The document discusses aseptic processing and sterile manufacturing. It defines aseptic processing as bringing together sterilized product, container, and closure under controlled conditions to prevent contamination. Key elements of aseptic processing include personnel, facility, equipment, and process. The document also outlines various quality control tests performed during manufacturing like appearance, pH, sterility, and drug content tests. It discusses facility design considerations for aseptic areas including utility locations, engineering areas, and maintenance facilities.

1. Presented by
Ms. Rashmi Nasare
M. Pharm 1nd yr
Under the supervision of
Mr. S.R. Manapure sir
Professor
ASEPTIC PROCESS TECHNOLOGY,
ADVANCED STERILE PRODUCT MANUFACTURING &
LYOPHILIZATION TECHNOLOGY

2. WHAT IS ASEPTIC PROCESSING?
• The production of sterile drug products by bringing
together the product, container, and closure that have
been subjected to different sterilization method
separately, and assemble them in an extremely high
quality environment by skilled personnel using the
right tools.

3. ASEPTIC PROCESSING: ESSENTIAL ELEMENTS
ASEPTIC
PROCESSING
PERSONEL
FACILITY
EQUIPMENT
PROCESS

4. CONCEPT OF STERILE/ ASEPTIC PROCESSING
• Sterile: Free from living organism
• Aseptic: Absence of pathogenic microorganism or technique
used to prevent microbial and particulate contamination
• Aseptic processing: The product and all of its contact parts
are sterilized separately and brought together under
exposed conditions where, if not properly under exposed
conditions where, if not properly controlled, could result in
contamination.

6. MANUFACTURING FLOWCHART

7. IN PROCESS QUALITY CONTROL
• IPQC means controlling the procedure involved in
manufacturing of the dosage forms starting from raw
material purchase to dispatch of the quality product in
ideal packaging.
• It monitors all the features of the product that may
effect its quality and prevents error during processing.
• It is activity perform between QA and QC department.

8. PURPOSE OF IPQC
• To ensure detectable and significant human errors.
• Equipment failure
• Abnormal interpretation.
• Adoption of given procedures.

9. IMPORTANCE OF IPQC
• To minimize human errors.
• Provide accurate, specific, and definite description of
the procedure to be employed.
• It is planned system to identify material and equipment
processed and operated.
• Used to detect error if and when it does occur.

10. IPQC TESTS
• These are the tests performed between QA and QC and
provides for the authorization of approved raw material
for manufacturing based on actual laboratory testing
generally called as IPQC such as physical, chemical,
microbiologic and biologic tests.

11. IPQC TESTS FOR OINTMENT
• Checking for uniformity and homogeneity of drug content
prior to the filling operation.
• Determining the particle size of the preparation when
appropriate.
• Checking the appearance, viscosity, specific gravity,
sediment volume and other physical parameters at
prescribed intervals.
• Testing for filling weight during the filling operation.
• Testing for leakage on the finished jars or tubes.

12. IPQC TESTS FOR SUSPENSION
• Appearance
• Photo microscopic examination
• Color, odor, taste
• Density
• PH value
• Clarity testing
• Pourability
• Viscosity
• Rheology

13. IPQC TESTS FOR EMULSION
• Appearance
• Clarity testing
• PH value
• Viscosity
• Rheology
• Drug content uniformity
• Particle size distribution
• Densities of phases

14. IPQC TESTS FOR SOLUTIONS(SVP
AND LVP)
• Clarity test( for particulate matter):By visual method
coulter counter method
Light obstruction technique
• Leakage testing( package integrity):visual method
bubble test
Dye test
vacuum ionization method

15. IPQC TEST FOR SOLUTIONS
• For fill volume
• PH
• Pyrogen testing:
• rabbit fever response test:
• Limulus amoebocytes lysate test
• Assay for drug content
• Sterility test: membrane filtration method ,Direct inoculation method

16. IPQC TEST FOR SOLUTIONS
• Test for packing container
• glass containers
• Water attack test
• Powder glass test
• plastic container-
Leakage test, collapsibility test,
transparency test, water vapor
permeability test.

