Advancement in Aseptic Processing

Aseptic processing produces contaminants, foreign bodies, and bacteria-free pharma products without using the terminal sterilizing method. In contrast to traditional pharma product that utilizes terminal sterilization to ensure sterility, aseptic processing products cannot use terminal sterilization because the final finished product cannot tolerate high temperatures for sterilization, which results in the deterioration of internal chemical compounds and API. 

Aseptic processing ensures product purity by various alternative methods, such as filtration, specialized equipment design, and other methods, during the manufacturing stage. 

Common methods of achieving sterility during aseptic processing include but are not limited to 

• Before manufacturing aseptic products, items (such as raw materials, equipment, tools, instruments, and containers) are individually sterilized to increase sterility. It eliminates any contamination or traces at the initial level before starting the manufacturing process.

• Strict environmental control procedures are deployed to provide sterile working conditions, such as area control, restricted operator movement, and controlled airflow to prevent the effect of contamination from the surrounding.

Aseptic processing is useful for products that cannot withstand high temperatures during terminal sterilization. 

Examples of these products include biologics and vaccines that lose efficacy and become ineffective when subjected to terminal sterilization. 

Advanced aseptic processing

Advanced aseptic processing is a term used to describe manufacturing processes executed with minimal human involvement, unlike traditional processes that require direct human involvement. Since humans are the major source of contamination, restricting humans in the manufacturing process greatly helps to control contamination. 

In advanced aseptic processing, humans execute manufacturing operations through mechanical parts, accessories, and tools purposely built to provide interaction between operators and the manufacturing process. Humans still control and execute manufacturing operations but have zero physical interaction with manufacturing processes and equipment. 

In traditional systems, humans fully do not have isolation between manufacturing equipment and process, and they have to interact with the manufacturing process physically. The human operator’s hand, wearables, and gown are some examples that directly connect with the product and equipment during manufacturing. It increases the probability of affecting the sterile product and process with foreign particles, contaminants, and microorganisms. 

Applications of advanced aseptic processing

Aseptic processing is commonly used for filling and sterility tests in the pharmaceutical industry. Let’s briefly discuss these applications. 

Aseptic Filling

Aseptic filling is the process of filling sterile drug products into containers without human intervention. Sterilized containers are fed to the machine from the input section of this equipment. The machine automatically transfers them to the filling station and performs filling, sealing, and capping in a controlled and sterile environment without direct interaction with humans.  

The vials are supplied to the filling machine in a Nest, in which vials are organized according to the filling orientation and are locked for smooth filling. 

A robotic arm with a filling needle pierces the vial's stopper and fills up to the desired volume. After filling, another robotic arm seals and caps the vial.

After the entire process, filled vials are transferred to the discharge station or output, where they can be collected. 

Sterility Testing

Sterility testing is a test performed on sterile products to ensure these products do not contain any viable microorganisms. In traditional methods, it is possible that the operator and environment can contaminate the test sample. By implementing aseptic conditions, sterility testing can be protected from the risk of contamination through the analyst and environment. 

The test samples, testing agents, tools, accessories, and other necessities are loaded into the aseptic equipment. The test bench and operators are isolated using a physical barrier. Human operators use gloves attached to the equipment to perform the required test without directly interacting with the test and bench.

Important components of equipment for advanced aseptic processing

The design of aseptic processing equipment differs and mainly depends on the application. However, every aseptic equipment must consist of basic design requirements, which include the following.

HEPA Filters

Like every pharma process and area, aseptic processing requires constant airflow, flowing in and out of aseptic equipment. To prevent contamination through airflow, HEPA filters are used at the air inlet to filter out contamination in the airflow stream. HEPA filters are contained in a filter assembly made up of SS316L.

Gloves

Gloves are attached to the aseptic processing equipment to enable humans to perform the required tasks. They are sealed with side walls to prevent penetration of foreign bodies and contaminants inside the equipment. Usually, they are up to shoulder length to provide maximum working length to the operators because the length of the gloves limits the working of humans.

