1.

CONCEPT
WHO adopted at 22nd Health assembly in July 1969 the Importance of GMP Maintenance of Quality of Pharmaceutical Products
Well accepted worldwide and most developed Countries have strengthened this with
statutes
Violations are severely dealt with
India- standards vary from State to State
GMP has become a part of Companys Philosophy and has its tacit acceptance
Consumer has the right to get best quality products for the price he pays
Manufacturer is responsible for the Product Quality and Performance
Product performance and bioavailability is paramount for cure of ailments
In India this concept is yet to find place
Having accepted this Philosophy, Company has to cater to
Continuous training & education of both present and new recruits
Continuously update the methods and incorporate the latest techniques
GMP is dynamic hence cGMP
Cost of failure is very high, hence adopt Prevention is better than cure proactive
Doing it right for the first time is most cost effective
Thinking starts from designing stage to prevent committing errors
Lay down right manufacturing procedures to be followed at the shop floor level
Conduct regular in-Company Self GMP Audit and implement course correction
GMP is more a Management Practice and an approach to Quality Assurance System
Merely complying to Statutes or GMP guide lines is not enough
Real success will come only if Concept of GMP is deeply ingrained in the minds of
people associated with the business, to make it a way of daily working life in the
Organization

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2. NOMENCLATURE
Analytical Method
A detailed description of the procedures to be followed in performing tests for conformity with
a Specification
Batch
A defined quantity of material or of bulk, intermediate or finished product that is uniform in
character and quality, and which has been produced during a defined cycle of manufacture.
To complete certain stages of manufacture it may be necessary to divide a batch into a
number of sub-batches, which are later brought together to form a final uniform batch. A
batch is sometimes described as a lot.
Batch Number (or Lot Number)
The designation of a batch by means of a distinctive combination of numbers and/or letters,
which identifies it and permits its history to be traced
Batch Manufacturing Record
A document stating the materials used and the operations carried out during the processing
of a given batch, including details of in-process controls, but normally excluding packaging
information. It should be based on the Master Formula and Method and be compiled as the
manufacturing operation proceeds.
Batch Packaging Record
A document stating the bulk product and packaging materials used, and the processes
carried out, during the packaging of a given batch, with details of in-process controls. It
should be based on the Master Packaging Instruction and be complied during the packaging
operation.
Bulk Product
Any product that has completed all processing stages up to, but not including, packaging
Contract Manufacture and/or Analysis
Manufacture and/ or Analysis ordered by one person or organization (the Contract giver) and
carried out by an independent person or organization (the Contract Acceptor).
Documentation
All the written production procedures, instructions and records, quality control procedures,
and recorded test results involved in the manufacture of medicinal product.

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Finished Product
A medicinal product, which has undergone all stages of manufacture, including packaging

Good Manufacturing Practice

Is that part of Quality Assurance aimed at ensuring that products are consistently
manufactured to a quality appropriate to their intended use? It is thus concerned with both
manufacturing and Quality Control Procedures.

In-Process Control
Tests made during the course of manufacture (including packaging) to ensure that the
resultant product will comply with its specification. Tests applied to the environment or to
equipment, as well as to products in process, may be regarded as a part of in-process
control.
Intermediate Product
A partly processed material which must undergo further processing before it becomes a Bulk
or Finished Product
Manufacture
The complete cycle of production of a medicinal product from the acquisition of all materials
through all processing and subsequent packaging to the dispatch of the finished product
(Unless the context otherwise requires, manufacture includes packaging).
Master Formula and Method
A document stating the starting materials, with their quantities, to be used in the manufacture
of a medicinal product, together with the manufacturing operations, including details of
specific in-process controls, but normally excluding packaging information.
Master Packaging Instruction

A document listing the components to be used for a stated container or package

together with a description of the method of packaging and with details of specific
in-process controls

The instructions should include the method of assembling the component parts, if
the package is complex.

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Packaging Material
Any material used in the packaging of a product. The term is not normally extended to cover
the outer packing or delivery cases used for transportation or shipment of orders. The
categories of packaging materials used are:

Packaging materials which come in contact with the product (often called Primary
Packaging Materials)

Printed packaging materials

Other packaging materials

Quality Control
Is that part of good Manufacturing Practice which is concerned with sampling, specification
and testing, and with the organization, documentation and release procedures which ensure
that the necessary and relevant tests are, in fact, carried out, and that materials are not
released for use, nor products released for sale or supply, until their quality has been judged
to be satisfactory. Quality Control is also used in the sense of the organizational entity,
which has the responsibility for these functions.
Quality Assurance
Is the sum total of the organized arrangements made with the object of ensuring that
products will be of the quality required by their intended use? It is Good Manufacturing
Practice plus original design and development. (Which may not strictly fall within the scope
of norms of GMP)

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3. HYGIENE
Objective
To avoid any sort of contamination, pharmaceutical products have to be produced with clean
materials, machines, and personnel. Personal hygiene therefore attains an important role in
GMP of Pharma Production.
Requirements of health, personal cleanliness, hygienic operation, protective clothing
applicable to all production people, maintenance staff and all other visitors have to be strictly
adhered to.
Scope: The scope covers

Personal Hygiene

Personal Hygiene - Sterile Products

Personal Hygiene

1. General Requirements & Responsibilities

Drugs are intended for treatment of disease & protection of health.
Drug manufacturers, have a special responsibility to ensure products are free from
contamination.
A major contributory factor - human body - carries organisms and particulate matter.
Every drug producer- complies with minimum requirement of health, personal cleanliness
and clothing to protect him and product.
Requirements apply to all persons entering production areas. Includes, visitors, maintenance
staff, senior management staff governmental & other inspecting authorities
Responsibility of Management to implement these requirements

2. Health
Written down requirements on minimum health requirements of all personnel working in
factory
Pre-employment medical exam, including eye, to be insisted upon, including temporary staff
Yearly Health checks up of all personnel including tests for communicable diseases.
Employees suffering from infectious disease like conjunctivitis, severe cold, should not report
for work
Employees reporting after absence from an illness involving communicable disease, should
not commence work, till assessed by Doctor
Staff should be encouraged to report infectious diseases, viz. Enteric and respiratory and
also any infectious diseases at home, so that temporary transfer to other departments can
be made.

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 Staff trained to report boils, carbuncles, open wounds, or rashes on exposed parts of body.
Such persons must be excluded from operations involving direct contact with materials
Supervisory staff should be trained to look for such signs or symptoms of unhealthy
conditions of their staff.
3. Personal Cleanliness
Strict attention should be given to personal hygiene
Staff encouraged to have regular baths and change underclothes frequently
Hands to be cleaned regularly certainly after visiting toilet
Nails to be clipped regularly
Carbolic soap to be used
Hair should be kept clean. Males encouraged to be clean shaven, beards if kept, should be
covered
Wearing of jewelry viz. Bracelets, pendants rings, earrings etc. to be discouraged
Women operators should wear a minimum make-up.
False eye lashes, false nails, hairpieces, wigs or any other beauty aids, likely to fall into
product, not to be permitted.
Staff to be advised on use of suitable jewelry at work
4. Hygienic Operations
Food and drinks not to be consumed in production/operational/storage areas
This includes chewing of paan, betel nuts etc.
Smoking must not be permitted in any of the operational areas. No Smoking areas to be
displayed prominently at points of entry to such areas.
Food, drink and smoking material should not be stored in operational areas, which could
adversely affect product quality. Personal medication should not permit in such areas.
Protective clothing pockets should not be used for storing food.
Staff to be trained to keep working areas clean and uncluttered, and clean and clear away all
items before starting another
Staff trained to keep their lockers cleans and tidies. Unclean lockers source-contamination
5. Protective Clothing
Protective clothing is not only for individual but also for protection of product from the
individual.
No person should enter the production area wearing street clothes.
Clean working garments and protective apparels viz. head, face, hand, shoe and arm
coverings must be worn.
While handling dangerous or volatile materials, suitable additional devices such as head

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covering, anti-dust masks safety goggles etc must be worn.

