APPLICATION NOTE

GMP Cleanroom Routine Environmental
Monitoring & Data Integrity
Introduction
Routine Environmental Monitoring in GMP cleanrooms is a manual process and can becomplex, involving thousands of sample data points per month, manual data transcription andall too frequently data gaps and integrity challenges. This paper shows how the new MET ONE
3400+ non-viable air particle counter from Beckman Coulter Life Sciences can be automatedto help manage these challenges.

Cleanroom Routine Environmental Monitoring and Data Integrity Challenges
Cleanroom environmental monitoring is done to demonstrate both that the cleanroom
is operating correctly prior to the start of manufacturing and during the manufacturing
period. Sample locations and frequencies are to be determined by a risk assessment.
FDA CGMP1 states: “An adequate aseptic processing facility monitoring program also willassess conformance with specified clean area classifications under dynamic conditions on aroutine basis.”
However, the various GMP guidelines and International ISO standards around non-viable
air particle counting in GMP cleanrooms are complex and often appear to give conflicting
advice, leading to confusion and sometimes incorrect interpretation. In the case of Routine
Environmental Monitoring, there is very little prescriptive advice and the onus is on thecleanroom owner to devise an appropriate monitoring plan and, in the frequently prescriptive
GMP industry, the lack of direct guidance leaves users struggling to know what to do and thetemptation is to either create over-burdensome monitoring programs or to try to simply use
the same sample locations for routine monitoring as would be used for classification. Bothare incorrect: the first because over-burdensome monitoring programs can lead to moreinterventions in the critical cleanroom zones than are necessary and the associated increased
risk of contamination events; the second because Routine Environmental Monitoring programs
should be based on a risk assessment of contamination threats to the product during the
manufacturing process and the rules for Classification do not take this into account, i.e. thesampling locations for monitoring may be very different to those used in classifying theroom itself once a risk assessment shows at which locations in the cleanroom the product isexposed to risk.
Carrying out a daily Routine Environmental program however still remains a manual processwith potentially thousands of records taken each month, all of which typically follow a paper
trail for review and approval and then are manually transcribed into electronic format.
The whole process remains exposed to data errors through simple human error.

Characterized by Ingenuity| 1Touch-Point 1:• Ensure

correct SOP• Read andunderstand
SOP

Touch-Point 2:

Touch-Point 3:

Touch-Point 4:

Touch-Point 5:

Touch-Point 7:

Manually type insample location
name, configure
sampling

Collect andcollate paper
print-outs,ensuring all
locations havebeen sampled

Add comments
to print-outs.
Manually assess
results against
Alert and ActionlevelsTake marked-up
print-outs andManually Reviewand Approve

photocopy
Touch-Point 6:
Manuallytranscribe
results to create
electronic record

Figure 1. Routine Environmental Monitoring Programs remain subject to human error

What are the implications of data integrity for GMP cleanroom users?
The FDA’s ALCOA advice clearly targets manual configuration and data transcription
practices.

Figure 2. The FDA 21CFR part 11 definition of complete, consistent and accurate dataThe 2018 FDA Guidance on 21CFR part 11 Data Integrity Guidance for Industry2 states“In recent years, FDA has increasingly observed CGMP violations involving data integrity
during CGMP inspections.” And goes on to state “These data integrity-related CGMP
violations have led to numerous regulatory actions, including warning letters, import alerts,and consent decrees.”

