When using a classification system, be cognizant of the implications.
Mundelein, Ill. O ver the past few years there has been an increasing trend to change from previous classification systems used to the ISO classification systems in ISO 14644-1. However, many companies have continued to use the tradition-
al Class 100, 10,000, 100,000 room classification system from
Federal Standard 209-e. In Europe, the GMPs as stated in Annex
1 utilize another system—Grades A through D.
Many global companies choose to use this classification
system. All of these systems are acceptable for use. However,
we have also tended to link the systems together, e.g., ISO 5/
Class 100/Grade A. This type of linkage is seen in the FDA’s
Guidance for Aseptic Processing (2004). If you are manufacturing an aseptic product and use this linked classification
system it is not likely to be an issue. However, if you are not
manufacturing an aseptically processed product, choosing
to link the classification systems together may lead to other
Federal Standard 209e
This document was written for use by federal agencies of the
United States. The scope of this document is defined as:
Equally important are the limitations identified in this
“The requirements of this document do not apply to equipment or supplies for use within cleanrooms or clean zones.
Except for size classification and population, this document
is not intended to characterize the physical, chemical,
radiological, or viable nature of airborne particles. No
universal relationship has been established between the
concentration of airborne particles and the concentration
of viable airborne particles. In addition to the need for
a clean air supply that is monitored for total particulate
contamination and that meets established limits, special
requirements are necessary for monitoring and controlling
other forms of contamination.”
Based upon these limitations, no requirements existed for
the viable microorganisms allowed to be present in support
of these classification systems. This system utilized classifi-
cations Class 10/Class 100/Class 10,000 and Class 100,000. It
also included references to an “M” system classification.
This document was subsequently retired and replaced by
ISO 14644-1 classification system
ISO 14644-1, Cleanrooms and associated controlled envi-ronments-Part 1: Certification of Air Cleanliness document,
was formally issued in 1999. This document establishes the
certification requirements for air cleanliness areas. This document has replaced the old Federal Standard 209-e (Class
100, 10,000 and 100,000 designations). Within this document
the various classification systems are based upon the requirements for counts associated with non-viable particulates. The
limits stated in this document are depicted in Table 1.
This document does not include specific requirements
for sterile or non-sterile product, nor does it include requirements for any parameter excluding non-viable particulates.
As such, unlike the FDA’s Aseptic Processing Guidance and
the EU’s GMPs Annex 1, there are no specified limits for viable microorganisms present.
FDA’s Aseptic Processing Guidance
In the FDA’s Guidance for Industry—Sterile Drug
Products Produced by Aseptic Processing—Current Good
Manufacturing Practice (2004)—which is limited in scope to
the manufacture of medicinal products using aseptic processing—there is a similar chart which includes the requirements
for both viable and non-viable microbial counts as part of the
classification system. This classification system is depicted in
Footnote “b” of this table indicates that ISO 5 particle concentration is equal to Class 100 and approximately equal to
EU Grade A. However the microbiological limits in this document are only applicable to aseptic processing. This statement has led many to arbitrarily equate ISO 5, Class 100, and
Grade A routinely. This statement of “equality” is frequently
shown in published literature and industry documents.
The European Union’s GMPs – Annex 1
For the European Union, the Drug GMPs are part of 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. This doc-