Wetstrilization.ppt

7/27/2019 Wetstrilization.ppt

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2013-10-22 Moist Heat Sterilization 1

VALIDATION OF

MOIST HEAT STEILIZATION

JM Tech.

Do-Young Ahn


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Definition

SterilizationThe act or process, physical or chemical, that destroys or eliminates

all viable microbes including resistant bacterial spores from a fluid or a

solid.Examples of sterilization methods are : steam treatment at 121, dry

heat at 230, flushing with a sterilizing solution such as hydrogen

peroxide (H2O2) or ozone (O3), irradiation, and filtration.

SterilityThe reduction of anticipated levels of contamination in a load to the

point where the probability of survival is less than 10-6.


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Definition

D-valueThe time in minutes required for a one-log or 90% reduction of a

specific microbial population under specified lethal conditions. For

steam sterilization it is determined at a constant temperature

z-valueThe number of degree of temperature change necessary to change the

D-value by a factor of 10.


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Definition

F value(lethal rate, instantaneous Fo)The F value is a measurement of sterilization effectiveness. F(T,z) is

defined as the equivalent time at temperature T delivered to a container

or unit of product for the purpose of sterilization, calculated using aspecific value of z.

Fo value(accumulated Fo)The term "Fo " is defined as the number of equivalent minutes of

steam sterilization at temperature 121.1C delivered to a container orunit of product calculated using a z-value of 10C.

Fo = 10^((121-T)/z)*t


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Methodology

Overkill SterilizationProvides a minimum 12 log reduction of a resistant BI w/ a known

D-value of not less than 1 minute.

Required minimal information on the bioburden

Bioburden/Bioindicator Sterilization

Provides a probability of survival of less than 1 in 106 for the

bioburden as demonstrated using a resistant BI w/ a known D-value.

BI may not be inactivated

Requires information on the numbers and heat resistance of the BI.

Requires ongoing monitoring or control over bioburden.


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Methodology

Bioburden Sterilization

Provides a probability of survival of less than 1 in 106 for the most

resistance bioburden expected in the load.

Requires information on the numbers and heat resistance of the BI.

Requires ongoing monitoring or control over bioburden.


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Sterilizer Cycle

Gravity DisplacementDifference of density

Density of air at 20 = 1.2 g/

Density of steam at 100 = 0.6 g/

Effectiveness of air elimination depends on the rate of steam supply

Air pocket : too rapidly

Diffusion into the steam : too slowly, more difficult to remove

Specially designed steam trap permitting the passage of largevolume of air


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Sterilizer Cycle

Prevacuum cycleA more effective method

By means of a mechanical vacuum pump or a steam eductor

Vacuum as low as 15~20 mmHg, apply for 8~10 min.

Pulsing cycleA series of alternating steam pulses followed by vacuum excursions

Air-steam mixtureTerminal sterilization of large volume parenterals

Air injection required to compensate the great expansion of air or

nitrogen in the head space above the liquid

Well mixed chamber : fan, raining effect by external pump w/ cooling


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Cycle Development

Consider factors into accountNature of the load : porous materials, heat sensitivity of the products

Type of the sterilizer

Employed containers and closures

Heat stable product : overkill approach

Heat liable product : bioburden approach

Bioburden studies : number of microorganisms

D-value studies : only highly resistant spore formers,BIER(biological indicator evaluator resistometer)

Inoculate the spore into the actual solutions

For solid materials, precut strips


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Preparing for Validation

Temperature sensing devices :

T type thermocouples(copper-constantan) encased in flexible sheaths

Premium grades of wire having 0.1 accuracy

Temperature standards

RTD traceable to the National Bureau of Standards , IPR, HTR

Calibration of thermocouples

At two temperatures : 0, 130

Correction factors

Stability : 0.03

Accuracy : 0.5


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Preparing for Validation

Autoclave

Validation nozzle and adaptor

Data logger : digital output and multi-channel deviceBIs or biological challenges