Characterized by Ingenuity | 2

The document states “Firms should implement meaningful and effective strategies to manage
their data integrity risks based on their process understanding and knowledge managementof technologies”. It goes on to state that records should be “checked,” “verified,” or “reviewed”.
The guidance suggests that it may be useful to ask the following questions:• Are controls in place to ensure that data is complete?
• Are activities documented at the time of performance?
• Are activities attributable to a specific individual?
• Can only authorized individuals make changes to records?
• Is there a record of changes to data?
• Are records reviewed for accuracy, completeness, and compliance with established standards?
How can Beckman Coulter MET ONE 3400+ automated particle counter help?
Workflow features of the new MET ONE 3400+ portable non-viable air particle counter thataddresses 21CFR part 11 ALCOA data records include:
1. Are controls in place to ensure that data is complete?		Electronic SOPs and sampling maps are uploaded and configured in the MET ONE
3400+. SOP version control is also done in the counter. Completed sample locations
turn green, allowing at a glance the user to see that the daily routine environmental
monitoring program has been completed and no samples missed.
2. Are activities documented at the time of performance?		Electronic records of the day’s sampling activities are created contemporaneously
in the MET ONE 3400+ counter and exported via Ethernet without the need for any
external software, ensuring the activities are correctly documented at the timeof performance.
3. Are activities attributable to a specific individual?		The MET ONE 3400+ utilizes Microsoft Active Directory for User Name and Password
credentials control and electronic signatures are attached to the electronic records thatthe counter creates ensuring that activities and records are attributable to a specificindividual.
4. Can only authorized individuals make changes to records?		The MET ONE 3400+ utilizes multi-level User Name and Password controls withconfigurable access rights to ensure only those authorized personnel can makechanges to records and any changes are recorded in the on-board Audit Trail.
5. Is there a record of changes to data?		Any changes are recorded in the on-board Audit Trail which can be quickly filtered andsorted to provide reports during audits.

Characterized by Ingenuity | 3

6.	Are records reviewed for accuracy, completeness, and compliance withestablished standards?		Remote review and approve via web-browser of sampling data by authorised
personnel is done in the counter itself and approved electronic records with electronic
signature sign-off are generated and exported straight from the counter via Ethernet,
avoiding paper trails and manual data transcription.

Figure 3. The MET ONE 3400+ with on-screen interactive Routine Environmental Monitoring mapConclusion
The MET ONE 3400+ has been designed to address the requirements of your 21CFR part 11
ALCOA data integrity requirements for GMP cleanroom routine environmental monitoring.

Instrument Application
MET ONE3400+

GMP routine

Relevant
Attributable
Regulations
EU GMP
Annex 1,CGMP, ISO
14644-1 &-2:2015

LegibleContemporaneously
createdMulti-level,Legible,
Secure PDF electronic
Microsoft
secure PDF records created in theActive
electronic
counter itself – noDirectory record export
manual data
Usernamefortranscription orandscanning of paper
Passwordreports
controlcreatesuniqueelectronic
signatures
for users

Original

Accurate

Original
electronic
recordcreateddirectly
inside thecounter

Your SOPs
and sampling
maps
uploaded
into thecounter withversion
control.
Completedrecords
reviewed andapproved for
accuracy inthe counter
remotely via
web-browser.
No manualcounterconfigurationor sample
location
entry

Characterized by Ingenuity | 4

References1.

Food and Drug Administration. Guidance for industry. Sterile drug products producedby aseptic processing – current good manufacturing practice, 2004. U.S. Department ofHealth and Human Services Food and Drug Administration Center for Drug Evaluation
and Research (CDER) Center for Biologics Evaluation and Research (CBER) Officeof Regulatory affairs (ORA) Division of Drug Information, HFD-240 Center for Drug
Evaluation and Research Food and Drug Administration 5600 Fishers Lane Rockville,
MD 20857 USA

2. Food and Drug Administration. Data Integrity and Compliance With Drug CGMP Questionsand Answers Guidance for Industry, 2018. 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) Divisionof Drug Information, HFD-240 Center for Drug Evaluation and Research Food and Drug
Administration 5600 Fishers Lane Rockville, MD 20857 USA© 2020 Beckman Coulter, Inc. All rights reserved. Beckman Coulter, the stylized logo and the Beckman Coulter product and service
names mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the United States and other countries.
For Beckman Coulter’s worldwide office locations and phone numbers, please visit Contact Us at beckman.com
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