Download - 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

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


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)


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

•


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


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


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



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



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


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.


UNICEF SUPPLY DIVISION

WAREHOUSE


• 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



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




• 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




• 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


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


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


Thank you for your attention

Any Questions?

Download - Dimitris Catsoulacos - Quality Assurance; GMP, GDP, APIs

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