Protective garments should not be worn outside factory premises. Practice of going into
street and back to work, in factory garments must be prohibited.
Protective clothing must be clean and laundered regularly (twice a week). The Laundering
contractor should have good facilities for washing and drying. Source of water used is
important.
Clothing must be worn properly, with buttons if present, should be fastened. Damages to the
clothing should be mended.
Headgear provided should cover the hair completely. Beards should be properly covered.
Protective garment should have no pockets above the waist level, to prevent any article
falling from the pocket into the product, during the course of work.
Sterile Products
1. General
Manufacture of sterile products especially Injectables require special procedures to prevent
contamination. Operators working and their clothes could become a source of
contamination.
2. Health
Staff with opens wounds, rashes, boils, or any other skin ailment must not be permitted to
work in and aseptic areas.
Staff suffering from upper respiratory tract infection, cold, coughs, hay fever etc. must not be
allowed to work in clean and aseptic areas.
Periodic checks for these conditions must be done.
All operators working in aseptic areas should be monitored microbiologically. Weakly swaps
of persons working in sterile areas viz. Nose, ear, skin, and throat may be taken. Weekly
finger dabs of the operators should be taken preferably at the end of days work.
3. Personal Cleanliness
Nails of operators working in aseptic areas should be regularly trimmed
Staff to be encouraged to keep hair short and clean shaven to minimize contamination from
hair,
Use of jewelry, cosmetics, rings and watches should not be allowed in sterile areas.
Attitude of cleanliness to be instilled in staff through training in basic elements of
microbiology

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4. Hygienic Operations
Number of persons working in sterile areas to be kept to a minimum

Inspection and control procedures to be done from outside, if possible

Restrict unnecessary movement of staff in sterile areas, to minimize contamination.

Maintenance staff working in sterile areas should observe same precautions on hygiene
5. Protective Clothing
Staff working in aseptic areas, should change into special garments provided viz. Head and
footgear. Such garments should be comfortable with loose fitting
Edges of garments should be sealed and seams should be enveloping. Garments should
have no external pockets and unnecessary tucks
Sterile garments should shed virtually no fibers or particulate matter and retain particles
shed by body.
Operators should wear sterilized single or two-piece trouser suits, gathered at wrists and
ankles and with high necks. Hair must be completely covered by suitable head gear and also
totally enclose, beard/mustache.
Footwear (Booties) should totally enclose the feet, and bottom edge of trousers should be
tucked inside booties.
Garments should be restricted for use only in relevant clean and aseptic areas.
Sterile garments should be properly stored and handled, to minimize contamination

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4. SANITATION

OBJECTIVE AND SCOPE

Operations in Pharmaceutical Production have to be carried out in clean areas to avoid
contamination. Cleaning of areas, equipment, and microbial monitoring are very important. Hence
aspects covered are
Selection and use of cleaning agents
Facilities and equipment for cleaning
Cleaning/disinfecting of manufacturing areas
Cleaning schedule
INTRODUCTION
Manufacturing areas require regular and frequent cleaning and disinfecting, and these are done:
1. Create and maintain a safe working environment
2. Remove dust and dirt, which are hazardous to product and operator
3. Minimize the risks of cross contamination, occurring between different products, made in the
same area
4. Reduce levels of contaminating microorganisms.
5. Water alone is not sufficient for cleaning and disinfecting.
6. Hence cleaning and disinfecting agents are necessary
DEFINITIONS

Cleaning agents

Materials which help to remove extraneous matter from surfaces

Disinfectants

Potent substances which destroy pathogenic micro-organisms but not necessarily resistant spores

Antiseptics

Reasonably non-toxic substances and can be applied to live tissues for killing microorganisms.
GENERAL PRECAUTIONS
1. Cleaning agents and disinfectants should be handled with care.

Potent and often hazardous

Manufacturers instruction- Use of protective gears viz. Gloves, eye-shield, aprons, safety
footwear etc.

2. Cleaning agents and disinfectants should not be mixed

Certain mixtures are known to be reactive and dangerous.

3. Disinfectants containing alcohol or other inflammable solvents should be stored and handled

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in a safe manner.
4. Do not substitute Cleaning agents or a disinfectant- by another

Ensure- the alternative is as effective as the original one.

5. Disinfectant - If to be diluted prior to use, a document should specify the procedure to be

adopted while diluting.
6. Shelf life of the diluted disinfectant should be specified in the standard operating procedure.
CLEANING AGENTS
Cleaning ability of any commercial preparation to be ascertained from the manufacturer
before selection
Its preferable to use- liquid cleaning agents. Cleaning preparations in powder form may
cause particulate contamination.
DISINFECTANTS
Disinfectants with varying levels of activity are available in the market. Suitable one should
be selected only on the basis of a test for potency done by a qualified microbiologist.
Ascertain whether disinfectant is compatible with the surfaces & appliances to be disinfected
Take care to ensure that disinfectant does not corrode or discolor the metal surface,
paintwork or flooring.
Obtain information on any possible health hazards
Use two or more alternative disinfectants at regular intervals to obviate proliferation of any
resistant strains of microorganisms.
Alternative should be of two different chemical types and not a different brand of the same.
USING CLEANING AGENTS/ DISINFECTANTS
1. Disinfectants- normally diluted before use as recommended by manufacturers. Dilutions
should be proper and procedure documented.
2. Dilutions made with freshly collected potable water. Avoid hard water- reduces effectiveness
of cleaning and efficacy.
3. Do not mix disinfectants of different chemical type and also with cleaning agents- Reduces
microbial activity
4. Use freshly diluted disinfected or cleaning solutions and use during the shift. Do not store
overnights pathogenic organisms can grow on storage.
5. Store diluted disinfectants as per SOPs.
6. Unused solutions must be drained and containers washed at the end of each day.
7. Destroy or deface original empty containers of manufactures, to prevent misuse, before
throwing away.

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CLEANING EQUIPMENT FOR MANUFACTURING AREAS

Depend on the nature of manufacture and surface of the facilities.
Routine for cleaning of non-aseptic manufacturing areas:
Equipment
1. Floor Mops

Made of sponge- squeeze type

Cotton mops do not shed fibers- cleaned daily after use with soap water, and stored dry.

2. Cloths and Sponges

Useful for cleaning walls, ceiling and equipment

Absorbent and non- shedding

But a limited life and discard regularly

Wash & dry in clean area

Nylon cloths - advantage -can be sterilized

3. Vacuum Cleaners

Preferred to brooms and brushes- dust free and free from fiber and bristles.

Portable vacuum cleaners or built in ones

Sterile areas need dedicated cleaners

Dust collecting bags cleaned after every use in case of portable

Central unit -cleaned at predetermined frequency

Provide cleaning port lines to prevent cross contamination of main vacuum lines

4. Mechanical Floor cleaners

Suitable for large manufacturing areas- but splash lot of water in surrounding areas, walls

Useful for cleaning sticky surface

Mop area and drain and clean mopped up water. Never store.

5. Jet cleaners

Devices spray hot water or detergent solutions

Fitted with different nozzles

Suitable for dislodging materials adhering to surface

6. Brooms

Not recommended as produces dust, which gets dislodged from one place to other.

Suitable for non -production areas

Swabbing should follow sweeping.

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CLEANING AND DISINFECTION PROCEDURE

Good housekeeping an important part of GMP

Sanitation assumes equal importance as other critical factors in pharmaceutical production

Operators to be made aware of importance

Cleaning/sanitation log book should be maintained

General Requirements
1. All procedures should be documented in simple language- understood by operators.
2. Procedure should include

Areas & surfaces e.g. Floors, walls, windows, doors etc to be cleaned

Cleaning agents to be used

Cleaning equipment

Frequency

3. Persons responsible for each activity

4. Frequent wet areas require regular treatment
5. Written procedure- cant be changed without approval from QC or Production Manager
6. Cleaning by contractors - same procedures apply- needs better supervision
7. Records to maintained- processing areas cleaned, name of person and date cleaned.
8. Display in each manufacturing area- Written sanitation program and schedule so that is person
are made familiar.

