Aseptic Processing Process Selection & Design Formulation & Compounding Primary Packaging Process Objectives Manufacturing flow charts Ointment Suspension Emulsion Dry powder Solution (SVPs & LVPs) References

1. Topic:- Aseptic Process Technology: Manufacturing flow
charts
Subject Name :- Pharmaceutical Manufacturing Technology
Subject Code:- MQA204T
Department of Pharmaceutical Quality Assurance
Smt. B. N. B. Swaminarayan Pharmacy College, Salvav–vapi
Presented by:-
Machhi Dhruvi A.
2nd sem M.Pharm.

2. CONTENTS
25-05-2022 2
Dhruvi Anilkumar Machhi
• Aseptic Processing
• Process Selection & Design
• Formulation & Compounding
• Primary Packaging
• Process Objectives
• Manufacturing flow charts
Ointment
Suspension
Emulsion
Dry powder
Solution (SVPs & LVPs)
• References

3. ASEPTIC PROCESSING
25-05-2022 3
Dhruvi Anilkumar Machhi
• Aseptic processing can be defined as the processing & packaging of sterile product
into sterilized containers & hermetic sealing with a sterilized closures in a manner that
prevents attack of viable microorganisms.
• Aseptic manufacturing means that the used drug substance & excipients were
sterilized appropriately & all materials, equipment & container closure systems were
used only after sterilization.
• All working steps were performed in so called clean areas to avoid contamination.
Therefore high standards have to be established concerning the manufacturing room,
the personnel, the equipment & the supply systems

4. 25-05-2022 4
Dhruvi Anilkumar Machhi
Container
Excipient
Closure
Drug
Product
Sterilization
Process
Sterilization
Process
Sterilization
Process
Sterilization
Process
Sterile Drug
Product
Sterile
Container
Sterile Closure
Sterile Excipient
Aseptic
Processing
Sterile
Final
Product

5. PROCESS SELECTION & DESIGN
25-05-2022 5
Dhruvi Anilkumar Machhi
• The production of sterile products is profoundly impacted both by formulation & the
selection of primary packaging components.
• Design parameters for a facility & selection of appropriate manufacturing
technologies for the product require that the formulation process and packaging
components be chosen & evaluated in advance.

6. FORMULATION & COMPOUNDING
25-05-2022 6
Dhruvi Anilkumar Machhi
• The vast majority of parenteral formulations are solutions requiring a variety of
tankage, piping, & ancillary equipment for liquid mixing or powder blending,
filtration, transfer, & related activities.
• Suspensions, ointments, & other similar products, including the preparation of the
solutions for lyophilized products, can be manufactured in the same or very similar
equipment.
• The scale of manufacturing can vary substantially, with the largest batches being well
in excess of 5000 L (typically for large - volume parenteral production), down to less
than 50 mL for radiopharmaceuticals or biologicals customized for a particular
patient.

7. PRIMARY PACKAGING
25-05-2022 7
Dhruvi Anilkumar Machhi
• The primary package for parenteral formulations provides protection to the sterile
materials throughout the shelf life.
• Glass:
It is ordinarily washed prior to sterilization/depyrogenation to reduce contamination
with foreign material prior to filling.
 In aseptic fill processes, the glass is then depyrogenated using dry heat.
This can be accomplished using either a continuous tunnel or a dry heat oven.
• Plastic components can be sterilized using steam, ethylene oxide, hydrogen peroxide,
or ionizing radiation. The γ irradiation is accomplished off - site by a subcontractor
with appropriate expertise.
• The Blow Fill seal (BFS) & Form Fill seal (FFS) are unique systems; in that the final
container is formed as a sterile container just prior to the aseptic filling step.

8. PROCESS OBJECTIVES
25-05-2022 8
Dhruvi Anilkumar Machhi
• Assuring appropriate control over these potential contaminants requires careful
attention to several factors:
facility design
equipment selection
sterilization procedures
cleaning regimens
management of personnel &
the process details associated with compounding, filling & sealing of product
containers.