Transfer System

Transfer systems are mechanisms by which items such as products, tools, accessories, and testing agents are placed inside the equipment. It can consist of doors, windows, and panels. It also consists of an airlock between the transfer mechanism and an aseptic area to prevent a mix-up of clean and dirt air.

Airlock is a small area that is separated from both the aseptic and transfer areas through doors interlocked with each other. Interlocking prevents the opening of both doors simultaneously, i.e., when the transfer side door is open, the aseptic side door cannot be open, and vice versa. Additionally, the door cannot be opened for a pre-determined time after closing any one door. 

When items are placed in the transfer mechanism, items remain in an airlock for a pre-determined time to make then items decontaminated. It can be performed through an air shower or any other process, which removes any foreign particles and is carried away by the force of flowing fluid. After a pre-determined time, the door can be opened, and items can be taken off the airlock.

Monitoring Systems

Monitoring systems monitor the aseptic equipment's inside environment and can trigger an alarm if variables drift out of range. It consists of various instruments and sensors able to detect and measure process variables.

The output of these sensors is connected to the main controller for automatic monitoring. The values of these sensors and instruments are also displayed on the control panel or local display for operator reference. Examples of variables that are monitored include temperature, pressure, particles, and airflow.

Airflow

Airflow controls the air flowing inside and outside of aseptic processing equipment. It consists of a motor-driven blower to generate the required amount of air. The main controller controls the motor, which takes input from the operator. 

Air blowers are connected to the equipment through the ducting system, which is used to supply air to its respective opening from the blower.

Types of equipment for aseptic processing in pharmaceutical industry

The pharmaceutical industry has many types of aseptic processing equipment for various functions and applications. Let’s discuss some common types.

Isolators

In simplest terms, isolators are aseptic equipment that provides a physical barrier between humans and the processing area that can be used for any relevant purposes, such as filling and testing. The controlled area is sealed by all means to prevent untreated or dirty air from flowing inside it. The isolator is provided with all the process requirements, such as airflow, filtration, tools, and accessories. 

HEPA filters are used inside the controlled area to provide the required level of purification. 

In the pharmaceutical industry, two types of isolators are used – Positive pressure and Negative pressure.

Positive pressure isolators remain positive w.r.to the surrounding environment, so airflow is outward from the controlled container. These isolators are used to protect the product or process being carried out. 

Negative pressure isolators remain negative w.r.to the surrounding area, and their airflow is inward from the controller area. These isolators provide personal or environmental protection, as the air remains inside the controlled area.

The isolator provides an automatic decontamination cycle, i.e., items can be automatically decontaminated when transferred into it.

Restricted Access Barrier Systems – RABS

Restricted Access Barrier Systems - RABS provides a physical barrier between the workbench and the human operator. However, they are inferior in functionalities and capabilities to isolators. 

RABS lacks automated decontamination cycles like in isolators and requires manual cleaning and decontamination through cleaning agents. 

Airflow in RABS is also simpler in design than in isolators. Instead of a series of supply-return ducts and associated HVAC components, RABS only includes supply fan supplying fans in a controlled manner through HEPA filters. After serving the aseptic equipment, this air flows out into the surrounding area. 

Robots

In Robot aseptic processing, human intervention is fully eliminated. Robots perform every function and application that humans carry out in isolator and RABS technology. 

Robotic aseptic processing is gloveless isolators and uses the capabilities of a robot for pharma processing. This aseptic processing can handle all routine operations, such as filling and testing. It provides flexibility in handling different containers for different sizes. Additionally, it eliminates the need for glove decontamination and testing, a common requirement for isolators and RABS. 

Robotics aseptic processing is extremely helpful for areas and products that are dangerous for humans, such as highly potent compounds. Additionally, robotics are extremely flexible and can be tailored for a number of applications just by changing the end of arm tooling, accessories, and programming. This contrasts isolator and RABS, where the entire equipment needs to be changed. 

About the Author

Muhammad Asim Niazi has a vast experience of about 11 years in a Pharmaceutical company. During his tenure he worked in their different departments and had been part of many initiatives within the company. He now uses his experience and skill to write interested content for audiences at PharmaSources.com.