Blow Fill Seal TechniqueBlow Fill Seal Technique Blow Fill Seal Technology refers to manufacturing technique used to

produce small, (0.1 ml) and (500 ml +) liquid filled containers.

Blow Fill Seal is a specialized packaging used in line forming and sealing

of polymeric material to a container of choice.

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BFS Technology

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• It refers to the technology and related equipment and procedures in which the

formation of the container, its filling with liquid pharmaceutical material, and

subsequent formation and application of a seal for container are achieved

aseptically in an uninterrupted sequence of operations without exposure to

nonsterile environment.

BFS Process Steps

• The BFS cycle can be divided into the following steps:

Step 1: Parison Extrusion

Step 2: Container molding

Step 3 : Container Filling

Step 4: Container Sealing

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ExtrudingExtruding BlowingBlowing FillingFilling SealingSealing Mould OpeningMould

Opening

Steps of Blow-Fill-Seal Technique

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Outline of the BFS Process

Polymer granules are fed to a machine hopper through an adiabatic screw

extruder.

Within extruder, polymer is subjected to high temperatures (>160°c) and

pressure (up to 350bar) and become molten.

It is extruded through a die and pin set to form open-ended tube of molten

polymer known as PARISON.

Parison – supported by sterile air that is fed into center of parison through

a sterilizing grade air filter.

Mold set in two halves moves over to the parison and closes around it.

Parison moved to filling position and containers are sealed by second mold

set, which forms the neck and closure of BFS containers.

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Parison ExtrusionParison Extrusion

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Filling Environment

Aseptic BFS machines are housed within classified clean areas of a

minimum specification of class M5.5 (Federal Standard 209E) for 0.5

mm particles and greater (or equivalent), at rest.

The new generation of BFS machines also is capable of operating

with significantly decreased particle levels.

The localized filling environment, or ‘‘air shower,’’ is of a higher

classification, which meets the specification of class M3.5 (FS 209E)

for 0.5 mm particles and greater.

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Blow-Fill-Seal (BFS)

Located in a Grade D environment.

Critical zone should meet Grade A (microbiological) requirements (particle

count requirements may be difficult to meet in operation).

Operators meet Grade C garment requirements.

Validation of extrusion process should demonstrate destruction of

endotoxin and spore challenges in the polymeric material.

Final inspection should be capable of detecting leakers.

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Air handling system

Grade

Maximum permitted number of particles/m3 equal or above

at rest in operation

0.5µm 5.0µm 0.5µm 5.0µm

A 3,520 29 3,500 29

B 35,200 293 3,52,000 2,930

C 3,52,000 2,930 35,20,000 29,300

D 35,20,000 29,300 not defined not defined

1. Air Classification as per Schedule M

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Grade ISO Class Particle/cum Class(SI)

A 5 100 3.5 M 3.5(filling)

B 6 1000 35 M 4.5

C 7 10000 350 M5.5 (preparation)

D 8 100000 3500 M 6.5

2. As per ISO

• No need to purchase and stock a range of pre-fabricated container and closures.

• Cleaning and sterilizing pre-fabricated container and closures are not required.

• A clean sterile container is made with in the BFS machine.

• The cost of material transport, storage and inventory control is reduced.

• Validation requirement are reduced.

• There is a large choice of neck and opening device shapes.

• Saving floor space.

• Less labour intensive than conventional one.

• The code number and variables can be moulded into container it-self

• With blow-fill-seal, you produce a one-piece, aseptically filled container with a built-in

safety seal.

• The blow-fill-seal process is suitable for heat-sensitive products

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Advantages over Conventional Aseptic Filling

Means of contamination

• Means of BFS container contamination

• Means of contamination from Product Components

• Equipment interventions and maintenance

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Validation of BFS Sytems

• Clean in Place (CIP)

• Steam in Place (SIP)

• Qualification of Aseptic Filling

• BFS Containers

• Filtration

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Packaging with Blow-Fill-Seal-Technology

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Conclusion

• Aseptic BFS technology for manufacturing of sterile liquid

product demonstrates high level of sterility assurance when

operated correctly to minimize container contamination and

obtain high standards.

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Aseptic processing Technique

References1. C S Sinclair and A Tallentire, “Predictive Sterility Assurance for Aseptic Processing”,

Sterilization of Medical Products, (R F Morrissey, ed.), VI, 1993, Polyscience

Publications, Montreal, pp. 97–114.

2. C S Sinclair and A Tallentire, “Performance of Blow-Fill-Seal Equipment under

Controlled Airborne Microbial Challenges”, J. Paren. Sci. Technol., 49 (6) 1995, pp.

294–299.

3. A Bradley, S P Probert, C S Sinclair, and A Tallentire, “Airborne Microbial Challenges of

Blow/Fill/Seal Equipment”, J. Paren. Sci. Technol., 45 (4) 1991, pp. 187–192.

4. P Poisson, “Non-Viable Particle Management During B/F/S Manufacturing

Operations”, BFS News, Autumn Edition, 1999, pp. 12–16.

5. P Poisson, C Reed and C Sinclair, “Challenge Testing of the KleenKut Parison Cutoff

Mechanism”, Joint Presentation, BFS User’s Group Annual General Meeting,

Switzerland, 14 June 2001.

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Questions…?

Thank you…!!