In 2011 this blog was listed as one of the top 10 blog in pharma technical information it is popular amongst the pharmacists and pharma industry professionals. We have published very important and very useful information for pharma industry professionals.

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

http://whoguideline.blogspot.com/2009/07/media-fill-test-assurance-of-sterility.html

B. Filtration Efficacy.
 ( Filtration Efficacy topic is disscused in last article you can read this over here http://whoguideline.blogspot.com/2010/02/aspects-of-validation-of-aseptic.html  )

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

http://whoguideline.blogspot.com/2009/11/us-fdas-requirements-of-documentation.html

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.

No comments:


What is 21 CFR Part 11, US FDA guidelines requirements of FDA compliance and CFR 21 Part 11.

What is a Site Master file of a pharmaceutical company

What is Generic Drug

What is Reference Listed Drug  ? ( RLD )

What is Pharmaceutical Equivalents

What is Pharmaceutical Alternatives

What is Therapeutic Equivalents

What are Post Market studies

Why a drug is bound to protein, What is protein binding?  What is drug absorption , distribution ?

Do Physical properties contribute to drug activity.

What is drug receptor , How a drug resistance occurs

Mechanism of drug resistance

What is drug interaction

Drug interaction, and its examples

What is first pass metabolism of a drug

What is What is 510(k) Clearances ?

What is 510(k) Clearances,

Premarket Notification for medical devices - PMN or 510(k)

What is a drug interaction

Examples of drug interactions


Antibiotic Definition and classification


Antibiotic Resistance and Antibiotic resistance mechanism

Antioxidants food supplements

Vitamin D Details on FDA cautions on accurate dosage of Vitamin D


What is an antibody? what is monoclonal and polyclonal antibodies?

Terminologies In vaccine Production

Multi stage testing of Virus vaccine production

Testing of vaccines at different stages of production

TESTING FOR ADVENTITIOUS AGENTS CELL PROPERTIES IN VIRAL VACCINE PRODUCTION

Enzyme linked immunosorbent assay ELISA

Raido Immuno assay

http://whoguideline.blogspot.com/2010/04/terminalogy-and-their-explanations.html

Pharmaceutical Aseptic Manufacturing Process Terms , Terminology and Definitions.

http://whoguideline.blogspot.com/2010/02/pharmaceutical-aseptic-manufacturing.html

Here are some articles which will be useful for you in further understanding of aspects of sterile dosage form manufacturing and regulatory affairs and good manufacturing practice in

pharmaceutical industry

Pharmaceutical Validation

Types of validations in pharmaceutical manufacturing


Requirements of documents for validation of sterilisation process

How to investigate OOS out of specification results

Determination of Phenol coefficient of a disinfectant

Sterility testing

Clean Room Classification

Time limitations in sterile pharmaceuticals processing

Aspects of validation of manufacturing process in sterile pharmaceuticals

Clinical Trials

Requirements of US FDA Inspections of Clinical Investigators of Clinical Trials

PROCEDURE OF AN INSPECTIONS OF CLINICAL TRIAL INVESTIGATOR BY US FDA HOW ARE CLINICAL INVESTIGATOR INSPECTIONS CONDUCTED?

US FDA INSPECTION OF CLINICAL INVESTIGATORS OUT OF UNITED STATES OF AMERICA

REPORTS AFTER AN INSPECTION OF A INVESTIGAOTR OF CLINICAL TRIALS

Controlling Pyrogens in injectable dosage forms

Media fill run process simulation aspects Validation of Aseptic Process and Sterilisation

New Drug Application (NDA) how to make a New Drug Application (NDA) to US FDA

Abbreviated New Drug Application (ANDA) What is ANDA , detailed information about ANDA preparation and submission to US FDA

How to make Investigational New Drug (IND) Application to US FDA

Drug applications submission to us fda Over the counter Drugs OTC drugs

BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS

Electronic record in pharmaceutical manufacturing industry

Good manufacturing practice in pharmaceutical industry

Pharmaceutical industry pharmaceutical companies and FDA latest updates