Establishing alert and action limits for clean room bioburden

C

carlosandrosie

#1
Hello everybody.

Even though I've been a member of the forum for a while this is actually my first post...

I'm looking for some insight on how to determine alert and action limits for bioburden in our Class 8 clean room.

2 years ago we started operations and since we have been monitoring bioburden levels (among other things) on a monthly basis. Now we fill it is time to establish alert and action limits.

However, by reviewing lots of standards and doing extensive research I have been unable to find any guideline on how to establish those. I found the 50/100 cfu guideline from FDA but that specifically applies to Drug products (we are a devices manufacturer).

Also found references in USP 797 but again, that applies to drug compounding environment.:nope:

Based on my findings it seems that there is no regulatory requirement for device manufacturers other than establishing your own limits, but I want to believe there is more than just setting them somehow arbitrarily based on historic data.

Any help/advise will be greatly appreciated. Thanks in advance to everyone who stops by.
 
Elsmar Forum Sponsor

Ajit Basrur

Staff member
Admin
#2
Hi carlosandrosie,

Hope to see more from you :)

Regarding testablishing the alert and action limits, USP 1116 would be an appropriate section. USP 1116 states "the principles and concepts of statistical process control are useful in establishing Alert and Action levels and in reacting to trends". Thiese limits also depend on the risk to your product.

In one of my previous organizations, we had set an alert of 50 cfu and action of 70 cfu against a final rejection of the product over 100 cfu.
 
J

Jimmy the Brit

#3
Based on my findings it seems that there is no regulatory requirement for device manufacturers other than establishing your own limits, but I want to believe there is more than just setting them somehow arbitrarily based on historic data.
Hi Carlos,

The guidance you are looking for can be found in ISO14698 Pts 1 & 2, "Cleanrooms and associated controlled environments - Biocontamination control". Part 1 is the guide to how to set up a system, including methods of detection, how to set effective limits and system verification. Part 2 is about the evaluation and interpretation of the data you generate. Both parts offer excellent guidance on managing levels of cleanroom bioburden.

The only true arbiter of the performance limits is you. What performance level do you need to protect your products adequately? What did you manage to acheive in the manned state during PQ or PV? Are you able to consistenly reach those levels or has the perfromance of the room wandered from the validated state?

If you are want guidance on "normal" room performance limits then Annex 1 of the EudraLex "rules governing medicinal products in the EU", Volume 4 EU guidance to GMP is the only standard I know of that spells out specific performance limits - I attach that table as a picture, but the document is freely available from the link above. The stated room grades align with the US room classifications as follows Grade A = class 100 (aseptic), Grade B = class 100 (non-aseptic), Grade C = class 10,000 and Grade D = class 100,000. Although this is a pharma standard, there is no reason that any cleanroom operating to these classifications should not be able to meet these performance limits - I believe the Grade C & D limits are very generous.

Hope this helps,

Jimmy
 

Attachments

R

Roland Cooke

#4
Jimmy, any idea why these standards aren't harmonized (under the MDD etc)?

The 14644 series isn't harmonized either.
 
J

Jimmy the Brit

#6
14644 parts 1-6 + 8 are FDA Recognized Consensus Standards, which I think implies that whatever problem exists in reaching harmonization, it probably isn't on this side of the pond.
ISO14698 1&2 are also FDA recognised. I have no idea why they are not globally harmonized, and wouldn't want to speculate about my European colleagues ability to agree on anything, including what to eat for lunch...
 
R

Roland Cooke

#7
ISO14698 1&2 are also FDA recognised. I have no idea why they are not globally harmonized, and wouldn't want to speculate about my European colleagues ability to agree on anything, including what to eat for lunch...

Hey, it only took us 27 years to agree on a definition of chocolate! :eek:
 
Last edited by a moderator:
C

carlosandrosie

#9
Gentlemen, thanks a lot for your repsonses to this thread. They are very much appreciated.
 

htcoztrk

Starting to get Involved
#10
Hi carlosandrosie,

In one of my previous organizations, we had set an alert of 50 cfu and action of 70 cfu against a final rejection of the product over 100 cfu.
Hello,
I'm little bir confused about the action limit. So you determined your maximum bioburden limit as 100 cfu/ product but why did you set the action limit as 70 cfu/ product? Should the action to be taken before the value exceed the maximum limit?
 