Cleaning procedure
General
1. Frequency should be laid down
2. Long production campaign -frequency less and shorter ones more
3. Interval between two cleaning not more than 3 days
4. Through cleaning after every product change over
5. Clean walls etc. regularly, vacuum cleaned 3 monthly
6. Validated cleaning program - yearly
Liquid and Ointment areas
1. Spillage mopped up immediately- not at the end of each shift
2. Floor is cleaned with hot water at end of each shift. Attend to walls and floor joints.
3. Weekly - entire-manufacturing areas including walls, platforms, pallets, and drains should be
cleaned with hot water/cleaning aids, flexible hose. Scrubbing machines may be used
4. Cleaning to be followed by disinfecting- by agents effective on moulds/water borne bacteria

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5. Ointment base traps, drains, equipment, washing areas require special attention.
6. Broken glass pieces must be removed from filling lines immediately- nylon brushes/dust pans
7. Clean all drains at regular intervals.
8. Pass steam and disinfectant solutions in drain openings in manufacturing areas at least 3
times a day.
Tablet and Capsule Manufacturing Area
1. Spillage to be cleaned up immediately
2. Remove powders by suction followed by wet mopping
3. Tracking of powder from footwear from one department to another by operators- avoided by
using mats
4. Wash mats daily and dry.
5. End of each shift- floor, wall ledges, and machine cubicles - cleaned with vacuum cleaner.
6. Use of brooms to be discouraged- Corridors washed with hot water and detergent dried.
7. Advisable to disinfect floor, walls and ceiling to prevent moulds especially when Vitamins and
other growth promoting products are used.
8. Special attention during monsoon- cleans and disinfects more frequently to prevent mould and
fungus growth.
CLEANING SCHEDULE
General
1. Code of GMP- written procedures must exist for sanitation, with details of procedures,
schedule, materials, safety precautions, and responsibility etc. to be stated.
2. Methods and materials to use must be described.
3. Cleaning schedule for each area- summarized - methods, stating, daily, weekly, monthly, and
yearly.
4. Procedures would depend on scale of operation, size, complexity of facilities, nature of floors,
walls, ceilings, product mix etc.

Typical schedule
Liquid Oral Manufacturing Area
Daily

Damp mop all accessible area-twice a day with cotton mops and 0.5% teepol (neutral
detergent) solution.

Wash sink and brackets with cleaning powder and water.

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Monday and Wednesday

Clean all vertical and horizontal surfaces- glass view panels, structural support of

equipment, work tables, telephones etc. with wet mop followed by drying.

Tuesday and Thursday

Clean platforms and all surfaces, using scrubbers. Hose down the platforms and walls-

Clean floors and flush out drainage channels.

Friday

Vacuum clean- dust from doors, windows, ledges, and louvers.

Clean walls, platforms, floors using mechanical scrubber, hose down all surfaces with water.

Use suction floor drier to remove water. Wipe with 0.1% Sodium hypochlorite sol, allow
drying.

Wipe down hand rails with detergent solution

Scrub equipment, washing area with powder, hose down and dry.

Fortnightly

De-dust all ledges, windows; exhaust fans, light fixtures, and insceticutors, with vacuum
cleaner.

Wash window glasses with cleaner, wipe and dry.

Damp-wipe all fixtures with sponge using 0.1% Tee pol solution.

Monthly

Clean with 0.1% detergent in hot water all surfaces including ceiling.

Dislodge all deposits of syrup.

Hose down with detergent solution.

Remove manhole covers and catch-pit baskets.

Remove debris and hose down with water.

Replace basket and sprinkle detergent.

Dust all shelves, floors, and walls, weighing scale with vacuum cleaner.

Damp wipe with detergent solution all surfaces.

Quarterly

Clean all areas and mezzanine floor using a vacuum cleaner

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5. TRAINING
SCOPE
Policy applies to all employees, including contract and temporary staff, production, testing,
distribution, (related activities) and marketing of products produced by the Company.
POLICY
Company must identify positions in Organization- performance may affect product quality.
Management responsible to ensure he has right Education - Training - Experience
Training must cover

Specific operations that employee performs

Relevant aspects of GMP and Companys Business Policy

Training to be carried by appropriately qualified individuals

SCOPE
1. Content of training program must include

GPM, personal hygiene, safety awareness and procedures

Personnel from Production, quality assessment, engineering and housekeeping staff

permanent + temporary)
Clear understanding of basic principles and their role and expectations in maintaining

good quality of Companys products

Training records for individual employees must be maintained

2. Special emphasis on training of staff working in aseptic areas, including housekeeping and
engineering staff
3. Special training for operators handling highly toxic or potent materials
4. Program should monitor effectiveness of training periodically
5. Emphasize on retention of production records for a definite period of time
6. Enable to

Review draft, approve, monitor the adequacy of standard Operating Procedures from
time to time

Issue instructions on production and quality assurance to persons concerned.

7. Monitor and ensure that validation of production process and equipment are adequate
8. Ensure that all significant changes to validated process, facilities, equipment, materials,
manufacturing steps, computer control systems, utilities are subject to comprehensive review
and approval by designated authorities including quality control personnel.

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REQUIREMENTS
All personnel involved in processing a drug product must have
1. Appropriate level of education, training and experience to enable them to perform the job
adequately
2. Training must be in areas specific to their responsibilities
3. Trained in GMP before they perform the job and subject to periodic re-training
4. Trained in safety procedures before they perform the jobs, and receive periodic re-training
5. Special training for personnel working in hazardous areas or controlled environments e.g.
Clean rooms, sterile areas, handling toxic materials, on how to minimize risk to personnel
and drug products.
FREQUENCY

After induction a follow-up training at sufficient frequency to ensure that employees are
familiar with latest GMP requirements.

The frequency will also be decided based on the results of self-GMP audit conducted by the
Company.

EFFECTIVENESS

Should be evaluated to ensure that the requirements are fully met with

DOCUMENTATION
Training program must be documented and records maintained to demonstrate that
1. All personnel - capable of performing their assigned tasks
2. All processes are carried out by appropriately qualified and trained personnel
3. Maintain records- contents of training program both in-house and external- received by the
individual employees
4. Maintain records- for a definite period of time depending on the Companys Policy.
MANUAL OF INSTRUCTION
1. Training manual - updated from time to time incorporating additional requirements of the
Company
2. An appropriate person- designated to oversee needs of Company - updating and issuing
instructions to participating departments

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6. CALIBRATION
Preamble

Instruments - critical part of Pharmaceutical Manufacture

Used to measure and record conditions and control various processes set to preset
parameters

Conditions are very critical for the product quality and inaccuracies - can mare the effect of
product

Continuous monitoring is paramount- Calibration

Objective

Determine difference in error between known and unknown reading

Adjust the output of equipment measured to bring it desired value

Proper calibration helps to produce materials within the specification

Prevent errors, reduce costs, reduce failure and re-work expenses

Procedures
The normal activities are
1. Documentation Program
2. Identification systems
3. Calibration Control Mechanism
4. SOPs for Calibration
5. Calibration Data Sheet
6. Handling and maintenance of Test Standards
7. Calibration Certification requirement
8. Pre-purchase Review of new Instrumentation
9. Review of Calibration Program
10. Training of Technicians
1. Documentation Program
i)

Documentation structure should include

Specifications

Standard Operating Procedures (SOP)

Forms, Data sheet and Check list

ii) Guide Lines for Documentation Forms

Specifications or SOP describing how to complete the Form

Forms should be designed for specific tasks

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A Typical Form will state

Item used

Environmental condition

Identification No

Calibration Completion Date

Instrument Standard Sheet

Calibration Status

Date and Time of calibration

Calibration Frequency

Calibration site

Calibration Due Date

iii) Calibration Program Documentation

Calibration dates-Instruments tagged with ID No. Date and review due date

Calibration date review- immediately against standard. Results within limits or not should
be reported

Calibration Documentation- within a week of calibration, data must be approved, signed

and taken in documents

iv) Documentation: This should include standard specification, raw data sheets, and the
calibration certificate
2. Identification Systems

Identification required both for documentation and systems.

Give each unit a unique identification number

XX-YY-I23 contains three fields

XX - consists of group of letters- location of plant

YY- indicate the equipment on which instrument fitted

I23- alpha numeric indicate type of equipment and inventory number

PR-RT2- TI6

PR- Location of Plant

RT2 - Reaction tank No.2

TI6- Temp indicator No.6

3. General Calibration Control Mechanism

Frequency - depend on amount of use, accuracy required and sensitivity of process or

system and past experience.

Also on manufacturers recommendation

Instrument affected by environment- calibrate at site

Each instrument must have unique No.

Records stored in record file

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3.1.

