Basic Concept of Form Fill and Seal Technology

1. FORM FILL AND SEAL TECHNOLOGY
Prepared by
Dr. Kandekar Ujjwala Y.
M. Pharm. PhD.
JSPM’s Rajarshi Shahu College of Pharmacy and Research, Tathwade,
Pune
PROCESS AUTOMATION IN
PHARMACEUTICAL INDUSTRY

2. • Aseptic Blow Fill Seal(BFS) technology is the process by which plastic
containers are formed, filled with sterile filtered product and aseptically
sealed in an uninterrupted sequence of operations within the controlled
sterile environment in a single machine.
• It is used for both small volume parenteral (SVP) (0.1 ml-99ml) and large
volume parenteral (LVP) (100ml and above).

3. HISTORY
Form-fill-seal or Blow-fill-seal technology was originally developed in Europe in 1930s.
It was introduced commercially for the first time in USA in 1960s by the company,
Rommelag.
• Over the last 20years, it has become prevalent technique in pharmaceutical companies.
• It is a robust, advanced aseptic processing technology
• Recognized worldwide by regulatory authorities like USFDA

4. PROCESS
The basic concept is formation, filling and sealing of plastic container in aseptic
environment.
The blow fill process can be divided into following main steps:-
▶ Parison extrusion
▶ Container moulding
▶ Container filling
▶ Container sealing
▶ Container discharge.

5. Parison extrusion:
Firstly, pharmaceutical plastic resin is
vertically heat extruded through a circular
throat and forms a tube called parison.
Container moulding:
The extruded tube is then enclosed within
a two part mould and then the tube is cut
above the mould.
Container filling:
The mould is transferred to sterile filling
zone where filling needles called mandrels
are lowered and used to inflate the flat tube
to form container within the mould.

6. Container sealing:
The mandrel is used to fill the container with
solution, following filling, mandrels are
removed and secondary top mould seals the
container.
Container discharge:
Filled and sealed containers are then
conveyed to labelling and packing sections.

9. Material Used
Polyethylene(PE)
Polypropylene(PP)
Polyvinyl chloride(PVC)
Requirement for Process:
Sterile air:
BFS machinery and its surrounding barriers should be designed to prevent the potential
for extraneous contamination.
Environment surrounding BFS process should generally meet grade A or class 100(IS0
5), or better, standards, depending on the design of the BFS machinery and the
surrounding room.
HEPA-filtered or sterile air provided should be used during the steps when sterile
products or materials are exposed. (e.g.,Parison formation, container moulding or filling
steps).
Only person who have qualified and appropriately growned should enter the classified
environment surrounding the BFS machinery.

10. ADVANTAGES:
• Reduce personnel intervention.
• No need to purchase and stock a range of prefabricated containers and their
closures.
• Cleaning and sterilization of prefabricated containers and closures is not required.
• The code numbers and variable data such as batch number and expiry date can be
• embedded onto the container itself.
• The cost of material transport, storage and inventory control is reduced.
• Validation requirements are reduced.
• There is a large choice of neck and opening device shapes.
• A single compact BFS machine takes the place of several conventional machines,
• saving floor space.

11. DISADVANTAGES
1.Particulate control:-
• Plastic extrusion and cutting process generate high levels of nonviable particulate.
For this reason BFS machine manufacturers have designed better machine enclosures to
isolate and protect contact surfaces from environmental conditions.
2. Temperature effects:-
BFS containers remain at an elevated temperature of up-to 60ºC for several seconds
after filling. To reduce the effect of temperature filled product can be cooled soon after
filling and sealing.
3. Oxygen and moisture effects:-
Plastic typically used for BFS containers provide a relatively low barrier to oxygen or
moisture , especially as compared to traditional glass containers(i.e., vials, syringes).
For oxygen sensitive products, filled units can be placed in foil pouches or other
secondary packaging.
Inert gases can be used in these secondary packages to lesser risk for oxygen
permeation.

12. APPLICATIONS:
BFS vials and bottles are ideally suited for unit dose applications.
Pharmaceutical:
Parenteral products.
OTC and prescription ophthalmic drops.
Inhalation solutions (for nebulizer).
Biotechnology products:-
Topical liquids, creams, gels, ointments.
Oral liquids.
Medical:-
Components to medical devices.
Diagnostics:-
Components in diagnostic kits.
Reagents in diagnostic products.
Food:-
Special food products such as soft drinks or milk products.

13. REFERNCES:
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)187-192(1991).
2. C.S.Sinclair and A.Tallentire, “Predictive Sterility Assurance for Aseptic Processing”
in R.F. Morrissey, ed.Sterilization of Medical Products, VI, Polyscience Publication,
Montreal,1993,pp.97-114.
3. P.Poisson, C.Reed, C.Sinclair, “Challenge testing of the KleenKut Parison Cutoff
Mechannism, Joint Presentation, BFS User’s group AGM, Switzerland June14, 2001.
4. C.S.Sinclair and A.Tallentire, “Performance of Blow-Fill-Seal Equipment under
Controlled Airborne Microbial Challenges”, J. Paren.Sci.Technol.49(6) pp.294-
299(1995).
5. P. Poisson. Non-Viable Particle Management During B/F/S Manufacturing
Operations, BFS News, Autumn Edition, 1999, PP.12-16.
6. U.K. Jain;D.C.Goupale; S.Nayak(2008). Blow-Fill-Seal(BFS) in Pharmaceutical
Packaging(2nd edn), “Pharmaceutical Packaging Technology”(pp.261-269).
Hyderabad: Pharma Med Press.