17. IPQC TEST FOR SOLUTION
• Inspecting for label check
• Uniformity of content
• Uniformity of weight
• Conductivity test

18. INTRODUCTION
• The preparation of sterile products using aseptic processing
• Aseptic processing involves practices and procedures to prevent
contamination from pathogens. The increasing reliance on automation
to minimize or eliminate operator intervention.
• The use of isolator and barrier concepts for aseptic processing and
assembly.
• This advanced techniques offers improved aseptic environment over
traditional clean room for pharmaceutical filling operations by
separating the filling area from the operators

19. MANUFACTURING AREA PLANNING
During facility designed ,process requirement specific for each
product requirement must be considered .also number of product
to be manufactured will impact facility design or area planning
Product type
 Chemical bulk drug substance(API)
Derived from chemical reaction .So facilities producing sterile API
will be required to provide protection to product during synthesis,
isolation , and bulk filing.
An adjuvant produced by precipitation is an example of sterile API

20. Potent compounds : classified as those chemical drug that
are considered toxic to humans when exposure limits are
exceeded, may cause allergic reaction ,birth defects, or
other conditions .
• for this reason it is acceptable to permit production of potent
compound in multiproduct facilities ,provided the suite is
segregated from other operation.
 Antibiotics : produced to treat bacterial or fungal infection
.it must be separated from other product as potential for
cross contamination . In addition to b-lactam (penicillin) and
non penicillin based(cephalosporin) antibiotic are not
permitted to produced in same facility as there is evidence
of intolerance for one antibiotic not another .

21. • To get this segregation ,it is required that separate
dedicated suite be constructed for each antibiotic family.
• Also after filling ,it is recommended to wash exterior of
vials produced in antibiotic facilities to limit uncontrolled
exposure to product .
 Biological product : this include therapeutic proteins
generated by fermentation or cell culture and inactivated
vaccines .the facility is to be designed in same way as API
production ,except that terminal sterilization is often not
feasible ,due to fragility of the product.

22. FACILITY TYPE
Single product, dedicated :this facility is designed to
produce a single product at one time, through the year
without concern for cross contamination with a second. The
facility can be operated to produce multi products in a series
of campaigns, converting between product
 Multiproduct multisite :this facility is designed to produce
multiple products simultaneously in multiple sterile suites.
sterile operation in each suite are to be segregated from one
another to ensure that cross contamination is prevented. It is
recommendation to clean and decontaminate any used
components or equipment prior to existing the suite and
entering the return corridor

23. PRODUCTION AREA DESCRIPTION:
• Conventional aseptic technology(open):in this the product is
exposed to the room environment during operation. for this reason,
aseptic operation are required to performed under ISO 5 condition
by sufficiently gowned operators, trained in aseptic techniques.
sterility assurance levels for aseptic operation, including filing of
vials or syringes, can be maximized through the use of barriers such
as restricted access barrier systems or isolators.
• Restricted access barrier(open and closed):a restricted access
barrier system RABS can be utilised in many applications in a fill
finish area. RABS provides an enclosed environment to reduce
contamination to product ,container, closure, compared to the risk
associated with conventional clean room operation.

24. Terminally sterilized product :whenever possible, it is
required to terminally sterilize filled unit of product.
terminal sterilization is known as an overkill sterilization.
sterilization can be steam, dry heat, gas, or radiation .
Classification of spaces :
classification designation for classified GMP spaces
include ISO 5(A), ISO 7 (B), ISO 8(C), and ISO 9(D),
which are assigned to spaces on the basis of specific
operational characteristic, product type , and or
technology used.

25. FLOOR SYSTEM
 Floor system are critical and primary support areas of aseptic manufacturing
facilities can be divided into two categories: sheet systems (PVC ,rubber ) and
resin-based multilayer system
 The appropriate selection of either system is dependent on the following criteria
1.Substrate conditions (new or existing concrete slabs )
2.Expected frequency of traffic (material loads )
3.Expected loading of traffic (heavy rolling loads such as tanks , carts, forklifts etc.)
 In controlled , non classified CGMP areas floor system such as pigmented
concrete sealer ,sheet vinyl and thinner resin based systems may considered for
cost and functional reasons

