1. Pharmaceutical Quality System in regard to Good Engineering Practice
Quality Director, R-Pharm GC
T.M. Vyazmina

2. Normative documents
Council of the Eurasian Economic Commission Resolution as of No. 77 “Concerning approval of  the Good manufacturing practice of EAEU”
Order of the Ministry of Industry and Trade of the RF as of 14 June, 2013 No.916 “On the Approval of Good Manufacturing Practice Rules”
ISPE Good Engineering Practice Guidelines
GOST R National standard of the Russian Federation. Manufacturing of medicinal products. Manufacturing systems and equipment for the production of medicines. General requirements.
ISPE Heating, Ventilation and Air Conditioning Guidelines
ISPE Process Gases Guidelines
ISPE “Pharmaceutical Engineering Guides for New and Renovated Facilities. Oral solid dosage form” Guidelines
ISPE “Pharmaceutical Engineering Guides for New and Renovated Facilities. Sterile Product Manufacturing Facilities” Guidelines
ISPE “Pharmaceutical Engineering Guides for New and Renovated Facilities. Water and Steam Systems” Guidelines
ISPE “Commissioning and Qualification of Pharmaceutical Water and Steam Systems” Guidelines

3. GEP definition GEP (Good Engineering Practice).
Established engineering procedures and standards used throughout the whole ‘lifecycle’ of the project for the purpose of getting cost-effective solutions.
System used by the qualified personnel for the implementation of individual solutions, and documentary support of the latter, which allows to track the events from customer’s demands to the final project (design). GEP documentation studies the goal, parties responsible, references, suppositions, calculation methods, conclusions and impact on other sides of the project (design). Requirements of Good Engineering Practice take in account industry-driven activities, performance specifications and safety requirements, as well as economic and normative requirements.
GEP guarantees that technical (engineering) project satisfies the customer’s requirements, is cost-effective, meets the norms, regulatory requirements and has explicit documentary support.
At the same time, philosophy, principles and approaches, engineering methods and standards related to technological equipment, engineering systems, clean rooms are applied throughout the whole lifecycle of the project.

4. Relation to other ISPE documents
ISPE guidelines
ISPE GAMP: Validation of process control systems
ISPE Guide: Commissioning and qualification
Critical engineering systems
ISPE Guide:
HVAC systems
ISPE Guide: Maintenance
ISPE Guide: Pharmaceutical engineering for new and renovated facilities
Good engineering practice

5. Regulation and registration documents for each stage
Pharmaceutical engineering for new and renovated facilities management structure PQ PV OQ
Risk identification, analysis and management
Chapter 1
Introduction
PQS
Chapter 2
Key definitions and philosophy IQ
URS
Chapter 3
Impact assessment
Chapter 4
Good engineering practice
Chapter 5
Commissioning
Chapter 6
Qualification procedures
SAT
Chapter 7
Enhanced project review
Chapter 8 IQ
Chapter 9 OQ
Chapter 10 PQ
Selection of supplier
References
Glossary
Utility programs
Annexes
Commissioning
Project documentation
FAT
Project specifications
Regulation and registration documents for each stage

6. GEP – Good Engineering Practice
Customer’s requirements С1
Project evaluation
Invitation to participate in a tender
Offers
Enhanced evaluation of the project С2
Contract, purchase order and payment schedule
Functional specification of the project
Payments
Design specification
FAT
Commissioning
SAT
Final payment
Acceptance
Change implementation С4 С3
Change approval
Project analysis
Spare parts inventory
Bill of materials
Registration of assets
Project plan
In-house standards for engineering activities
Calibration master list
Maintenance tasks
Calibration and maintenance
schedule
Maintenance historical data
Configuration record
Assessment of change impact
С1>Requirements
С2>Project
С3>Time-cost relationship
С4>Maintenance use
Change request
Any source
Improvement request
KPI data
Production activities
Production plan
Records on training of operating personnel
Training materials
Records on training of maintenance personnel
GEP – Good Engineering Practice

7. Key definitions Three main aspects of Good Engineering Practice:
Project engineering
Conventionally practiced actions
Operations and maintenance
Project engineering: actions related to the launch of new or heavily modified equipment or facilities.
Conventionally practiced actions: actions, which are a part of project engineering and of common maintenance activities and operations.
Operations and maintenance: actions required for maintaining the equipment and facilities in due state and their use for production purposes.

