Sterile Pharma Products

8/2/2019 Sterile Pharma Products

http://slidepdf.com/reader/full/sterile-pharma-products 1/28

Sterile Pharmacutical Products

Presented by- Mr. Nandan Shinde

(M.Pharm, Quality Assurance,1st

Year)

Guided By-Mr. Sanjay Kshirsagar.

AISSMS COLLEGE OF PHARMACY,PUNE



Introduction

These are very critical and sensitive products.

They need to be free from living micro-organisms, pyrogens and unacceptable particulate matter.

They required to be handled carefully in predefined

environmental conditions.



Objectives To review basic GMP requirements in the manufacture

of sterile pharmaceutical products

To review air classifications for activities related to the

manufacture of sterile products

To review the different types of sterilization methods

To review quality assurance aspects in the manufacture

and control of sterile products



OVERVIEWPERSONNELBUILDING AND PREMISESHVAC SYSTEM

WATER & STEAM SYSTEMEQUIPMENTPROCESSESSTERILIZATION

QUALITY CONTROLSANITATIONFINISHING OF STERILE PRODUCTSDOCUMENTATION



Stages involved in manufacturing

Starting materials.

Area monitoring and control.

Equipment control.

Discipline in aseptic processing area.

Washing and sterilization of primary. containers.

Solution preparation and filtration.

Filling, sealing and inspection.



Personnel

Minimum number of personnel in clean areas

Especially during aseptic processingInspections and controls from outside.

Training to all including cleaning and maintenance

staff Initial and regular

Manufacturing, hygiene, microbiology

Supervision in case of outside staff



Personnel

High standards of hygiene and cleanliness

Periodic health checks

No shedding of particles

No introduction of microbiological hazards

No outdoor clothing

Changing and washing procedure

No watches, jewellery and cosmetics



Personnel

Clothing of appropriate quality:

Grade D

hair, beard, moustache covered

Protective clothing and shoes

Grade C

Hair, beard, moustache covered

Single or 2-piece suit (covering wrists, high neck), shoes

Grade A and B

Headgear, beard and moustache covered, masks, gloves

No shedding of fibres, and retain particles shed by operators



Personnel

Outdoor clothing not in change rooms leading to

grade B and C rooms

Change at every working session, or once a day (if supportive data)

Change gloves and masks at every working session

Disinfect gloves during operations

Washing of garments – separate laundry facility

No damage, and according to validated procedures



Garments

No outdoor clothing into aseptic area.

Non shedding,tight wave material for garments. latex or suitable plastic material for gloves.

Safety goggles with side extensions.

Documentation of cleaning.sterilization of garments.



Building and premises

Proper location of services like water, steam, gases

etc is important.

It must be build on proper foundation with standard

materials

Manufacturing area must be clearly separated into

support area. Separate man and material entry is needed.

Doors should always open towards high air pressure

area.



Various grades for aseptic

preparation

Grade Types of operations done

A Aseptic preparation and filling

B Background room conditions

C Preparation of solution to be filtered

D Handling of components after washing



Precautions to be taken in aseptic area

Walls, floors, ceiling, doors, windows must be of impervious, non- shedding, non cracking quality.

Sinks and drains should not be there in Grade A and B.

Use of intercom improves communication between asepticand non-aseptic area.

Personal welfare areas like rest rooms ,canteen must be

separated from manufacturing area Animal house should beaway from manufacturing area.

All pipes and ducts should be marked with contens and

direction of flow of their contents



Air Classification SystemSterile ProductionGrade At rest In operation

maximum permitted number of particles/m 3

.33- .33µm > µm3 .33- .33µm > µ3

A 3333 3 3333 3

B 3333 3 333333 3333

C 333333 3333 3333333 33333

D 3333333 33333 not defined not defined



HVAC SYSTEM TEMPERATURE – A,B,C area 23°c±2 °cRELATIVE HUMIDITY – 45%± 5%

AIR VELOCITY-80-120 feet/minDIFFERENTIAL PRESSURE- 15 pascalHEPA FILTER INTEGRITY- DOP test, 6months

LAFU-in class A,vertical or horizontal

VIABLE & NOVIABLE PARTICULATE COUNT-tocofirm the class of air

AIR SYSTEM FAILURE ALARM(ASFA)-in A & Bgrade , audio or audio visual.



Water and steam system

1. Purified water

1. water for injection

It is prepared by deionization,distillation,reverseosmosis, ion-exchange etc.

It must fullfill pharmacopeal specifications likeconductivity, heavy metals, microbial count etc.

WFI must fullfill requirments of ‘purified water’ inaddition bacterial endotoxin test also.



10.1 – 10.5

Equipment

TYPES OF EQUIPMENT

MATERIAL OF CONSTRUCTION-SS316INSTALLATION

VALIDATION-periodicaly

STANDARD OPERATING PROCEDURE

SPECIAL ISSUES OF BFS-

design,sterilization,reproduciblity,cleaning,validation.



Manufacture of sterile preparations

Classification of clean areas

Manufacturing operation in an appropriateenvironment cleanliness level

Minimize risks – particulate and microbiologicalcontamination – product and material

Meet classification "at rest"

(i.e. "completed installation, equipment installedand operating, but no operating personnel

present").



Manufacture of sterile preparations

To reach Grade B, C and D, the number of air changes

should be appropriate to the size of the area, number of personnel, equipment present

Minimum of 20 air changes per hour

Clean up time about 15-20 minutes

Good airflow pattern in the area

HEPA-filtered air

Suitable methods to determine particulate matter



Processing

Minimise contamination – all stages including beforesterilization and during processing

No unsuitable materials, e.g. live microbiologicalorganisms

Minimize activities

staff movement controlled and methodical

avoid shedding of particles

Temperature and humidity comfortable

Containers and materials in the area



Processing

Components, bulk product containers and equipment

fibre generation no recontamination after final cleaning

stage properly identified

sterilized when used in aseptic areas

Used in clean areas, passed through double-ended sterilizers

or use triple wrapping

Gas used to purge solution or blanket a product – passed

through a sterilizing filter



Processing

Bioburden monitored

Starting materials – microbiological contamination should be

minimal

Monitored as per specification



STERILIZATIONMOIST HEAT- aq.,h2o wettable material,121°

for 15min

DRY HEAT-non aq.,

FILTRATION- pore size o.22ų

GASEOUS- ethylene oxide

RADIATION-gamma rays



Quality ControlSamples for sterility testing should be representativeFrom parts of the batch, most at risk

Aseptic filling – at beginning and end of batch filling,and after interruptionsSterility of the batch ensured through validation

Validated sterilization cycle Media fill

Sterility test procedure as per pharmacopoeia, and validatedfor each product

Batch processing records, sterility testing records,environmental records should be reviewed



Quality ControlEndotoxin testing for injectable products

Water for injection, intermediate and finished product

Always for large volume infusion solutions

Pharmacopoeia method, validated for each product

Failure of the test – investigation

Corrective action



Finishing of productsContainers closed by means of validated methodsSamples checked for integrity

Visual inspection under suitable and controlled conditions: illumination and background eyesight checks of operators allowed frequent breaks

Other methods: validated, and equipment performance checked at

intervals results recorded

Sterile Pharma Products

Documents

Transcript of Sterile Pharma Products