Hierarchy of Calibration Standards

Primary Standard-

Reference calibrating equipment available with approved National Laboratories- normally 4 times
more accurate than transfer standard

Transfer Standard or Secondary Standard-

Equipment used to calibrate measuring standard equipment- 4 times more accurate than
measuring Standard

Measuring Standard

Instrument used to measure process parameters

3.2.

Classification of Instruments

Classified as Critical, Major, Reference depending on process importance

Critical- Performance affects process and product

Major Instruments- affects process or product

Reference Standard- Convenience - do not affect process or product

3.3.

Calibration intervals

Aseptic core instruments- minimum twice a year

Critical Equipment- 6 monthly intervals

Major Equipment- 12 monthly intervals

Reference Instruments- at time of installation

3.4.

Calibration Control Mechanism

Ascertain- list of instruments to be calibrated in a month from data sheet.

Issue status report to Production department

3.5.

Calibration Due date

First date of the month after actual due date

Instruments exceeding calibration due date must be documented

Calibration tags should be fixed after calibration

3.6.

3.7.

Damaged Instruments
Should be removed till they are repaired
Documentation
Instrument standard specification and raw calibration are used to support Calibration
Control Mechanism.

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3.8.

Calibrating equipment

Primary reference Standard, Transfer Standard that is calibrated using primary reference
standard

Some of the commonly used equipment:

Universal Calibrator

Pressure/Vac. Gauge

Digital Equipment

Multipoint Temp Scan

Stable Thermo bath

Autoclaves/Sterilize

Temperature Gauge

Stand Sol Kit

Dead Weight Tester

pH meter

4. Standard Operating Procedure

Guide line for approval of calibration specification, procedure and forms.

SOP should outline detailed step-by-step action to be taken of calibrating equipment

employed.
A typical SOP

Section Engineering: Instrumentation

Subject: Procedure for Calibration of Temperature Indicators, Controllers and Recorders

Objective- to establish a procedure for Calibration

Responsibility: Instrumentation Engineer/Electronic Technician

Equipment Used: Universal Calibrator

Procedure
1. Connect the output terminals of the temperature calibrator to the inputs terminals of instrument
2. Apply appropriate millivolt (taking cold junction compensation i.e. CJC into account) or
resistance corresponding to the ambient temperature.
3. Observe reading on the display and compare it with ambient temperature.
4. Adjust potentiometer marked AMBIENT if required and bring the reading and display, to the
ambient temperature.
5. Apply mille volts (taking CJC into account) or resistance corresponding to the full span in
operating range of the instrument.
6. Observe reading on display
7. If the reading differs from actual span, adjust potentiometer marked span till display shows
exact span reading
8. Apply requisite millivolt (taking CJC into account) or resistance corresponding to 0%, 25%,
50%, 75% and 100% of the range of the instrument and note the readings observed on
display.

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9. Apply proper millivolt (taking CJC into account) or resistance corresponding to 100%, 75%, 50
25%, and 0% of the range and note readings
10. Observe deviation of the actual readings from set values
11. If relationship is nonlinear, adjust the potentiometer marked LINEAR if any.
12. Repeat steps (2 to 11) till proper ambient span adjustments and linearity are observed.
13. For controllers, adjust the set point to 25% of the operating range.
14. Apply proper millivolt (taking CJC into account) or resistance corresponding to a value which is
more than 25% of the range
15. Confirm that output relay is operating
16. Change set point to 50% of the range and repeat step 14 and 15
5. Calibration Data Sheet
Type of Instrument:
a) Instrument Identification Number:

Description

Model No.

Serial No

Range /Scale
b)

Instrument Standard Used:

Description

Model No

Serial No

Precision/Accuracy

c) SOP Procedure Number to be followed

d) Calibration Date and Time
e) Calibration site
f) Environmental Conditions
Temperature

Humidity

Pressure

g) Calibration Completion Date

h) Calibration Status: Accepted/ Rejected
i)

Calibration Frequency

j)

Next calibration Due Date

k) Name & Signature of Calibrating Technician

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6. Handling and Maintaining Test Standards

Procedure
1. Before using or handling a system, determine the problems involved in using the instruments.
Some requires balancing and some instruments zeroed before use.
2. Use Primary Standard against Transfer Standard.
3. Check instrument working properly before switching off.
4. Store instruments in proper place. Improper storage can affect performance
5. Improper temperature can affect performance.
6. Avoid mishandling- might affect performance.
Documentation
1. Calibration sites temperature and humidity must be documented
2. Calibration supervisor must document

Improper instrument performance

Improper handling and consequent damage to instruments

Improper environmental conditions

If a Vendor performs calibration, the following should be done.

1. Vendors name address
2. Calibration Site
3. Calibration completion date
4. SOP or specification and its issue date
5. Instrument standard
Description

Model No

Serial No

Precision/Accuracy

Serial No

Range/Scale

6. Instrument being calibrated

Description

Model No

7. Summary of data at various data collection intervals and the correction value for both
instrument and standard
8. Environmental conditions
9. Calibration frequency, next due date and exceptional conditions
10. Name and signature of calibrating technicians
11. Summary of report and audit findings
8. Pre-Purchase Review of New or modified Instruments
8.1. Instrumentation Review
a. Determine what instrument is expected to do, capacity?
b. Determine how functions, what control mechanisms.

Page | 22

c. Design not self limiting- Restrict use and future use.

d. What Process and Instrument? Should not over ride.
e. New instrument not affect other monitoring instruments no need to recalibrate
f.

If so, what should be calibrated?

g. Check whether Calibration department has adequate standards

h. Determine when initial calibration done and schedule
8.2 New calibration equipment
a. New calibration equipment should comply with specification regarding hierarchy of
calibration standards and precision ratio.
b. New calibration equipment - buy along with new equipment
c. New and modified instruments must have an instrument master record - stating
calibration criteria.
9. Review of Calibration Program
Must be reviewed yearly and altered as necessary. Review concerns

Frequency of calibration and performance of instrument

Operating procedure calibration

Consistent performing instrument - consider for reduction in calibration frequency

Frequency can be reduced one level in a year.

Calibration done at entire range of instrument from 25% to 100% accuracy

Amendment in new SOP will succeed the old one, and recorded.

10. Training of Technicians

Training includes persons performing field calibrations
Operations Training
a. Instructor should give proper demonstrations on safety aspects, correction measures,
documentation, efficiency, instrument care, calibrations limits, approval time limits and
deviation reporting
b. Trainee to carry out procedure under observation of instructor
c. Instructor should list out all documents reviewed, date and trainees check list, to make
him a qualified technician for an operation
Ongoing training
a. Each technicians training check list should be reviewed continuously
b. Trainee check list - maintained by department instructor
c. When new procedures is incorporated- all technicians, approvers, reviewers must receive
formal training and documented.

Page | 23

7. CONTAMINATION CONTROL
FEATURES

Contamination- unwanted presence of material, component or product in another raw

material

Source unknown and not easy to test

Prevention is very important

Objective- Identify some causes and outline some measures to prevent it

PROCEDURES
1. Receiving

Pre-entry Cleaning

Clean containers thoroughly before taking inside

SOP to followed

Vacuum cleaning preferred

Avoid wooden cases- harbor pests. Open outside

Report any contamination from vehicle

Check container Integrity- segregate damaged ones- subject to detailed examination

2. Sampling

SOP evolved to prevent contamination

Sample only one material at a time

Sample in segregated cubicle-minimize risks

Dedicated tools for sampling

Prescribe and follow procedure for cleaning tools

Do not return residues to original container

Validate all procedures regularly, ensure compliance

3. Dispensing

Lay down detailed procedures- ensure followed

Equip dispensing cubicles -dust extraction system

Dispense only one material at a time

Use clean scoops for each material- and product

Ensure containers are clean before use

Clean weighing equipment and bench each time

Use disposable gloves

Do not use ceiling fans in dispensing cubicles

Page | 24

4. Production

Segregate each production activity

Provide adequate dust extraction equipment

Evolve suitable cleaning procedure operation wise

Ensure effective of procedures- validate

Identify parts not assessable- each equipment

Train personnel- special care for cleaning

Check integrity of oil seals- tend to leak

Use dedicated accessories- filter bags, dust covers, sleeves

5. In-process Control

Do not return samples drawn for tests to original container

Common facilities used in in-process control- a source of major contamination.

