Dr Jean Denis Mallet, ECA & Former Head of the French Pharmaceutical Inspection Dpt. AFSSAPS
Andreas Nuhn, Principal Consultant GMP-Compliance
Jørgen Pedersen, NNE Pharmaplan
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
GMP criteria and requirements for recovery time, air changes, air velocity, differential pressures, …
Usage of flow visualisation tools
The different concepts possible from 100 0.000000resh air to recirculation
Different production types and the influence on HVAC systems and their GMP relevance
Requirements for the construction site
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?