoing stability program for the API in accordance with ICH Q1A(R2) (Stability Testing of New Drug Substances and Products) and ICH Q1B (Photostability Testing), as applicable. Penterra shall promptly notify Meridian, in writing, of any out-of-specification (OOS) or out-of-trend (OOT) stability results, and shall provide Meridian with copies of all stability reports and data upon Meridian's reasonable request. In the event that stability data indicates a need to modify the API retest date, storage conditions, or Specifications, Penterra shall initiate the change control process set forth in Article 7 and shall cooperate with Meridian to assess and address any regulatory filing implications in the Territory.

3.6 Raw Material and Component Control. Penterra shall ensure that all raw materials, starting materials, intermediates, process aids, solvents, reagents, and components used in the manufacture of the API meet established specifications and are sourced from approved, qualified suppliers. Penterra shall maintain an approved supplier list and shall conduct periodic qualification and audits of its raw material and component suppliers in accordance with cGMP. Penterra shall notify Meridian of any change in raw material or component source through the change control process set forth in Article 7.

3.7 Environmental and Facility Standards. Penterra shall ensure that the API manufacturing facility (Alkerra Manufacturing Inc.) meets all cGMP requirements for environmental controls, including temperature, humidity, particulate, and microbiological monitoring, clean room classifications, and utility qualifications. Penterra shall notify Meridian in writing of any material changes to the manufacturing facility, equipment, utilities, or environmental conditions that may affect the quality of the API, in accordance with Article 7. Penterra shall maintain a current facility master file and Drug Master File (DMF) and shall make such files available to Meridian and applicable Regulatory Authorities as needed to support regulatory filings in the Territory.

3.8 Personnel Qualifications. Penterra shall ensure that all personnel involved in the manufacture, testing, quality assurance, and quality control of the API are appropriately trained, qualified, and experienced for their assigned roles, in accordance with cGMP. Penterra shall maintain documented training records for all such personnel. Penterra shall notify Meridian of any change in key quality personnel (including the head of quality assurance, head of quality control, and head of production at the API manufacturing facility) within fifteen (15) business days of such change.

3.9 Technology Transfer Support. Penterra shall provide all necessary technical assistance, documentation, analytical methods, process descriptions, CMC data packages, and personnel support for the technology transfer of PPC-4187 manufacturing processes and analytical methods to Meridian's designated Asia-Pacific manufacturing facility, as detailed in the Technology Transfer Agreement. Penterra shall make qualified subject matter experts available to participate in on-site technology transfer activities, training, process demonstration runs, analytical method transfers, and validation activities at Meridian's designated facility. The technology transfer shall be completed within twenty-four (24) months of the Effective Date (i.e., by October 20, 2025). Penterra shall cooperate with Meridian to prepare and submit all documentation required by Regulatory Authorities in the Territory in connection with the technology transfer, including site transfer supplements, variations, and CMC updates.

ARTICLE 4 — QUALITY RESPONSIBILITIES OF MERIDIAN (PURCHASER / LICENSEE)

4.1 Receipt and Incoming Testing. Meridian shall perform incoming quality control testing of each batch of API received from Penterra against the Specifications set forth in Appendix 1A. At a minimum, Meridian shall perform identity testing (by HPLC and IR spectroscopy) on each incoming batch of API. Full release testing, including assay, impurity profiling, residual solvents, particle size distribution, water content, and microbiological testing, shall be performed in accordance with Appendix 1A. Meridian shall document all incoming testing results and shall compare such results against the CoA provided by Penterra. Any discrepancies between Meridian's incoming test results and Penterra's CoA results shall be investigated in accordance with Section 14.1 of this Agreement.

4.2 Finished Product Manufacturing. Meridian shall manufacture Licensed Products (25 mg and 50 mg film-coated tablets of Penteracitinib) in compliance with cGMP, Applicable Laws, and all applicable Territory regulations. During the initial period prior to completion of technology transfer, Meridian shall manufacture Licensed Products using API supplied by Penterra under the Supply Agreement. Following successful completion of the technology transfer in accordance with the Technology Transfer Agreement (targeted for completion by October 20, 2025), Meridian shall manufacture Licensed Products at Meridian's designated Asia-Pacific manufacturing facility, using API manufactured at such facility or at an approved alternative facility. Meridian shall ensure that all manufacturing equipment is qualified, all manufacturing processes are validated, and all analytical methods are validated or verified in accordance with ICH and applicable Regulatory Authority requirements.

4.3 Release Testing and Batch Release. Meridian shall be responsible for all finished product release testing and batch release decisions for Licensed Products intended for distribution in the Territory. Each batch of Licensed Product released for distribution shall be accompanied by a Certificate of Analysis certifying conformance to the Specifications set forth in Appendix 1B. Meridian shall ensure that no batch of Licensed Product is released for distribution unless all applicable testing has been completed and all results conform to Specifications, all Deviations have been investigated and resolved, and a qualified and authorized individual has approved the release. Meridian shall maintain complete and accurate batch release records, including all testing data, Deviation investigations, and release approvals.

4.4 Storage and Distribution. Meridian shall store API and Licensed Products under the conditions specified in Appendix 2 (Storage and Shipping Conditions). Meridian shall maintain appropriate storage facilities, including temperature- and humidity-controlled areas, and shall implement validated monitoring systems (including continuous temperature monitoring, data loggers, and alarm systems) to ensure that storage conditions are maintained within specified ranges at all times. Meridian shall maintain chain-of-custody documentation for all API and Licensed Products in its possession or under its control. Meridian shall ensure that all distribution activities are conducted in compliance with Good Distribution Practice (GDP) and applicable Territory regulations.

4.5 Qualified Person / Authorized Person. Meridian shall designate a Qualified Person (QP) or equivalent authorized individual under applicable Territory regulations who shall be responsible for batch release of Licensed Products in each applicable jurisdiction within the Territory. The identity and qualifications of each such designated individual shall be communicated to Penterra upon designation and upon any change in such designation. Meridian shall ensure that each QP or authorized individual has the authority, qualifications, training, and access to information necessary to discharge his or her batch release responsibilities in accordance with cGMP and Applicable Laws.

4.6 Subcontracting. Meridian may subcontract any manufacturing, testing, packaging, labeling, storage, or distribution activities related to the API or Licensed Products only with prior written notification to Penterra, which notification shall be provided at least forty-five (45) days before the commencement of any such subcontracted activities. Each such subcontractor shall be required to comply with cGMP, Applicable Laws, and the applicable requirements of this Quality Agreement. Meridian shall enter into a quality agreement with each such subcontractor and shall remain fully responsible for the performance of its subcontractors. Penterra shall have the right to audit any such subcontractor in accordance with Section 10.4 of this Agreement.

4.7 Pharmacovigilance Interface. Quality-related aspects of safety reporting shall be coordinated with the Pharmacovigilance Agreement between the Parties (once executed). Product quality complaints that may involve or be associated with adverse events, adverse drug reactions, or other safety-related matters shall be immediately referred to the designated pharmacovigilance contact under the Pharmacovigilance Agreement. Meridian shall establish and maintain internal procedures to ensure that its quality assurance and pharmacovigilance functions communicate promptly and effectively regarding such complaints.

ARTICLE 5 — SPECIFICATIONS

5.1 API Specifications. The Specifications for the API (PPC-4187, Penteracitinib) are set forth in detail in Appendix 1A to this Agreement. The API Specifications include, without limitation, the following parameters and acceptance criteria:

(a) Identity: Identification by high-performance liquid chromatography (HPLC) — retention time consistent with Reference Standard; identification by infrared spectroscopy (IR) — spectrum consistent with Reference Standard;

(b) Assay: Not less than 98.0% (w/w) by HPLC;

(c) Related Substances / Impurity Profile: Any individual specified impurity: not more than 0.15%; any individual unspecified impurity: not more than 0.10%; total impurities: not more than 0.50%;

(d) Residual Solvents: In accordance with ICH Q3C(R8), including limits for all solvents used in the final synthetic step and purification;

(e) Particle Size Distribution: As specified in Appendix 1A, determined by laser diffraction;

(f) Water Content (Karl Fischer): As specified in Appendix 1A;

(g) Heavy Metals / Elemental Impurities: In accordance with ICH Q3D(R1);

(h) Microbiological Limits: Total aerobic microbial count (TAMC): not more than 1,000 CFU/g; total combined yeasts and molds (TYMC): not more than 100 CFU/g; absence of specified organisms (including Escherichia coli) per pharmacopeial requirements.

All testing shall be performed using validated analytical methods, including pharmacopeial methods and in-house validated methods as specified in Appendix 1A.

5.2 Finished Product Specifications. The Specifications for the Licensed Products (25 mg and 50 mg film-coated tablets of Penteracitinib) are set forth in detail in Appendix 1B to this Agreement. The Finished Product Specifications include, without limitation, the following parameters and acceptance criteria:

(a) Appearance: Film-coated tablets of specified shape, color, dimensions, and markings;

(b) Identification: Identification by HPLC — retention time consistent with Reference Standard;

(d) Dissolution: As specified in Appendix 1B, using the approved dissolution method;

(e) Uniformity of Dosage Units: Meets acceptance criteria per USP/Ph. Eur. requirements;

(f) Degradation Products: Any individual specified degradation product: not more than the limit specified in Appendix 1B; any individual unspecified degradation product: not more than 0.20%; total degradation products: not more than the total limit specified in Appendix 1B;

(g) Water Content (Karl Fischer): As specified in Appendix 1B;

(h) Microbial Limits: TAMC: not more than 1,000 CFU/g; TYMC: not more than 100 CFU/g; absence of specified organisms per pharmacopeial requirements;

(i) Dimensions: Tablet diameter and thickness within specified ranges;

(j) Hardness: Within specified range;

(k) Friability: Not more than 1.0% (w/w).

All testing shall be performed using validated analytical methods, as specified in Appendix 1B. Testing methodologies shall conform to ICH Q6A (Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products) and applicable pharmacopeial test methods.

5.3 Reference Standard Specifications. The Specifications for the PPC-4187 Reference Standards are set forth in Appendix 1C to this Agreement. Reference Standards shall be characterized by multiple orthogonal analytical methods, including nuclear magnetic resonance spectroscopy (NMR), mass spectrometry, HPLC purity determination, elemental analysis, and X-ray powder diffraction (XRPD) to confirm Crystalline Form A, as claimed in U.S. Patent No. 11,345,678.

