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STERILE PHARMACEUTICAL PRODUCTS
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CONTENTS Introduction Objective Manufacture of sterile preparations Personnel Building and premises Water and steam system Equipment Processing Sterilization Sanitation References
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INTRODUCTION Sterile pharmaceutical products are very critical and
sensitive products. Any failure in quality and purity of these products may directly affect the safety of the patients being treated.
Certain elements are required to be in processing of Sterile pharmaceutical products .
e.g. :- 1) Trained personnel 2)Layouts of plant 3)SOP 4)Process should be pre-validated
5)Production under guidance of authorized person
6)Use LAF
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OBJECTIVE
To review personnel. To review general requirement building
and premises. To review equipment. To review the different types of
sterilization methods. To review equipment To review processes.
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MANUFACTURE OF STERILE PREPARATIONS
A)COMPARISON OF VARIOUS GRADES DESCRIBED IN VARIOUS GUIDE LINES:-
sr.no.
U.S. Federal Standards 209(E)
MHRA/TGA
ISO standards
Metric grade
1 Class100 A & B 5 M 3.52 Class10,000 C 7 M 5.53 Class1,00,000 D 8 M 6.5
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C)TYPE OF OPERATION CARRIED OUT IN VARIOUS GRADES FOR ASEPTIC
PREPARATION:-
Grade Type of operations for aseptic preparations
A
Aseptic preparation and filling.
B Background room conditions for activities requiring Grade -A
C Preparation of solutions to be filtered
D
Handling of components after washing
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PERSONNEL FACTORS ARE REQUIRED TO BE IN
PERSONNEL:-
1)Training of persons.
2)Gowning or dress management.
3)some specific requirements for working in
sterile products
manufacturing area.
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1)TRAINING OF PERSONS:-
Training of persons working in Aseptic Processing area should cover following aspects:-
a)Quality and sterility productb)Type of contaminationc)Source of contaminationd)Control of contamination
I)By clean rooms II)By people III)By cleaning and disinfection
e)Training on sterilization
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a)QUALITY AND STERILITY PRODUCT:-
People working in this area, should be emphasized on the importance of their behavior, knowledge and skills which they utilize for the quality of the product.
People should be trained about:- Manufacturing
Hygiene Sterilization Process
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LIVING 1)MICRO-ORGANISAMS
(e.g. bacteria, mould, yeasts and
viruses. )2) Pyrogens
NON-LIVING1)Undesired
chemicals 2)Inactive dust,
powder or fiber
b)Type Of Contamination
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I.Bacteria-carrying particles from-Skin, Hair, Beard, Gut, Saliva, Nose, Mouth, Throat etc.
II.Environment around us
III.Water
IV.Containers and closure
V.Raw material
VI.Dusty, dirty premises
VII.Uncleaned or wet equipment and containers
c) Source of contamination
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d)Control of contamination
1)Control of contamination by clean Rooms:-
o Air is supplied under pressureo Use filters o Use different grade or class of clean room.o Surface of walls, floors, ceilings, fittings, work
top must be hard, smooth and unbroken.o Wall coated with antifungal epoxy paint layer. o Air locks
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2)Control of contamination by people:-
o High standards of hygiene and cleanliness
o Periodic health checks
o No eating, chewing, drinking and smoking
o No outdoor clothing
o Changing and washing procedure
o No watches, jewellery and cosmetics
o Do not move vigourously
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3)Control of contamination by cleaning and
disinfection:-
SOP of cleaning and disinfection.
Use automatic equipment.
Use vacuum for shucking dust & do not use
compressed air.
Cleaning of wall start at the top and work down.
Use right cleaning and disinfectants.
Equipments are clean after use.
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e)Training on sterilization:-
Laid-down procedure should be followed.
Record should be maintained.
Necessary to checked integrity of the
products.
To ensure the product, materials, equipment
are not mixed up after the sterilized.
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2)GOWNING OR DRESS MANAGEMENT:-
Outdoor clothing not in change rooms leading to Grade B and C rooms
Change at every working session, or once a day
Change gloves and masks at every working session
Disinfect gloves during operations Washing of garments – separate laundry
facility No outdoor clothing Changing and washing procedure No watches, jewellery and cosmetics
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AREA WISE GOWNING REQUIREMENTS CAN BE TABULATED:- SR.NO
ITEMES OF DRESS GREDEA&B
GRADEC
GRADED
1 Head Gear or hood Y N N
2 Nose or Face mask Y Y N
3 One piece boiler suit Y Y Y
4 Rubber or plastic shoes Y Y Y
5 Shoe cover or booty Y Y/N Y/N
6 Non powder rubber or plastic gloves(sterilized)
Y Y/N Y/N
7 Cap Y Y Y
8 Beard mask Y Y Y
9 Safety goggles Y N N
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3)SOME SPECIFIC REQUIREMENTS:-
Restrict number of people in aseptic area.
