Considerations for Aseptic Processing and Sterile Fill-Finish Manufacturing

 

When considering aseptic processing and sterile fill finish, we account for certain things.

Three of those considerations we mainly consider among other things are:

1. Drug Product Component
2. Dispatch System
3. Cleanroom equipment 

Drug Product Components

Injectable sterile drugs are frequently the first pharmaceuticals that come to mind when one says "sterile fill finish" (e.g., liquids filled in vials or syringes). While emulsions, suspensions, and liquid solutions are frequent choices for sterile aseptic fill finish activities, powder fills and lyophilization (i.e., freeze-drying to retain and acquire better stability) are frequently carried out under aseptic circumstances.

Regardless of form factor, every component that makes up a drug product needs to be sterilized before aseptic fill finish. This covers all excipients used in a formulation, such as water for injection (WFI), active pharmaceutical ingredients (APIs), and others. 

Sterilization is also required for equipment and container systems and we make sure that at Abbvie Contract Manufacturing, we sterilize all our equipment. 

The following techniques are FDA-recommended for sterilizing parts and equipment and we use both:

1. Heat Sterilization
   
   

The most popular form of sterilization for processing equipment is heat sterilization, which involves exposing a component to either dry heat or moist heat (autoclaving) for fill finish.

2. Radiation Sterilization
   
   

Gamma rays or other electromagnetic radiation is used during radiation sterilization to kill germs on a component. If a component is heat-sensitive, it might be advantageous.

3. Filter Sterilization
   
   

Filter sterilization is a technique in which a component is dissolved in a solution (WFI or another appropriate vehicle) and passed through a membrane with a pore size of 0.2 microns or less. This eliminates bacteria and other germs. However, it is ineffective if a formulation component's particle size is too large (e.g., suspensions). 

Furthermore, bacterial endotoxins must be regulated at the raw material stage; this does not eradicate them.

4. Ethylene Oxide Gas Sterilization
   
   

Ethylene Oxide Gas Sterilization is a technique that exposes a component to ethylene oxide (EtO) for an extended period of time in order to sterilize bulk API powder and container systems. Heat- and moisture-sensitive components can be sterilized using this technique.

Studies that confirm the procedure is appropriate for a particular component and does not result in degradation or failure should be considered when choosing a sterilizing method for medicine fill finish. 

Written procedures and suitable standards for accepting or rejecting contaminated components must also be included with each of these approaches.

Dispatch System

Vials, syringes, bottles, cartridges, and ampoules are just a few examples of glass or plastic container systems that can be processed aseptically and put through sterile fill-finish processes. Single-dose blow-fill-seal (BFS) containers made of plastic and more recent multidose, sterile-delivery packaging may also be alternatives for ophthalmic medicines.

Pre-sterilization is usually used in glass containers to get rid of foreign objects. A succession of wash and rinse cycles using ultra-pure water make up the procedure (WFI if the container is for a parenteral drug product). 

The containers are then routinely sterilized and depyrogenated using dry heat to kill germs and eliminate endotoxins. 

Based on validation experiments that alter circumstances and gauge the uniformity of sterilization and depyrogenation under various container loading scenarios, the precise parameters of sterilization and depyrogenation are determined.

Cleanroom Equipment

In cleanrooms that are intended to accommodate the flow of people, materials, and equipment during a manufacturing process processing and sterile fill-finish operations take place.

An environment that is strictly regulated for employee access, contamination levels, pressurization, temperature, and humidity is known as a clean room. Multiple rooms with various levels of control make up the cleanroom suite. 

This type of layout, known as a "cascading" design, sees an improvement in air quality as one approaches the facility's aseptic center. In supporting areas where operations like dressing, nonsterile preparation, and formulation can happen, the flow of people, things, and equipment begin.

The Critical Area, which has received ISO 5 certification, maintains the highest degree of air quality. The critical area involves handling sterile materials before, during, and after filling and sealing processes (e.g., aseptic connections, sterile component additions). 

The fact that the medicine and its components are exposed to the environment makes it crucial that the actions of the staff, the level of pollutants, the pressurization, temperature, and humidity in this space are strictly regulated, maintained, and constantly watched.

At Abbvie Contract Manufacturing, we consider all requirements for aseptic processing and sterile fill finish by meeting and exceeding FDA standards. Pharmaceutical fill finish manufacturing is what we do, and we are good at it.