Supplier and Supply Chain Qualification and Supply Chain Verification Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group

Life Sciences Innovation Forum - Regulatory Harmonization Steering Committee (LSIF-RHSC)

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Agenda

• Supplier and Supply Chain Qualification

– Introduction

– Classification of Suppliers and materials

– Quality assessment

– Ongoing monitoring and evaluation

• Supply Chain Verification

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Agenda

• Supplier and Supply Chain Qualification

– Introduction

– Classification of Suppliers and materials

– Quality assessment

– Ongoing monitoring and evaluation

• Supply Chain Verification

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Good Distribution Practice (GDP) Good Manufacturing Practice (GMP)

Patient

An Overview of the Supply Chain

• Challenges – Well regulated, however complex due to domestic / regional requirements – Many hand overs as of different material owners – Demands, Safety stocks, shelf life – Economic and business aspects

API Starting material

Drug Substance & Excipients

Drug Product Packaging Warehouse

Distribution Affiliates Wholesaler Pharmacy

Supply Chain Management

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Aims Selecting suppliers that can consistently

provide materials of the required

SISE QP

Identify

Strength

Efficacy

Quality

Purity

Safety

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Scope • API • API starting materials • Excipients • Intermediate and bulk

products • Primary/Secondary

packaging materials

Materials

• Wholesale distributor • Computer system provider • Validation and qualification

specialists • Contract laboratory

Service provider

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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References to supplier management in PIC/S GMP

1.0 The attainment of quality objective

• Senior management

• Staff in many different departments and at all levels

• Company’s suppliers

• Distributors

2.9 Responsibilities of the heads of Production and Quality Control

• The approval and monitoring of suppliers of materials

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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References to supplier management in PIC/S GMP

4.14 Specifications for starting and primary or printed packaging materials

• A description of the materials, including the approved suppliers

4.23 The records of the receipts should include

• Name of suppliers and manufacturer…

4.29 Supplier audits • Written policies,

procedures, protocols, reports and the associated records of actions taken

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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5.25/5.26 Purchase of starting materials

• Should involve staff who have a particular and thorough knowledge of the suppliers

• Purchased from approved suppliers named in the relevant specification

• Purchased directly from the producer

• Specifications established discussed with the suppliers

5.26 All aspects of the production and control of the starting material in question

• Procedures should be documented in a formal quality agreement or specification.

• Discussed with the manufacturer and the supplier

References to supplier management in PIC/S GMP

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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References to supplier management in PIC/S GMP Annex 11

COMPUTERISED SYSTEMS

• When suppliers and services provider are used to provide, modify or retain a computerised system or related service or for data processing, formal agreements must exist

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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References to supplier management in PIC/S GMP 5.2 Qualification of

suppliers • Wholesale distributor

should possess authorisation.

• Appropriate qualification and approval of suppliers should be performed.

• Carry out due diligence checks before entering a new contract with supplier

5.3 Qualification of customers

• Customers should possess authorisation to supply drug to public.

• Periodic rechecks customers authorisation.

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Agenda

• Supplier and Supply Chain Qualification

– Introduction

– Classification of Suppliers and materials

– Quality assessment

– Ongoing monitoring and evaluation

• Supply Chain Verification

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Classification of Materials Level of regulations on GMP according to risk

Secondary Packaging materials

Primary packaging, Printed packaging

materials

Critical

Minor

Leve

ls o

f Ris

k

Major

APIs

Moderate

Starting Material

Excipients

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Classification of Suppliers(supply chain)

Distributors

Materials Manufacturers

User

Agents

Trader

Broker

Low Risk

High Risk of Mix-up Repackaging Relabeling

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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1 = Well established company or a company that is already a supplier/Buy Direct from Manufacturers 5 = Unknown technical competence company / Buy from Agency

Risk Assessment Matrix Example

Risk of material

1

2

5

3

4

A B C Ris

k of

Sup

ply

Cha

in

Low High API Packaging

materials Excipients

High Increasing Requirement of Evaluation

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Agenda

• Supplier and Supply Chain Qualification

– Introduction

– Classification of Suppliers and materials

– Quality assessment

– Ongoing monitoring and evaluation

• Supply Chain Verification

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Evaluation Procedure of Suppliers Questionnaire on GMP & Document review

On-site audit

Approved

Quality agreements

Testing of sample

Approved with conditions Reject

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Questionnaire

Quality system

GMP compliance (where applicable)

Manufacturing conditions

Understanding of Suppliers (Manufacturer or Agents)

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Opportunity for a harmonized Questionnaire • Design of questionnaire

– Follow Annex II of Annex 20 of the PIC/S GMPs (Annex II in ICH Q9)

• Documentation requirement – Specifications and analytical test method (Certificate of Analysis) – Manufacturing/packaging/labelling details – Materials Safety Data Sheets (MSDS) – Certificates regarding Quality system, residual solvents, etc... – BSE/TSE evaluation, if applicable

• Status of manufacturers – Manufacturing/establishment license(where applicable), GMP

Certificate, ISO Certificate – History of GMP compliance and inspection history (where applicable) – Manufacturing single product or multiple product – Manufacturing specific product (e.g., high sensitizing product , other

products posing a high cross contamination risk)

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Testing of Sample • Materials should be tested for critical quality attributes

and include both chemical and microbiological tests.