26. WALL SYSTEM
• It is composed of site fabricated assemblies (concrete block or
metal stud /gypsum board wall with applied coatings) pre
manufactured assemblies (modular clean room partition system
)or a hybrid of the two.
Wall system also evaluated on the basis of
 Expected frequency of reconfiguration /relocation
 Ease of modification ( future installation / removal of panels, door,
windows, etc.)
 Design and construction schedule
 Regulations set by building code authorities and recommendation
by insurance

28. CHANGE ROOM
Personnel access to all controlled areas should be through change
rooms. Change rooms concept may vary from single closest size
rooms to expensive multi room complexes.
Entrance to change room area is normally through vestibules whose
door are electrically interlocked so that both cannot be opened
simultaneously ,thus maintaining the necessary air pressure
differential to prevent the entry of airborne contamination
Upon entry to change room wash sinks are provided for scrubbing
hands and forearms. Special filtered air driers are available to
minimize creation of particulate contamination

29. In some facilities ,a foamed type of alcohol is dispensed on
hands which then evaporates. This is used to eliminate need
for tap water and sinks in the gowning rooms ,since this can
be potential source of contamination.
After hands are dry ,garments are taken from dispensers and
donned while moving across a dressing bench . As a final
gowning step ,aseptic gloves are put on and sanitized.
Separate de gowning rooms are provided where the clean
room garments can be discarded prior to leaving the controlled
zone.

30. CHANGE ROOM

31. PERSONNEL FLOW
• The movement of personnel should be planned during the design of
individual plant areas
• Each individual production area may have a smooth and efficient
personnel flow pattern ,a discontinuous or crowded pattern may
develop when several individual production area plants are
combined.
• Security concern about the personnel flow may include minimizing
access to controlled substances and minimizing the personnel traffic
in or near work area where controlled substances are handled
• The flow of material and personnel through corridors are inefficient
and unsafe path for moving material ,particularly if heavy forklifts are
required

32. • Parenteral plants ,like any other plant have visitors
and the degree of access to be granted must be
determined.
• A glassed mezzanine or balcony provides absolute
solution yet may give an excellent view of the process,
but not adaptable for single floor layouts.
• Discontinuous and crowded flow pattern can decrease
production efficiency, increase security problems, and
increase the problem of maintaining a clean
environment

33. UTILITIES AND UTILITY EQUIPMENT LOCATION
• Utilities : piping system in particular ,must be initially and
often periodically cleaned and serviced.
• Exposed overhead piping is not acceptable from a
cleanliness or contamination standpoint since it collect dirt is
difficult to clean and may leak .buried or concealed pipe may
require unacceptable demolition for cleaning or repair
• Whenever possible ,major utility distribution services should
located outside of clean areas.
• Distribution systems be exposed and not buried with in walls
or ceilings

34. UTILITIES EQUIPMENT LOCATION
• Public utilities require space for metering.in addition to meeting
electrical power system require for switchgear and transformer.
• Water system usually require treatment to ensure consistent
quality. Plant generated utilities typically require steam boilers,
air , compressors ,and distillation , the typical boiler room
approach.
• Although a central location minimizes distribution problems and
minimizes service distribution distances.
• Proper equipment maintenance is difficult in foul weather
especially winter . heavy equipment may damage the roof
structure, particularly if the equipment location may requires
numerous penetration through the roof which coupled with
equipment vibration will invariably lead to leakage.

35. ENGINEERING AND MAINTENANCE
• From an engineering stand point , even a location outside
the plant can serve well if access to the production area by
engineers for field work is not too difficult often particularly
in small or less complex plants, maintenance or other pant
service functions such as utilities or combined with
engineering , making an in plant location desirable.
• Maintenance responsibilities cover all area of the plant
and can generally be grouped into two categories
1.plant maintenance
2.production maintenance

36. • Production maintenance is a direct production support function
and include all the routine and recurring operation maintenance
work. production maintenance facilities are usually minimal.
• Plant maintenance operation ,in contrast are more diverse.
They vary from heavy maintenance on production equipment to
cosmetic work on the building exterior and often include plant
service function such as sanitation, ground sweeping, or waste
disposal.
• Facilities required are extensive and mostly include provisions
for equipment cleaning. disassembly major rebuilding of
equipment and painting and these operation can present a
contamination risk to pharmaceutical operation and must be
isolated