Extra vigilance required - product with same color and similar appearance

6. Work in process

Material segregated and properly labeled

7. Packaging

Primary packaging components - bottles, caps -handle for one product at a time.

If more than one product- segregate and handle

Common Component- Surplus quantities issued for one product- cannot be used for
another product

Dust or color from product can contaminate another

Clean packing equipment before using for another

Institute a line clearance system before starting

8. General Precautions

Follow unidirectional flow of materials

Personnel made aware of hazards of contamination

Operators to wear clean and suitable garments

Regular training of operators to avoid risks of contamination

Air supply should be suitably filtered

Water major source of contamination- Ensure regular monitoring- microbial organisms

Page | 25

8. VALIDATION
MEANING
Validation to prove that a process works using scientific and statistical principle to produce
acceptable product.
OBJECTIVE

Validation determines process variables and set acceptable limits -in process controlsspecifies

Alert levels - set to indicate deviation from accepted level.

Action levels- range for corrective action.

BENEFITS

Reduced testing-raw, bulk and finished products

Improves QA, reduces cost- optimization

Enables effective and rapid trouble shooting

Enables better system and maintenance

Shortens lead time- low inventories

Empowers employees-control process & improve

Assurance that specific process will consistently produce a predetermined quality of

product

1. GUIDELINES

Protocols established through effort- Production, Quality operations, Engineering.

All protocols documented

Changes/deviation critical- understood & revalidated

i.

Prospective Validation- establish documented evidence that a system works- prior to

implementation

ii.

Concurrent Validation- establish documented evidence data generated during actual

process

iii.

Retrospective Validation- establish documented evidence based on review and

analysis of historical data

2. APPLICABILITY
Process validation expects qualification
2.1. Analytical quality test procedures
2.2. Instruments
2.3. Personnel

Page | 26

2.4. Raw and packing materials

2.5 Equipment design, installation and operation
2.6 Facility design, installation and operation
2.7 Critical support systems

Water (DM, Distilled, Water for Injection)

Steam

Compressed air

Nitrogen and other gases if any used

Drainage system

HVAC (Heating, Ventilation, and Air Conditioning)

2.8. Manufacturing process

2.9. Product design (formulation and Product Development)

2.1.

Analytical and quality Test procedures

Qualification requires that test procedure demonstrates suitable accuracy, precision,
specificity, sensitivity and ruggedness of method

Precision or repeatability is variability within a given laboratory, affected by analyst,

environmental conditions, laboratory equipment; none of is constant from time to time

2.2.

Instruments
Many processing instruments used- Calibration is essential- thermometer, pressure
gauges, relative humidity meters, conductivity meters, timers, and alarms.

Laboratory instruments- balances, spectrophotometers, chromatographs, calculators,

computers, pH meters

2.3.

Personnel Qualification

Qualification by training and experience is essential

Untrained persons can negate work done in qualifying process and other components of
process

Qualified person trained in all aspects of job, technical, supervisory

Training should emphasize necessity of not making changes in a validating process

without sufficient data

2.4.

Raw and Packaging Materials

Set specification based on process used and end product

Additional tests, particle size for suspensions

Vendors need to be qualified as manufacturers

Page | 27

2.5.

Equipment design, installation and operation

Selection followed by installation- verify equipment performs well- Establish fail safe
devices- no-fill detection in tablets

Written procedures available for each operation of equipment and process step

Training of operators to use equipment and follow process

Cleaning procedures- product change over- clearance

Computer controlled equipment challenged to ensure that system will work under variety
of conditions

2.6.

Vendors requested to supply software to validate system

Facility design, installation and operation
Facility qualification, include design, installation, construction and maintenance and
monitoring

Flow of material

Area and equipment lay out available

Room surfaces, to facilitate ease of cleaning

Drawing and written specification for all equipment

Adequate supervision during construction to ensure design parameters are met

On-going preventive maintenance schedule should be established

2.7.

Water Qualification

Schematic drawing of water source must be available

Water quality, specifications, testing methods should be documented

Frequency of inspection of filters, DM units, traps, storage tanks, distribution pipe lines,
valves etc should be established and documented

Water treatment efficacy qualified and calibrated with conductivity meter

Cleaning sanitizing procedures documented

Trouble shooting, corrective steps after failure, qualify

Use seamless pipes for DM, water for Injection, & sloped

Storage of Water for Injection to prevent stagnation water and microbial growth

Sterilization of water for Injection by steam or hydrogen peroxide

2.8.

Manufacturing Process
Every formulation must have a Master Formulation Order, specifying raw materials,
quality, quantity per lot, approved by responsible persons

Documented and validated step by step procedure

Each step qualified to validate the complete process

Page | 28

2.9.

Guidelines for Sterile Products

Dispensing
Balances calibrated
Formulation is current
Ingredients dispensed and countersigned

Component preparation
pH meters, balances, conductivity meter calibrated
Materials issued are countersigned
Identify and dedicate containers with proper labels

Compounding
Equipment clearance before use
Environment controls as per GMP
Compounding parameters within limits
Blend uniformity

Sterile filtration
Manufacturers Quality Assurance Certificate for filter
Check Integrity of filters before use
Ensure filter sanitation frequency
Check UV lamp intensity testing and replacement frequency

Filling
Filling under aseptic conditions
Filling heads deliver predetermined volumes

Sealing
Sealed containers are leak tested

Particulate inspection
Examine units under black and white background

Packaging
Line clearance obtained before starting
Verify stereos used for overprinting- current product lot

2.10.

Product design
Manufacturing procedure validated for Product Development- at least three pilot lots
produced

Fix tentative limits for critical variables- modified after stability studies

Methodology to monitor critical variables

Monitor three production lots- before confirmation

Page | 29

9. WATER FOR PHARMACEUTICAL USE

OBJECTIVE
Guide line for production of water for Pharmaceutical use and high critical areas

Purified Water for oral dosage forms

Water for injection (WFI) for parenteral

Water for drinking purposes to meet health standards

Untreated water - non-potable for non-critical use e.g. fire fighting, cooling water

1. Responsibilities
a. Head of manufacturing unit to ensure water systems are designed and operate under
standard conditions
b. Plant Engineer -written instructions- inspection of water systems, pumps, treatment
plants, traps, tanks, line
c. Cleaning and sanitizing systems, frequency
d. Corrective actions, if quality fails
e. Water system should indicate, source, treatment, storage, distribution, outlets,
drainage and sampling
f.

QC Manager responsible for- monitoring performance

g. Taking corrective actions- failures

h. Written procedures for sampling, testing, for records
2. Types of Water
a. Source water- Varies- Periodically monitored- WHO guide lines available
b. Potable Water- Meet drinking standards, not production, but used for bulk chemical
manufacture
c. Purified Water- Meet standard Specifications of Pharmacopoeia
d.

Prepared from potable water

e. Distillation, ion- exchanges or reverses osmosis. Used in non- parenteral preparations

f.

Water for Injection- Meet standards- prepared by distillation of potable water- prevent
entertainment

g. Water for final Rinse- same chemical/microbial quality as WFI - not necessarily
prepared by distillation

Page | 30

3. Water treatment systems

Several systems available- depend on the requirement of Organization or Country.

Storage conditions are critical

1. Coarse Filtration

Deionization (CDI)

2. Carbon Beds

6. Reverse Osmosis

3. Chemical additives

7. Ultra Filtration

4. Water Softeners

8. Distillation

5. Deionization (DI) and Continuous

9. Micro retentive Filters/ Ultraviolet Lights

1. Coarse Filtration- Remove coarse particulate > 10 microns prevent damage to system.
Cause microbial growth, blocking. Back washing important

2. Carbon Beds- Remove organic and oxidizing chemicals- absorption, Control includes, steam sanitation, stagnant conditions leading to biofilm- monitoring

3. Chemical additives- oxidizing agents for microbial control, sod hypochlorite, chlorine,
flocculating, and sodium bisulfate, Control levels to prevent excess of additives

4. Water Softeners- Resins to remove cat ions and anions (cal and Ma) -protect downstream
units i.e. RO membranes, deionization resins and stills

5. Deionization (DI) and Continuous Deionization (CDI): Improve chemical characteristics

by replacing cat ions and anions- Normally mixed bed exchangers are used

6. Reverse Osmosis (RO) - Uses high-pressure differential to force water through semipermeable to remove chemical, microbial and colloidal endotoxin. Failure of membrane to
be detected

7. Ultra Filtration-(UF) - Mechanical separation against osmosis in RO system- Pressure

differential is lower than RO. Used to remove bacteria, colloids, suspended solids. UF
membranes can be used as final filters

8. Distillation- Reliable method for WFI, Main concern is entrainment, flooding, and variations
during start-up operation and contamination of steam. Eliminated through continuous
conductivity sensing and monitoring

9. Micro retentive filters- separate material of 0.05 to 10-micron range- prevents

microorganism but not endotoxin. Sensitized regularly, since formation of biofilm is
common

10. Ultraviolet light- Low microbial maintained by using wavelengths of 254 nanometers with
a residence time of 15 seconds, Good for maintaining low levels but not well for major bio
burden. Replace bulb regularly.