8. Scope of Good Engineering Practice Operations and maintenance
Project engineering
Operations and maintenance
Conventional practices
Project infrastructure
Project organization
Profit analysis
Planning and monitoring
Engineering
Project analysis
Construction
Compliance with GxP norms
Commissioning
and qualification
Handover
Standards and procedures
Documentation practices
Change control
Innovations and continuous improvement
Calibration
Asset management
Supplier management
Equipment storage
Documentation
Manuals and records
Routine maintenance
Maintenance after breakdown
Internal audit
Waste management
Equipment decommissioning
Equipment and facilities inheritance

9. Quality project plan
Quality project plan should determine acceptable quality standards and how the required quality will be attained and assessed (e.g. analysis stages, approval, supplier quality management).
Quality project plan needs to cover:
Change control procedure and its implementation
Application of risk management strategy (how to manage risks and when to perform their assessment)
Review, agreement and approval of documents before their issuance at predefined stages (concept, approved for design engineering and approved for construction)
Identification, coding of documents and version control
Identification of equipment and control and measuring instruments
Project analysis and progress analysis
Distribution and control of documents

10. Comparison of non-conformities
Non-conformities of all levels
Only critical and major non-conformities 1
Construction and maintenance of premises
Potential contamination (chemical, physical, microbiological) 2
Construction and maintenance of equipment
Batch release procedures 3
Production documentation 4
Quality system documentation (elements/procedures) 5
Personnel training
Sterility assurance 6
Cleaning validation
Process validation 7 8
Product quality review
Deviation investigation 9
Audit of suppliers and subcontractors
Quality system documents (elements/procedures) 10
Calibration of measuring instruments
Regulatory requirements (registration dossier)

11. Comparison of non-conformities, %
Non-conformities of all levels
Only critical and major non-conformities 1
Production 24%
Production 27 % 2
Quality system 20% 3
Quality control 14%
Premises and equipment 17% 4
Premises and equipment 14%
Validation 14% 5
Validation 12%
Quality control 9% 6
Personnel training 8%
Regulatory issues 6% 7
Equipment maintenance 7%
Equipment maintenance 5% 8
Regulatory issues 1%
Personnel training 3%

12. Non-conformities
Differences in identification of production area objects for qualification and in technical and process documents of the project.
HEPA-filters remain unidentified in clean production premises, which impedes traceability of their preventive maintenance.
Absence of filters on exhaust devices in clean production premises, which bears the risk of contamination of internal surfaces of HVAC ducts.
Airtight installation of grids on exhaust systems during dusting production stages implies lack of technical availability of periodic cleaning of the space between the air grid and the filter.
Technical means for the control of air flow resistance in HEPA filters letting the air in clean production premises are unavailable, which does not allow to keep the level of filter cleanliness under control.
Equipment operation logbook does not allow to track down all stages of lifecycle of technological equipment (FAT/SAT/IQ/OQ/PQ/PV, shutdowns, breakages, repairs, etc.)

13. Non-conformities
Construction, operation and maintenance of air handling systems do not allow to feed sufficiently purified air to production premises. In the solids and liquid dosage areas, premises are not classified according to cleanness grades. No purification of the incoming air.
No continuous monitoring of aerosol particles in the aseptic core area of sterile production.
Dispensing room for raw materials in non-sterile production department does not have air cleaning system.
Room surfaces are made of materials, which do not allow to clean and disinfect them repeatedly. It creates a risk of product contamination.

14. THANK YOU FOR YOUR ATTENTION!!!
Questions?