5.4 Specification Changes. Any proposed change to the Specifications for the API, Licensed Products, or Reference Standards shall require the prior written agreement of both Parties and shall be processed through the change control procedures set forth in Article 7 of this Agreement. Prior to implementation of any Specification change, the Parties shall jointly assess the regulatory filing implications of such change in all applicable jurisdictions, including the Territory and any territories retained by Penterra. No Specification change shall be implemented until all necessary regulatory variations, supplements, amendments, or notifications have been filed or the Parties have mutually agreed to a filing timeline. All approved Specification changes shall be documented in a revised version of the applicable Appendix and distributed to both Parties.

ARTICLE 6 — DEVIATION AND CAPA MANAGEMENT

6.1 Deviation Reporting. Each Party shall promptly identify, investigate, and document any Deviation from approved processes, procedures, Specifications, or quality standards occurring at its own facility or at the facility of any of its CMOs in connection with the manufacture, testing, storage, or distribution of API or Licensed Products. Each Deviation shall be classified by the responsible Party as follows:

(a) Critical Deviation: A Deviation that has resulted in, or may have resulted in, the release of product that does not conform to Specifications or that poses a risk to patient safety;

(b) Major Deviation: A Deviation that has a potential impact on product quality, cGMP compliance, or data integrity, but has not resulted in the release of non-conforming product;

(c) Minor Deviation: A Deviation of an administrative, procedural, or documentation nature with no direct impact on product quality or patient safety.

6.2 Notification. The Party experiencing or discovering a Deviation shall notify the other Party's Quality Contact within forty-eight (48) hours of discovery if the Deviation is classified as critical, and within seventy-two (72) hours of discovery if the Deviation is classified as major. Notification shall be in writing (email to the designated Quality Contact is acceptable for purposes of initial notification) and shall include a preliminary description of the Deviation, the affected batch(es), the initial risk assessment, and any immediate containment actions taken. Minor Deviations shall be reported to the other Party in summary form at the periodic quality review meetings described in Section 12.2.

6.3 Investigation. The Party responsible for the Deviation shall conduct a thorough root cause analysis using appropriate investigation tools (e.g., Ishikawa diagram, 5-Why analysis, fault tree analysis, or equivalent systematic methodology). Root cause analysis for critical Deviations shall be completed within thirty (30) calendar days of discovery. Root cause analysis for major Deviations shall be completed within thirty (30) calendar days of discovery, unless an extension is mutually agreed upon. Investigation reports for critical and major Deviations shall be shared with the other Party within ten (10) business days of completion of the root cause analysis. The other Party shall have the right to review and comment on such investigation reports and to request additional investigation if the root cause analysis is deemed insufficient.

6.4 Corrective and Preventive Action (CAPA). Corrective and preventive actions (CAPAs) shall be identified and implemented to address the root causes of critical and major Deviations and to prevent recurrence. CAPA plans for critical and major Deviations shall be shared with the other Party for review and comment prior to implementation. Each CAPA shall include defined action items, responsible individuals, target completion dates, and effectiveness verification criteria. The responsible Party shall document the implementation and effectiveness verification of each CAPA and shall make such documentation available to the other Party upon request. CAPAs that are not effectively implemented within the agreed-upon timeline shall be subject to escalation in accordance with Section 12.3.

6.5 Impact Assessment. Each Deviation investigation shall include an assessment of the impact of the Deviation on product quality, patient safety, regulatory compliance, and data integrity, including an evaluation of the impact on previously released batches, batches in process, and batches in quarantine. Where a Deviation may affect more than one batch, the responsible Party shall identify all potentially affected batches and shall implement appropriate containment actions pending completion of the investigation.

6.6 Trending. Both Parties shall perform periodic trending of Deviations, out-of-specification results, out-of-trend results, and CAPA effectiveness data to identify systemic or recurring issues. Trending data shall be reviewed at least quarterly and shall be discussed at the periodic quality review meetings described in Section 12.2. Where trending analysis identifies a systemic issue, the responsible Party shall initiate a CAPA to address the underlying cause.

ARTICLE 7 — CHANGE CONTROL

7.1 Notification of Proposed Changes. Either Party proposing a change to any aspect of the manufacture, testing, packaging, labeling, storage, or distribution of the API or Licensed Products shall notify the other Party in writing prior to implementation of such change. Without limitation, changes subject to this Article 7 include changes to: (a) Specifications; (b) manufacturing processes (including synthesis routes, formulation, and process parameters); (c) testing and analytical methods; (d) manufacturing facilities or sites; (e) equipment (including major process equipment and critical instruments); (f) raw material, starting material, or component sources or grades; (g) packaging or labeling; (h) storage or shipping conditions; (i) key quality personnel; and (j) any other aspect of the manufacturing, testing, or quality system that may affect product quality, safety, efficacy, or regulatory status.

7.2 Classification of Changes. Proposed changes shall be classified as follows:

(a) Critical Changes: Changes that have the potential to affect product quality attributes, safety, efficacy, identity, strength, purity, or regulatory status, including but not limited to changes to synthesis routes, critical process parameters, Specifications, manufacturing sites, or primary packaging. Critical changes require the prior written approval of both Parties before implementation.

(b) Major Changes: Changes that have a potential but less significant impact on product quality, manufacturing process, or analytical methods, including but not limited to changes to non-critical process parameters, secondary suppliers, non-critical equipment, or ancillary testing methods. Major changes require prior written notification to the other Party, accompanied by a risk assessment and supporting data. The notified Party shall have thirty (30) calendar days to review and provide written comments or objections.

(c) Minor Changes: Administrative, editorial, or documentation changes with no direct or indirect impact on product quality, safety, efficacy, or regulatory status. Minor changes require notification only to the other Party, which may be provided at the next periodic quality review meeting.

7.3 Evaluation and Approval. Critical changes shall not be implemented until the written approval of both Parties has been obtained. Each Party shall evaluate proposed critical changes within thirty (30) calendar days of receipt of the change request and all supporting documentation. Meridian shall be responsible for assessing the regulatory filing impact of all proposed changes in the applicable Territory jurisdictions, including NMPA, PMDA, MFDS, TGA, and all other relevant Regulatory Authorities. Penterra shall be responsible for assessing the regulatory filing impact of all proposed changes in its retained territories. Neither Party shall unreasonably withhold, condition, or delay its approval of a proposed critical change.

7.4 Regulatory Filings. The Party responsible for regulatory submissions in the affected jurisdiction shall file all necessary variations, supplements, amendments, or notifications with the applicable Regulatory Authority before or concurrently with change implementation, as required by Applicable Laws. Each Party shall provide the other Party with copies of all regulatory submissions and approvals relating to changes processed under this Article 7 that may affect the other Party's regulatory filings or quality obligations.

7.5 Documentation. All change requests, assessments, approvals, rejections, and implementation records shall be maintained in a change control log that is accessible to both Parties. The change control log shall include, at a minimum, the change request number, description of the proposed change, classification, risk assessment, regulatory assessment, approval or rejection status, implementation date, and effectiveness verification (if applicable). Each Party shall retain change control records for the period specified in Section 13.2.

7.6 Emergency Changes. Notwithstanding the foregoing, changes that are required to address an immediate threat to product quality, patient safety, or regulatory compliance may be implemented prior to obtaining written approval of the other Party, provided that: (a) the other Party's Quality Contact is notified verbally within twenty-four (24) hours of implementation of the emergency change; (b) written notification, including a description of the change, the justification for emergency implementation, and a preliminary risk assessment, is provided to the other Party within five (5) business days; and (c) a formal change request is submitted through the change control process within five (5) business days of implementation. Emergency changes shall be reviewed retrospectively at the next periodic quality review meeting.

ARTICLE 8 — COMPLAINT HANDLING

8.1 Product Quality Complaints. Each Party shall promptly notify the other Party's Quality Contact of any product quality complaint received relating to the API or Licensed Products. Notification shall be provided within five (5) business days of receipt of the complaint, or sooner if the complaint involves a potential patient safety concern. Notification shall include a summary of the complaint, the affected product and batch number(s) (if known), and any available supporting information.

8.2 Investigation Responsibility. Investigation responsibilities for product quality complaints shall be allocated as follows:

(a) Complaints relating to API quality (including complaints regarding identity, purity, impurities, physical characteristics, or contamination of the API) shall be investigated by Penterra;

(b) Complaints relating to finished product quality (including complaints regarding dissolution, disintegration, appearance, packaging, labeling, or contamination of the Licensed Product) shall be investigated by Meridian; and

(c) Where the root cause of a complaint is uncertain or may involve both the API and the finished product, the Parties shall conduct a joint investigation, coordinated by the Party that received the complaint.

8.3 Response Timelines. The investigating Party shall provide an initial assessment of each complaint within five (5) business days of receipt. A full investigation report, including root cause analysis, impact assessment, and any corrective or preventive actions taken or planned, shall be completed and shared with the other Party within thirty (30) calendar days of receipt of the complaint. Where a complaint requires regulatory reporting, the investigating Party shall ensure that all applicable reporting obligations are met within the timeframes required by Applicable Laws.

8.4 Trending and Reporting. Both Parties shall maintain a complaint database or tracking system and shall perform periodic trending of product quality complaints to identify patterns, clusters, or emerging quality issues. Complaint summaries and trending data shall be shared between the Parties at periodic quality review meetings described in Section 12.2.

8.5 Interface with Pharmacovigilance. Product quality complaints that involve or may involve adverse events, adverse drug reactions, or other patient safety concerns shall be immediately referred to the designated pharmacovigilance contact under the Pharmacovigilance Agreement between the Parties. The quality and pharmacovigilance functions of each Party shall collaborate to ensure timely and coordinated evaluation, reporting, and follow-up of all such complaints.

