dimitris catsoulacos - quality assurance; gmp, gdp, apis

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UNICEF’s Quality Assurance System for Procurement of Finished Pharmaceutical Products UNICEF Industry Consultation with Manufacturers and Suppliers of Finished Pharmaceutical Products 29 th 30 th September 2016, Supply Division, Copenhagen Dimitris Catsoulacos Quality Assurance Specialist

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Page 1: Dimitris Catsoulacos - Quality Assurance; GMP, GDP, APIs

UNICEF’s Quality Assurance System for

Procurement of Finished Pharmaceutical

Products

UNICEF Industry Consultation with Manufacturers and

Suppliers of Finished Pharmaceutical Products29th – 30th September 2016, Supply Division, Copenhagen

Dimitris Catsoulacos – Quality Assurance Specialist

Page 2: Dimitris Catsoulacos - Quality Assurance; GMP, GDP, APIs

Source: UNICEF Supply Division

CONTENT

• UNICEF’s Quality Assurance System

• Pre- Qualification Activities

• Good Manufacturing Practice Inspections & Findings

• International Collaboration on Good Manufacturing Practice

• UNICEF’s Warehouse and Good Distribution Practice

Page 3: Dimitris Catsoulacos - Quality Assurance; GMP, GDP, APIs

Source: UNICEF Supply Division

UNICEF’S QUALITY ASSURANCE

SYSTEM• WHO “Model Quality Assurance System for Procurement Agencies

MQAS” - TRS 986 Annex 3

• Pharmaceutical Inspection Cooperation Scheme (PIC/S) principles on Quality System Requirements for GMP Inspectorates

• Good Distribution Practice- WHO Good Distribution Practices for Pharmaceutical Products. TRS 957, Annex 5

- European Union Guidelines of 5th November 2013 on Good Distribution

Practice of medicinal products for human use

• Documentation system in place- Quality manual- Division procedures- Centre procedures

* All procurement activities are centralized in UNICEF Supply Division (procurement by UNICEF country offices requires authorization)

Page 4: Dimitris Catsoulacos - Quality Assurance; GMP, GDP, APIs

Source: UNICEF Supply Division

PRE-QUALIFICATION ACTIVITIES

Medicinal Products

Product Questionnaire as in WHO “Model Quality Assurance System for Procurement Agencies MQAS” - TRS 986 Annex 3

Manufacturers/ Suppliers

• Review of Good Manufacturing Practice information:• - Technical Questionnaire• - Manufacturing license• - GMP certificates• - Site Master File• - Recent Inspection Reports

Contract Manufacture is accepted if both the manufacturer and the sub-contractor are approved by UNICEF

Page 5: Dimitris Catsoulacos - Quality Assurance; GMP, GDP, APIs

Source: UNICEF Supply Division

GMP INSPECTIONS

Plan Performance Report

• Agree on inspection date

• Request Site Master File

• Request Manufacturing License/ Authorization

• Provide inspection plan in advance

• Extend invitation to local authority

• On site inspection performed by UNICEF inspector or qualified UNICEF representative

• Verify compliance with WHO GMP Guidelines

• GMP inspection report within 3 weeks of inspection date

• Manufacturer’s response/CAPA plan expected within 1 month of inspection report receipt.

• Official closing letter

Decision making process- Evaluation of GMP information- Regulatory framework in the country where the manufacturer is located- Prior UNICEF experience

Page 6: Dimitris Catsoulacos - Quality Assurance; GMP, GDP, APIs

Source: UNICEF Supply Division

INSPECTIONS – KEY FACTS

• 133 GMP inspections carried out 2011 - 2015

• 24 manufacturers found GMP non-compliant

• Re- inspection based on a risk based approach (frequency 2-5 years)

• Annual inspection plan established

2011

2012

2013

2014

2015

0

5

10

15

20

25

30

35

40

45

18 13

16

41

45

Page 7: Dimitris Catsoulacos - Quality Assurance; GMP, GDP, APIs

Source: UNICEF Supply Division

MOST FREQUENTLY ENCOUNTERED

DEFICIENCIES PER CATEGORY (1)

• QUALITY MANAGEMENT

- Quality risk management principles not fully implemented

- Poor handling of changes, deviations

- Weak investigations – poor CAPA implementation

- Incomplete Product Quality Reviews

• ORGANIZATION AND PERSONNEL

- Senior management responsibilities not well defined

- Training in product release poorly documented

- Training in aseptic procedures

Page 8: Dimitris Catsoulacos - Quality Assurance; GMP, GDP, APIs

Source: UNICEF Supply Division

MOST FREQUENTLY ENCOUNTERED

DEFICIENCIES PER CATEGORY (2) • FACILITIES

- Poor separation between controlled and non-controlled areas- Inappropriate construction materials – poor maintenance - Incorrect flow of personnel and materials - Risk of cross-contamination between penicillins and cephalosporinsdue to facility design- Double standard facilities - local vs export market

