VALIDATION OF DRY HEAT STERILIZATION METHODS

Pharma Admission

Pharma courses

pharma admission

pharma courses

 

TUNNEL STERILIZER VALIDATION
Principles as described above for the physical process validation of batch ovens apply also in the validation of tunnel sterilizers; however, in addition to the variables affecting batch oven validation, tunnel sterilizers have an extra variable-belt speed. This variable can be held constant by maintaining the same belt speed throughout the validation process and not changing it after validation has been completed.

BIOLOGICAL PROCESS VALIDATION OF DRY-HEAT STERILIZATION CYCLES
If a dry-heat process is claimed to produce sterile commodities, micro-organisms known to be most resistant to dry heat must be used to prove the ability of the dry-heat cycle to destroy them at the coolest location in the load. If the dry-heat process is claimed to produce both sterile and pyrogen-free commodities, validation studies must be done using both micro-organisms and microbial endotoxins.  The most widely used biological indicators for dry heat have been spores of B. subtilis; however, spores of other bacterial species may be used if they are shown to have greater resistance to dry heat. At 170°C, even the most resistant microbial spore form will have a D value of 6 to 10 min. At temperatures required to depyrogenate, microbial spores will have D values of only a few seconds. The acceptable Z value for microbial dry-heat resistance is 20°C.

A suggested step-by-step sequence in the microbial validation of a dryheat process for sterilizing and depyrogenating large-volume glass containers by a convection batch oven is presented.

This process include following steps:
Select the type of biological indicator to be used in monitoring process lethality. Calibrate the biological indicator in its carrier medium.

Place spore carrier in approximately 12 glass bottles located at the previously determined coolest area of the oven.

Run a complete cycle using the desired loading pattern for future dry heat overkill cycles.

After the cycle, aseptically transfer the spore strip to vessels of culture media and also use appropriate positive and negative controls.   

Determine the number of survivors by plate-counting or fraction negative methods.

Use following Eqn to determine the number of spore log reduction (SLRs):

ENDOTOXIN CHALLENGE IN THE VALIDATION OF DRY-HEAT STERILIZERS
The most controversial aspect of endotoxin challenge testing is how much endotoxin challenge to use.

The step-by-step procedure for the endotoxin validation of a dry-heat process may be as follows:
1. Inoculate commodity samples with a known amount of endotoxin (e.g., 10–100 ng Escherichia coli lipopolysaccharide, obtainable from several commercial sources). The endotoxin should be contained in a volume of water equal to the residual water volume following the washing procedure used prior to sterilization.

2. Thermocouples should be placed in commodities adjacent to those containing endotoxin for temperature monitoring and correlation with LAL test results.

3. Endotoxin destruction should be ascertained at the coolest location of the load. Load configurations should be identical to those used in the microbial validation studies.

4. Several endotoxin challenge samples should be done per cycle, and the studies must be adequately replicated (3–5 repeats).

5. Following the dry-heat cycle, aseptically transfer the units containing endotoxin to an aseptic area for extraction procedures, sampling, and conducting the limulus amebocyte lysate (LAL) test.

6. F values required for endotoxin destruction at various temperatures and/or cycle time–temperature variations can be determined using a Z value of 54°C and the following equation:

Fendo. = Δt Σ 10(T−170)/54

When the validation studies described in this section have been completed, all data are analyzed and a decision is made concerning their acceptability. If acceptable, the entire validation procedure and all appropriate supporting data are documented in a bound manual. If the studies are unacceptable because of unsubstantiated claims of the process or a lack of reproducibility, further testing must be performed or process variables changed followed by additional validation studies.