ARTICLE 9 — RECALLS AND FIELD SAFETY CORRECTIVE ACTIONS

9.1 Recall Decision. Meridian shall have primary decision-making authority for recalls, market withdrawals, field safety corrective actions, and field alerts relating to Licensed Products in the Territory. Penterra shall have primary decision-making authority for recalls, market withdrawals, and field safety corrective actions relating to Licensed Products in its retained territories. Notwithstanding the foregoing, each Party shall consult with the other Party before initiating any voluntary recall or field safety corrective action, and shall give due consideration to the other Party's views regarding the scope, timing, and manner of such action. In the event that a Regulatory Authority mandates a recall, the Party subject to such mandate shall comply with the Regulatory Authority's requirements and shall promptly notify the other Party.

9.2 Notification. The Party initiating or becoming aware of a recall or field safety corrective action shall notify the other Party's Quality Contact within twenty-four (24) hours of the decision to initiate the recall or of receipt of a Regulatory Authority mandate for recall, whichever is earlier. Such notification shall include a description of the affected product and batch(es), the reason for the recall, the scope and geography of the recall, and any immediate actions taken.

9.3 Investigation. The Parties shall conduct a joint investigation to determine the root cause of any recall. Each Party shall cooperate fully and shall provide all relevant documentation, records, samples, and information necessary to support the investigation. The investigation shall be completed as expeditiously as practicable, and a written investigation report shall be prepared and shared between the Parties.

9.4 Cost Allocation. The costs and expenses associated with any recall (including without limitation logistics, transportation, storage, destruction, replacement product, customer notifications, regulatory notifications, and legal costs) shall be allocated as follows:

(a) If the recall is attributable to a defect in the API (including non-conformance with API Specifications, contamination, or manufacturing deficiency at the API manufacturing site), Penterra shall bear all reasonable and documented recall costs;

(b) If the recall is attributable to a defect in the finished product manufacturing process, packaging, labeling, storage, or distribution activities of Meridian (or its CMOs or subcontractors), Meridian shall bear all reasonable and documented recall costs;

(c) If the recall is attributable to both the API and the finished product, or if the root cause cannot be determined after a diligent investigation, the Parties shall share all reasonable and documented recall costs equally (50%/50%).

Nothing in this Section 9.4 shall limit either Party's rights to indemnification under the License Agreement or any other agreement between the Parties.

9.5 Regulatory Notification. Each Party shall be responsible for notifying the applicable Regulatory Authorities in its respective territory of any recall or field safety corrective action, in accordance with Applicable Laws and within the timeframes required by such Regulatory Authorities. Each Party shall provide the other Party with copies of all regulatory notifications and correspondence relating to any recall.

9.6 Mock Recalls. Both Parties shall conduct mock recall exercises at least once per calendar year to verify recall readiness, including the ability to identify and trace affected batches, notify distribution channels, and communicate with Regulatory Authorities. Mock recall results shall be documented and reviewed at the periodic quality review meetings described in Section 12.2. Any deficiencies identified during mock recall exercises shall be addressed through the CAPA process described in Section 6.4.

ARTICLE 10 — REGULATORY INSPECTIONS AND AUDITS

10.1 Regulatory Inspections. Each Party shall promptly notify the other Party's Quality Contact of any Regulatory Authority inspection that relates to or may affect PPC-4187 API or Licensed Products, whether conducted at such Party's own facility or at the facility of any of its CMOs. Notification shall be provided within forty-eight (48) hours of the inspection announcement or the commencement of the inspection, whichever is earlier. Such notification shall include the identity of the inspecting Regulatory Authority, the scope and nature of the inspection (e.g., routine GMP inspection, pre-approval inspection, for-cause inspection), and the scheduled or actual date(s) of the inspection.

10.2 Inspection Support. Each Party shall cooperate and provide reasonable support to the other Party during Regulatory Authority inspections, including without limitation making available relevant documentation, records, and qualified personnel for interviews and discussions with inspectors. Where an inspection at one Party's facility requires access to information held by the other Party, the Party holding such information shall use commercially reasonable efforts to provide such information in a timely manner.

10.3 Inspection Outcomes. Each Party shall promptly share with the other Party copies of all inspection observations, findings, citations, and reports received from any Regulatory Authority in connection with an inspection relating to PPC-4187 API or Licensed Products, including without limitation FDA Form 483 observations, Warning Letters, Import Alerts, NMPA inspection reports and corrective action notices, PMDA GMP inspection results, MFDS inspection findings, and TGA inspection reports. Copies of proposed responses to inspection observations shall be shared with the other Party for review and comment prior to submission to the Regulatory Authority, to the extent such responses relate to matters that may affect the other Party's operations or regulatory filings.

10.4 Right to Audit. Each Party shall have the right to audit the other Party's manufacturing, testing, packaging, labeling, storage, and distribution facilities, and those of its CMOs, to the extent related to PPC-4187 API or Licensed Products, upon reasonable prior written notice of not less than thirty (30) calendar days. Audits shall be limited to one (1) audit per calendar year per facility, unless a for-cause audit is warranted due to a critical quality issue, a Regulatory Authority action, or a significant Deviation or complaint trend, in which case the auditing Party may conduct additional audits upon reasonable notice. Each audit shall be conducted during normal business hours and shall be conducted in a manner that minimizes disruption to the audited Party's operations. The audited Party shall provide the auditing Party with reasonable access to facilities, documentation, records, and personnel. Audits shall be conducted by qualified audit personnel.

10.5 Audit of Alkerra Manufacturing Inc. Meridian shall have the right to audit Alkerra Manufacturing Inc.'s manufacturing and testing facility located at 5200 Meridian Parkway, Research Triangle Park, North Carolina 27713, upon reasonable prior written notice, to verify cGMP compliance for API manufacture and to assess the facility's compliance with the requirements of this Agreement. Penterra shall facilitate Meridian's access to Alkerra Manufacturing Inc.'s facility for purposes of such audits, and shall ensure that its quality agreement with Alkerra Manufacturing Inc. includes an appropriate audit clause permitting such access by Meridian or its designated auditors. The frequency, scope, and scheduling of audits of Alkerra Manufacturing Inc. shall be subject to the limitations set forth in Section 10.4, except that the first audit may be conducted within six (6) months of the Effective Date.

10.6 Audit Reports. The auditing Party shall prepare an audit report following each audit, which report shall include a summary of observations, findings, and any corrective action requests (CARs). The audit report shall be shared with the audited Party within thirty (30) calendar days of completion of the audit. The audited Party shall provide written responses to all audit observations and CARs within thirty (30) calendar days of receipt of the audit report. Responses shall include proposed corrective and preventive actions, responsible individuals, and target completion dates. The auditing Party shall review and provide feedback on proposed corrective actions. Implementation and effectiveness of corrective actions shall be verified by the auditing Party, either through remote review or follow-up audit.

10.7 Pre-Approval Inspections. The Parties shall cooperate to support pre-approval inspections (PAIs) by NMPA, PMDA, MFDS, TGA, and other Territory Regulatory Authorities in connection with regulatory filings for PPC-4187 Licensed Products. Each Party shall use commercially reasonable efforts to ensure that its facilities and the facilities of its CMOs are in a state of inspection readiness at all times. Penterra shall cooperate with Meridian to facilitate pre-approval inspections of the API manufacturing facility (Alkerra Manufacturing Inc.) by Territory Regulatory Authorities, including by providing access to the facility, personnel, and documentation, and by assisting with translation of documents where required.

ARTICLE 11 — ANNUAL PRODUCT QUALITY REVIEW

11.1 Scope. Each Party shall conduct an Annual Product Quality Review (APQR) for the products within its area of responsibility: Penterra shall prepare an APQR for the API (PPC-4187, Penteracitinib), and Meridian shall prepare an APQR for the finished Licensed Products (25 mg and 50 mg film-coated tablets). The APQR shall be conducted in accordance with ICH Q7 (for API), applicable cGMP requirements, and the Parties' respective quality system procedures.

11.2 Content. Each APQR shall include, at a minimum, a review of the following:

(a) a summary of all batches manufactured during the review period, including batch yield data and trending;

(b) a review of all Deviations, including classification, root cause analysis, and CAPA effectiveness;

(d) a summary and trending of product quality complaints;

(e) a review of stability data, including any OOS or OOT results;

(f) a review of all out-of-specification investigation results;

(g) a review of critical process parameter and in-process control data, including process capability analysis;

(h) a summary of regulatory inspection outcomes, audit observations, and corrective actions;

(i) a review of raw material and component supplier performance (for API);

(j) a review of any returned, rejected, or recalled product; and

(k) a summary of any other significant quality events or trends.

11.3 Sharing. Each Party shall share its completed APQR (or a comprehensive summary thereof acceptable to both Parties) with the other Party within ninety (90) calendar days following the end of the review period. The review period shall be the calendar year (January 1 through December 31), unless otherwise agreed in writing by the Parties.

11.4 Joint Review. The Parties shall discuss APQR findings, conclusions, and recommended actions at the periodic quality review meeting held in the first quarter of each calendar year (or at a specially convened meeting, if necessary). Action items arising from the joint APQR review shall be documented in the meeting minutes and tracked to completion.

ARTICLE 12 — QUALITY GOVERNANCE AND COMMUNICATION

12.1 Quality Contacts. Each Party shall designate a primary Quality Contact and an alternate Quality Contact for purposes of day-to-day communication and coordination under this Agreement. The initial Quality Contacts of each Party are set forth in Appendix 3. Either Party may change its designated Quality Contact(s) at any time by providing written notice to the other Party. The Quality Contacts shall serve as the primary points of contact for all quality-related matters under this Agreement, including Deviation notifications, change control communications, complaint notifications, audit scheduling, and regulatory inspection notifications.

12.2 Periodic Quality Review Meetings. The Parties shall hold periodic quality review meetings on a quarterly basis (approximately every ninety (90) calendar days). Meetings may be conducted in person, by videoconference, or by teleconference, as mutually agreed. The agenda for each periodic quality review meeting shall include, at a minimum, the following topics:

(a) review of Deviations and CAPA status (critical, major, and trending of minor);

(b) review of change controls in progress and recently implemented;

(d) review of stability data and any OOS or OOT results;

(e) regulatory updates, including inspection outcomes, pre-approval inspection status, and filing activities;

(f) technology transfer progress (until completion of technology transfer);

(g) review of open action items from prior meetings;

(h) any other quality matters raised by either Party.

