The blow-fill-seal (BFS) technique is a specialized packaging method for producing small liquid-filled containers in a continuous, integrated process. Polymer granules are extruded into a tube, or parison, filled with liquid, and sealed without exposure to the non-sterile environment. Key steps include parison extrusion, container molding, aseptic filling without interruption, and container sealing. BFS provides advantages over conventional filling by integrating forming, filling and sealing in a continuous sterile process without pre-fabricated containers.

2. 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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3. 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.

4. 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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5. ExtrudingExtruding BlowingBlowing FillingFilling SealingSealing Mould
Opening
Mould
Opening
Steps of Blow-Fill-Seal Technique
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6. 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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8. Parison ExtrusionParison Extrusion
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10. 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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11. 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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12. 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

13. • 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

14. Means of contamination
• Means of BFS container contamination
• Means of contamination from Product Components
• Equipment interventions and maintenance
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15. Validation of BFS Sytems
• Clean in Place (CIP)
• Steam in Place (SIP)
• Qualification of Aseptic Filling
• BFS Containers
• Filtration
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16. Packaging with Blow-Fill-Seal-Technology
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17. 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

18. References
1. 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…?
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