Quality Risk Management: Excipients

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Gilbert Richard
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1 Quality Risk Management: Excipients ExcipientFest 2012 Presented by: Londa Ritchey, M.S. Director, Supplier Qualification Global Quality Operations Pfizer, Inc.

2 Agenda Regulatory Environment Material Quality System Elements On-Going Monitoring Risk Management Summary 2

3 Today s Focus Integration of QRM into Material Quality Systems Requirements Note: This is one Pharma User s perspective 3

4 Why Focus on Ingredients? Regulatory expectations of Ingredient Safety are evolving 4

5 Increased Regulatory Expectation Quality Risk Management Security of the Supply Channel On Site Audits of Material Suppliers Capture Material Supply Channels Quality Agreements with Critical Material Suppliers Supplier s Suppliers Supplier- Original Mfg Repacker Distributor Warehouse Pharma production site Supplier s Suppliers Material Supply Channel Expectations Capture each material Supply chain to each pharma location Capture each Supplier and Role for each material Each Party in the Supply Channel evaluated against the appropriate quality standard

6 Quality Systems Guidance Management of Outsourced Activities and Purchased Materials- ICH Q10- Section 2.7 (a) Assessing.the suitability and competence to carry out the activity or provide the material using a defined supply chain (e.g., audits, material evaluations, qualification); (b) Defining the responsibilities and communication processes for quality related activities of the involved parties. (c) Monitoring and review of the quality of the material from the supplier, and the identification and implementation of any needed improvements; (d) Monitoring incoming ingredients and materials to ensure they are from approved sources using the agreed supply chain. Quality Risk Management- ICH Q9

Material System Elements Pre- Use Pharma

7 Material System Elements Pre- Use Pharma User- Material System Use Period Post- Use Robust Quality System Evaluation & Approval of Materials Evaluation & Approval of Suppliers Receipt and Inspection Sampling and Testing Retain Management Destruction Procedural Controls Training/ Qualification GMP Documentation Investigations Computerized Systems Validation Core Requirements Acceptance Criteria Inventory Control CAPA Monitoring Change Management Management Review ICH Q10 Storage

8 Managing Material Sourcing Risks Material Risks Material Precursors Origins of the material BSE/TSE, GMO Allergens, Residual solvents other material source risks Process capability, CQA defined Specificity of test method, Incentive/demand Supplier Risks Primary industry serviced, Pre-audit Quality assessment, Audit rating, Category sourced Country of Mfg Quality History Quality Agreement Open CAPA Control of starting materials Quality Culture Supply Channel Risks Transparency Number of parties in SC Repackaging /Relabeling Tamper Evidence Original Mfg CoA, other documentation Transportation qualification Associated Parties- direct access 8

solely for the purposes of presenting an example and does not reflect confidential

9 Capturing Supply Channels Essential to understanding Material, Supplier and Supply Channel risks Sub-roles for Processor Note: The data shown here has been created solely for the purposes of presenting an example and does not reflect confidential supplier data Each supplier must have a qualification status prior to Approval of Supply Channel

Collect and review material risk data Material Sourcing Questionnaires GMP Pre-audit assessment Security Allergens, GMO BSE/TSE Residual Solvents Other General Material Questions Material Supply

10 Collect and review material risk data Material Sourcing Questionnaires GMP Pre-audit assessment Security Allergens, GMO BSE/TSE Residual Solvents Other General Material Questions Material Supply Channel Survey Know Critical Quality Attributes of Material Material Qualification Understand Process Capability/normal process variability for Material Understand Stability of Material Share Intended Pharmaceutical use with Supplier Qualify material in process and stability System for Material Approval should include review and acceptance of Material Supply Channel 10

11 1. Evaluate Pre-Qualification Risk Profile Security Questionnaire Pre-Audit Questionnaire Business intelligence Supplier Approval 9. Continuous improvement initiatives 10. Supplier Quality Metrics review 11. Re-assessments of supplier status - max. frequency 2. Quality Systems Audit 3. Quality Agreement 4. Risk Control plan for outstanding concerns 5. Document Approval decision 6. Monitor compliance to specifications, QA and MFG standards 7. Complaints/CAPA management and trending 8. Notification Management- change, Quality, other 11

12 Supplier Audit Considerations Auditor(s) focus on material category and Pre-Qualification Risk Profile Re-audit frequencies based on: Material type On-going risk profile Performance history Document specific Supply Channel Management reviews Review Changes since last audit Audit specific role of Supplier in Supply Chain GMP, GDP, GIP Elevate significant findings immediately for management review Update Risk profile and create risk control plan as needed Sample Audit Questions-SCS SUPPLY CHAIN SECURITY Is there a supply chain security program/plan? Is there awareness / sensitivity around the importance of supply chain security? Do they have procedures and processes in place to prevent supply chain related adulteration, diversion, and counterfeiting? Are there procedures in place to respond to supply chain related events? Is there a good supplier quality management program (selection, oversight, etc.) that incorporate supply chain risks? Are there effective processes and databases for supply chain transparency? Do the supplier quality management principles extend to warehousing and transportation providers? Are any processes in place to gather supply chain related intelligence from the market? 12