12.3 Escalation. Quality issues that cannot be resolved at the Quality Contact level within a reasonable period (not to exceed thirty (30) calendar days) shall be escalated to the respective Heads of Quality of each Party. If the Heads of Quality are unable to resolve the issue within an additional fifteen (15) calendar days, the issue shall be further escalated to the Joint Steering Committee (JSC) established under Article 3 of the License Agreement, which JSC comprises three (3) representatives from each Party. The JSC shall endeavor to resolve escalated quality issues in good faith within thirty (30) calendar days. Disputes that cannot be resolved through escalation shall be subject to the dispute resolution provisions of Article 17.2 of this Agreement.

12.4 Ad Hoc Communications. Either Party may request ad hoc quality meetings or communications at any time to address urgent quality matters, emerging issues, or matters that cannot reasonably await the next scheduled periodic quality review meeting. The other Party shall use commercially reasonable efforts to accommodate such requests on a timely basis.

12.5 Meeting Minutes. Minutes of each periodic quality review meeting and each ad hoc quality meeting shall be prepared by the Quality Contact of the hosting Party (alternating between the Parties for periodic meetings) and shall be circulated to all attendees and the Quality Contacts of both Parties within ten (10) business days following the meeting. Meeting minutes shall include a summary of topics discussed, decisions reached, and action items assigned (including responsible Party, responsible individual, and target completion date). Action items shall be tracked to completion and reviewed at each subsequent periodic quality review meeting until closed.

ARTICLE 13 — DOCUMENTATION AND RECORD RETENTION

13.1 Documentation Standards. All quality documentation prepared, reviewed, approved, and maintained by either Party in connection with this Agreement shall comply with cGMP requirements and applicable data integrity standards, including the ALCOA+ principles (Attributable, Legible, Contemporaneous, Original, Accurate; plus Complete, Consistent, Enduring, and Available). Each Party shall maintain documented standard operating procedures governing the creation, review, approval, revision, and archival of quality records. Electronic records and electronic signatures shall comply with 21 CFR Part 11 and applicable Territory regulations governing electronic records and electronic signatures.

13.2 Record Retention. Records relating to API manufacture and supply (including batch production records, testing records, stability data, Deviation investigations, CAPA records, change control records, complaint records, and audit reports) shall be retained by Penterra for at least ten (10) years after the expiry date of the last batch manu

