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This blog mainly talks about QMS,cGMP,Regulatory Filings & Guidelines,Validation & Qualifications,Drug Stability,FDA 483s &Media Fill.
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Sunday, 20 October 2013
Sterile Dosage Forms - Aseptic Processing And Terminal Sterilization
STERILE DOSAGE FORMS
ASEPTIC PROCESSING AND
A dosage form is said to be sterile when it is free
Sterile dosage forms are prepared and stored under
aseptic conditions. The dosage form is made sterile by using different methods
Dosage forms that require to be sterile are:
TYPES OF STERILIZATION
There are two broad methods to produce a sterile
drug product: 1. Terminal
Sterilization 2. Aseptic
Processing of sterilized unit components. There are basic differences between
the production of sterile drug products using aseptic processing and production
using terminal sterilization. Terminal sterilization should be utilized when
the product and container/closure system are able to withstand the terminal
The terminal sterilization process usually
involves filling and sealing product containers under high quality
environmental conditions designed to minimize microbial and particulate
contamination of the product. This minimization of upstream bioburden reduces
the challenge to the subsequent sterilization process. In most cases, the
product, container, and closure have low bioburden, but are not sterile at the
time of filling. The product is then subjected to a sterilization process in
its final container. There are various methods of terminal sterilization
including: 1. Moist Heat Sterilization 2. Irradiation 3. Ethylene
Oxide (typically for assembled components/kits) Types of sterilization cycles
·Generally used for heat stable materials.
·Designed to provide a
significant level of sterility assurance regardless of the number and
resistance of the actual bioburden organisms in the load.
·Results in greater heat/exposure input to the product or items
2.Bioburden Based cycle:
·Requires studies to determine the number and resistance of the
microorganisms found in the product and the bioburden load of the incoming
components and containers/closures.
·Cycle development to destroy the microbial load, but not degrade
·Routine bioburden monitoring of batches and ongoing knowledge of
the heat/exposure resistance of organisms found in product bioburden,
container/closure bioburden and environmental monitoring samples.
B. ASEPTIC PROCESSING
Aseptic processing presents a higher risk of microbial
contamination of the product than terminal sterilization. In an aseptic filling
process, the drug product, containers and closures are sterilized separately
and then brought together under an extremely high quality environmental
condition designed to reduce the possibility of a non-sterile unit. Aseptic
processing involves more variables than terminal sterilization. Any manual or
mechanical manipulation of the sterilized drug, containers, or closures prior
to or during aseptic filling and assembly poses the risk of microbial
Some types of aseptic processing involve
manual manipulations of sterile components, containers, and closures in addition
to routine operator interventions in the critical area. Humans are a
significant source of contamination in traditional aseptic processing,
especially in production lines that require operators to routinely enter
critical areas (Class 100, ISO 5, or Grade A) of the filling line. Aseptic
processing systems based on more advanced control-based technologies, such as
Restricted Access Barrier Systems (RABS) and Blow-Fill-Seal systems, are
designed to reduce human interventions in the critical areas of the fill line
while an isolator system completely separates the aseptic filling line from the
external environment and minimizes employee interaction with the critical area.