Measuring Bioburden for Cleaning Validation Protocols
Measuring Bioburden for
Cleaning Validation Protocols
Destin A. LeBlanc
Cleaning Validation Technologies destin@cleaningvalidation.com November 2004
A3P Canada
1
Why address?
For process equipment
Initial regulatory focus: drug active and cleaning agent
FDA guidance not apply to micro residues
But do address micro concerns on storage
Practical matter
Microbial residues are related to cleaning process Microbial residues are potential contaminants of next product
2
Issues?
Probably not a problem except…
Little or no documentation
Approaches to control
Setting limits
Analysis & sampling
Documentation strategies
New validation
Already validated process
CEHT (expiry)
3
Control measures
Bioburden of raw materials
“Cleaning” itself
Sanitizing agents
Drying of equipment
4
Good cleaning
Factors hostile to microbes --
High temperature pH extreme
Oxidizer (biocidal)
Surfactant (wetting, physical removal)
Removal of chemical residues -Microbe “trap”
Nutrient
In most cases, effective cleaning can meet microbial control objectives
5
Separate sanitizing step
Possible agents
Hypochlorite
Quats
Alcohol
Hydrogen peroxide
Peracetic acid
May require final rinse (exc. alcohol & peroxide) Another residue concern
6
Final rinse
Rinse to remove sanitizing agent residues Unless rinse with sterile water, will reintroduce organisms into system
7
Sanitizing option
Sanitize after storage (as opposed to after cleaning)
Address rinsing
Address worst case & demonstrate effective sanitation under those conditions Storage time & conditions
Worst case “starting conditions”
8
Is sanitizing necessary?
Major issue: microbes in equipment at beginning of subsequent manufacturing process How demonstrate – data is critical
Scale-up studies (after clean/after sanitize comparison)
Monitoring data on just cleaning
9
Drying
Heat
Alcohol
Time
Issue addressed in FDA
Cleaning Validation Protocols
Destin A. LeBlanc
Cleaning Validation Technologies destin@cleaningvalidation.com November 2004
A3P Canada
1
Why address?
For process equipment
Initial regulatory focus: drug active and cleaning agent
FDA guidance not apply to micro residues
But do address micro concerns on storage
Practical matter
Microbial residues are related to cleaning process Microbial residues are potential contaminants of next product
2
Issues?
Probably not a problem except…
Little or no documentation
Approaches to control
Setting limits
Analysis & sampling
Documentation strategies
New validation
Already validated process
CEHT (expiry)
3
Control measures
Bioburden of raw materials
“Cleaning” itself
Sanitizing agents
Drying of equipment
4
Good cleaning
Factors hostile to microbes --
High temperature pH extreme
Oxidizer (biocidal)
Surfactant (wetting, physical removal)
Removal of chemical residues -Microbe “trap”
Nutrient
In most cases, effective cleaning can meet microbial control objectives
5
Separate sanitizing step
Possible agents
Hypochlorite
Quats
Alcohol
Hydrogen peroxide
Peracetic acid
May require final rinse (exc. alcohol & peroxide) Another residue concern
6
Final rinse
Rinse to remove sanitizing agent residues Unless rinse with sterile water, will reintroduce organisms into system
7
Sanitizing option
Sanitize after storage (as opposed to after cleaning)
Address rinsing
Address worst case & demonstrate effective sanitation under those conditions Storage time & conditions
Worst case “starting conditions”
8
Is sanitizing necessary?
Major issue: microbes in equipment at beginning of subsequent manufacturing process How demonstrate – data is critical
Scale-up studies (after clean/after sanitize comparison)
Monitoring data on just cleaning
9
Drying
Heat
Alcohol
Time
Issue addressed in FDA