Course No 156624-5 April 2017, Costs: Non-ECA Members: EUR 1.690,--ECA Members: EUR 1.490,--EU GMP Inspectorates: EUR 845,--APIC Members: EUR 1.590,--(All prices excl. VAT)If you have any questions, please contact us:Tel.: +49 (0)6221 / 84 44 0 E-Mail: info@concept-heidelberg.de Jesper Kure, NNE Pharmaplan Dr Lars Kreye, Boehringer Ingelheim Dr Jean Denis Mallet, ECA & Former Head of the French Pharmaceutical Inspection Dpt. AFSSAPS Andreas Nuhn, Principal Consultant GMP-Compliance J�rgen Pedersen, NNE PharmaplanKnowing 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.sound barrier for ac unit Qualification � which serves the verification of the correct functioning of the production rooms � merges into the routine monitoring. ac unit floodingMoreover, the systems in place for requalification, change control, deviation and maintenance ensure the GMP status to be kept.ac unit electric billThis 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 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) 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 What to do for maintenance? Trending of data, evaluation, the PQR GMP in Pharmaceutical Development Sterile / Aseptic Manufacturing GMP for APIs and Excipients GMP Basic Training Courses General Contractor: Devel Construction This Project consisted of 60,000 square feet of all new Class 10, Class 100, Class 1000, and Class 10,000 Clean Room. The environmental requirement was -69 degrees +/- 1 degree F 45%RA +/- 5%. (3) Haakon Custom Air Handlers (52) Hunt Air recirculating air handlers (2) Centrifugal chillers and (2) cooling towers KLA Tencor B5W Clean Room General Contractor: San Jose Construction The KLA building 5 west cleanroom is a 30,000 square foot class 100 space with a small class 10 assembly area. The HVAC system included the installation of (8) chilled water recirculation air handling units and (1) chilled water makeup air handling unit complete with steam humidifier.

New variable speed secondary pumps were install and connected to the existing site chilled water system along with new 10” chilled water main piping from the utility yard to the new air handling equipment. The process piping included CDA, Nitrogen and instrument vacuum. A complete process cooling water system was installed, including a cooling water skid complete with a heat exchanger, buffer tank, variable speed pumping and UV purification. General Contractor: Devcon Construction For the Compugraphics Clean Room project, UMI worked with an existing older clean room system comprised of 3 packaged AC units and 7 transfer fans ducted to HEPA filters in the clean room. UMI’s scope in the clean room consisted of: A new controls system to bring one the clean room AC units online only in a backup capacity A scrubbed exhaust system with connections to emergency power and new AWN system A supply fan system with controls that allow the clean room to maintain positive pressure even in case of power failure

Repairing existing ductwork above the clean room ceiling to minimize leakage and maximize clean room air flow Balancing of air flow at HEPA filters Controls systems interlocks with plumbing systems UMI installed a humidifier system at the roof to maintain the clean room at 40% RH +/- 5% Addition of supplemental cooling via a chilled water pre-cooling system to deal with the added heat load in the clean room from a higher tool density and higher outside air intake than intended at the original building design General Contractor: Slymar Construction Location: Lodi & Sunnyvale, CA Cepheid is a molecular diagnostic company that is # 1 in the industry due to its accurate genetic and organism based diseases. To accomplish these accurate test we have designed and built systems to support multiple clean rooms and dry rooms to meet their requirements of certified products going out the door. In our designs we have provided multiple chillers ,cooling towers, Air handlers, Heat exchangers, compressors and hundreds of HEPA filters to meet there clean room required temp and low levels of particulates.