Cleanliness class levels required for pharmaceutical manufacturers

Ho Chi Minh City, November 12th, 2021

The three basic principles of GMP are:

1) minimizing human error, 2) preventing contamination and deterioration of pharmaceutical products, 3) designing a system that can ensure quality at a high level. These are also key factors to contribute to ensuring product quality. Since we cannot place the entire production line in a closed environment, creating and maintaining a production environment that is resistant to contamination and prevents quality deterioration is the most important factor in creating a standard pharmaceutical. To ensure that the production environment is resistant to contamination and does not degrade in quality, it is necessary to maintain a certain level of cleanliness for that production environment.

A closed space where the dusts or airborne particles, if appropriate, the temperature, humidity and airflow, etc. are able to be controlled is called a cleanroom. The performance of a cleanroom is represented by the cleanliness classified in accordance with the number and size of the particles permitted per a curtain volume of air. The cleanliness classification suggested in Federal Standard 209E of the USA had been long used. It was abolished along with the establishment of the ISO 14644-1 by International Organization for Standardization yet it is still conventionally being used. But it has been recently pushed to be superseded by the ISO standard. In ISO 14644-1, the class level of cleanliness is specified by the maximum allowable number of particle with a specified size per 1m3 of air and it has been widely used as a common cleanroom standard.

An industrial cleanroom is often referred to the cleanroom used for the manufacture of semi-conductors or fine machinery, while the cleanroom used for the manufacture of pharmaceuticals and food products is called a biological cleanroom since it needs a function in microbial control as well. Particularly, in terms of the environment for manufacturing sterile drug products, its necessary cleanliness class level has been described into GMP requirements.  The 3 regulatory parties (U.S., EU and Japan), have adopted their own designations relating to the environment cleanliness for sterile products manufacture. U.S. FDA specified the standard in the “Guidance for Industry Sterile Drug Products Produced by Aseptic Processing Current Good Manufacturing Practice”, EU designated it in “EU GMP Annex1” while Japan specified it in the “Guidance on the Manufacture of Sterile Pharmaceutical Products by Aseptic Processing” under the Ministerial ordinance issued by the Ministry of Health, Labour and Welfare.

On the other hand, as for the environment for non-sterile drug products such as for solid dosage form, though WHO has published the Supplementary Guidelines on “Good Manufacturing Practices for Heating, Ventilation and Air-conditioning Systems for Non-sterile Pharmaceutical Dosage Forms” in Annex 5 of WHO Technical Report Series, No.961, 2011, there is no other official guideline showing specific designation on it. Therefore, each manufacturer usually establishes control class level for their production just by taking reference to the distinctively specified guidance on sterile drug products. In practice, most manufacturers have their process areas controlled at a level of Class

Due to the lack of detailed regulations and the difference in guiding documents, it is necessary to have the guidance from experienced experts in pharmaceutical production to apply for each specific case.