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Friday, February 26, 2010

Aspects of Validation of Aseptic Process and Sterilisation , Sterilization of Equipment, Containers, and Closures

Aspects of Validation of Aseptic Process and Sterilisation , Sterilization of Equipment, Containers, and Closures

We had divided topic "Aspects of Validation of Aseptic Process and Sterilisation" in to three parts .

A. Process Simulations :
This process simulation, also known as a media fill , We have a very good article over this blog about Media fill you can read this over here

B. Filtration Efficacy.
 ( Filtration Efficacy topic is disscused in last article you can read this over here  )

C. Sterilization of Equipment, Containers, and Closures :

Equipment surfaces that contact sterilized drug product or its sterilized containers or closures must be sterile so as not to alter purity of the drug (211.67 and 211.113). Where reasonable contamination potential exists, surfaces that are in the vicinity of the sterile product should also be rendered free of viable organisms. It is as important in aseptic processing to validate the processes used to sterilize such critical equipment as it is to validate processes used to sterilize the drug product and its container and closure. Moist heat and dry heat sterilization, the most widely used, are the primary processes discussed in this document. However, many of the heat sterilization principles discussed in this guidance are also applicable to other sterilization methods.

Sterility of aseptic processing equipment should normally be maintained by sterilization between each batch.(If appropriate, alternate intervals can be defined, justified, and supported by validation studies.)

Following sterilization, transportation and assembly of equipment, containers, and closures should be performed with strict adherence to aseptic methods in a manner that protects and sustains the product's sterile state. Articles are difficult to sterilize, special attention should be given to the sterilization of filters, filling manifolds, and pumps. Some other examples include certain locations of tightly wrapped or densely packed supplies, securely fastened load articles, lengthy tubing, the sterile filter apparatus, hydrophobic filters, and stopper load.

Ultimately, cycle specifications for such sterilization methods should be based on the delivery of adequate lethality to the slowest to heat locations. A sterility assurance level of 10-6 or better should be demonstrated for a sterilization process.
For more information, please also refer to the US FDA'S guidance  entitled Guideline for the Submission of Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products.

See this over here

The sterilizer validation program should continue to focus on the load areas identified as most difficult to penetrate or heat. The suitability of the sterilizer should be established by qualification, maintenance, change control, and periodic verification of the cycle, including biological challenges. Change control procedures should adequately address issues such as a load configuration change or a modification of a sterilizer.

2. Equipment Controls and Instrument Calibration

For both validation and routine process control, the reliability of the data generated by sterilization cycle monitoring devices should be considered to be of the utmost importance. Devices that measure cycle parameters should be routinely calibrated. Written procedures should be established to ensure that these devices are maintained in a calibrated state. For example, we recommend that procedures address the following:
Temperature and pressure monitoring devices for heat sterilization should be calibrated at suitable intervals. The sensing devices used for validation studies should be calibrated before and after validation runs.

• Devices used to monitor dwell time in the sterilizer should be periodically calibrated.

• The microbial count of a biological indicator should be confirmed. Biological indicators should be stored under appropriate conditions.

• If the reliability of a vendor’s Certificate of Analysis is established through an appropriate qualification program, the D-value of a biological indicator (e.g., spore strips, glass ampuls) can be accepted in lieu of confirmatory testing of each lot. However, a determination of resistance (D-value) should be performed for any biological indicator inoculated onto a substrate, or used in a way that is other than described by the vendor. D-value determinations can be conducted by an independent laboratory.

• Where applicable, instruments used to determine the purity of steam should be calibrated.

• For dry heat depyrogenation tunnels, devices (e.g. sensors and transmitters) used to measure belt speed should be routinely calibrated. Bacterial endotoxin challenges should be appropriately prepared and measured by the laboratory.

To ensure robust process control, equipment should be properly designed with attention to features such as accessibility to sterilant, piping slope, and proper condensate removal (as applicable). Equipment control should be ensured through placement of measuring devices at those control points that are most likely to rapidly detect unexpected process variability. Where manual manipulations of valves are required for sterilizer or SIP operations, these steps should be documented in manufacturing procedures and batch records. Sterilizing equipment should be properly maintained to allow for consistent, satisfactory function. Routine evaluation of sterilizer performance-indicating attributes, such as equilibrium (come up) time is important in assuring that the unit continues to operate as per the validated conditions.

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