QUALITY AGREEMENT
Between
PENTERRA PHARMACEUTICALS CORP.
and
MERIDIAN BIO THERAPEUTICS LIMITED
Entered into pursuant to that certain Exclusive License Agreement dated October 2, 2023 (Effective Date: October 20, 2023) between Penterra Pharmaceuticals Corp. and Meridian Bio Therapeutics Limited (the "License Agreement")
Form attached as Exhibit F to the License Agreement
To be executed within sixty (60) days of the Effective Date (on or before December 19, 2023)
Compound: PPC-4187 (Penteracitinib)
FORM — FOR EXECUTION
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ARTICLE 1 — DEFINITIONS
As used in this Quality Agreement (this "Agreement"), the following terms shall have the meanings set forth below. Capitalized terms used but not otherwise defined in this Agreement shall have the meanings ascribed to them in the License Agreement.
1.1 "Active Pharmaceutical Ingredient" or "API" shall mean the active pharmaceutical ingredient for PPC-4187 (Penteracitinib), a selective Janus kinase 1 (JAK1) inhibitor, as manufactured at the facility of Alkerra Manufacturing Inc., located at 5200 Meridian Parkway, Research Triangle Park, North Carolina 27713, United States, or such other facility as may be designated in writing by Penterra and approved by Meridian in accordance with Article 7 (Change Control) of this Agreement.
1.2 "Applicable Laws" shall mean all federal, state, provincial, national, and local laws, statutes, regulations, rules, orders, guidelines, guidances, and standards applicable to the manufacture, testing, packaging, labeling, storage, distribution, and supply of the API and Licensed Products, including without limitation current Good Manufacturing Practice (cGMP), International Council for Harmonisation (ICH) guidelines, and all applicable regulations, requirements, and guidances of relevant Regulatory Authorities, including the United States Food and Drug Administration (FDA), the National Medical Products Administration of the People's Republic of China (NMPA), the Pharmaceuticals and Medical Devices Agency of Japan (PMDA), the Ministry of Food and Drug Safety of the Republic of Korea (MFDS), the Therapeutic Goods Administration of Australia (TGA), and all other Regulatory Authorities having jurisdiction within the Territory.
1.3 "Certificate of Analysis" or "CoA" shall mean a document issued by the supplying Party certifying that a specific batch of API or Licensed Product has been tested and conforms to the applicable Specifications set forth in Appendix 1 hereto, including a summary of all test results, methods used, and acceptance criteria.
1.4 "Certificate of Compliance" or "CoC" shall mean a document issued by the supplying Party certifying that a specific batch of API or Licensed Product was manufactured in compliance with cGMP and the approved manufacturing process, including confirmation that all critical process parameters were within established ranges and that all manufacturing operations were performed in accordance with the approved batch production record.
1.5 "cGMP" shall mean current Good Manufacturing Practice as defined under applicable regulatory frameworks, including without limitation Title 21 of the United States Code of Federal Regulations, Parts 210 and 211 (21 CFR Parts 210 and 211), ICH Q7 (Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients), the European Union Guidelines to Good Manufacturing Practice (EU GMP), and comparable regulations, guidelines, and standards applicable in the Territory, as each may be amended, updated, or superseded from time to time.
1.6 "Contract Manufacturing Organization" or "CMO" shall mean Alkerra Manufacturing Inc. or any successor, substitute, or additional manufacturer engaged by Penterra or Meridian for the manufacture, testing, packaging, or labeling of API or finished Licensed Products, as applicable, and as approved in accordance with the terms of this Agreement and the License Agreement.
1.7 "Deviation" shall mean any departure from approved processes, procedures, specifications, quality standards, or other documented requirements, whether planned or unplanned, including without limitation out-of-specification (OOS) results, out-of-trend (OOT) results, process excursions, equipment malfunctions, and deviations from approved batch production records or standard operating procedures.
1.8 "Effective Date" shall mean October 20, 2023, being the Effective Date of the License Agreement.
1.9 "Licensed Product" shall mean the finished pharmaceutical product containing PPC-4187 (Penteracitinib) as the active ingredient, in 25 mg and 50 mg film-coated tablet formulations, as further described in the Specifications set forth in Appendix 1B hereto, and any additional dosage forms or strengths that the Parties may agree to add by written amendment to this Agreement.
1.10 "License Agreement" shall mean the Exclusive License Agreement dated October 2, 2023, effective October 20, 2023, between Penterra Pharmaceuticals Corp. and Meridian Bio Therapeutics Limited, as the same may be amended, restated, supplemented, or otherwise modified from time to time in accordance with its terms.
1.11 "Penterra" shall mean Penterra Pharmaceuticals Corp., a corporation organized and existing under the laws of the State of Delaware, United States of America, with its principal place of business and headquarters located at 400 Pharma Drive, Suite 800, Princeton, New Jersey 08540, United States.
1.12 "Meridian" shall mean Meridian Bio Therapeutics Limited, a limited company incorporated and existing under the laws of Hong Kong SAR (Company Registration No. 2847631), with its principal place of business and headquarters located at 18/F, Blossom Tower, 88 Queen's Road Central, Hong Kong SAR.
1.13 "Quality Contact" shall mean the designated quality representative from each Party responsible for day-to-day communication under this Agreement, as identified in Appendix 3 hereto, or such replacement designee as may be notified in writing to the other Party from time to time.
1.14 "Recall" shall mean any corrective action resulting in the return, withdrawal, retrieval, or market correction of any API or Licensed Product from the market, clinical supply chain, or distribution channels, whether voluntary or mandated by a Regulatory Authority, including without limitation field safety corrective actions.
1.15 "Reference Standard" shall mean the analytical reference standards for PPC-4187 (Penteracitinib) supplied by Penterra for use by Meridian in quality control testing, method validation, and analytical method transfer, together with all associated characterization data, certificates of analysis, and stability information.
1.16 "Regulatory Authority" shall mean any governmental, quasi-governmental, or regulatory authority, body, agency, department, bureau, commission, council, or instrumentality having jurisdiction over the research, development, manufacture, testing, distribution, marketing, or sale of pharmaceutical products in any jurisdiction, including without limitation the FDA, NMPA, PMDA, MFDS, TGA, Health Sciences Authority of Singapore (HSA), Thai Food and Drug Administration (Thai FDA), National Pharmaceutical Regulatory Agency of Malaysia (NPRA), Badan Pengawas Obat dan Makanan of Indonesia (BPOM), Food and Drug Administration of the Philippines (Philippines FDA), Drug Administration of Vietnam (DAV), and the Taiwan Food and Drug Administration (TFDA).
1.17 "Specifications" shall mean the analytical, chemical, physical, and microbiological specifications for the API and Licensed Products, including all test parameters, analytical methods, and acceptance criteria, as set forth in Appendix 1 hereto (including Appendix 1A for API, Appendix 1B for Finished Products, and Appendix 1C for Reference Standards), as the same may be amended from time to time in accordance with the change control procedures set forth in Article 7 of this Agreement.
1.18 "Supply Agreement" shall mean the API Supply Agreement between Penterra and Meridian for the supply of clinical and commercial API at a transfer price of Penterra's fully-burdened manufacturing cost plus a fifteen percent (15%) markup, for an initial term of three (3) years following the Effective Date, as contemplated by the License Agreement and as may be extended or amended in accordance with its terms.
1.19 "Technology Transfer Agreement" shall mean the Technology Transfer Agreement between Penterra and Meridian governing the transfer of PPC-4187 (Penteracitinib) manufacturing process know-how, analytical methods, Chemistry, Manufacturing, and Controls (CMC) documentation, and related intellectual property, to be completed within twenty-four (24) months of the Effective Date (i.e., by October 20, 2025), as contemplated by the License Agreement.
1.20 "Territory" shall mean the Asia-Pacific territory as defined in Schedule D to the License Agreement, comprising the following countries, territories, and jurisdictions: the People's Republic of China (including Hong Kong Special Administrative Region and Macau Special Administrative Region), Japan, the Republic of Korea, Australia, New Zealand, Singapore, the Kingdom of Thailand, Malaysia, the Republic of Indonesia, the Republic of the Philippines, the Socialist Republic of Vietnam, and Taiwan.
Any capitalized term used herein that is not defined in this Article 1 shall have the meaning ascribed to such term in the License Agreement. In the event of any inconsistency between a definition set forth in this Agreement and the corresponding definition in the License Agreement, the definition in the License Agreement shall control unless this Agreement expressly provides otherwise. References to any statute, regulation, or guideline shall be deemed to include all amendments, restatements, replacements, and successor provisions thereto.
ARTICLE 2 — PURPOSE AND SCOPE
2.1 Purpose. The purpose of this Quality Agreement is to establish the quality-related responsibilities, obligations, and procedures governing: (a) the supply of API and Reference Standards by Penterra to Meridian; (b) the manufacture, testing, storage, release, and distribution of Licensed Products by Meridian in the Territory; and (c) the quality aspects of the technology transfer activities between the Parties. This Agreement is intended to ensure that all API and Licensed Products are manufactured, tested, stored, released, and distributed in compliance with cGMP, Applicable Laws, and the Specifications, and to define the respective quality obligations of each Party in a manner consistent with ICH Q7, ICH Q10, and applicable Regulatory Authority expectations.
2.2 Scope. This Quality Agreement covers the following quality-related activities and obligations:
(a) the supply of API by Penterra (directly or through Alkerra Manufacturing Inc. as its CMO) to Meridian during the initial three (3)-year supply term under the Supply Agreement, including incoming quality control, testing, acceptance, and rejection procedures;
(b) technology transfer activities governed by the Technology Transfer Agreement, including the transfer of manufacturing process know-how, analytical methods, and CMC documentation, and the quality oversight obligations of each Party during such transfer;
(c) Meridian's manufacture of finished Licensed Products (25 mg and 50 mg film-coated tablets of Penteracitinib) at Meridian's designated Asia-Pacific manufacturing facility, including during the period following completion of technology transfer;
(d) quality control, quality assurance, and release testing obligations of each Party with respect to API and Licensed Products, respectively;
(e) change control procedures applicable to the API, Licensed Products, Specifications, manufacturing processes, testing methods, facilities, equipment, and raw material sources;
(f) deviation management and corrective and preventive action (CAPA) procedures;
(g) product quality complaint handling, investigation, and resolution;
(h) recall and field safety corrective action procedures;
(i) regulatory inspection readiness, audit rights, and cooperation obligations;
(j) annual product quality review requirements;
(k) documentation, record retention, and data integrity standards; and
(l) quality governance, communication, and escalation mechanisms.
2.3 Relationship to Other Agreements. This Quality Agreement supplements, and is subject to the terms and conditions of, the License Agreement, the Supply Agreement, and the Technology Transfer Agreement. Nothing in this Agreement is intended to modify, limit, or supersede any right or obligation of either Party under the License Agreement, the Supply Agreement, or the Technology Transfer Agreement, except as expressly provided herein. In the event of any conflict or inconsistency between the terms of this Quality Agreement and the terms of the Supply Agreement with respect to quality-related matters (including but not limited to Specifications, testing, release, storage, change control, deviation management, CAPA, complaints, recalls, and regulatory inspection cooperation), the terms of this Quality Agreement shall prevail. In the event of any conflict or inconsistency between the terms of this Quality Agreement and the terms of the License Agreement, the terms of the License Agreement shall prevail. The Pharmacovigilance Agreement between the Parties, once executed, shall govern pharmacovigilance-related matters; quality-related aspects of safety reporting shall be coordinated as provided in Section 4.7 and Section 8.5 of this Agreement.
2.4 Regulatory Context. This Quality Agreement has been drafted in compliance with, and the Parties' obligations hereunder shall be performed in accordance with, the following regulatory frameworks and guidelines, as applicable:
(a) ICH Q7 — Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients;
(b) ICH Q10 — Pharmaceutical Quality System;
(c) EU GMP Annex 16 — Certification by a Qualified Person and Batch Release;
(d) 21 CFR Parts 210 and 211 — Current Good Manufacturing Practice for Finished Pharmaceuticals (U.S.);
(e) 21 CFR Part 211 Subpart J — Records and Reports;
(f) applicable regulations, guidelines, and guidances of the FDA, NMPA, PMDA, MFDS, TGA, and other Regulatory Authorities having jurisdiction within the Territory; and
(g) ICH Q1A(R2), ICH Q1B, ICH Q2(R1), ICH Q3A(R2), ICH Q3B(R2), ICH Q3C(R8), ICH Q3D(R1), ICH Q6A, and other applicable ICH guidelines.
Each Party shall remain responsible for monitoring changes to Applicable Laws and regulatory expectations within its respective jurisdictions and for promptly notifying the other Party of any such changes that may materially affect the quality obligations set forth herein.
ARTICLE 3 — QUALITY RESPONSIBILITIES OF PENTERRA (SUPPLIER)
