21 CFR parts 210 & 211 states about current GMP requirements for biological products covered by 21 CFR 600-680. Sections 210.2(a) and 211.1(b) provide that where ever it is impossible to comply with the applicable regulations, the regulation specifically applicable to the drug product in question shall supercede the more general regulations. You need to factor 21 CFR 211.113(b) which states, ” A appropriate written procedures, which are designed to prevent microbiological contamination’s of drug products which are purporting to be sterile, should be established and followed. Such procedures should include validation of such sterilisation process.”
Aseptic process of manufacturing of sterile pharmaceuticals is a process of manufacturing which involves transfer of a sterile drug in to a sterile container manually or automated procedure in a sterile and aseptic aria.
While other way in process of terminal sterilization , all containers are rendered sterile by dry heat sterilization or autoclaveing .
Media fill runs for sterile dosage form manufacturing validation
Media fills is a process which simulates the risk of contamination which arises during the process of filling of sterile dosage form in both terminal sterilization as well as aseptic process, a sterilized placebo of a dosage form. Placebo should be chosen to be of similar flow & filling performance characteristics to the sterilized dosage form to mimics exactly with the normal conditions of the aseptic process of production, as most critical operation within aseptic manufacture is the aseptically filling stage. At the point of filling, sterile dosage form is at highest level of risk of contamination from environmental or air-borne microorganisms while it is being transferred from one container to other.
Media fill is a process simulation it should be done so that it simulates the exact routine production process, which includes steps in formulation, filtration and filling stages. This will vary in relation to the type of product to be filled, example .liquid or solid dosage forms, and all process simulation is a completely unique event .
The study should be performed using a microbiological growth media in place of a active medicament. it can be treated as a ‘worst case’ scenario as most of the pharmaceutical products do not support microbiological growth. Selection of medium in Midia fill run is based on its ability to integrate into the process at the earliest step and can be introduced in to the filling process by filtration. Growth promotion a characteristic has to allow recovery of a typical flora recovered from environmental monitoring programs. Many times microbiological media themselves become a a source of contamination so this can be avoided by media irradiation and can be presented either in the dehydrated format or as a ready to use broth.
latest culture media, are available in market which are specially made for media fill trials, possess certain characteristics which allows process simulations; they are irradiated so that they can be used for introduction into compounding areas, can be dissolve in cold water and we can have filtration performance.
Sterile dosage form may get contaminated by surface-to-surface transfer of microorganisms from personnel as well as the manufacturing equipment. Freedom from microorganism of such manufacturing equipment is very important factor. Effective cleaning and decontamination procedures are important aspects of aseptic manufacture. Aseptic manufacture brings a sterile dosage form and the finished presentations pre-sterilised product-contact components together without contaminating them. It is also essential for equipment to be maintained sterile in between clean-downs. Unprotected environments where contamination by air-borne microorganisms is inevitable. Hence aseptic filling equipment are placed in areas that are protected from the general contaminated environment ie clean rooms.
During midia fill run personnel, components, equipment, movement and services in and out of protected areas needs also to be controlled if the protective barriers are to be effective in preventing contamination. Necessary intrusions to be brought into the aseptic areas through some form of decontamination or sterilisation process, example, via a double-ended autoclave. Personnel should be gowned in sterilised clothing that prevent skin borne and hair borne micro organisms, respiratory and digestive activities from contaminating the aseptic area, the manufacturing equipment, or any component of the sterile preparation . Personnel should be trained for aseptic techniques of working in aseptic areas, a specific localized protection must be provided to a written procedure for aseptic operations and techniques should be provided to operators.
CASE STUDY OF A MEDIA FILL TEST FAILED
You will get detailed information about pharmaceuticals and pharmacy related to pharmaceuticals manufacturing over this blog about following topics
Quality management guide for pharmaceuticals
Quality Guide for pharmaceuticals
Quality assurance in pharmaceuticals Pharmaceuticals guide
Quality assurance for pharmaceuticals manufacturing
Pharmacy guide Sterile dosage form
c GMP for pharmaceuticals.
Sterile dosage form manufacturing and its requirements.