CLEANING VALIDATION

PRESENTED BY MR.VILAS KAMBLEM.PHARM.(II-SEM)

GUIDED BY MRS. USHA

SHINDE

PAD.DR.D.Y.PATIL COLLEGE OF PHARMACY AKURDI,PUNE.

CONTENTCleaning validation

Introduction

Importance of cleaning and it’s validation

Factor in cleaning validation

Product

Equipment

Facilities

Cleaning method

Cleaning agent

Sampling

Testing

Reference

INTRODUCTION Cleaning and

decontamination is one of the major and critical activity in pharmaceutical operations. The four basic requirement of cGMP are_

IdentitySafety,Strength Purity.

INTRODUCTIONCleaning validation involve

following same basic issue like Equipment and area Product Material of construction of the

equipment.Cleaning agent and its

concentration.Degree of cleaning expected.

INTRODUCTIONDefinition “A process of attaining and documenting sufficient evidence to give reasonable assurance, given the current state of science and technology that the cleaning process under consideration dose, what is purports to do”

INTRODUCTIONRequirement of cGMP in cleaning 21 CFR 211.67 (a) “Equipment and utensils shall be cleaned, maintained, and sanitized at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements”.

IMPORTANCE OF CLEANING AND ITS VLIDATION

Heart of pharmaceutical activityRelated to safety and purity of

the productsLevel of cleanliness is achieved

by clean procedure which depends on its validation

Cleaning method if performed confidently, method produced reproducible result

FACTOR IN CLEANING VALIDATION

PROUCT EQUIPMENT FACILITIES

CLEANING METHOD SAMPLING TESTING

LIMITS AND ACCEPTANCE CRITERIA

PRODUCT Prime objective of cleaning validation is to

assure complete or near to complete removal of the various materials processed earlier in the equipment or area. This include following categories of materials

e.g. Residue of previous processed material Cleaning agent used Any other material e.g. trace of oil, water, etc Fibers from any cleaning accessories used like

cloths, sponge, brush, etc.

EQUIPMENT The cleaning method should

consider the following points related to equipment

MATERIAL OF CONSTRUCTI

ON

• Compatibility of material with cleaning agent.

COMLEXITY OF

EQUIPMENT

• Complex equipment are clean by suitable devices.

• Also method must evolved to achieve the cleanliness of such area.

EQUIPMENT Pharmaceutical equipment can be

consider from various angles for cleaning purpose.

PARTS OF EQUIPMENT • Which come in contact

with processing material.

• Do not come in contact with processing material.

MECHANICAL SIDE OF EQUIPMENT • Motor• Gear box• Chain drives etc.

ELECTRICAL PANALS OF

EQUIPMENT

EQUIPMENT The cleaning procedure must

clearly define the procedure for each of the above aspects of the equipment.

Movable or fixed

Ability of drying of the

part of equipment.

Ability of protecting the

clean equipment

EQUIPMENT The above mentioned factors and

similar other factors if any, should be considered while designing the cleaning method for an equipment.

FACILITIESBuildings and Surroundings. Buildings:-It incorporate following

areas, each of these area may require different cleaning level, and hence the cleaning method will also vary from area to area.

CORRIDORS OFFICES

FACILITIES

STORE AND WARE HOUSE STORE AND WARE HOUSE

COLD ROOM

A.C.STORE

PACKAGING

MATERIAL

ENGINEERING

STORES

FACILITIES

OTHER AREA

CHANGE ROOM

NONSTERILE OPERATION

STERILE

OPERATION

PROCESSING AREA

NON STERIL

E OPERATION

STERILE

OPERATION

PACKAGING AREA

PRIMARY

PACKAGING

SECONDARY PACKAGING

UTILITIES AREA

E.G WORK SHOP,BOILER HOUSE,WATE

R STATION ETC.

FACILITIESSurrounding:- It incorporates following

area ROAD IN THE POT

LAWNS AND

GARDEN

SECURITY INSTALLATI

ONLAMP POST

TRETMENT PLANT AREA

RAW WATER SOURCES LIKE WELL, TUBE WELL ETC.

FACILITIESFor each of above areas the QA person

should design cleaning method and write cleaning SOP covering following points

Cleaning equipment used Cleaning agent with their concentrationFrequency of cleaning Procedure Responsibility for supervising RecordsAcceptance criteria

CLEANING METHOD Cleaning The act of removing dirt or something undesirable

CLEANING METHOD Designing of a cleaning method

is an important task. This process start with considering following point.

What is being cleaned?VESSELS EQUIPMENT

FACILITIES CONTAINERS

CLEANING METHOD What are the contaminant?

API EXCIPIENTS DECOMPOSED MATERIAL

MICROORGANISM ENDOTOXINS PARTICULATE

MATTER

CLEANING AND

SANITISING AGENT

OIL AND MACHINE

LUBRICUNT DUST AND

FIBRES

ANY OTHER

CLEANING METHOD Any other What is the level of cleanliness

expected and it’s acceptance criteria

Cleaning equipment Cleaning agent Who is doing to do cleaning Writing sop and maintaining

record.

CLEANING METHOD Once the above points is

collected then the cleaning method can be written and tested by actual practice to validate the method.

CLEANING AGENT Cleaning Agents : Cleaning agents are

generally different types of chemical agents like

Surfactants liquid soaps Specially compounded powders or

liquids etc.

CLEANING AGENT Compatible with the

areas/equipment to be cleaned.The concentration of the cleaning

agents must be decided on the nature of the agents and the cleaning requirements.

The traces of cleaning agents must be detected preferably by a physio-chemical method like pH, color test, etc.

CLEANING AGENT Using precautions must be known

while cleaning with cleaning agent.

These agent must be easily available , economically affordable and easy to handle.

SAMPLING Sampling : Sampling is required

to evaluate the effectiveness of cleaning method . This is done by sampling the area, which is cleaned to detect the residual contaminants cleaning.

There are the different methods of sampling. Some of the common methods used in Pharma Industry are :

SAMPLING o Swabs:-It is widely used technique

SWAB THE SPONGE IN SOLVENT e.g.

WATER OR ALCOHOL.

COLLECT THE SAMPLE FROM SPECIFIC AREA

TEST THE SAMPLE BY DIFFERENT

METHODS

SAMPLING o Rinse or solvent wash Measured area of cleaned surface is rinsed

or solvent washed

Collect

solvent

Tested for

trace of

contaminant

SAMPLING o Placebo:- It meaning that non useable

material testing e.g. like starch, lactose.

Test the starch for contamin

ation

Collect starch

Test starch on equipmen

t

SAMPLINGTesting:- There are different testing

method as-

Visual inspection PHAnalytical and instrumental

methodChromatographic method

REFERENCE Potdar M.A, Pharmaceutical

Quality Assurance,Publishied by Nirali Prakashan,Second edition reprint 2010,8.1-8.44

Chitlange S.S. Chaudhari P.D. Shirsat A.E. and Sangshetti J.N.Pharmaceutical Validation, Publishers by Suyog Publishers & Distributors Pvt.Ltd,First Edition April 2014,6.1-6.24