classification, gowning requirements, and the
microbiological control limits and frequencies.
It isn’t even likely that the process required the
level of control specified for Grade A.
This scenario changes somewhat if the
non-sterile bulk is also a biologic product. In
Annex 2, it indicates that one needs to take
into account the requirements for classification
and cascading room classifications specified in
Annex 1. There are provisions to utilize quality
risk management procedures when considering
this requirement. For example, you may have
a risk analysis and control program that shows
the microbiological control procedures may not
be required for your process at the levels stated
for the specified room grade.
For companies that manufacture products
It is very important that you understand the
for both the United States and Europe, should
you choose to utilize a classification system
other than the Grades A through D it is crucial
that you have a document that explains the
relationship of your classification system to the
European classification system.
implications of the classification system you use
and to use them wisely.
• EU (2008) 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.
• Annex 1 Manufacture of Sterile Medicinal Products
(corrected version). European Commission.
Brussels. 25 November 2008 (revised).
• EU (2012) EudraLex The Rules Governing
Medicinal Products in the European Union
Volume 4 EU Guidelines for Good Manufacturing
Practice for Human and Veterinary Use. Annex 2
Manufacturer of Biological Active Substances and
Medicinal Products for Human Use. European
Commission. Brussels. Deadline for coming into
compliance 31 January 2013. (SANCO/AM/sl/
• FED-STD-209e (1992) Federal Standard 209-e
Airborned Particulate Cleanliness Classes in
Cleanrooms and Clean Zones. This standard is
approved by the Commissioner, Federal Supply
Service, General Services Administration, for the
use of all Federal Agencies.
• FDA (2004) Guidance for Industry, Sterile Drug
International Organisation for Standardisation.
Products Produced by Aseptic Processing – Current
Good Manufacturing Practice. U.S. Department
of Health and Human Services. Food and Drug
Administration. Center for Drug Evaluation and
Research (CDER) Center for Biologics Evaluation
and Research (CBER) Office of Regulatory Affairs
(ORA) Pharmaceutical CGMPs
• ISO (1999) International Standard 14644-1:
Cleanrooms and associated controlled environ-
ments-Part 1: Certification of Air Cleanliness.
• ISO (2003) International Standard ISO 14698-
2:2003 Cleanrooms and associated controlled
environments — Biocontamination control —
Part 2: Evaluation and interpretation of biocon-
• FDA (2001) ICH Q7A Good Manufacturing
Practice Guidance for Active Pharmaceutical
Jeanne Moldenhauer is the Vice President of
Excellent Pharma Consulting. She has over 25
years of experience in the pharmaceutical, bio-tech, and device industries. She is very active in
PDA, has authored many books and articles, and
can be reached at firstname.lastname@example.org.
Maximum permitted number of particles per m3 equal to
B 3,520 29 352,000 2,900
or greater than the tabulated size
At rest In operation
Grade 0.5 μm 5.0 μm 0.5 μm 5.0 μm
A 3,520 20 3,520 20
C 352,000 2,900 3,520,000 29,000
D 3,520,000 29,000 Not defined Not defined
Table 4: EU GMPs Annex 1 Recommended Limits for Particulate Contamination
INTERPHEX is a leading annual pharmaceutical and biopharmaceutical trade show. Key decision makers find the networking
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IPC APEX Expo 2014
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The 2014 PDA Annual Meeting will offer formal sessions and informal networking opportunities focused on key areas of interest
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Fundamentals of Random
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Wayne Tustin will discuss vibrations from earthquakes, aboard
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