dimitris catsoulacos - quality assurance; gmp, gdp, apis
TRANSCRIPT
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
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)
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
•
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
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
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
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
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
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.
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
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
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
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
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
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
Source: UNICEF Supply Division
Thank you for your attention
Any Questions?