Page | 31

4. Storage/Distribution and Piping

Crucial to prevent microbial invasion, Heated, recirculating system is most reliable.

Approaches:

Storage and recirculating systems at 75 to 80 C

Storage at 75 to 80 C

Recirculating between ambient and 60 C

Total system at 55 to 60 superheated periodically to 75 C

Avoid dead legs of any type, including fittings

Material of construction important- polished surfaces

Distribution piping configured as recirculating loop

Protect vents by micro retentive filters

5. Microbiological purity
Limits for microbial contamination are set for

Drinking Water

Purified Water

WFI

Fix limits for endotoxin

Maintain Conductivity instruments and calibrate regularly

Validate all systems that treat water for pharmaceutical use

Establish Test frequency- potable and purified water weekly. WFI - twice a week

Page | 32

10. ASEPTIC PROCESS CONTROL

OBJECTIVE

Sterile Products are free from microorganisms, pyrogen, with high standards of quality
and purity

Greater significance- maintaining high standards for sterility- than on End product testing

Ensure design parameters and setting up practices and precautions and following them
consistently meet conditions.

GOWNING AREA- RREQUIREMENT

Must be adjacent to sterile area

Maintain air pressure differentials to prevent flow of air between gowning areas to other
areas.

Easy to disinfect- flushed with filtered air

Mechanism to open only one door at a time

Restricted to only operating personnel

Adequate facilities for washing, disinfecting, drying hands, storage of clean sterile
garments and disposal of used garments

GOWNING PROCEDURE- STERILE ROOM ENTRY

Access to clean and aseptic areas only through change room, the general procedure
Change over from street clothes to factory uniform and footwear
Wash hands and feet with soap and water before putting factory uniform
Air pressure differentials should sweep air from aseptic area to change rooms and
non-sterile corridor
Doors of change room not to be opened simultaneously before entry/exit to sterile
area
Stagger entry- pre-determines no. of persons using room minimum

Page | 33

ENTRY PROCEDURES
First Change Room

Enter after ensuring room is under positive pressure

Remove factory clothing and footwear. Keep at the designated proper place

Disinfect arms up to elbows and swab feet with disinfectant solution. Renew disinfectant
solution.

Before entering second change room, stand on a mat soaked with antiseptic, kept at the
entrance

Push door open with elbow, without contaminating wet hands, and ensure first entrance
door is shut.

Second Change Room

Dry washed hands and arm with foot-operated hot air drier. Pick up sterilized garments
and put on as follows

Sterilized head gear (hood, stored under UV lamp) should be put on first, covering hair,
nose and mouth

Put on sterile suit or tunic, so that the lower end of hood is tucked to neck of suit, with
arms gathered at wrist.

Put on sterile trousers so that they cover lower portion of suit. Trousers should not
sweep the floor, but gathered at the ankle.

Third Change Room

Pick up sterilized booties and put them while crossing over a step-over bench provided in
the room. Tuck in the trouser bottom inside bootie, which is then laced up.

Insert the booted feet into footwear reserved for use in sterile area and previously
washed. Put on visor goggles

Put on sterilized gloves with suit tucked inside gloves

Swap gloves with alcohol or antiseptic, enter aseptic room, by pushing doors open with
elbow

End of work, remove gloves and deposit for washing. Change garments in reverse order
and deposit for washing. Gowns may be kept under UV and during short breaks

Garments can be re-used only after cleaning and sterilization

Mandatory to display gowning procedure in change in the form of display and sequence
of changing
Page | 34

Operators working in clean and aseptic areas should open and shut doors gently. Do not
rush or run in the rooms and avoid talking

FUMIGATION OF ASEPTIC AREA

Control of environment essential to keep bio-burden low
Formaldehyde is normally used

Formaldehyde is irritating to eyes and skin. Rubber gloves and goggles must be worn

37% formaldehyde solution is placed on stainless steel container with perforated lid.
Place container on hot plate. Put off blower during fumigation

Potassium permanganate can be used as alternate to heating,

Seal off entrance to areas and leave it undisturbed for some time to ensure proper
sterilization

Prior to fumigation entire area must be cleaned and sanitized. Put off air supply and UV
lights

Formaldehyde vapors are effective at a relative humidity of not less than 50% at 25c.
Monitoring humidity and temperature during fumigation is essential.

After exposure for adequate time interval, put on exhaust fan. Room is flushed with clean
filtered air.

Clean surfaces with suitable disinfectant

Switch on UV lamps

Expose nutrient agar at various locations, to ensure that microbial load is within limits.

Page | 35

11. CLEANING & MONITORING - MANUFACTURING EQUIPMENT

CONCEPTS
All manufacturing equipment must be cleaned and sanitized regularly. SOP should be written
down and must be available at the shop floor level. The document should state:

Date of Issue

Revision No

Due date of next revision

Signature of writer, authorizing and issuing authority

Brief statement of purpose of SOP and intended use

Person responsible for cleaning and maintenance

Schedule of cleaning, sanitation and maintenance

Detailed description of method of cleaning to be employed

Methods of dismantling and assembling equipment

Removal of identity of the previous batch/product

Protection of clean equipment from contamination

Inspection procedures before use

Record keeping of cleaning, maintenance, sanitation and final inspection

Procedures to ensure achievement of appropriate level of cleanliness by sampling,

testing, inspection or validation

Sensitive analytical methods to check residue levels

CLEANING SYSTEM

Cleaning system must be automatic with the following:

Equipment to be cleaned

Equipment used for cleaning process

Selection and qualification of cleaning materials

Method of dismantling and assembling

SOP should state

Cleaning methods
Sampling methods
Testing methods
Inspection procedures

Product contact surfaces must be smooth, non- reactive and easily accessible and nonPage | 36

absorbent
SELECTION OF CLEANING AGENTS
Cleaning agents must fulfill:

Non- corrosive

Not stain the equipment

Compatible with the equipment surface to be cleaned

Solubilize the drug product residue within a short time

Anti-microbial in nature

Safe both to user and cleaning equipment

VALIDATION OF CLEANING PROCESS

Validation of cleaning process is of utmost importance

Ensure that desired level of cleanliness is achieved every time

Effectiveness of cleaning must be validated

Critical areas where residue can accumulate Red spot identified

Baffle plate-to prevent contamination from mixing rotor - is a major source where
particles can accumulate

Sampling Methods

Swab Technique- Potential areas swabbed with cotton swab wetted in solvent and
extracted in same solvent and tested. Useful in determining microbial residues

Solvent Rinse Method- Rinse with solvent of known volumes given to the cleaned
equipment and aliquot analyzed for residues

Placebo Rinse Method- Residues which are difficult to flush out are removed by
duplicating process with a placebo and analyzing the residues

HPLC - employed for determining residues

CLEANING GUIDE LINES

GENERAL

Cleaning done in specially designed areas

Operators must wear protective clothing, shoes, gloves, head gear

Cleaned parts to be covered and stored in dust free area and properly labeled

Cleanliness and suitability to be checked before use

SOP should be written down. A model:

Disconnect machine from the mains
Close hazardous utilities being fed to the machine
Page | 37

 Dismantle machine parts coming in direct contact with product

Wash all SS parts with 0.5% Tee pol. Use live steam
Wash all rubber gaskets with 0.5% Tee pol or suitable agent
Dust painted MS body parts of machine. Clean with 0.5% Tee pol solution.
Wipe all clean dismantled parts with lint free cloth
Certify effectiveness of cleaning system, sample residues
Take a trial run, to check machine is running properly
Cover machine with lint free synthetic fiber so prevent re-contamination with dust
Complete all related documentation records

Complete and through cleaning necessary at product change over

For dedicated products, clean at end of each shift

All dedicated manufacturing lines, end of last shift or weekends- through cleaning

Carry out swab test on all cleaned equipment for residues of previous product

Swab/rinse tests revalidated for product change over on non-dedicated lines every three
months or earlier

Swab tests validated every six months for dedicated ones

For products containing steroids or biologically active materials, swab tests done after
every change over

Page | 38

12. PACKAGING & LABELING

Packaging and labeling controls are very essential and attention must be given:

Minimize the risk of cross-contamination

Prevent mix-ups or substitutions

Physical segregation of packaging of different products

Requirements
Examination and usage

Labels or packaging material to be released on specification

Maintain records of each shipment of labels/packaging material

Separately store labels and packaging material of diff. Prod.