Drug sensitivity test for employees.
Medical check-up.
Psychological persons.
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BUILDING AND PREMISES
Design:- avoid unnecessary entry of supervisors and
control personnel operations observed from outside
In clean areas, all exposed surfaces:- smooth, impervious, unbroken permit cleaning and disinfection no uncleanable shelves, cupboards,
equipment proper installation of pipes and ducts, no
unsealed openings
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Changing rooms:-
designed as airlocks
effective flushing with filtered air
separate rooms for entry and exit desirable
hand washing facilities
interlocking system for doors
visual and/or audible warning system
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WATER AND STEAM SYSTEM:-PEURIFIED WATER WATER FOR INJECTION
1) Clear, colorless, odourless , tasteless.
1)Clear, colorless, odourless , tasteless.
2) pH- 5 to 7.5 2)pH- 5 to 7.5
3) Residue on evaporation : not more than 0.001%.
3) Residue on evaporation : not more than 0.001%.
4)Conductivity :nmt4.3µ /cm². 4)Conductivity :nmt1.1µ /cm²at 20°C
5)Microbial count-Maximum 100CFU/ml.
5)Microbial count:- a)Bacteria :- 10CFU/100ml. b)Fungi :- Nill
Pure steam:-
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EQUIPMENT
I. Type of equipment
II. Materials of construction
III. SOP
IV. Validation of equipment
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I. Type of equipment
a) Washing machineb) Sterilizers e.g. Dry het sterilizers, autoclavec) filling machines for ampules and vialsd) Plugin and sealing machine for ampules and
vialse) Labelling machine
II. Materials of construction
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III. Validation of equipment Equipments validated before use Record should be maintained
IV. SOP calibration, cleaning, operations and maintenance
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PROCESSING1)Starting materials:- Microbiological contamination should be
minimal.2)Area monitoring and control:- Viable /Non-viable particulate mater, air
velocity, presser differentials, Temp., relative humidity, personnel hygienic, Light level.
3)Equipment Control:-
Validation – should not compromise the processes. New processing procedures validated revalidation after significant changes and regular
intervals
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4)Discipline in Aseptic processing area
5)Washing and sterilization of primary containers:-
as short as possible time limit validated
6)Solution preparation and Filtration:- as short as possible maximum time set for each product
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7)Filling, Sealing and Inspection:- Takes place in Grade A & B. Equipment validation. I.P.Q.C. inspection. Medically fit workers. Labeling of filled & sealed container.
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STERILIZATION
Methods of sterilization:-
1)Moist or dry heat
2)Irradiation (ionizing radiation)
3)Sterilizing gaseous agents (e.g. ethylene
oxide)
4)Filtration
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1)Sterilization by moist or dry heat:-
I) Sterilization by dry heat:-
• For non-aqueous liquids, dry powders, equipment
• Air circulation in the chamber
• Positive pressure in chamber to prevent entry of non-sterile
air
• validation
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II)Sterilization by moist heat (autoclave):-
• Water-wettable materials only, and aqueous
formulations
• Items are wrapped
• Temperature, time and pressure monitored
• Quality of the steam – no contamination
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III) Sterilization by radiation :-
• Suitable for heat-sensitive materials and
products
‹ confirm suitability of method for
material
‹ ultraviolet irradiation not acceptable
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IV)Sterilizing by gaseous agents:-
Only when no other method is suitableE.g. ethylene oxide, hydrogen peroxide
vapourValidation: also prove the gas has no
damaging effect on productTime and conditions for degassingDirect contact with microbial cells essentialHumidity and temperature equilibrium
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V)Sterilizing by filtration :-
Through a sterile filter of 0,22 µm or less, into previously sterilized containers
remove bacteria and mouldsnot all viruses or mycoplasmasConsider complementing with some
degree of heat treatment
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SANITATION Frequent, thorough cleaning of areas necessary
Written SOP
Regular monitoring to detect resistant strains of
microorganisms
Chemical disinfection
Monitoring of disinfectants and detergents
Frequent monitoring in areas where aseptic operations
are carried out
settle plates, volumetric air samples, surface sampling
(swabs and contact plates)
sampling methods should not contaminate the area
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REFERENCES1. “Pharmaceutical quality assurance,”by
prof. Manohar A.Potdar,nirali prakashan pageno.13.1-13.60
2. www.newagepublishers.com3. Whglib.doc.who int/trs/who4. www.fda gov/ucm5. www.extemp.je sterile preperat6. bookGoole.com/.com pharmacutical
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THANK YOU