3.1 Manufacturing and Supply of API. Penterra shall ensure that the API is manufactured at Alkerra Manufacturing Inc. (located at 5200 Meridian Parkway, Research Triangle Park, NC 27713), or at such other approved substitute facility as may be designated in accordance with Article 7 (Change Control), in compliance with cGMP, Applicable Laws, and all relevant regulatory commitments. Penterra shall ensure that each batch of API supplied to Meridian conforms to the Specifications set forth in Appendix 1A. Penterra shall maintain oversight of Alkerra Manufacturing Inc.'s manufacturing operations through a quality agreement between Penterra and Alkerra Manufacturing Inc., and shall be responsible for ensuring that Alkerra Manufacturing Inc. operates in compliance with cGMP and the requirements of this Agreement. API shall be supplied to Meridian at Penterra's fully-burdened manufacturing cost plus a fifteen percent (15%) markup, as provided in the Supply Agreement. Penterra shall be responsible for ensuring that each batch of API is manufactured using the approved manufacturing process, validated analytical methods, and qualified equipment, and that all critical process parameters and in-process controls are within established ranges.
3.2 Certificate of Analysis and Certificate of Compliance. Penterra shall provide a Certificate of Analysis (CoA) and a Certificate of Compliance (CoC) with each batch of API shipped to Meridian. The CoA shall set forth the test results for all parameters specified in Appendix 1A, including the analytical methods used, acceptance criteria, and actual results obtained. The CoC shall certify that the batch was manufactured in compliance with cGMP and the approved manufacturing process, that all critical process parameters were within established ranges, and that no unresolved Deviations impacting product quality are outstanding for such batch. Each CoA and CoC shall be signed by an authorized quality representative of Penterra or its CMO.
3.3 Reference Standards. Penterra shall supply Reference Standards for PPC-4187 (Penteracitinib), including the primary Reference Standard and any working standards, to Meridian for use in quality control testing, analytical method validation, and analytical method transfer activities. Each lot of Reference Standard shall be accompanied by comprehensive characterization data, including purity determination, spectroscopic characterization, and a certificate of analysis. Penterra shall notify Meridian in advance of any change in Reference Standard lot designation and shall provide sufficient lead time for Meridian to qualify replacement lots. Penterra shall bear the cost of supplying Reference Standards during the term of the Supply Agreement; thereafter, the Parties shall negotiate in good faith regarding cost allocation for ongoing Reference Standard supply.
3.4 Batch Records and Documentation. Penterra shall maintain complete and accurate executed batch production records, packaging records, and testing records for each batch of API manufactured and supplied to Meridian, for a minimum of ten (10) years from the date of batch release or such longer period as may be required by Applicable Laws. Penterra shall provide copies of executed batch production records (including in-process testing data, environmental monitoring data, and equipment use logs) to Meridian upon Meridian's reasonable written request, within thirty (30) days of such request. Such records shall be provided in English or accompanied by a certified English translation.
3.5 Stability Program. Penterra shall establish and maintain an ongoing stability program for the API in accordance with ICH Q1A(R2) (Stability Testing of New Drug Substances and Products) and ICH Q1B (Photostability Testing), as applicable. Penterra shall promptly notify Meridian, in writing, of any out-of-specification (OOS) or out-of-trend (OOT) stability results, and shall provide Meridian with copies of all stability reports and data upon Meridian's reasonable request. In the event that stability data indicates a need to modify the API retest date, storage conditions, or Specifications, Penterra shall initiate the change control process set forth in Article 7 and shall cooperate with Meridian to assess and address any regulatory filing implications in the Territory.
3.6 Raw Material and Component Control. Penterra shall ensure that all raw materials, starting materials, intermediates, process aids, solvents, reagents, and components used in the manufacture of the API meet established specifications and are sourced from approved, qualified suppliers. Penterra shall maintain an approved supplier list and shall conduct periodic qualification and audits of its raw material and component suppliers in accordance with cGMP. Penterra shall notify Meridian of any change in raw material or component source through the change control process set forth in Article 7.
3.7 Environmental and Facility Standards. Penterra shall ensure that the API manufacturing facility (Alkerra Manufacturing Inc.) meets all cGMP requirements for environmental controls, including temperature, humidity, particulate, and microbiological monitoring, clean room classifications, and utility qualifications. Penterra shall notify Meridian in writing of any material changes to the manufacturing facility, equipment, utilities, or environmental conditions that may affect the quality of the API, in accordance with Article 7. Penterra shall maintain a current facility master file and Drug Master File (DMF) and shall make such files available to Meridian and applicable Regulatory Authorities as needed to support regulatory filings in the Territory.
3.8 Personnel Qualifications. Penterra shall ensure that all personnel involved in the manufacture, testing, quality assurance, and quality control of the API are appropriately trained, qualified, and experienced for their assigned roles, in accordance with cGMP. Penterra shall maintain documented training records for all such personnel. Penterra shall notify Meridian of any change in key quality personnel (including the head of quality assurance, head of quality control, and head of production at the API manufacturing facility) within fifteen (15) business days of such change.
3.9 Technology Transfer Support. Penterra shall provide all necessary technical assistance, documentation, analytical methods, process descriptions, CMC data packages, and personnel support for the technology transfer of PPC-4187 manufacturing processes and analytical methods to Meridian's designated Asia-Pacific manufacturing facility, as detailed in the Technology Transfer Agreement. Penterra shall make qualified subject matter experts available to participate in on-site technology transfer activities, training, process demonstration runs, analytical method transfers, and validation activities at Meridian's designated facility. The technology transfer shall be completed within twenty-four (24) months of the Effective Date (i.e., by October 20, 2025). Penterra shall cooperate with Meridian to prepare and submit all documentation required by Regulatory Authorities in the Territory in connection with the technology transfer, including site transfer supplements, variations, and CMC updates.
ARTICLE 4 — QUALITY RESPONSIBILITIES OF MERIDIAN (PURCHASER / LICENSEE)
4.1 Receipt and Incoming Testing. Meridian shall perform incoming quality control testing of each batch of API received from Penterra against the Specifications set forth in Appendix 1A. At a minimum, Meridian shall perform identity testing (by HPLC and IR spectroscopy) on each incoming batch of API. Full release testing, including assay, impurity profiling, residual solvents, particle size distribution, water content, and microbiological testing, shall be performed in accordance with Appendix 1A. Meridian shall document all incoming testing results and shall compare such results against the CoA provided by Penterra. Any discrepancies between Meridian's incoming test results and Penterra's CoA results shall be investigated in accordance with Section 14.1 of this Agreement.
4.2 Finished Product Manufacturing. Meridian shall manufacture Licensed Products (25 mg and 50 mg film-coated tablets of Penteracitinib) in compliance with cGMP, Applicable Laws, and all applicable Territory regulations. During the initial period prior to completion of technology transfer, Meridian shall manufacture Licensed Products using API supplied by Penterra under the Supply Agreement. Following successful completion of the technology transfer in accordance with the Technology Transfer Agreement (targeted for completion by October 20, 2025), Meridian shall manufacture Licensed Products at Meridian's designated Asia-Pacific manufacturing facility, using API manufactured at such facility or at an approved alternative facility. Meridian shall ensure that all manufacturing equipment is qualified, all manufacturing processes are validated, and all analytical methods are validated or verified in accordance with ICH and applicable Regulatory Authority requirements.
4.3 Release Testing and Batch Release. Meridian shall be responsible for all finished product release testing and batch release decisions for Licensed Products intended for distribution in the Territory. Each batch of Licensed Product released for distribution shall be accompanied by a Certificate of Analysis certifying conformance to the Specifications set forth in Appendix 1B. Meridian shall ensure that no batch of Licensed Product is released for distribution unless all applicable testing has been completed and all results conform to Specifications, all Deviations have been investigated and resolved, and a qualified and authorized individual has approved the release. Meridian shall maintain complete and accurate batch release records, including all testing data, Deviation investigations, and release approvals.
4.4 Storage and Distribution. Meridian shall store API and Licensed Products under the conditions specified in Appendix 2 (Storage and Shipping Conditions). Meridian shall maintain appropriate storage facilities, including temperature- and humidity-controlled areas, and shall implement validated monitoring systems (including continuous temperature monitoring, data loggers, and alarm systems) to ensure that storage conditions are maintained within specified ranges at all times. Meridian shall maintain chain-of-custody documentation for all API and Licensed Products in its possession or under its control. Meridian shall ensure that all distribution activities are conducted in compliance with Good Distribution Practice (GDP) and applicable Territory regulations.
4.5 Qualified Person / Authorized Person. Meridian shall designate a Qualified Person (QP) or equivalent authorized individual under applicable Territory regulations who shall be responsible for batch release of Licensed Products in each applicable jurisdiction within the Territory. The identity and qualifications of each such designated individual shall be communicated to Penterra upon designation and upon any change in such designation. Meridian shall ensure that each QP or authorized individual has the authority, qualifications, training, and access to information necessary to discharge his or her batch release responsibilities in accordance with cGMP and Applicable Laws.
4.6 Subcontracting. Meridian may subcontract any manufacturing, testing, packaging, labeling, storage, or distribution activities related to the API or Licensed Products only with prior written notification to Penterra, which notification shall be provided at least forty-five (45) days before the commencement of any such subcontracted activities. Each such subcontractor shall be required to comply with cGMP, Applicable Laws, and the applicable requirements of this Quality Agreement. Meridian shall enter into a quality agreement with each such subcontractor and shall remain fully responsible for the performance of its subcontractors. Penterra shall have the right to audit any such subcontractor in accordance with Section 10.4 of this Agreement.
4.7 Pharmacovigilance Interface. Quality-related aspects of safety reporting shall be coordinated with the Pharmacovigilance Agreement between the Parties (once executed). Product quality complaints that may involve or be associated with adverse events, adverse drug reactions, or other safety-related matters shall be immediately referred to the designated pharmacovigilance contact under the Pharmacovigilance Agreement. Meridian shall establish and maintain internal procedures to ensure that its quality assurance and pharmacovigilance functions communicate promptly and effectively regarding such complaints.
ARTICLE 5 — SPECIFICATIONS
5.1 API Specifications. The Specifications for the API (PPC-4187, Penteracitinib) are set forth in detail in Appendix 1A to this Agreement. The API Specifications include, without limitation, the following parameters and acceptance criteria:
(a) Identity: Identification by high-performance liquid chromatography (HPLC) — retention time consistent with Reference Standard; identification by infrared spectroscopy (IR) — spectrum consistent with Reference Standard;
(b) Assay: Not less than 98.0% (w/w) by HPLC;
(c) Related Substances / Impurity Profile: Any individual specified impurity: not more than 0.15%; any individual unspecified impurity: not more than 0.10%; total impurities: not more than 0.50%;
(d) Residual Solvents: In accordance with ICH Q3C(R8), including limits for all solvents used in the final synthetic step and purification;
(e) Particle Size Distribution: As specified in Appendix 1A, determined by laser diffraction;
(f) Water Content (Karl Fischer): As specified in Appendix 1A;
(g) Heavy Metals / Elemental Impurities: In accordance with ICH Q3D(R1);
(h) Microbiological Limits: Total aerobic microbial count (TAMC): not more than 1,000 CFU/g; total combined yeasts and molds (TYMC): not more than 100 CFU/g; absence of specified organisms (including Escherichia coli) per pharmacopeial requirements.
All testing shall be performed using validated analytical methods, including pharmacopeial methods and in-house validated methods as specified in Appendix 1A.
5.2 Finished Product Specifications. The Specifications for the Licensed Products (25 mg and 50 mg film-coated tablets of Penteracitinib) are set forth in detail in Appendix 1B to this Agreement. The Finished Product Specifications include, without limitation, the following parameters and acceptance criteria:
(a) Appearance: Film-coated tablets of specified shape, color, dimensions, and markings;
(b) Identification: Identification by HPLC — retention time consistent with Reference Standard;
(c) Assay: 95.0% to 105.0% of label claim by HPLC;
(d) Dissolution: As specified in Appendix 1B, using the approved dissolution method;
(e) Uniformity of Dosage Units: Meets acceptance criteria per USP/Ph. Eur. requirements;
(f) Degradation Products: Any individual specified degradation product: not more than the limit specified in Appendix 1B; any individual unspecified degradation product: not more than 0.20%; total degradation products: not more than the total limit specified in Appendix 1B;
