The European Commission has implemented a set of standards for anyone who is located in Europe and is involved in the manufacture of sterile products. (4) cleanroom grades; A, B, C, and D are defined in the EudraLex, The Rules Governing Medicinal Products in the European Union Volume 4 EU Guidelines to Good Manufacturing Practice Medicinal Products for Human and Veterinary Use.
The goal of these requirements are to minimize risks of microbiological, particulate and pyrogen contamination during the preparation and sterilization process.
Cleanroom Grade A, B, C, and D Classification Chart
|MAXIMUM PERMITTED NUMBER OF PARTICLES/M^3 EQUAL TO OR ABOVE|
|at rest (b)||in operation||Federal Standard 209E and the ISO classifications approximate equivalency|
|Grade||0,5m m||5m m||0,5m m||0,5m|
|A||3 500||0||3 500||0||100, M 3.5, ISO 5|
|B(a)||3 500||0||350 000||2 000||100, M 3.5, ISO 5|
|C(a)||350 000||2 000||3 500 000||20000||class 10000, M 5.5, ISO 7|
|D(a)||3 500 000||20 000||not defined (c)||not defined (c)||class 100000, M 6.5, ISO 8|
This chart is intended for reference only. Make sure to follow protocol specific to your cleanroom.
(a) In order to reach the B, C and D air grades, the number of air changes should be related to the size of the room and the equipment and personnel present in the room. The air system should be provided with appropriate filters such as HEPA for grades A, B and C.
(b) The guidance given for the maximum permitted number of particles in the “at rest” condition corresponds approximately to the US Federal Standard 209E and the ISO classifications as follows: grades A and B correspond with class 100, M 3.5, ISO 5; grade C with class 10000, M 5.5, ISO 7 and grade D with class 100000, M 6.5, ISO 8.
(c) The requirement and limit for this area will depend on the nature of the operations carried out.
Terminally sterilized products
Filling of products that are unusually at risk of contaminants within the environment. For example: filling of a container is slow or particularly exposed to the environment for more than a few seconds.
Background environment for grade A zone operations.
Filling of products or preparation of solutions that are unusually at risk of contamination.
Preparation of products and components for subsequent filling.
Aseptic preparation and filling of sterile ointments, creams, suspensions and emulsions
Background environment for grade A zone operations, when needed for transfers and other less-critical tasks..
Preparation of solutions that need to be sterile filtered.
Handling of components after washing.
Wondering about Federal Standard 209E and ISO approximate equivalents?
- Grade A is equivalent to class 100 or ISO 5
- Grade B is also equivalent to class 100 or ISO 5
- Grade C is equivalent to class 10,000 or ISO 7
- Grade D is equivalent to class 100,000 or ISO 8
Maintaining these environments
Cleanroom Grades A – D should employ a broad range of techniques and cleaning practices to meet these guidelines. This includes an air circulation system that works effectively. The use of HEPA filters and ULPA filters aid in air circulation and removal of particulate from the environment.
Additional measures should be taken by cleanroom personnel to further minimize risk for contamination.
- Cleanroom sticky mats upon entry
- Ensure the proper cleanroom garments are worn. See cleanroom gowning requirements for more information.
- Clean surfaces using appropriate cleanroom wipes and sterile wipes when necessary
- Clean larger surfaces using tacky rollers and or cleanroom mops