Basic Clean Room Requirements Designs for GMP Clean Rooms What is a clean room?A clean room (GMP cleanroom), in my mind are a combination of engineering design, fabrication, finish and operational controls (control strategy) that are required to convert a “normal” room to a “clean room”. In this blog I will attempt to explain the necessary characteristics of a regulated company clean room not producing potent chemicals or active or hazardous biologicals. If there are significant containment requirements, the requirements would be outside the scope of a “simplistic” blog like this. In a pharmaceutical sense, clean rooms are those rooms that meet the code of GMP requirements as defined in the sterile code of GMP, i.e. Annex 1 of both the and Guides to GMP and other standards and guidance as required by local health authorities. So why do I need a clean room?There is no GMP requirement in the EU and PIC/S (i.e. TGA) GMP guidance’s for the manufacture of non-sterile medicinal products in a “clean room”, but we do use clean areas that are effectively ventilated with filtered air where the products or open clean containers are exposed.
Airlock An enclosed space with two or more doors which is interposed between two or more rooms, e.g., of differing classes of cleanliness, for the purpose of controlling the airflow between those rooms when they need to be entered. An airlock is designed for use either by people or for goods and/or equipment.
On the other hand, for the manufacture of sterile medicinal products, clean rooms are mandatory, as defined in Annex 1 of the EU and PIC/S GMPs. This Annex defines a number of additional requirements besides the airborne particulate concentration limits used to classify clean rooms.In a nutshell, if you manufacture a non-sterile medicinal product, you should be very careful about classifying or grading your clean areas, for example, classifying a room as “Grade D”. Whilst not a code requirement, many regulators, like the Australian TGA will expect you to fully comply with all of the requirements for a Grade D room as defined in Annex 1, even if it’s not a GMP code requirement. If you have classified the room as Grade D, you will need to live with the consequences and costs of maintaining this level of clean room cleanliness during operation. What type of clean room do I need?If you are a manufacturer of non-sterile medicinal products, you should define your own clean room / area standards using national and international standards. Usually manufacturers will define an airborne particulate concentration standard class such as ISO 8 (at rest), outline gowning and a pressure cascade regime, defining a “clean corridor” design or a “dirty corridor” design.If you are a manufacturer of sterile medicinal products, you must follow the EU or PIC/S GMPs, namely Annex 1. “Clean corridor” or a “Dirty corridor”?When considering pressures cascades, the pharmaceutical engineers should consider a design philosophy to have a “clean corridor” or a “dirty corridor” design, which we will now explain through an example.
Typically, low moisture medicinal products such as tablets or capsules are dry and dusty, therefore more likely to be a significant cross-contamination risk. If the “clean” area pressure differential was positive to the corridor, the powder would escape out of the room and enter the corridor, and is likely then to be transferred into the next door cleanroom. Thankfully, most dry formulations do not readily support microbial growth, so as a general rule, tablets and powders are made in “clean corridor” facilities, as opportunistic microorganisms floating in the corridor don’t find environments in which to thrive.
This means that the rooms are negatively pressurised to the corridor.For aseptic (processed), sterile, or low bio-burden and liquid medicinal products, the opportunistic microorganisms usually will find supportive media in which to flourish, or in the case of an aseptically processed product, a single microorganism could be catastrophic. So these facilities are normally designed with “dirty corridors” as you want to keep potential microorganisms out of the cleanroom. Unlike powders, droplets of liquid don’t generally “leap up” and float around the facility.Designs can become complicated if the products or raw materials are highly potent, which cause occupational health and safety issues, or if there is a need for biological containment. These are outside the scope of clean room basics, reading this blog on could assist. If you want to know more, our can help. Which way should my clean room doors swing?Unless you have power-assisted doors, all doors should open into the room with the higher pressure. Double-leafed doors are notorious for causing the pressure differential balancing of rooms to drift off as the door springs gradually weaken and the doors leak air between rooms at levels outside of the design parameters.Annex 1, Clause 47 specifically states that sliding doors are not permitted in sterile plants as they typically create uncleanable recesses, projecting ledges and recesses.
For these reasons they should not be used in non-sterile facilities either. What are the sources of contamination in a clean room?It should be noted that cleanrooms do not eliminate contamination altogether, they control it to an acceptable level.Our real concern is actually microbial contamination in most cases. Room typeACHCommercial kitchens & Toilets15–30Smoking rooms10–15Laboratories6–12Classrooms3–4Warehousing1–2MicronA micron (or micrometre) is a millionth of a metre. A human hair is around 100 microns thick.
Particles less than 50 microns cannot be seen by a naked eye. Bacteria measure 1 or 2 microns. HEPA filtersHEPA stands for High-efficiency particulate air.