(g) Water Content (Karl Fischer): As specified in Appendix 1B;
(h) Microbial Limits: TAMC: not more than 1,000 CFU/g; TYMC: not more than 100 CFU/g; absence of specified organisms per pharmacopeial requirements;
(i) Dimensions: Tablet diameter and thickness within specified ranges;
(j) Hardness: Within specified range;
(k) Friability: Not more than 1.0% (w/w).
All testing shall be performed using validated analytical methods, as specified in Appendix 1B. Testing methodologies shall conform to ICH Q6A (Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products) and applicable pharmacopeial test methods.
5.3 Reference Standard Specifications. The Specifications for the PPC-4187 Reference Standards are set forth in Appendix 1C to this Agreement. Reference Standards shall be characterized by multiple orthogonal analytical methods, including nuclear magnetic resonance spectroscopy (NMR), mass spectrometry, HPLC purity determination, elemental analysis, and X-ray powder diffraction (XRPD) to confirm Crystalline Form A, as claimed in U.S. Patent No. 11,345,678.
5.4 Specification Changes. Any proposed change to the Specifications for the API, Licensed Products, or Reference Standards shall require the prior written agreement of both Parties and shall be processed through the change control procedures set forth in Article 7 of this Agreement. Prior to implementation of any Specification change, the Parties shall jointly assess the regulatory filing implications of such change in all applicable jurisdictions, including the Territory and any territories retained by Penterra. No Specification change shall be implemented until all necessary regulatory variations, supplements, amendments, or notifications have been filed or the Parties have mutually agreed to a filing timeline. All approved Specification changes shall be documented in a revised version of the applicable Appendix and distributed to both Parties.
ARTICLE 6 — DEVIATION AND CAPA MANAGEMENT
6.1 Deviation Reporting. Each Party shall promptly identify, investigate, and document any Deviation from approved processes, procedures, Specifications, or quality standards occurring at its own facility or at the facility of any of its CMOs in connection with the manufacture, testing, storage, or distribution of API or Licensed Products. Each Deviation shall be classified by the responsible Party as follows:
(a) Critical Deviation: A Deviation that has resulted in, or may have resulted in, the release of product that does not conform to Specifications or that poses a risk to patient safety;
(b) Major Deviation: A Deviation that has a potential impact on product quality, cGMP compliance, or data integrity, but has not resulted in the release of non-conforming product;
(c) Minor Deviation: A Deviation of an administrative, procedural, or documentation nature with no direct impact on product quality or patient safety.
6.2 Notification. The Party experiencing or discovering a Deviation shall notify the other Party's Quality Contact within forty-eight (48) hours of discovery if the Deviation is classified as critical, and within seventy-two (72) hours of discovery if the Deviation is classified as major. Notification shall be in writing (email to the designated Quality Contact is acceptable for purposes of initial notification) and shall include a preliminary description of the Deviation, the affected batch(es), the initial risk assessment, and any immediate containment actions taken. Minor Deviations shall be reported to the other Party in summary form at the periodic quality review meetings described in Section 12.2.
6.3 Investigation. The Party responsible for the Deviation shall conduct a thorough root cause analysis using appropriate investigation tools (e.g., Ishikawa diagram, 5-Why analysis, fault tree analysis, or equivalent systematic methodology). Root cause analysis for critical Deviations shall be completed within thirty (30) calendar days of discovery. Root cause analysis for major Deviations shall be completed within thirty (30) calendar days of discovery, unless an extension is mutually agreed upon. Investigation reports for critical and major Deviations shall be shared with the other Party within ten (10) business days of completion of the root cause analysis. The other Party shall have the right to review and comment on such investigation reports and to request additional investigation if the root cause analysis is deemed insufficient.
6.4 Corrective and Preventive Action (CAPA). Corrective and preventive actions (CAPAs) shall be identified and implemented to address the root causes of critical and major Deviations and to prevent recurrence. CAPA plans for critical and major Deviations shall be shared with the other Party for review and comment prior to implementation. Each CAPA shall include defined action items, responsible individuals, target completion dates, and effectiveness verification criteria. The responsible Party shall document the implementation and effectiveness verification of each CAPA and shall make such documentation available to the other Party upon request. CAPAs that are not effectively implemented within the agreed-upon timeline shall be subject to escalation in accordance with Section 12.3.
6.5 Impact Assessment. Each Deviation investigation shall include an assessment of the impact of the Deviation on product quality, patient safety, regulatory compliance, and data integrity, including an evaluation of the impact on previously released batches, batches in process, and batches in quarantine. Where a Deviation may affect more than one batch, the responsible Party shall identify all potentially affected batches and shall implement appropriate containment actions pending completion of the investigation.
6.6 Trending. Both Parties shall perform periodic trending of Deviations, out-of-specification results, out-of-trend results, and CAPA effectiveness data to identify systemic or recurring issues. Trending data shall be reviewed at least quarterly and shall be discussed at the periodic quality review meetings described in Section 12.2. Where trending analysis identifies a systemic issue, the responsible Party shall initiate a CAPA to address the underlying cause.
ARTICLE 7 — CHANGE CONTROL
7.1 Notification of Proposed Changes. Either Party proposing a change to any aspect of the manufacture, testing, packaging, labeling, storage, or distribution of the API or Licensed Products shall notify the other Party in writing prior to implementation of such change. Without limitation, changes subject to this Article 7 include changes to: (a) Specifications; (b) manufacturing processes (including synthesis routes, formulation, and process parameters); (c) testing and analytical methods; (d) manufacturing facilities or sites; (e) equipment (including major process equipment and critical instruments); (f) raw material, starting material, or component sources or grades; (g) packaging or labeling; (h) storage or shipping conditions; (i) key quality personnel; and (j) any other aspect of the manufacturing, testing, or quality system that may affect product quality, safety, efficacy, or regulatory status.
7.2 Classification of Changes. Proposed changes shall be classified as follows:
(a) Critical Changes: Changes that have the potential to affect product quality attributes, safety, efficacy, identity, strength, purity, or regulatory status, including but not limited to changes to synthesis routes, critical process parameters, Specifications, manufacturing sites, or primary packaging. Critical changes require the prior written approval of both Parties before implementation.
(b) Major Changes: Changes that have a potential but less significant impact on product quality, manufacturing process, or analytical methods, including but not limited to changes to non-critical process parameters, secondary suppliers, non-critical equipment, or ancillary testing methods. Major changes require prior written notification to the other Party, accompanied by a risk assessment and supporting data. The notified Party shall have thirty (30) calendar days to review and provide written comments or objections.
(c) Minor Changes: Administrative, editorial, or documentation changes with no direct or indirect impact on product quality, safety, efficacy, or regulatory status. Minor changes require notification only to the other Party, which may be provided at the next periodic quality review meeting.
7.3 Evaluation and Approval. Critical changes shall not be implemented until the written approval of both Parties has been obtained. Each Party shall evaluate proposed critical changes within thirty (30) calendar days of receipt of the change request and all supporting documentation. Meridian shall be responsible for assessing the regulatory filing impact of all proposed changes in the applicable Territory jurisdictions, including NMPA, PMDA, MFDS, TGA, and all other relevant Regulatory Authorities. Penterra shall be responsible for assessing the regulatory filing impact of all proposed changes in its retained territories. Neither Party shall unreasonably withhold, condition, or delay its approval of a proposed critical change.
7.4 Regulatory Filings. The Party responsible for regulatory submissions in the affected jurisdiction shall file all necessary variations, supplements, amendments, or notifications with the applicable Regulatory Authority before or concurrently with change implementation, as required by Applicable Laws. Each Party shall provide the other Party with copies of all regulatory submissions and approvals relating to changes processed under this Article 7 that may affect the other Party's regulatory filings or quality obligations.
7.5 Documentation. All change requests, assessments, approvals, rejections, and implementation records shall be maintained in a change control log that is accessible to both Parties. The change control log shall include, at a minimum, the change request number, description of the proposed change, classification, risk assessment, regulatory assessment, approval or rejection status, implementation date, and effectiveness verification (if applicable). Each Party shall retain change control records for the period specified in Section 13.2.
7.6 Emergency Changes. Notwithstanding the foregoing, changes that are required to address an immediate threat to product quality, patient safety, or regulatory compliance may be implemented prior to obtaining written approval of the other Party, provided that: (a) the other Party's Quality Contact is notified verbally within twenty-four (24) hours of implementation of the emergency change; (b) written notification, including a description of the change, the justification for emergency implementation, and a preliminary risk assessment, is provided to the other Party within five (5) business days; and (c) a formal change request is submitted through the change control process within five (5) business days of implementation. Emergency changes shall be reviewed retrospectively at the next periodic quality review meeting.
ARTICLE 8 — COMPLAINT HANDLING
8.1 Product Quality Complaints. Each Party shall promptly notify the other Party's Quality Contact of any product quality complaint received relating to the API or Licensed Products. Notification shall be provided within five (5) business days of receipt of the complaint, or sooner if the complaint involves a potential patient safety concern. Notification shall include a summary of the complaint, the affected product and batch number(s) (if known), and any available supporting information.
8.2 Investigation Responsibility. Investigation responsibilities for product quality complaints shall be allocated as follows:
(a) Complaints relating to API quality (including complaints regarding identity, purity, impurities, physical characteristics, or contamination of the API) shall be investigated by Penterra;
(b) Complaints relating to finished product quality (including complaints regarding dissolution, disintegration, appearance, packaging, labeling, or contamination of the Licensed Product) shall be investigated by Meridian; and
(c) Where the root cause of a complaint is uncertain or may involve both the API and the finished product, the Parties shall conduct a joint investigation, coordinated by the Party that received the complaint.
8.3 Response Timelines. The investigating Party shall provide an initial assessment of each complaint within five (5) business days of receipt. A full investigation report, including root cause analysis, impact assessment, and any corrective or preventive actions taken or planned, shall be completed and shared with the other Party within thirty (30) calendar days of receipt of the complaint. Where a complaint requires regulatory reporting, the investigating Party shall ensure that all applicable reporting obligations are met within the timeframes required by Applicable Laws.
8.4 Trending and Reporting. Both Parties shall maintain a complaint database or tracking system and shall perform periodic trending of product quality complaints to identify patterns, clusters, or emerging quality issues. Complaint summaries and trending data shall be shared between the Parties at periodic quality review meetings described in Section 12.2.
8.5 Interface with Pharmacovigilance. Product quality complaints that involve or may involve adverse events, adverse drug reactions, or other patient safety concerns shall be immediately referred to the designated pharmacovigilance contact under the Pharmacovigilance Agreement between the Parties. The quality and pharmacovigilance functions of each Party shall collaborate to ensure timely and coordinated evaluation, reporting, and follow-up of all such complaints.
ARTICLE 9 — RECALLS AND FIELD SAFETY CORRECTIVE ACTIONS
9.1 Recall Decision. Meridian shall have primary decision-making authority for recalls, market withdrawals, field safety corrective actions, and field alerts relating to Licensed Products in the Territory. Penterra shall have primary decision-making authority for recalls, market withdrawals, and field safety corrective actions relating to Licensed Products in its retained territories. Notwithstanding the foregoing, each Party shall consult with the other Party before initiating any voluntary recall or field safety corrective action, and shall give due consideration to the other Party's views regarding the scope, timing, and manner of such action. In the event that a Regulatory Authority mandates a recall, the Party subject to such mandate shall comply with the Regulatory Authority's requirements and shall promptly notify the other Party.
9.2 Notification. The Party initiating or becoming aware of a recall or field safety corrective action shall notify the other Party's Quality Contact within twenty-four (24) hours of the decision to initiate the recall or of receipt of a Regulatory Authority mandate for recall, whichever is earlier. Such notification shall include a description of the affected product and batch(es), the reason for the recall, the scope and geography of the recall, and any immediate actions taken.