The final document will be reviewed and approved by various plant disciplines (engineering, microbiology, production, etc.) before the dry-heat sterilizer is considered fully validated and released for use. [Nash Robert A, Wachter Alfred H,]

YOUR COMPANY VALIDATION STANDARD OPERATING PROCEDURE

SOP No. Val. 700.20           Effective date: mm/dd/yyyy

Approved by:

TITLE:   Hot Air Sterilization Tunnel Certification and Validation Guideline

AUTHOR:           _________________________________________

                                                Name/Title/Department

                              _________________________________________

                                                       Signature/Date

CHECKED BY:  _________________________________________

                                                Name/Title/Department

                              _________________________________________

                                                       Signature/Date

APPROVED BY:________________________________________        

                                                Name/Title/Department

                              _________________________________________

                                                     Signature/Date

REVISIONS:

No.

Section

Pages

Initials/Date

 

 

 

 

 

 

 

 

 

 

 

 

SOP No. Val. 700.20        Effective date: mm/dd/yyyy

Approved by:

SUBJECT:  Hot Air Sterilization Tunnel Certification and Validation Guideline

Purpose
To provide a written procedure to be used as a guideline for the certification and validation of a dry heat sterilizer

Responsibility
It is the responsibility of production manager, validation manager and concerned departmental managers to follow the procedure. The quality assurance manager is responsible for SOP compliance.

Introduction
Laminar flow sterilization tunnels are widely used in high-speed aseptic manufacturing. Typically, laminar flow tunnels contain three sections: 1. preheating, 2. heating, and 3. cooling.

Sterilization occurs at temperatures higher than 300°C in the heating section. After sterilization, cooling is necessary before container filling. It is therefore very important to keep conditions sterile in the cooling section (up to the filling station) by keeping the cooling section at a slight positive pressure towards the tunnel room (2 to 3 Pa). A higher overpressure would result in cooling the heating section with cooling air, decreasing the sterilization efficiency of the heating section.

The certification activities include a series of process documentation and qualification studies that start with the initial installation of a steriliza­tion system and continue as process engineering changes or new or revised product introductions are required. Qualification activities comprise instal­lation, operational, change, and performance phases.

Procedure

1.   Installation Qualification (IQ)
The initial IQ hot air sterilizer tunnel certification shall consist of the development of the following information package:

Hot air sterilizer tunnel dimensions

Product carrier description

Utility support system description

Sterilizer equipment description

Equipment control system description

2.   Process Description
Description of the sterilization medium employed

Description of the cycle steps and process functions initiated during the sterilization process

Type of process control employed, i.e., time and temperature or product container control

System operating procedures and system flow diagrams.

SOP No. Val. 700.20            Effective date:  mm/dd/yyyy      

Approved by:

3.   Product Safety
To confirm that product safety considerations have been addressed, review of tunnel construction and operation materials for product contact potential or suitability shall be documented. Tunnel construction materials, which contact the sterilization medium, shall be identified. This would include:

Product carriers

All exposed potential medium contact surfaces including heating and cooling sections

Heat generating, cooling, and conveying system

Equipment lubricants with potential product contact implications must be verified as not jeopardizing product integrity. Lubricants should be identified.

4.   CRITICAL PROCESS INSTRUMENTATION LIST
Temperature control and monitoring systems

Pressure control and monitoring systems

Carrier drive monitoring systems

Critical system alarms

The following equipment installation qualification checks shall be performed:

4.1   DOP TESTS OF HEPA FILTERS
Test objective
To demonstrate that HEPA filters are properly installed by verifying the absence of bypass leakage and other defects such as tears and pinhole leaks

Test method
This test is performed only by certified or previously trained personnel who introduce DOP aerosol upstream of the filter through a test port and search for leaks downstream with an aerosol photometer. Filter testing is performed after operational air velocities have been verified and adjusted where necessary.

NOW YOU CAN ALSO PUBLISH YOUR ARTICLE ONLINE.

SUBMIT YOUR ARTICLE/PROJECT AT articles@pharmatutor.org

Subscribe to Pharmatutor Alerts by Email

FIND OUT MORE ARTICLES AT OUR DATABASE


 

Pages

FIND MORE ARTICLES