Transcript
Quality Risk Management: Excipients
ExcipientFest 2012
Presented by:
Londa Ritchey, M.S.
Director, Supplier Qualification
Global Quality Operations
Pfizer, Inc.
Agenda
•Regulatory Environment
•Material Quality System Elements
•On-Going Monitoring
•Risk Management Summary
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Integration of QRM into
Material Quality Systems Requirements
Note: This is one Pharma User’s perspective
Today’s Focus
Why Focus on Ingredients?
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Regulatory expectations of Ingredient Safety are evolving
Distributor Warehouse
Supplier-Original Mfg
Pharma production site Repacker
Supplier’s Suppliers
Supplier’s Suppliers
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
Increased Regulatory Expectation
Capture Material Supply Channels On Site Audits of Material Suppliers
Quality Agreements with Critical Material Suppliers
Quality Risk Management Security of the Supply Channel
Material Supply Channel Expectations
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
Evaluation &
Approval of Suppliers
Evaluation &
Approval of Materials
Acceptance Criteria
Receipt and Inspection
Inventory Control
Storage
Sampling and Testing
Retain Management
Destruction
Procedural Controls
Training/ Qualification
GMP Documentation
Investigations
Change Management
Computerized Systems Validation
Monitoring
CAPA
Management Review
Robust Quality System Pre- Use
Use Period
Post- Use
Cor
e R
equi
rem
ents
IC
H Q
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Pharma User- Material System
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
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Capturing Supply Channels
Sub-roles for Processor
Each supplier must have a qualification status prior to Approval of Supply Channel
Note: The data shown here has been created solely for the purposes of presenting an example
and does not reflect confidential supplier data
Essential to
understanding Material, Supplier and Supply
Channel risks
Material Qualification
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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 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
Supplier Approval
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1. Evaluate Pre-Qualification Risk Profile • Security Questionnaire • Pre-Audit Questionnaire • Business intelligence
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
9. Continuous improvement initiatives
10. Supplier Quality Metrics review
11. Re-assessments of supplier status - max. frequency
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
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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?
Sample Audit Questions-SCS
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Quality Agreement
Considerations • 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 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.
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)
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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
Receipt and Inspection
Observe & Report
Provide Overall Economic Adulteration Awareness Training
Sampling and Testing The number of containers to be sampled should consider
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
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Note, When accepting test results from a Supplier’s CoA, The Supplier also becomes a Contract Laboratory
component attribute variability degree of precision desired past quality history of the supplier confidence levels quantity needed for reserve where required material risk profile information quantity needed for analysis and
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
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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
Retains and Destruction 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
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On-going Monitoring
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
E-systems enable information sharing &
alerts regarding supplier performance
Signals for change in Risk Profile
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
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
Quality Event Risk Evaluation
Documented
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
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