Sterile Dosage Forms - Aseptic Processing And Terminal Sterilization

STERILE DOSAGE FORMS   ASEPTIC PROCESSING AND TERMINAL  STERILIZATION

 

A dosage form is said to be sterile when it is free from:

v Microorganisms

v Spores

v Pyrogens

v Pathogens

Sterile dosage forms are prepared and stored under aseptic conditions. The dosage form is made sterile by using different methods of Sterilization:

Dosage forms that require to be sterile are:

v Ophthalmics

v Pulmonary drug delivery

v Parenterals:

·       Injectables

·       Infusions

·       Implants

 

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 sterilization process.

A.TERMINAL STERILZATION

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 include:

1.    Overkill method:

·       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 being sterilized.

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 the product.

·       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 contamination.

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.