HEPA filters are one of the most important elements of a cleanroom. They consist of a large, box shaped filter that removes airborne particles of specific sizes very efficiently. They must also be monitored and tested regularly to make sure they are still integral.HEPA filters are composed of a mat of randomly arranged fibres, which are typically composed of fiberglass with diameters between 0.5 and 2.0 microns.
Key factors affecting function are fibre diameter, filter thickness, and filter face velocity. Dispersed oil particle testing / Integrity TestingDispersed oil particle testing or integrity testing is a testing procedure to ensure that a HEPA filter meets its efficiency specification and is properly seated and sealed in its frame. AirlockAn airlock is a room where personnel, materials or equipment are transferred into or out of a cleaner environment. It can be the size of a small “cupboard”, or a large room where personnel change into and out of cleanroom garments, or where a forklift can enter. Clean room classification – ISO ClassThis refers to the level of cleanroom particulate cleanliness based on a number of airborne particles of a certain size per cubic metre. ISO 8 is the starting cleanroom level. A sterile cleanroom for the pharmaceutical industry will need to achieve ISO 5.
![Airlock System In Pharmaceutical Industry Airlock System In Pharmaceutical Industry](https://slideplayer.com/slide/12535496/75/images/74/AIR+HANDLING+SYSTEM+IN+PHARMACEUTICAL+MANUFACTURING.jpg)
Classes better than ISO 5, that is ISO 4 are generally only required for the electronics industry. Clean room classification – Annex 1 or ISO?Grades A through to D refer to cleanroom cleanliness for sterile products only, these Grades can be related to the ISO Classes, but they are not the same.The classification of 100, 10,000, and 100,000 normally refers to the withdrawn FED-STD-209 E Airborne Particulate Cleanliness Classes in Cleanrooms and Clean zones which was cancelled on November 29, 2001 by the U.S. General Services Administration (GSA).This was superseded by International Standard ISO 14644, Cleanrooms and controlled environments-Part 1: Classification of air cleanliness, and Part 2: Specifications for testing and monitoring to prove continued compliance with ISO 14644-1. Room recovery rateThe time it takes from a contamination event to the room regaining its designed cleanliness level as per the GMP requirements. Particle countA test that samples a fixed volume of air and captures, filters and counts airborne particles by their size. This is performed when the cleanroom is “at rest” or “in operation”. For pharmaceutical operations, both airborne viable (alive) and non-viable (not alive) particle counts are performed.
This is performed as part of the certification of a cleanroom and during regular environmental monitoring. Clean room certificationA series of tests that are performed to show that a cleanroom is operating at to its required class or grade. More clean room jargonIf you would like to know more, you can follow the links below.A, optimising your clean room, n, now you know it all, take the.Eudralex Vol 4:FED-STD-209E:WHO Annex 3:WHO Annex 5:WHO Annex 6:Page last updated July 16, 2019. /. /Dee, thanks for the clarification request, I should have been clearer in my blog.In my mind, one of the basis tenants of GMP or QMS are, “say what you are going to do” and the “do what you said”, it you don’t you are not complying with your own QMS and any auditor should cite the non compliance.Specifically relating to this subject, if the company assesses the risk associated with your (non-sterile) product requiring Grade D air classification, then the regulatory will assess your company against this standard.Hope that makes sense?. /.
/Very specific information on the clean rooms. Now sir can you help me to get the information for three different condition for pressure differential. WHO says 5 to 20 Pascal’s will be safe limit but if I want to decide NLT limit for these different conditions.
Only one limit for each condition (no lower and upper limits).1. What will be the DP limit for classified to unclassified rooms2.What will be the DP limit for classified to classified rooms with different grades e.g. C to D.3.What will be the DP limit for classified to classified rooms with same grades e.g.
Compact Airlock Vibratory Sifter The Russell Compact Airlock achieves OEL value of 1μg/m3The new Compact Airlock Sieve™ adds a new dimension to screening technology for the pharmaceutical industry. The unique design has evolved as a result of close consultation with many of the top pharmaceutical companies around the world. The new Compact Airlock Sieve™ is the first real advancement in pharmaceutical sieving technology for ten years, with its validatable pneumatic clamping system giving large improvements in product containment (OEL value of 1 μg/m 3) and operator health and safety.The Russell Compact Airlock Sieve™ has a patented pneumatic lock, which gives an even and high clamping force across all sealing faces. The clamping force therefore guards against powder leakage more effectively than traditional band clamps or over-centre toggle clamps. Also, to assist with FDA process approval, this pneumatic clamping system can be validated to provide a unique and measurable seal. The Russell Compact Airlock Sieve™ offers large improvements in product containment while reducing dust and improves the health and safety of operators, especially in the pharmaceutical industry.