Loads


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Validation Protocol

Protocol should include

Objectives of the validation

Responsibilities of validation personnel and operatingdepartment personnel

Identification and description of the sterilizer and its

process control

Identification of SOPs :equipmentCalibration of instrument : SOPs and/or description

Identification and calibration of the temperature monitoring

equipment


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Validation Protocol

A description of the following studies

Bioburden determination studies(if applicable)

Empty chamber heat distribution studies

Container mapping studies(if applicable)Loaded chamber heat penetration studies

Microbiological challenge studies

Evaluation of drug product cooling water(if applicable)

Integrity testing of vent filter

Acceptance criteria

References

Review and approval


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Heat Distribution Studies

To demonstrate the temperature uniformity and stability of the

sterilizing medium throughout the sterilizer

Conduct on both the empty and loaded chamber with max. and

min. load configurations

Acceptance criteria : Less than 1of the mean temperature

Conduct 3 runs to obtain consistent results

Distribution of the thermocouples : geometricalrepresentatives, exhaust drain, adjacent to the control sensor

At least 10 probes, normally 15~20 probes


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Heat Distribution Studies

At loaded chamber heat distribution test, the thermocouples

should be positioned in the same locations used for empty

chamber heat distribution

Avoid contacting solid surfaces

Do not place within any containers

Data should be obtained at regular intervals


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Container Mapping

To determine the coolest point within the liquid filled

container

Temperature mapping should be conducted on all the different

container types, sizes and fill volume to be validated

The number of the thermocouples used depends on the

container volume

Possible to use a single thermocouple at different positions,

and can be conducted in a smaller autoclave or retort

Penetration thermocouples should be positioned at the cold

spothaving lowest temperature or Fo


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Heat Penetration Studies

To determine the coolest point(s) within the specified load

and configuration, and to assure that these points be

consistently exposed to sufficient heat lethality

Prior to conduct heat penetration studies, determine max.

and min. load configurations

Probed container at the cold spot should be distributed

uniformly throughout the load

Penetration thermocouple are positioned at points within

the process equipment suspected to be the most difficult

for steam heat penetration


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Heat Penetration Studies

Lethal rate can be determined from the temperature data

by the following formula :

L = log-1

(To-Tb)/z = 10^((To-Tb)/z)A summation over time of the lethal rate at a series of

temperature(accumulated lethality)

Fo = 10^((121-T)/z)*t

Regard to product stability


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Microbial Challenge Studies

Biological challenges are employed during heat penetration

studies in order to demonstrate the degree of process

lethality provided by the sterilization cycle

Microorganism frequently utilizedOverkill :Bacillus stearothermophilus and Clostridium sporogenes

Bioburden : Calibrated BIs from environmental and process

isolates such asE. coli

Type of BI :Spore strips or spore suspension into the suspending medium

Microbial challenge studies are conducted concurrently with

the heat penetration studies


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Validation Report

Common elements of all reports :

Identification of the task report by number

Reference to protocol

A brief summary of the range of operational conditionsexperienced and how they were controlled

A procedure for maintaining control within the approved range

A summary and analysis of the experimental results

A brief description of any deviation

Conclusion

Review and approval

Cycle development reports are not usually a part of the

validation report


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Maintenance of Validation

A routine calibration program for all instruments critical to the

operation of the sterilizer and its support system

A preventative maintenance program including periodic

operational rechecks and comparison to OQ record

Routine monitoring of bioburden and periodic BI

challenges(optionally)

Operating records and equipment logs

Process and equipment change control procedures including

review to establish whether additional validations are required

On-going validation


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Controversial Issues

Incubation of the sterility test : 7 days vs. 14 days

USP provide information concerning critical parameters for

Parameteric Release

Reduction extent and frequency of revalidation

Verification of D-value of BIs

Use of alternative toB. stearothermophilus as a BI

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