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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