What is the BFS? Advantages of BFS

Blow Fill Seal – BFS technology is the latest in  Pharma product processing that allows pharma manufacturers to contain a drug product in plastic container, that take any shape and form. This process is specifically helpful to contain biological products that can face molecule degradation, when using conventional methods. Initially it was being used for liquid products and Large Volume Parental, but now it is also being considered and applied for injectable.

What is the BFS?

BFS is a technology in which a drug container is formed, immediately filled and sealed in a sterile environment. The entire process is completed in a single stage, in a single machine without taking the product at other location and machine.

The material of construction for the container is plastic, and requires plastic grain of sufficient size and shape to match the required physical characteristics of the container. The plastic grain is fed to the extruder section of machine that eventually converts it into the container.BFS is commonly used for primary packaging and has been recognized by major regulatory bodies around the world as a manufacturing process for sterile injectable. 

BFS process

The BFS process is a continuous process within a machine and is completed in a single process.  Let’s briefly explore this processes

Extrionus

It is the first stage of the process where molten plastic granules are extruded into a die mold of the desired container that enables the plastic to take the container shape.

It is executed at high temperatures that melts the plastic, and is pressed through a small orifice opening in the mold. The pressing enables the molten plastic to take the shape of continuous tube. At this stage, the die mold is open from the center

Blowing

The blowing is the second stage where the hot molten plastic is subject to pressurized sterile gas, and as a result, the hot molten plastic takes the shape of the mold. At this stage the basic physical appearance of the container take its shape.

The sterile gas can be any inert gas, such as nitrogen. Vacuum is also used in some machines to aid the blowing process

Filling

In the filling process product is filled into the molded plastic.  Nozzles enter into the molded container usually from top to start filling, up to a specific level. To prevent contamination in the product, nozzles and openings are showered with sterile gas.

After liquid has been filled, nozzle retract back to their home position to for the next stage process.

Sealing

In this stage the mold is sealed. During this process, the plastic takes the shape of the container with the liquid inside. The resultant is a finished container that can be used as usual filled container.

De-flashing and scrapping

This is the last stage in the BFS process,  where the excess plastic is scrapped from the container edges for container physical finish.

After this process, the containers are delivered outside the machine for collection and further stages.

Advantages of BFS

Let's discuss some advantages of BFS in the pharmaceutical industry

Less human intervention

Humans are the main source of contamination in Pharmaceutical industry. An effective way of reducing contamination is by restricting humans to perform routine operation and automating these processes. The BFS can effectively apply this phenomenon and can provide good protection against human contamination.

In the BFS machine, the process take place with the minimal human intervention. The container formation and filling process is performed in an enclosed environment that becomes unable for humans to interact with. Additional measures, such as showering with sterile gas and particle monitoring also increase the integrity of the process

No container defects

Containers defects are common in conventional processing and greatly contribute to the contamination. It also causes defect in product at different stages, some of them are described below

· During transportation and handling, containers have the higher risk of damage, and a single container can also damage other containers.

· Variation in container manufacturing also changes the approved specification of the container, and becomes un-fit for being used for pharmaceutical operation.

· Container can also break during the filling process due to many reasons such as machine fault, operational error or operator’s fault. This becomes dangerous for the humans and can cause contamination in the product

· Glass containers requires cleaning and sterilization, prior to filing. Additionally filled containers also require autoclaving for terminal sterilization

The BFS technology on the other hand is free from above mention limitations due to the inherent design feature. Plastic granules enter the machine for container formation, eliminating the problem of damage and breakage.

Variation in container manufacturing process is also eliminated because plastic grain is the source of container manufacturing, the specification of which can be validated during its sourcing. Subsequently, container damage in the machine is also eliminated

Contamination control

BFS technology provides greater contamination control in contrast to conventional methods due to features such as less human intervention and in-process container formation. The filling compartment is installed in class A environment, connected to other part of machine (located lower grade areas) through appropriate filters and cleaning mechanisms

BFS technology does not require conventional processes such as washing and de – pyrogenation, and are combined in a single process. Elimination of these processes prevents problems associated with these stages such as temperature problem, area and machine error.

Universal container design

Conventional packaging containers specifically comes in a standardized size & shape, and pharma and drug manufacturers have to match their dosages to these available container designs. Unlike, a pharma manufacturer who’s dosage size doesn't match the available containers, they have to change their product characteristics.

BFS technology has not this limitation because the plastic granules can be melted into any physical characteristics by developing a custom mold and container can be formed in less time.

This approach provides the Pharma manufacturer advantages, some of them are described below

· Pharma product manufacturer can manufacture different size product in a single machine without costly and time consuming changeovers

· It allows Pharma product manufacturer to diversify their product portfolio to meet various demand requirements.

· It provides an opportunity for cost saving by reducing the material consumed and less shipping cost. On the contrary, conventional glass containers cannot be custom designed. If less volume of pharma product is supplied in an available large sized container it will increase the cost of shipping per unit of product.

Less particles 

Conventional glass containers are prone to contamination at different stages during their inherit design process, such as during sealing process that generates black particles due to burning of glass particles.

For the BFS technology there have been some traces of plastic particulates at different stages. This problem can be mitigated by improve design and enhanced feature, and provides better particle control as compared to conventional processing systems.

The enclosed design, appropriate filters and showering by sterile air are one of many features that help to reduce particulate material.

Consideration for BFS technology

Let's discuss some consideration for selecting an operating BFS

Drug compatibility

One of the consideration for the BFS technology is the compatibility of the drug product with the plastic being used. It is essential for both drug and plastic to not react with each other that must be verified during validation and qualification stage.

Viscous products

For highly viscous products, such as ointments, it becomes difficult to push the product as compared to the liquid products. This limits the usage of BFS technology with viscous products

Regulatory guidelines

Let’s discuss some regulatory guidelines for blow fill seal technology for the United States.

In the United States, the FDA is the regulatory body for the US. It provides guidelines about BFS in its guidance “Sterile Drug Products Produced by Aseptic Processing — Current Good Manufacturing Practice”.

Some important points related to BFS are described below

· This guideline identifies three critical steps that pose danger due to particle contamination, or with surrounding air as, and are as follows

o Parison is cut

o Parison is moved under the mandrel

o Mandrel is removed

· BFS machine, and its surrounding must be designed so as to prevent contamination with any potential source.

· The product contact surface must be sterile

· A validated steam in place system must be used for sterilization.

· The classified environment should meet Class 100,000 (ISO 8 )

· HEPA filtered or sterile air should be used during when sterile products or materials are exposed.

· Class 100 ( ISO 5) should be used in critical areas

· Class 100 (ISO 5) airborne level should be maintained

· Qualified personnel with proper gowning should be allowed to enter in classified environment around the BFS machine

· Apply specialized measures to reduce particle levels that can pose potential contamination

· Control particles generated during plastic extrusion, cutting or sealing

· Control airflow to move generated particles outward

· Used additional features such as Barrier and Pressure Vacuum

· Establish an adequate preventive maintenance program to keep the integrity of cooling, heating and other utility systems.

· Pay special attention to critical parts and process during Validation and Qualification.

· During plastic material selection, determine , if the material is safe for pharma product

· Apply various in-process control techniques.

· Monitor the microbial air quality with adequate sampling plan

· Reliable inspection of each batch should be performed properly to identify defective units.

· Investigate critical defects such as wall thickness, container , closure interface deficiency and poorly formed closures.

About the Author:

Muhammad Asim Niazi

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.