• Test data will be evaluated to determine if the Materials conforms to the acceptance criteria provided by the supplier as well as to USP, EP, and/ JP compendia, and the drug product manufacturer’s specifications.

• The reported result should be compared to the materials supplier’s acceptance criteria for determining compliance to the specification and or certificate of analysis claim(s).

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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On-Site Audit Auditor Strategy

QA/QC/Production department/QP

Auditors training

Auditors Qualification

Join Audit or Contract Third Party

Risk-Based Approach

Check List Use

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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On-Site Audit: Criteria

Quality management

Personnel

Facilities &Equipment

Documentation & Records

Materials

Production & IPC

Packaging

Storage & Distribution

Laboratory control

Consider environmental, Health and safety aspects and business continuity

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Results of Assessment and Rating • Completely satisfactory

– Material status: Approval – Fully flexible use of material

• Mainly satisfactory – Material status: Conditional approval – Ongoing supply with well defined increased oversight and/or

restricted supply

• Partially satisfactory – Material status: Quarantine – Quarantine with no supply until corrective actions are

implemented

• Not satisfactory – Material status: Reject – Supplier disqualified or no supply until actions are implemented

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Quality Agreements (1) • Reliability of supply

• GMP standards and specifications to be met

• Documentation including completeness and accuracy of certificates of analysis, GMP certificates, labelling.

• Transportation and monitoring of transport conditions

• Particular attention should be given to suppliers of printed packaging materials with respect to security and this should include how waste is controlled

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Quality Agreements (2) • Communication of notifiable events (e.g. complaints,

recalls, changes, inspection findings, out of specification investigations)

• Access rights to conduct on-site audits as applicable

• Responsibilities and accountabilities of both parties

• Governance over sub-contracting

• Prompt investigation of quality issues identified by the purchaser

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Agenda

• Supplier and Supply Chain Qualification

– Introduction

– Classification of Suppliers and materials

– Quality assessment

– Ongoing monitoring and evaluation

• Supply Chain Verification

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Ongoing Monitoring • Specification (results on certificate of analysis and own

results)

• Statistical Evaluation of Quality Control data for critical parameters (if applicable) to identify any adverse trends

• Product Quality Review (trend analysis)

• Packaging, sealing, labelling

• Number of Customer complaints, rejected batches

• Delivery dates and quantities

• Certificates and other documents

• Other aspects

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Periodic Evaluation (Re-Audit) • The decision for auditing/re-auditing suppliers should be

risk based,

• The frequency of the re-audit should by dynamic and depending on the risk rating. Example: – Completely satisfactory: 5 years – Mainly satisfactory: 3 years – Partially satisfactory: 1 year

• In the case of serious complaints, unsatisfactory response on remediation plans or any doubts with respect to conformance with the respective technical/quality agreement

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Periodic Evaluation • Regulatory or GMP/compliance issues(where

appropriate) • Conformance with respective technical/quality

agreement • Periodic full testing of material • Assessment of changes • Reaction on audit and remediation plan (if audit had

taken place)

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Agenda

• Supplier and Supply Chain Qualification

– Introduction

– Classification of Suppliers and materials

– Quality assessment

– Ongoing monitoring and evaluation

• Supply Chain Verification

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Supply Chain Verification • Aims

– Ensure that each incoming delivery has been sourced from the approved manufacturer through the approved and monitored supply chain

• Verification methods – Scrutiny of all delivery: customs documentation, certificates

of analysis, material itself, etc. – Compared to previous shipments – Personnel involved in goods receiving should be trained

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Supply Chain Verification • Materials obtained through agents, brokers, traders,

distributors, re-packers and re-labellers should provided documentation – Name and address of the original manufacturer and other

parties involved in the supply chain – Purchase orders – Bills of lading and other transportation documents – Authentic certificates of analysis including those of the

original manufacturer

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Example-Double check (during receiving material)

- Purchase Order - Approved Supplier List

COA from API Manufacturer

Label on the container

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Example - Repackaging Critical point - Mix-up - Cross contamination - Lack of detail information for label

Roadmap for Global Medical Product Integrity and Supply Chain Security Manufacturing Practices Work Group: SUPPLY CHAIN VERIFICATION

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Conclusion: Implement GMP / GDP

Incoming delivery has been sourced from the approved manufacturers

Received through the approved and monitored supply chain

Supplier and Supply Chain Qualification

Supply Chain Verification