CLEANING HOLD TIME STUDIES
APIC Cleaning Validation guideline states, “For both dedicated and multi-product
facilities, the frequency with which the cleaning procedure should be performed
should be validated to assess the risks related to potential degradation and
microbiological contamination’’.
Eudralex Annex 15 states, “The influence of the
storage time before cleaning and the time between cleaning and use taken into
account to define (dirty and clean) hold times should be assessed during
cleaning validation.
The World Health Organization (WHO) states,
“The period and conditions for storage of unclean equipment
before cleaning, and the time between cleaning and equipment reuse, should form
part of the validation of cleaning procedures”.
Health Canada states, “Time-frames
for the storage of unclean equipment, prior to commencement of cleaning, as
well as time frames and conditions for the storage of cleaned equipment should
be established”
PICS
states, “The
period and when appropriate, conditions of storage of equipment before cleaning
and the time between cleaning and equipment reuse, should form” part of the validation of cleaning procedures.
This is to provide confidence that routine cleaning and storage of equipment
does not allow microbial proliferation”.
The US FDA
Guide to Inspections Validation of Cleaning Process states, “Always check for the
presence of an often critical element in the documentation of the cleaning
processes; identifying and controlling the length of time between the end of
processing and each cleaning step. This is especially important for topicals,
suspensions, and bulk drug operations. In such operations, the drying of
residues will directly affect the efficiency of a cleaning process”.
Dirty Equipment Hold Time (DEHT):
DEHT is
defined as the time between end of use of the equipment and the start of
equipment cleaning.
The
purpose of validating the dirty equipment hold time is to provide
evidence that the length of time equipment may sit idle prior to cleaning and
the condition under which this storage occurs will not challenge the ability of
the cleaning process to remove process or microbial residues.
Keeping residues on equipment surfaces prolonged time may make them harder to remove and
thus challenge the ability of the cleaning process to clean the residuals. Also,
permitting process residues, media, or solutions to settle in equipment or open to environment may allow to occur microbial
proliferation that challenges the capability of the cleaning
cycle to successfully remove microbial contamination.
Methodology
for Validation:
Held
dirty equipment after processing for an extended period of time (for example 24
hrs.) before cleaning and monitor chemical & microbial contaminants at
specified periods (for example 0 hrs., 8 hrs., 12 hrs., 16 hrs., and 24 hrs.)
- It would be ideal to discuss with manufacturing team to identify longest time interval that equipment would be uncleaned after usage.
- It would be ideal to use worst case approach to select equipment / equipment train for the study.
- Rinse & swab sampling techniques to be used for monitoring of both active and cleaning agent contents along with total microbial count from swab samples.
Clean Equipment Hold Time (DEHT):
CEHT is
defined as the time between completion of the cleaning of the equipment and the
equipment re-use.
The
purpose of validating the clean equipment hold time is that nothing
stays clean forever. There are possibilities for re-contamination of cleaned
equipment through endogenous sources (growth of microorganism already present
in equipment) as well as exogenous sources (such as entry of external
contamination in to equipment)
If
equipment is stored wet for a sufficient time, there is a reasonable
probability microbes will readily grow to an unacceptable level and that make
equipment unsuitable for manufacturing usage.
Methodology
for Validation:
Held
Clean equipment for an extended period of time (for example 7 days) before re-use
and monitor chemical & microbial contaminants at specified periods (for
example 1st day, 2nd day, 3rd day, 4th
day, 5th day, 6th day and 7th day.)
- It would be ideal to discuss with manufacturing team to identify longest time interval that equipment would be unused after cleaning.
- It
would be ideal to use worst case approach to select equipment / equipment train
for the study.
- Rinse
& swab sampling techniques to be used for monitoring of both active and
cleaning agent contents along with total microbial count from swab samples.
Refer below for other details.
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