13 Cover the supply channel parties for Ingredient materials with Agreements Agreements with all Distributors and Repackers of Ingredients Template language to include security provisions Define roles/responsibilities/ communication pathways Change notifications, quality events, etc Subcontractor and supplier controls Approval signifies Acknowledgement that material is used for a pharmaceutical product intended for human consumption. Sample Supply Chain Integrity provisions for agreement Quality Agreement Considerations Supplier shall utilize tamper evidence packaging. Supplier shall provide identifying information on tamper evidence device(s) as requested. Supplier shall maintain knowledge of the original manufacturers of each critical material used in the production and packaging of Material intended for Customer. Supplier shall Qualify transportation services/carriers contracted by Supplier to distribute Material to customer, as relates to maintaining the quality and integrity of the Material enroute to Customer. 13

14 Acceptance Criteria Formal agreement on specifications for materials May be documented in a quality agreement, specification agreement, or material approval document Critical quality attributes for materials should be defined based on Use- specifications should include these Change Management required for specifications Quality Agreement includes change notification requirements Understand packaging (including tamper evidence) and shipping requirements for materials Retest or expiry dating from Supplier should be justified by data (and documented) 14

Receipt and Inspection OBSERVE Keep a general awareness of material drums and package appearance, for example: color, size, closure, label, container markings tamper evidence

Subtle or obvious damage to container(s) Change in receiving paperwork, CoA, CoC, Bill of Lading, other certifications, etc.

15 Receipt and Inspection OBSERVE Keep a general awareness of material drums and package appearance, for example: color, size, closure, label, container markings tamper evidence device If there is a tamper evidence device, is it intact? Subtle or obvious damage to container(s) Change in receiving paperwork, CoA, CoC, Bill of Lading, other certifications, etc. REPORT Any person who notes a discrepancy has the responsibility to report it to a Supervisor Review the finding as soon as possible with QA Use pictures to capture discrepancies, if possible. Document and follow-up with the supplier for clarifying discrepancies Observe & Report Provide Overall Economic Adulteration Awareness Training 15

16 The number of containers to be sampled should consider Sampling and Testing component attribute variability past quality history of the supplier quantity needed for reserve where required degree of precision desired confidence levels material risk profile information quantity needed for analysis and The tests performed should be consistent with risk profile. High Risk materials- may require additional tests or samples Use Information from the Material Risks Questionnaires Additional Surveillance testing may be needed for Supply Chain Security risks Material Test Method specificity Impurity Monitoring Discrepancies should be investigated and notification to Supplier Trending of discrepancies/abnormalities and review with management Note, When accepting test results from a Supplier s CoA, The Supplier also becomes a Contract Laboratory 16

17 Inventory Control and Storage Monitored & secure inventory. Documented material use Reconciliation procedures & investigations for out of tolerance reconciliation( +/-) Bags or boxes shall be stored off the floor Material shall be handled and stored in a manner to prevent contamination Segregated areas should be provided for the storage of rejected, recalled or returned materials Review of pallets composition to assure no TBA issues Storage area monitored for temp, humidity. Alarms, investigation for out of tolerance. Must be electronic or physical segregation of materials in different status 17

Retains stored under storage conditions listed on original material label Stored in limited access area Destruction of retains past defined

shall be identified and controlled under a quarantine system designed to prevent their use.

18 Retains stored under storage conditions listed on original material label Stored in limited access area Destruction of retains past defined retain period Stored in packaging consistent/similar in composition to material package at receipt Retains and Destruction Rejected components, shall be identified and controlled under a quarantine system designed to prevent their use. Rejected materials and products should be clearly marked as rejected and stored separately in restricted areas. They should either be returned to the suppliers or, where appropriate, reprocessed or destroyed

Notifications Quality Agreement Conformance Timely & Adequate Response, Trends Preventative Focus,

19 On-going Monitoring Signals for change in Risk Profile Supplier Performance E-systems enable information sharing & alerts regarding supplier performance Complaints CAPA Change Management Quality Notifications Quality Agreement Conformance Timely & Adequate Response, Trends Preventative Focus, On-time Prior to Change Quality Mgmt Timely Notices Quality Event Analysis Operation & Notifications as Agreed 19

20 Embedded Quality Risk Management Supplier Selection -risk evaluations SCS risks, Quality risk, Business risk, EHS risk Document quality agreement or audit refusals Evaluate Quality Issues Notifications coming from supplier Material Shortage notifications Known material adulteration events Critical Industry events Quality Event Risk Evaluation 1) Impact to patient safety and compliance 2) Impact to product released, materials in warehouse, next incoming receipt 3) Possible mitigations 4) Initial use of or continued use decision 5) Quality Management approval QP as applicable Documented

21 In Summary. Define requirements for Material Quality System in Procedures Procedures should embed steps for risk evaluation and decision points Continuous monitoring of risk profile is needed GMP Documentation required for each quality system step and risk decision Procedures should require investigation of discrepancies Embed Quality Risk Management into Supplier Quality Management Systems 21

Annex 6. Good trade and distribution practices for pharmaceutical starting materials

Annex 6. Good trade and distribution practices for pharmaceutical starting materials Annex 6 Good trade and distribution practices for pharmaceutical starting materials Introduction 212 1. Quality management 213 2. Organization and personnel 214 3. Premises 215 4. Procurement, warehousing