Nikolaus Ferstl, University Hospital of Regensburg
Dr Lars Kreye, Boehringer Ingelheim
André Lourenco, NNE
Dr Jean Denis Mallet, Former Head of the French Pharmaceutical Inspection Dpt. AFSSAPS
Andreas Nuhn, Principal Consultant GMP-Compliance
This course outlines the principles of planning, qualification and operation of cleanrooms & barrier systems and their associated HVAC systems in the GMP environment. Both the protection concepts and the premises for aseptic and non-sterile manufacturing will be addressed.
Knowing the regulatory requirements on rooms and HVAC systems is an absolute prerequisite for all further steps like design, qualification and operation of clean rooms.
It is therefore essential to be aware of all restrictions and relations between material and personnel flows before starting with the building of clean rooms for pharmaceutical manufacturing. This is the starting point for the zone concepts and the required airlocks.
The clean room itself consists of floor, wall and ceiling systems suitable for the intended use. Now, which systems are suitable for which clean zones or processes? How can an isolator be integrated in the concept?
The classification and qualification of the rooms have to be done after the construction. The formal requirements on qualification are the same for clean rooms dedicated to the manufacture of both sterile and non-sterile dosage forms. Only the contents to be examined and fulfilled are different.
Qualification – which serves the verification of the correct functioning of the production rooms – merges into the routine monitoring. Moreover, the systems in place for requalification, change control, deviation and maintenance ensure the GMP status to be kept.
This course is directed at staff in pharmaceutical engineering departments and production, involved in the planning, qualification or operation of clean rooms.
Engineering companies and GMP-planners are also the target group of this course.
GMP requirements for clean rooms and HVAC systems in the pharmaceutical industry
- The EU GMP guide, Annex 1 and 15, ISO Norms and other GMP relevant guidelines
- Definition of cleanliness: particles and microbiological limits
- Comparison of EU und US requirements
- Requirements during planning, construction and operation
- Experiences from inspections
- Considering of the frame conditions: premises, number of floors, products, technologies
- Estimation of the required spaces (with regards to the equipment and production capacities)
- Requirements according to the different clean room zones
- How to develop material and personal flows: from process to layout
- Planning with the technical room book
- Specific pressures cascades and airlock requirements
- Examples for zone concepts for sterile and non-sterile manufacturing including highly potent compounds
HVAC systems: from planning to commissioning
- Background for HVAC-Systems
- Design criteria
- GMP criteria and requirements for recovery time, air changes, air velocity, differential pressures, …
- Usage of flow visualisation tools
- The different concepts possible from 100% fresh air to recirculation
- Different production types and the influence on HVAC systems and their GMP relevance
- Control strategies
- Energy aspects
- Requirements for the construction site
- Monitoring systems
GMP requirements for clean rooms walls, ceilings and floors
- Description of requirements coming from planning, ISO norms and GMP Guidelines
- Overview of the different wall and ceiling systems used in the pharmaceutical industry
- Components of wall systems: terminals, doors and Windows
- The GMP-compliant clean room drain
- Floors: Slip-resistance vs. GMP
- Requirements for silicone joints (and coves)
- Assignment of the different systems to the different clean room classes – which walls, ceilings and floors are appropriate/allowed for which cleanliness class?
- Specifying the intended quality: the URS
- How to determine the specified quality of walls, ceilings and floors
- Definition of Isolator & RABS Systems
- Pros & Cons of the different Systems
- Prerequisites for the usage of isolator/RABS
- Technical implementation of a barrier system
Particle testing and the ISO 14644
- Leak testing of filters
- Measuring over and under pressure
- Determination of the number of air changes
- Measurement of the recovery time
- Particle measurement and classification of the room
- Requirements for particle counters
- Number of measuring points and volumes according to ISO
- Air flow study, smoke study (UDF)
- Documentation of results
Qualification of clean room & HVAC System
- Definitions: classification, qualification, requalification, monitoring and recurring tests
- Organisation of the qualification of rooms and HVAC systems
- Usage and example of a risk analysis
- Steps taken in URS, DQ, IQ, OQ, and PQ
- Tests in the different qualification stages
- Typical problems in clean room and HVAC systems qualification
- Periodic requalification – which tests are really necessary?
Operation of clean rooms / barrier systems
- Recurring particle measurements
- Routine microbiological monitoring
- Tests for isolators
- What to do for maintenance?
- Trending of data, evaluation, the PQR