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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