• EQUIPMENT - UTILITIES- Inappropriate design and qualification of HVAC system – Unknown airflow patterns - Air re-circulation without HEPA filtration - Incomplete validation/ qualification/ calibration of production equipment

Page 9: Dimitris Catsoulacos - Quality Assurance; GMP, GDP, APIs

Source: UNICEF Supply Division

MOST FREQUENTLY ENCOUNTERED

DEFICIENCIES PER CATEGORY (3)

• PRODUCTION

- Manufacturing process not validated or not validated for all batch sizes

- Incomplete maintenance and cleaning records – line clearance

- Media Fills

• QUALITY CONTROL

- Incomplete analytical method validation

- Poor qualification and control of API suppliers

- On-going stability not always carried out

- Establishment and handling of working standards

Page 10: Dimitris Catsoulacos - Quality Assurance; GMP, GDP, APIs

Source: UNICEF Supply Division

INTERNATIONAL COLLABORATION

ON INSPECTIONSUNICEF relies on WHO PQ of vaccines, HIV, Malaria and TB products

Joint inspections with WHO PQ, ICRC, MSF

UNICEF is a Partner to the Pharmaceutical Inspection Cooperation Scheme (PIC/S)

UNICEF shares inspection reports and information with internationalpartners and vice versa

GMP reports and information from partners is used to prioritize and insome cases to waive GMP inspections

Good Manufacturing / Good Distribution Practice - Training

It is expected that manufacturers that are found GMP non-compliant byUNICEF partners inform UNICEF immediately.

Page 11: Dimitris Catsoulacos - Quality Assurance; GMP, GDP, APIs

Source: UNICEF Supply Division

UNICEF SUPPLY DIVISION

WAREHOUSE

UNICEF SUPPLY DIVISION

• holds an Emergency Relief Authorization issued by the DanishHealth and Medicines Agency

• is legally authorized to procure, hold, supply and exportmedicinal products including narcotics and psychotropics

• has to comply with Danish and EU Pharmaceutical Legislation –Compliance with EU Good Distribution Practice Guidelines

• operations subject to repeated inspections by the Danish Healthand Medicines Agency

Page 12: Dimitris Catsoulacos - Quality Assurance; GMP, GDP, APIs

Source: UNICEF Supply Division

UNICEF SUPPLY DIVISION

WAREHOUSE – GDP OPERATIONS (1)

• Personnel Training

GDP training sessions – Written evaluation – Records

• Premises and Equipment

Authorized access only

Cleaning programmes – Preventive pest control - Records

Appropriate storage conditions –Temperature and Humidity monitoring

Qualification, calibration and maintenance of equipment – Records

Page 13: Dimitris Catsoulacos - Quality Assurance; GMP, GDP, APIs

Source: UNICEF Supply Division

UNICEF SUPPLY DIVISION

WAREHOUSE – GDP OPERATIONS (2)

• Receipt

Cleaning - Barcode verification – Special Storage Conditions

Visual inspection – Product – Dosage Form – Strength – Quantity

Packing List – Certificate of Analysis – Manufacturer – Expiry date

• Storage - Picking

Electronic allocation of storage position

Special Storage Conditions – Cold Room

First Expiry – First Out principles

Electronic system controls for product picking and expiry date

Page 14: Dimitris Catsoulacos - Quality Assurance; GMP, GDP, APIs

Source: UNICEF Supply Division

UNICEF SUPPLY DIVISION

WAREHOUSE – GDP OPERATIONS (3)

• Complaints - RecallsComplaints Database – Investigations – CAPA

Recall procedure – Instructions – Records

• Self – inspectionsPlan – Records – CAPA

• Annual Sampling and Testing ProgrammeSelection of products based on risk factors - experience

Quality Control performed by contract laboratories (WHO prequalified)

* Pre-Delivery Inspections of Direct ShipmentsThird party/ Country Office

Visual controls – Random sampling

Page 15: Dimitris Catsoulacos - Quality Assurance; GMP, GDP, APIs

Source: UNICEF Supply Division

MOST FREEQUENTLY ENCOUNTERED

DISCREPANCIES AT GOODS RECEIPT

• No packing list

• Missing certificate of analysis

• Loose labels on primary containers

• No package leaflet

• Certificate of analysis does not state the manufacturing site

• Very short remaining shelf life

Page 16: Dimitris Catsoulacos - Quality Assurance; GMP, GDP, APIs

Source: UNICEF Supply Division

STORAGE CONDITIONS DURING TRANSPORT

GDP Requirements

• Storage conditions for medicinal products should be maintained during

transportation within the defined limits as described by the

manufacturers

• Risk assessment of delivery routes should be used to determine where

temperature controls are required

• Equipment used for temperature monitoring during transport should be

maintained and calibrated at regular intervals

All manufacturers/suppliers will be requested to start documenting correct

shipment conditions

Page 17: Dimitris Catsoulacos - Quality Assurance; GMP, GDP, APIs

Source: UNICEF Supply Division

Thank you for your attention

Any Questions?