Thread starter Similar threads Forum Replies Date
A Help establishing regulatory requirements - Plastic dental cartridge syringe US Food and Drug Administration (FDA) 0
K ISO 13485 section 5.3 Quality Policy - No framework for establishing and reviewing quality objectives ISO 13485:2016 - Medical Device Quality Management Systems 2
N Use part of high risk device for establishing low risk device EU Medical Device Regulations 0
J ISO 13485:2016 Section 6.2 - Documenting the process for establishing competence ISO 13485:2016 - Medical Device Quality Management Systems 6
M Establishing a FTQ (First Time Quality) process for an engine assembly line Quality Tools, Improvement and Analysis 1
R Establishing the quality policy for ISO 9001:2015 ISO 9000, ISO 9001, and ISO 9004 Quality Management Systems Standards 10
N Establishing a monthly scrap cost target Lean in Manufacturing and Service Industries 11
T Establishing -F- datum - need advice Inspection, Prints (Drawings), Testing, Sampling and Related Topics 2
S Establishing a Gage R&R Studies Program in a Testing Laboratory Gage R&R (GR&R) and MSA (Measurement Systems Analysis) 1
M Establishing traceability from calibrated glassware to non calibrated ones General Measurement Device and Calibration Topics 5
O Establishing SPC for small batches of 10-15 units Statistical Analysis Tools, Techniques and SPC 10
M Establishing Metrics - Where do you document metrics? AS9100, IAQG, NADCAP and Aerospace related Standards and Requirements 7
alonFAI Establishing a Receiving Inspection Procedure Document Control Systems, Procedures, Forms and Templates 5
optomist1 Establishing Sigma or Capabilty Indices for Automotive Safety Quality Tools, Improvement and Analysis 1
S Establishing an MSA Plan and Justification Suggestions wanted Gage R&R (GR&R) and MSA (Measurement Systems Analysis) 1
M Establishing a QMS - What Daily/Weekly/Monthly activities in Auto Industry IATF 16949 - Automotive Quality Systems Standard 4
T Help establishing a good Customer Complaints Procedure? ISO 9000, ISO 9001, and ISO 9004 Quality Management Systems Standards 3
V Process Validation Guidance establishing the Integration with QbD - April 2012 Pharmaceuticals (21 CFR Part 210, 21 CFR Part 211 and related Regulations) 1
M Establishing Ranges for Weights for Calibration Verification of a Micro-Balance Calibration Frequency (Interval) 1
D Preparing for ISO 29001/API Q1- Establishing Control Features Oil and Gas Industry Standards and Regulations 3
D Establishing Key Process Characteristics (KPC's) Quality Tools, Improvement and Analysis 6
C New Quality Manager - Establishing Teams in different Business Units Quality Manager and Management Related Issues 4
H Noob Frequency Distribution and establishing achievable goals Using Minitab Software 2
K How to apply IEC 62366 and what shall be changed in establishing a Technical File ISO 13485:2016 - Medical Device Quality Management Systems 2
M Establishing monthly production targets with varying number of employees Lean in Manufacturing and Service Industries 6
A Why do I need batch size in establishing control plan to certain AQL?? AQL - Acceptable Quality Level 4
E Need help establishing a DMR (Device Master Record) 21 CFR Part 820 - US FDA Quality System Regulations (QSR) 3
K Basis for Establishing Gage Tolerancing - "Gage Maker's Tolerances" General Measurement Device and Calibration Topics 4
K Establishing the Environmental Aspects and Impacts for a Septic Tank Miscellaneous Environmental Standards and EMS Related Discussions 5
M Establishing simple procedure and work instruction using chart or photo or video Document Control Systems, Procedures, Forms and Templates 2
L Criteria for Establishing Control Plan Sample Size and Inspection Frequency FMEA and Control Plans 7
K Inventory Management - Establishing a procedure for Inventory Management Document Control Systems, Procedures, Forms and Templates 2
K Establishing Item Codes for Production Raw Materials Misc. Quality Assurance and Business Systems Related Topics 2
O Establishing the current value of KPI's (Key Performance Indicators) Manufacturing and Related Processes 1
Y Establishing and Measuring Individual Performance to Product Quality Standards Misc. Quality Assurance and Business Systems Related Topics 5
E Establishing a biocompability test lab for testing EN 10993 series EU Medical Device Regulations 1
D Establishing and controlling process capability - Meaning of Phrases Capability, Accuracy and Stability - Processes, Machines, etc. 2
P Establishing Thickness Specifications from Measured Data Capability, Accuracy and Stability - Processes, Machines, etc. 11
A Initial condition for establishing significant environmental aspects Miscellaneous Environmental Standards and EMS Related Discussions 1
S Establishing Control of Regulations that concern my company Quality Manager and Management Related Issues 12
D Establishing New Training Procedure - Past Training of Existing Employees Training - Internal, External, Online and Distance Learning 6
J Establishing Proposal Metrics in a Factory Construction Company Quality Tools, Improvement and Analysis 6
A How to do Equipment Validation - Establishing our ISO 13485 QMS procedures Qualification and Validation (including 21 CFR Part 11) 28
B True Position without tertiary datum? Establishing a proper rotation Inspection, Prints (Drawings), Testing, Sampling and Related Topics 12
Coury Ferguson Interpretation of IAF Guide 62 - Establishing the Competence of the Auditors Registrars and Notified Bodies 11
S Establishing Internal Audit Nonconformity Level Criteria - Major vs. Minor? Internal Auditing 46
H Establishing Employee Competencies and Training - Future Training Plan ISO 9000, ISO 9001, and ISO 9004 Quality Management Systems Standards 10
P China - Establishing Quality Systems for Chinese Suppliers Supplier Quality Assurance and other Supplier Issues 8
Q Feedback System (8.2.1) - Requirements for "..establishing a documented procedure..." ISO 13485:2016 - Medical Device Quality Management Systems 5
Douglas E. Purdy Transition to ISO 9001:2000 - RFI - 009, RFI-003, & Establishing a QMS ISO 9000, ISO 9001, and ISO 9004 Quality Management Systems Standards 9

Similar threads

Top Bottom