Cleanroom is required to prevent contamination during manufacturing of a product. The product can be a biologic or a semiconductor. I would like to discuss about the cleaning methods practiced in medicinal product industry.
European regulation (EMA) is specific in some areas, for their requirement in cleaning procedures in GMP areas. For instance, the intervals between use and cleaning as well as cleaning and reuse should be validated. Cleaning intervals and methods should be determined (EMA correspondence Annex 15, clause 38) Also, disinfectants and detergents should be monitored for microbial contamination; dilutions should be kept in previously cleaned containers and should only be stored for defined periods unless sterilized. Disinfectants and detergents used in Grades A and B areas should be sterile prior to use (EMA correspondence Annex 1, clause 62)
On the other hand, US FDA is more general in their regulatory requirement for cleaning procedures in GMP areas. The requirements for US FDA and EMA for cleaning procedures in GMP area are similar, except for sewage and refusal were the US FDA has specifically mentioned it in their regulation (21 CFR 211.50).
There are guidances and recommendations, provided by various organizations and societies, for maintaining the level of cleanliness required in a cleanroom area. I would like to discuss some of the factors that are considered for cleaning a cleanroom.
Generally, five types of cleaning equipment are used in cleaning:
1. Vacuuming (wet or dry) - It is relatively inexpensive and since no cleaning solution is required, there is no contaminants introduced. However, a wet vacuuming is more efficient because of the additional drag force from the liquid helps in removing the particle.
2. Wet wiping (damp mopping or wiping) - Cleanrooms are often cleaned with a mop and a bucket. For efficient cleaning, a 3-bucket system is preferred.
3. Tacky roller and tacky mats- I have seen a lot of companies using tacking mats. Tacky materials remove contaminant by the technique of adhesion method
4. Wiper- Wipers are dampened (not saturated) with a detergent or a disinfectant solution and used in cleanroom to wipe surfaces and remove contamination
5. Squeegees- It is used to clean windows and tacky cleanroom flooring
Cleaning solution used in cleaning cleanroom is selected based on following factors:
1. Non-toxic to people
2. Non-corrosive
3. Non-inflammable or low flash point
4. Fast drying
5. Harmless to cleanroom surfaces
6. Leaves no contamination that is harmful to the product
7. Reasonably priced.
Ideally, you will not find any cleaning solution that satisfies all the above requirements. Use of alcohol is preferred since it acts as a good bactericidal and evaporates immediately, leaving no residue. Generally, phenol and chlorine-based compounds are less preferred in cleaning critical cleanrooms because of its toxicity. However, chlorine-based compounds are used because they can kill spores, which are not killed by other acceptable disinfectants.
The type of cleaning methods that need to be used depends on the type of room to be cleaned. There are three zones in a cleanroom: 1. Critical zone- where the product is exposed to contamination, 2. Main zone- area surrounding the critical zone, 3. Other- changing areas, ancillary areas etc. Stringent cleaning methods should be employed for cleaning critical zone as compared to ancillary areas. The frequency of cleaning the room and time spent for cleaning the room should be determine and validated. The best way for ascertaining the frequency of cleaning is by measuring the surface particle contamination immediately after cleaning and after pre-determined intervals; so as to determine how long it does takes for the particle concentration to reach at an unacceptable limit. Also, the surface contamination sampling area should be the area which is most difficult to clean. There are various test analytical methods available now to measure the particle concentration. Additionally, there are test that are carried out to ascertain that cleaning are carried out appropriately.
Finally, organize all the documents and schedules so that these can be easily reviewed and managed.
Standards for cleaning, decontamination, and surface cleanliness in industries for higher level of cleanliness are documented in various standards and recommendation:
1. ISO standards (14644-5)
2. IEST-RP-CC-018.2
3. VDI 2083
Some good books to read:
1. Cleanroom Technology: Fundamentals of Design, Testing and Operation, 2nd Edition. ISBN: 978-0-470-74806-0
2. Introduction to Contamination Control and Cleanroom Technology. ISBN: 978-3-527-61313-7
Mopclean Image: http://www.springgrovecleanroom.ie/facility.html
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