9.3 Investigation. The Parties shall conduct a joint investigation to determine the root cause of any recall. Each Party shall cooperate fully and shall provide all relevant documentation, records, samples, and information necessary to support the investigation. The investigation shall be completed as expeditiously as practicable, and a written investigation report shall be prepared and shared between the Parties.
9.4 Cost Allocation. The costs and expenses associated with any recall (including without limitation logistics, transportation, storage, destruction, replacement product, customer notifications, regulatory notifications, and legal costs) shall be allocated as follows:
(a) If the recall is attributable to a defect in the API (including non-conformance with API Specifications, contamination, or manufacturing deficiency at the API manufacturing site), Penterra shall bear all reasonable and documented recall costs;
(b) If the recall is attributable to a defect in the finished product manufacturing process, packaging, labeling, storage, or distribution activities of Meridian (or its CMOs or subcontractors), Meridian shall bear all reasonable and documented recall costs;
(c) If the recall is attributable to both the API and the finished product, or if the root cause cannot be determined after a diligent investigation, the Parties shall share all reasonable and documented recall costs equally (50%/50%).
Nothing in this Section 9.4 shall limit either Party's rights to indemnification under the License Agreement or any other agreement between the Parties.
9.5 Regulatory Notification. Each Party shall be responsible for notifying the applicable Regulatory Authorities in its respective territory of any recall or field safety corrective action, in accordance with Applicable Laws and within the timeframes required by such Regulatory Authorities. Each Party shall provide the other Party with copies of all regulatory notifications and correspondence relating to any recall.
9.6 Mock Recalls. Both Parties shall conduct mock recall exercises at least once per calendar year to verify recall readiness, including the ability to identify and trace affected batches, notify distribution channels, and communicate with Regulatory Authorities. Mock recall results shall be documented and reviewed at the periodic quality review meetings described in Section 12.2. Any deficiencies identified during mock recall exercises shall be addressed through the CAPA process described in Section 6.4.
ARTICLE 10 — REGULATORY INSPECTIONS AND AUDITS
10.1 Regulatory Inspections. Each Party shall promptly notify the other Party's Quality Contact of any Regulatory Authority inspection that relates to or may affect PPC-4187 API or Licensed Products, whether conducted at such Party's own facility or at the facility of any of its CMOs. Notification shall be provided within forty-eight (48) hours of the inspection announcement or the commencement of the inspection, whichever is earlier. Such notification shall include the identity of the inspecting Regulatory Authority, the scope and nature of the inspection (e.g., routine GMP inspection, pre-approval inspection, for-cause inspection), and the scheduled or actual date(s) of the inspection.
10.2 Inspection Support. Each Party shall cooperate and provide reasonable support to the other Party during Regulatory Authority inspections, including without limitation making available relevant documentation, records, and qualified personnel for interviews and discussions with inspectors. Where an inspection at one Party's facility requires access to information held by the other Party, the Party holding such information shall use commercially reasonable efforts to provide such information in a timely manner.
10.3 Inspection Outcomes. Each Party shall promptly share with the other Party copies of all inspection observations, findings, citations, and reports received from any Regulatory Authority in connection with an inspection relating to PPC-4187 API or Licensed Products, including without limitation FDA Form 483 observations, Warning Letters, Import Alerts, NMPA inspection reports and corrective action notices, PMDA GMP inspection results, MFDS inspection findings, and TGA inspection reports. Copies of proposed responses to inspection observations shall be shared with the other Party for review and comment prior to submission to the Regulatory Authority, to the extent such responses relate to matters that may affect the other Party's operations or regulatory filings.
10.4 Right to Audit. Each Party shall have the right to audit the other Party's manufacturing, testing, packaging, labeling, storage, and distribution facilities, and those of its CMOs, to the extent related to PPC-4187 API or Licensed Products, upon reasonable prior written notice of not less than thirty (30) calendar days. Audits shall be limited to one (1) audit per calendar year per facility, unless a for-cause audit is warranted due to a critical quality issue, a Regulatory Authority action, or a significant Deviation or complaint trend, in which case the auditing Party may conduct additional audits upon reasonable notice. Each audit shall be conducted during normal business hours and shall be conducted in a manner that minimizes disruption to the audited Party's operations. The audited Party shall provide the auditing Party with reasonable access to facilities, documentation, records, and personnel. Audits shall be conducted by qualified audit personnel.
10.5 Audit of Alkerra Manufacturing Inc. Meridian shall have the right to audit Alkerra Manufacturing Inc.'s manufacturing and testing facility located at 5200 Meridian Parkway, Research Triangle Park, North Carolina 27713, upon reasonable prior written notice, to verify cGMP compliance for API manufacture and to assess the facility's compliance with the requirements of this Agreement. Penterra shall facilitate Meridian's access to Alkerra Manufacturing Inc.'s facility for purposes of such audits, and shall ensure that its quality agreement with Alkerra Manufacturing Inc. includes an appropriate audit clause permitting such access by Meridian or its designated auditors. The frequency, scope, and scheduling of audits of Alkerra Manufacturing Inc. shall be subject to the limitations set forth in Section 10.4, except that the first audit may be conducted within six (6) months of the Effective Date.
10.6 Audit Reports. The auditing Party shall prepare an audit report following each audit, which report shall include a summary of observations, findings, and any corrective action requests (CARs). The audit report shall be shared with the audited Party within thirty (30) calendar days of completion of the audit. The audited Party shall provide written responses to all audit observations and CARs within thirty (30) calendar days of receipt of the audit report. Responses shall include proposed corrective and preventive actions, responsible individuals, and target completion dates. The auditing Party shall review and provide feedback on proposed corrective actions. Implementation and effectiveness of corrective actions shall be verified by the auditing Party, either through remote review or follow-up audit.
10.7 Pre-Approval Inspections. The Parties shall cooperate to support pre-approval inspections (PAIs) by NMPA, PMDA, MFDS, TGA, and other Territory Regulatory Authorities in connection with regulatory filings for PPC-4187 Licensed Products. Each Party shall use commercially reasonable efforts to ensure that its facilities and the facilities of its CMOs are in a state of inspection readiness at all times. Penterra shall cooperate with Meridian to facilitate pre-approval inspections of the API manufacturing facility (Alkerra Manufacturing Inc.) by Territory Regulatory Authorities, including by providing access to the facility, personnel, and documentation, and by assisting with translation of documents where required.
ARTICLE 11 — ANNUAL PRODUCT QUALITY REVIEW
11.1 Scope. Each Party shall conduct an Annual Product Quality Review (APQR) for the products within its area of responsibility: Penterra shall prepare an APQR for the API (PPC-4187, Penteracitinib), and Meridian shall prepare an APQR for the finished Licensed Products (25 mg and 50 mg film-coated tablets). The APQR shall be conducted in accordance with ICH Q7 (for API), applicable cGMP requirements, and the Parties' respective quality system procedures.
11.2 Content. Each APQR shall include, at a minimum, a review of the following:
(a) a summary of all batches manufactured during the review period, including batch yield data and trending;
(b) a review of all Deviations, including classification, root cause analysis, and CAPA effectiveness;
(c) a review of all change controls processed during the review period;
(d) a summary and trending of product quality complaints;
(e) a review of stability data, including any OOS or OOT results;
(f) a review of all out-of-specification investigation results;
(g) a review of critical process parameter and in-process control data, including process capability analysis;
(h) a summary of regulatory inspection outcomes, audit observations, and corrective actions;
(i) a review of raw material and component supplier performance (for API);
(j) a review of any returned, rejected, or recalled product; and
(k) a summary of any other significant quality events or trends.
11.3 Sharing. Each Party shall share its completed APQR (or a comprehensive summary thereof acceptable to both Parties) with the other Party within ninety (90) calendar days following the end of the review period. The review period shall be the calendar year (January 1 through December 31), unless otherwise agreed in writing by the Parties.
11.4 Joint Review. The Parties shall discuss APQR findings, conclusions, and recommended actions at the periodic quality review meeting held in the first quarter of each calendar year (or at a specially convened meeting, if necessary). Action items arising from the joint APQR review shall be documented in the meeting minutes and tracked to completion.
ARTICLE 12 — QUALITY GOVERNANCE AND COMMUNICATION
12.1 Quality Contacts. Each Party shall designate a primary Quality Contact and an alternate Quality Contact for purposes of day-to-day communication and coordination under this Agreement. The initial Quality Contacts of each Party are set forth in Appendix 3. Either Party may change its designated Quality Contact(s) at any time by providing written notice to the other Party. The Quality Contacts shall serve as the primary points of contact for all quality-related matters under this Agreement, including Deviation notifications, change control communications, complaint notifications, audit scheduling, and regulatory inspection notifications.
12.2 Periodic Quality Review Meetings. The Parties shall hold periodic quality review meetings on a quarterly basis (approximately every ninety (90) calendar days). Meetings may be conducted in person, by videoconference, or by teleconference, as mutually agreed. The agenda for each periodic quality review meeting shall include, at a minimum, the following topics:
(a) review of Deviations and CAPA status (critical, major, and trending of minor);
(b) review of change controls in progress and recently implemented;
(c) review of product quality complaints and complaint trends;
(d) review of stability data and any OOS or OOT results;
(e) regulatory updates, including inspection outcomes, pre-approval inspection status, and filing activities;
(f) technology transfer progress (until completion of technology transfer);
(g) review of open action items from prior meetings;
(h) any other quality matters raised by either Party.
12.3 Escalation. Quality issues that cannot be resolved at the Quality Contact level within a reasonable period (not to exceed thirty (30) calendar days) shall be escalated to the respective Heads of Quality of each Party. If the Heads of Quality are unable to resolve the issue within an additional fifteen (15) calendar days, the issue shall be further escalated to the Joint Steering Committee (JSC) established under Article 3 of the License Agreement, which JSC comprises three (3) representatives from each Party. The JSC shall endeavor to resolve escalated quality issues in good faith within thirty (30) calendar days. Disputes that cannot be resolved through escalation shall be subject to the dispute resolution provisions of Article 17.2 of this Agreement.
12.4 Ad Hoc Communications. Either Party may request ad hoc quality meetings or communications at any time to address urgent quality matters, emerging issues, or matters that cannot reasonably await the next scheduled periodic quality review meeting. The other Party shall use commercially reasonable efforts to accommodate such requests on a timely basis.
12.5 Meeting Minutes. Minutes of each periodic quality review meeting and each ad hoc quality meeting shall be prepared by the Quality Contact of the hosting Party (alternating between the Parties for periodic meetings) and shall be circulated to all attendees and the Quality Contacts of both Parties within ten (10) business days following the meeting. Meeting minutes shall include a summary of topics discussed, decisions reached, and action items assigned (including responsible Party, responsible individual, and target completion date). Action items shall be tracked to completion and reviewed at each subsequent periodic quality review meeting until closed.
ARTICLE 13 — DOCUMENTATION AND RECORD RETENTION
13.1 Documentation Standards. All quality documentation prepared, reviewed, approved, and maintained by either Party in connection with this Agreement shall comply with cGMP requirements and applicable data integrity standards, including the ALCOA+ principles (Attributable, Legible, Contemporaneous, Original, Accurate; plus Complete, Consistent, Enduring, and Available). Each Party shall maintain documented standard operating procedures governing the creation, review, approval, revision, and archival of quality records. Electronic records and electronic signatures shall comply with 21 CFR Part 11 and applicable Territory regulations governing electronic records and electronic signatures.
13.2 Record Retention. Records relating to API manufacture and supply (including batch production records, testing records, stability data, Deviation investigations, CAPA records, change control records, complaint records, and audit reports) shall be retained by Penterra for at least ten (10) years after the expiry date of the last batch manu

QUALITY AGREEMENT

PENTERRA PHARMACEUTICALS CORP.

MERIDIAN BIO THERAPEUTICS LIMITED

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