Destroy obsolete packaging materials

Monitor printing devise to ensure proper imprint

Issuing and control of Labels

Strict control while issuing

Mislabeling is a common hazard and exercise adequate control.

Store Printed packaging materials separately and transport in sealed containers

Responsibility rests with Factory Manager

Labels to be properly coded, identity of material, & current

Detailed written procedure for issuance and storage

On-line rejection should be accounted, destroyed, recorded

Check correctness of labels, before use

Reconcile labels issued, used, returned, destroyed

Returned labels stored properly to prevent mix-up

Different products must have distinct appearance for labels and packaging materials.

Educate the supplier to take adequate steps to prevent mix-up at stage of printing.

Not to print different products at the same time.

Labels to be kept under quarantine till cleared by QC

All printed material Checked for size, appearance, details etc.

Pre-printed labels not to overprinted with different name

Over printed Batch coding must be authorized

Issue a known quantity of labels under proper security

Page | 39

Packaging and labeling operations

Important to ensure use of correct labels for each product, Written procedure should be detail:

Procedures for prevention of mix-up and cross contamination

Steps taken to ensure work area clean, clear and free. A line clearance to be performed

Drug product identified with a proper lot or control number

Display Name and Lot No being packed

Packaging department-check correctness of packaging material

Printing by hand to be checked at regular intervals

Check containers are clean before use

Filling and sealing followed by labeling, if stopped, adequate care taken to prevent mixup

Check electronic readers are working properly

Embossed information should be distinct, and not fade away

On-line checks for - appearance, completeness and correctness of packaging materials

used, overprinting is correct, line controls are functioning

Samples taken not to be returned to packing line

All discrepancies should be investigated and recorded

On completion of operation, all un-used batch-coded material should destroyed and

recorded

Packaging Specification
Use of right packaging materials is very important for quality of the final product. Guide lines are:

Master Packaging Instructions should be created. Listing all components with their
specifications to be used

For every product, all components to be listed in detail along with coding and over
printing instructions

Specimen should be attached for easy identification

Special Instructions- packing moisture sensitive products

LINE CLEARANCE
Important to inspect packaging and labeling facilities and clear all materials before starting

Filing/Packaging line and areas close to it should be cleared of materials from previous
product

Rejects, inadequately filled bottles, broken or damaged packs, strips, empty pouches,
Page | 40

should be removed

Spillage on lines should be cleaned

Left over labels, cartons to be removed

Equipment, certified clean and tagged, by supervisor

Equipment used, re-inspected for cleanliness, before use

Details of cleaning, recorded in Equipment Cleaning and Use Log sheets

After satisfactory line clearance, relevant details filled in and initialed by supervisor, in
order format

Filling or packing should not commence before satisfactory checking and line clearance

If filling/packaging is interrupted for some time, a new line clearance is necessary

PACKAGING INSTRUCTIONS
At times variations are required depending on market needs for each product. Such variations
should be clearly stated. Normal details:

Name of Product

Description, pharmacopoeia form, strength

Pack size - number, weight, volume

List of materials required for standard batch size, code reference number for each
specification

Specimen sample, Batch no, shelf life etc

Special precaution required if any, including inspection details if any

Brief description of packaging operation, including any subsidiary operations or

equipment to be used

Overprinting details, batch no. date of manufacture, expiry date, retail price, physicians
sample- not for sale

Any specific labeling requirement

DRUG PRODUCT INSPECTION

Examine correctness of label, right containers used

Representative sample collected and visually examined

Record results in batch control records

Page | 41

13. PRODUCT CODING

Objective

Easy Identification or tagging of Product, so that History can be traced easily

Coding of Inputs
1. Supplier

All raw materials are coded;

exceptions are sugar, starch, produced in bulk

2. Packaging materials

Not mandatory and end-user can assign lot No.

Coding by Receiver

Not mandatory, But system of Numeric or Alpha numeric used

Control No Lot No.

On receipt of material

Original I.D. No;

Is not of much significance.

User assigns a specific or unique identification number

E.g. Number of certification of Analysis.

System should provide complete history of Lot till consumption and disposal

Printed Packaging Material:

Art Work- May carry a unique code number

0931. 2. 93 Finished Product code/ Second Version/ Year

Help to check on packing lines to monitor packaging materials in use

Bar Code:
Single code Bar- Printed at the edge of materials viz. Labels or carton. Bars provide
check and prevent mix-up and easy to inspect
Multicolor Bars- Help to quickly check all colors of a multicolor are printed or not
Spacing and location of Bars- Distinct shift in position of code bars, size, and spacing
between consecutive bars are helpful in establishing conformance to standard.
Cyclic codes- Help in establishing period (a month) when component was printed.
Used normally in paperboard cartons clock in inner flap indicate month of printing.
Supplier code- Asked to incorporate a logo

Page | 42

Batch coding:

Provisions of Drugs and Cosmetics Rules 1945 are applicable. How the conditions are left to
the manufacturer.

CODE- could be alpha numeric.

The system should be simple and practical.

Ease of documentation during manufacture.

Operational convenience

Space should be available for batch coding

Subsequent documentations at stages viz., excise, invoicing, to stockiest/ trade must not be
over looked

Page | 43

14. REWORK AND RE PROCESSING

Objective

Residues of drug product re worked using authorized method, validated to demonstrate

suitability, of meeting specifications without altering the product quality

General Guidelines:
1. A minimum value of material below which re processing not to be considered to be set
2. Investigate reasons for out of specifications to minimize recurrence.
3. Maintain register giving quantities and reasons
4. Re processing or re labeling should be rare
5. Normal manufacturing process applicable unless evidence to prove alteration of quality,
shelf life and stability
6. Re processing method to be authorized and documented, after potential risks evaluated and
found negligible
7. Need for additional testing of reprocessed product to be considered viz. Re grinding and re
granulation of tablets affect tablet dissolution
8. At times original release specifications of product may not be applicable. Revise
specifications. Review constantly quality of re processed products.
9. Residues and reworked or recovered material may adversely affect product quality. Must not
be used in subsequently batches.
10. Deciding factor for use or not is the stability of batches containing known amount of
residues.
11. Collect stability incorporating varying amounts of residues of varying ages.
12. Stability profile should not be different from standard batches without any residues
13. If stability is different, ascertain period for which product will meet end of life specifications.
Life period of such batches to be suitably amended.
14. If sufficient quantities can be re processed into are processed batch, discard residues from
re processed batches
15. Residues from inspection stage containing foreign matter viz. Metal particles should not be
re used.
16. Batches containing residues are not released by QC, until batches from residues came are
fully tested and certified for use.

Page | 44

Specific Requirements:

Method of handling residues, additions to fresh batch are documented and approved by the
Quality Control Manager

Batches containing residues are subjected to additional tests before release

Batch Manufacturing records should indicate that the batch contains residues, with the
details of origin of residues, and quantities used

Any reduction of normal shelf life recommended by quality control should be recorded, in
batch packaging Order and labeling order instructions

Page | 45

15. WAREHOUSING
OBJECTIVE

To provide adequate facilities and systems for storage, handling of raw and packaging
materials required for manufacture and packaging of Pharmaceutical Products

SCOPE

Good Warehousing practice include

Guide lines for receiving, verifying, inspecting, all incoming raw materials

Premises for storage of materials

Handling of raw and packaging materials

Weighing of materials for batch production

Storage and handling of finished goods

General Guidelines:
1. Receive materials against specific supply advice (Purchase Order)
2.

