What is Aseptic process sterile dosage form?
The parenteral dosage form is required to be sterile and free from viable and non-viable microorganisms’ bacterial contamination as well as viral contamination. Aseptic process sterile dosage form manufacturing involves filling of sterile drug in to sterile containers and closures, inside a sterile environment clean room.
Since the injectable dosage form drug is directly injected into the bloodstream intramuscularly or into vein (Intravenously) with the help of syringe and needle. It is called sterile dosage form since the process of sterilization is applied during the manufacturing of the drug product.
It’s not only the microbial contamination but the presence of the bacterial secretions like endotoxins and exotoxins are also of big concern, as they may cause serious anaphylactic reaction if they enter in to blood stream and may go to cerebellum and cause damage to tissues like brain and heart.
These endotoxins are small protein molecules and are capable of eliciting immune reactions anaphylaxis which cause rise in temperature, shock and death. These protein molecules are called pyrogen due to their ability to give rise to fever, (pyrogenic —pyrogen).
It’s not only the drug solution but the primary packing material that comes in contact with the drug product is required to be sterile and pyrogen free.
Methods of sterilization of Drug product:
Thermostable liquids are made sterile by autoclaving at 1200 and at 15 PSI pressure for 30 minutes. Assisted with terminal sterile filtration.
Thermolabile liquid is made sterile by filtration through filters of pore size less than 0.2 micron G2 filters, a series of sintered glass of polytetrafluoroethylene filters are used to filter the liquid before the final filling into the primary container.
Methods of sterilization of Primary Containers and closures:
Dry heat sterilization at 230 degree celsius for two hours, containers and closures are sterilized in the oven at high temperature, the plugs made up of bromobutyl rubber also sustain the temperature and are made sterile.
Gamma radiation: The final drug as well as the primary containers can be made sterile with the help of gamma radiation, this is a very effective method to achieve sterilization.
Requirements of clean room for aseptic procedure sterile dosage form:
Clean room which will be used to fill the sterile drug product with aseptic process is also required to support the sterile filling, means the there should not be viable and nonviable particles at the point of filling, this is achieved by placing a laminar air flow unit which supply the heap filtered air to the spot of filling, the cleanness level at the point is of ISO 5 or Class 100 or Class A.
The immediate surrounding the filling point is Class 1000, the air flow is maintained so that the inside the filling spot air is not contaminated with air from the outer periphery.
The pressure differential between the core filling area and the passage is maintained not less than 15 PSI
The equipment which comes in direct contact with primary containers and products is sterilized with a steam suitable sterilization method.
Man and man movement in the sterile filling: The person working in the sterile filling must not have any contagious disease, free from any disease like TB. Free from any viral and bacterial infection, healthy individuals.
Man and man movement are the main reasons which cause the highest number of particle generation and pose risk of contamination therefore the control of man movement can be restricted with the help of Restricted access barrier systems, Sterile dosage form processing Isolators. Gowning used by man is sterilized by autoclaving, contact with the inner surface machine by a person with his bare hand should be restricted, sterile gloves should be used.
How to maintain the sterility of the clean room?
Sterilization of the clean room with the help of Hydrogen peroxide and Silver ions contain liquid fogging is found to be effective, before filling the equipment nozzles and duct lines are washed with sterile water for injection, and dried in place under HEPA filtered sterile air, in case of dry powder for injection is to be filled. After fogging with disinfectant solution cleaning of equipment and sterilization is performed before filling.
Risk assessment for sterile dosage form filling.
Validation of sterile drug filling in aseptic process sterile dosage form manufacturing.
Sterile dosage form filling is assessed with its capability to maintain sterility of the dosage form being filled, it is ascertained with the help of media fill runs.