Blow-Fill-Seal

Advanced Aseptic Filling Technology

A globally-trusted drug packaging process,
reimagined for injectables.

Blow-Fill-Seal (BFS) has evolved over 60 years to become trusted and relied-upon way to package sterile liquid pharmaceuticals. Its versatility enables it to package dose volumes ranging from 0.2mL to more than 500mL.

BFS Manufacturing Unit

Today, BFS is primarily used in the pharmaceutical industry, where it fills and finishes more than 50 billion units a year of biologics, vaccines, pharmaceuticals and other sterile liquids including OTC products.

But what makes BFS truly special is its combination of reliable aseptic filling with its speed and efficiency of production for any size output. In fact, due to its enclosed process and reliability, the industry considers BFS to be an advanced aseptic process.

It is for these reasons and more that BFS is the heart of ApiJect’s Technology Platform, enabling ApiJect and 3rd parties to solve drug delivery challenges with new injection and inhalation systems.

BFS fills small and large molecules.

A range of small and large molecule drug products, including vaccines, have been tested in BFS, with many coming to market. Notable examples include rotavirus, RSV, and influenza vaccines, as well as Albuterol, Tiotropium, Dornase alfa, and Budesonide.

All drug products intended for delivery in ApiJect Prefilled Injectors will have to go through stability and compatibility testing in the low-density polyethylene (LDPE) container. ApiJect is well-positioned to help and support this testing which, depending on the product, can be completed in a number of months.

A proven, efficient, and reliable manufacturing process.

BFS is a continuous filling process that requires almost no human intervention, which is the main source of contamination for conventional aseptic filling processes.

In a process that takes just a few seconds, LDPE plastic resin is extruded into a mold to form the BFS Container, aseptically filled with the drug, and then sealed – all within an ISO Class 5 environment.

The output varies by BFS machine, drug product, batch size, and other variables, but higher-end models such as a Rommelag® bp460-20 that ApiJect uses today can produce a strip of 25 BFS containers with 0.65mL fills every 3 seconds, for up to a potential 15 million units a month.

Blow-Fill-Seal is a continuous scalable process.

BFS is a highly-efficient, low-human intervention process that aseptically fills sterile liquid drugs in pharmaceutical-grade LDPE primary packaging.

01 Extruding

BFS machine pours molten plastic into tube shape (“parison”) inside Class A clean space.

02 Blowing

Airstream blows parison open. Bottom mold closes to create 2-chamber shape.

03 Filling

Rod inserted to fill parison with precise dose of liquid vaccine or medicine.

04 Sealing

Upper mold closes, sealing the top of container.

Laser Etched
Laser-Etched Label.

BFS enables inline labeling during the manufacturing process. Each strip of Containers that emerge from the BFS machine can have the lot number and expiration date laser-etched on to each dose’s label tab. An adhesive label may also be applied to the other side of the label tab if further drug information is required at the dose level.

Punching and Testing
Punching and Testing.

Once the laser-etched strip of BFS containers is released from the BFS machine, the excess plastic trim is “punched” away. Then, the strip of 25 BFS containers is separated into 5-container “cards.” 

Each card is taken through a leak detection process that uses a vacuum decay method. This is followed by an automated visual inspection processes to detect anything that is critical to quality. BFS generates few to no particulates in this process, and the raw materials themselves are not a source of particulates.

Pouching Process
Pouching, Labeling, 
and Cartoning.

Each card is pouched within foil wrap to help avoid vapor loss and protect against sunlight and oxygen. Product identification, lot and expiry details are printed on the foil wrap.

Finally, each wrapped card is efficiently packed in a carton and then a box, and prepared for shipping. The small and compact size of a BFS container potentially allows for efficient use of a cold chain, if required.

Benefits of the BFS process.

Technician on machine

Alternative Supply Chain

Traditional glass vials and syringes use a multi-facility, complex international supply chain to fill and finish drugs. BFS uses an alternative supply chain that is more compact and resilient. The only raw material needed for BFS (other than the drug) is pharmaceutical-grade plastic resin, which is widely available and can be sourced locally in all major countries. Further, resin can be stored relatively long periods of time, allowing for stockpiling in case of emergencies.

manufacturing process

BFS means speed and efficiency

Blow-Fill-Seal is known for its high-efficiency output. For example, a Rommelag® bp460-15 BFS machine is projected to aseptically package up to 25,000 units per hour for ApiJect Prefilled Injectors. But what is less well known is that BFS provides many additional inherent benefits. These include aseptic filling at scale, no preservatives needed in the drug product, and almost no human intervention.

Vials

Polymers Allows for Volume Flexibility

BFS Containers are made from pharmaceutical-grade polymers, such as low-density polyethylene (LDPE) and standard polyethylene (PE). ApiJect's containers are made of LDPE, a common material used in most pharmaceutical manufacturing today, such as drug product holding bags and carboys. The inherent malleability of plastic makes it possible for BFS to manufacture Containers in a wide range of volumes and shapes. In order to maintain efficiency and ensure quality, ApiJect is producing a range of molds to fill all major injectable drug dose sizes.

Thermometer

Controlling Fill Temperature

Filling temperature is often a concern when filling and finishing delicate molecules in BFS, because the drug or vaccine is put into a hot plastic container. But thanks to consistent research and advancements in BFS technology over the last 25+ years, these issues can be largely mitigated. ApiJect utilizes a variety of processes and BFS Container designs to minimize the temperature peak and its duration.

Get in touch to learn more about BFS.

Interested to learn more about how BFS combined with ApiJect's injection technology can grow your drug products? Contact us today.

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