9. MANUFACTURING FLOW CHARTS
• Manufacturing flow charts shows a typical manufacturing pattern i.e. starting
from dispensing of raw materials till it gets packaged in sterile containers.
• In aseptic manufacturing, various means of Sterilization processes are opted as
per the requirement of the final product to be produced & the aseptic conditions
are maintained throughout process.
25-05-2022 9
Dhruvi Anilkumar Machhi

10. OINTMENT
• Ointments are semisolid preparations intended for topical application.
• They are used to provide protective & emollient effects on the skin or carry
medicaments for treating certain topical ailments.
• Ointments intended for ophthalmic purposes are required to be sterile. When
applied to the eyes, they reside in the conjunctival sac for prolonged periods
compared to solutions & suspensions & improve the fraction of drug absorbed
across ocular tissues.
• It is prepared by 2 methods:
1. Trituration Method
2. Fusion method
25-05-2022 10
Dhruvi Anilkumar Machhi

11. 25-05-2022 11
Dhruvi Anilkumar Machhi
Mixing with Base
Spatulation or
Trituration
Levigation
Size Reduction
Mix remaining base to
produce final weight
Homogenization
Aseptic Filling
TRITURATION METHOD
API/
Excipients
Sterilization
Packaging
Material
Sterilization
Equipment/
Instrument/
Machinery
Sterilization

12. 25-05-2022 12
Dhruvi Anilkumar Machhi
Grate the waxy base
Melt using water bath
Add small volume phase in large volume phase
Melt high melting point
base first & add low melting
point base in it
Cooling under stirring
Soft mass of 40 ̊C
Dissolve oil soluble drugs
Homogenization
Filling
Melt base together
FUSION METHOD
Packaging Material
Homogenizer
water bath
Grater
S
T
E
R
I
L
I
Z
A
T
I
O
N

13. SUSPENSION
• The dispersed system is named as a “suspension” when the liquid dosage form is
accomplished by the distribution of a solid phase suspended in a liquid matrix.
• The solid phase of a suspension is usually the drug substance, which is insoluble
or very poorly soluble in the matrix.
• It is a heterogeneous mixture in which the solute particles do not dissolve, but get
suspended throughout the bulk of the solvent, left floating freely in the medium.
25-05-2022 13
Dhruvi Anilkumar Machhi

14. • A flow diagram of the key steps in the manufacturing of sterile aqueous
suspensions is illustrated in Figure.
25-05-2022 14
Dhruvi Anilkumar Machhi
API Micronize
Sterilize
High
Shear
Mixer
Filling
Formulation
Vessel
Sterile
Filtration
Vehicle
Aseptic Manufacturing flow chart of Suspension

15. 25-05-2022 15
Dhruvi Anilkumar Machhi
Drug/ API +
Internal phase
External phase +
Emulsifiers
Emulsification
O/W or W/O emulsion
Filtration
EMULSION
• Emulsion is a mixture of two or more liquids that are normally immiscible with
each other.
• It is a dispersed system in which the dispersed phase is composed of small
globules of a liquid distributed throughout the vehicle in which it is immiscible.
Sterilization
Packaging
Packaging Material
Emulsion Finished Product

16. 25-05-2022 16
Dhruvi Anilkumar Machhi
DRY POWDER
• A pharmaceutical powder is a mixture of finely divided drugs or chemicals in a
dry form meant for internal or external use.
• They are available in crystalline or amorphous form.
S
T
E
R
I
L
I
Z
A
T
I
O
N
Packaging Material
Weighing Balance
Sieves / Screens
Pulveriser/ Mills
Weighing of each
ingredient
Mixing
Sieving
Size Reduction
Packaging
Mixers / Blenders

17. SOLUTIONS (SVPs & LVPs)
• The term SVPs has been officially defined by USP as "an injection that is
packaged in containers labelled as containing 100 ml or less" & LVPs applies to
injection that is intended for IV use & packed in containers holding 100 ml to 1
liter.
• SVPs include pharmaceutical products (otic, ophthalmic & parenteral), diagnostic
agents, biologicals, etc.
• The parenteral preparation may be solution, suspension, emulsion & powder for
reconstitution.
• The LVPs include blood collecting units with anticoagulants, diagnostic agents,
irrigating solutions, IV fluids, etc.
25-05-2022 17
Dhruvi Anilkumar Machhi

18. 25-05-2022 18
Dhruvi Anilkumar Machhi
Aseptic Manufacturing flow chart of Solutions
Ingredients,
Vehicles,
Additives
WFI
Compounding Filtration
Aseptic
Filling &
Sealing
Sterilization
Containers
Washing
Equipment
Containers
Closures
Equipment
Inspection &
IPQC
Sterilization
Packaging
Material
Packaging &
Labelling
Finished
Products
Product output
Storage

19. REFERENCES
1. Shayne Cox Gad, Pharmaceutical Manufacturing Handbook, John Willey &
Sons, New Jersey, 2008, pp: 100-104, 268, 316
2. Omar A. Salman, “Manufacturing Of Sterile Aqueous Suspensions: A Primer”
https://www.bioprocessonline.com/doc/manufacturing-of-sterile-aqueous-
suspensions-a-primer-0001
25-05-2022 19
Dhruvi Anilkumar Machhi

20. Thank you
25-05-2022 20
Dhruvi Anilkumar Machhi