Each consignment should accompany written document which should state

Name of material

Name of manufacturer

Batch No., date of manufacture/expiry date as applicable

Quantity of material batch wise

Number of containers, Quantity per container

3. Delivered material received by designated person responsible for the warehouse

4. Materials are checked for cleanliness and pack integrity. Damaged/broken containers are
segregated and reported accordingly
5. All receipts are numbered and taken into stock as per system employed to enable review
and first in first out basis.
6. Each container labeled indicating
7.

Serial No. of receipt ***************

Name of material(as followed in Company Register)

Total Quantity, including Number of containers

Date of receipt

Labeled material must state

Under Test

Awaiting Approval or any such legend.

Material must not be used by Production until approved by Quality Control.

Distinct color label may be used

Page | 46

PREMISES
Must have separate areas suitable size, and construction for

Receiving (initial inspection, cleaning, check weighing)

Sampling (adequate facilities to prevent cross contamination during sampling)

Storage (including specified air-conditioned, cold rooms, store for hazardous chemicals)

Dispensing) adequate facilities to prevent cross contamination during dispensing)

Rejected materials (secure storage facilities for goods to be returned to supplier, or to be

destroyed or rendered unusable)

Free of insects, birds, and pests

Facilities for pest control treatment

Storage of Raw Materials

Storage conditions

General storage area or special storage depending on material and required conditions

Must not be stored on ground but off floor on pallets

Segregation
1. To be sampled
2. Under Test
3. Approved
4. Rejected
5. Storage area for hazardous materials with restricted entry

Storage of Packaging Materials:

1. Primary packaging materials
2. Bottles, vials, ampoules, tins, tubes, stored as they are to prevent contamination
3. Printed packaging materials properly identified pack size etc.
4. Printed materials- labels, foils, cartons, stored in secured area with restricted entry
5. Proper identity maintained- check labels before issue
Page | 47

6. Do not store similar looking labels at same place

7. Special instruction Control of labeling Materials should be including in control documents
8. Air conditioned store for foils, temperature sensitive, moisture sensitive materials

Handling and Issue of Raw Materials:

1. Attention to cross contamination, safety hazards
2. Keep containers always secured
3. Dust extraction facilities are required
4. Use of protective clothing, hand gloves, face masks
5. Handling inflammable materials
6. Safety data sheets must available handy
7. Materials prone to support microbial growth
8. Materials issued only against written work order
9. Issues against Packaging Material Order
10. Adequate check before issuing printed materials
11. Difficult to issue specific quantities, but keep proper count
12. Unused materials returned to warehouse
13. Take care while re-issuing returned materials
Warehousing of Finished Products:
1. Proper storage area, with suitable environment control
2. Only Quality Control approved material released for sale
3. Good housing requirement
General Guidelines:

Suitable racking and storage

Arrangement for temperature and humidity control

Arrangements to prevent flooding, entry of rain water

Suitable firefighting equipment

Separate area for receiving orders/dispatch

Page | 48

Premises

Safe and orderly receipt of materials

Segregated area-quarantine for rejected materials

No. of exits should be minimum

Arrangements for storage on racks and pallets

Proper lighting and ventilation

Storage for housekeeping, pest control equipment

Warehousing Procedure

Stocks received against proper documents with all details viz. Batch No., quantity, Analytical
reports

Under test to be maintained under quarantine

Stock rotation on First in First out basis

Order require dispatch of variety of products, arrangement for order picking and assembling

Order and assembling area close to minimize distance traveled

Storage of picked stock on shelves for easy checking

Picking and assembling of order done against a standard, dated, serially numbered
documents

Assembled product checked for accuracy before dispatch

Batch details to be recorded

Dispatch of Finished Goods:

Only released products to be dispatched

Adequate precaution to prevent spillage/breakage on transit

Vehicles carrying goods must be clean and well protected

Free from infestation

Do not give strong odors to contaminate the product

Vehicle has ability to withstand weight

Page | 49

Returned Goods

Goods returned properly accounted with reasons

Isolate returned goods- clearly labeled

Quality control Manager to examine and instruct to re process or destroy

Destruction to be supervised by responsible person

Re processing done according to instructions from Quality control Manager

Weighing of materials
General Guidelines

Skilled operation- to be done by designated person

Observe safety precautions

Moisture sensitive materials- separate cubicle

Choose right type of balance- minimum weight should reflect error. Follow guide lines of
manufacturer

Check balance is clean- no dust- no contaminants

Check zero error before first use

Record tare weight

When two or more lots are used- record amounts from each lots

Label each material:

Name of material

Product used for

Tare/ net weight

Upon receiving at manufacturing area, check

Labels against formulation order

Cross check weight

Sheet signed- becomes part of record

Page | 50

16. RETURNED GOODS

OBJECTIVE

Finished products returned to Company for various reasons for reprocessing/destruction.

Clear guidelines should exist for handling such items

SCOPE
Provide clear guidelines for
1. Classification of returned goods
2. Responsibilities/Authorities for dealing with such situations
AUTHORITY AND RESPONSIBILITY

Head of Quality Control or his nominee responsible to formulate procedures and

implementation

CLASSIFICATION OF RETURNED GOODS

Date expired goods

Damaged/broken primary containers

Leaky/broken seals of closures of containers

Mutilated/smudged labels- unidentifiable

Soiled labels- aesthetically not presentable

Products recalled, voluntarily for reasons/Company

Products recalled under directive of Drug Control

HANDLING PROCEDURE: General Guidelines

All returned goods should be properly

Documented

Inspected

Accounted

Labeled (to identify primary cause for return)

Segregated/quarantined till further action is taken

Ensure that statutory requirements are met

All operation/actions are well documented

Date Expired Goods

Destruction to be authorized by designated person

All destruction to be supervised by responsible person

Contents destroyed so that Product not usable in any manner what so ever

All primary and secondary container with printed matter destroyed to render them unusable

All operations documented to reconcile stock received and stock destroyed

Safety and health of employees to be considered.

Page | 51

Damaged/Broken Primary Containers

Goods examined by designated person to ascertain for re-use/recovery

Product recovered, carefully evaluated for quality, efficacy and safety.

Mere conformity to specification is not enough, to return such product to stock

Possibility of non-detectable contamination and/or degradation product not overlooked

If felt, that the damage to primary container can make the contents unusable/unsafe,
contents shall be destroyed.

Leaky/broken Seals of Primary Containers

Contents are likely to be exposed to unknown environment.

Therefore considered unsafe

To be destroyed

Mutilated labeling:

Product unidentifiable

To be destroyed

Soiled labels, product identifiable

Designated person to examine.

If only loss of aesthetic appeal and present ability to user

Without comprising safety/security of product quality, decide on method of redressing for

balance shelf life.

Document redressing operation

Store redressed stocks separately. Should be identifiable throughout

Unfit stock to be destroyed

Returned Goods:

Same as any returned goods

Dealt separately

Page | 52

17. PRODUCT RECALL

OBJECTIVE
Define a system for

Speedy and efficient removal of unsatisfactory material from market

Assign responsibility for implementation once decision of recall has been made

RECALL APPROVING AUTHORITY

Managing director/President/Head of Company

There must be a written and approved procedure of a person responsible for initiating recall,
sampling from market.

NEED FOR RECALL

Considered urgently and implemented without any delay if

Evidence that continued presence in market can pose risk to health to the use

Local regulatory authority directs a recall.

CRITERIA FOR RECALL

Health hazards to the user because of product defect

Extent of recall (viz. consumer, retail, wholesale, In Company)

Significance of defect, or cause on batches

PRE-RECALL INVESTIGATIONS & CONFIRMATION

Product complaint from field staff referred to QC Dept. for investigation, recommendation

Batches of product found not satisfactory, evaluated for level of re call (In Company,
wholesale, retail)

Approving authority shall approve within 2 days

Any notice of recall from drug control Authorities in house investigation completed within 2
days, unless special reasons- and longer investigation time

On approval of recall, a Recall Co-ordination Committee, consisting of QC/Sales &

Marketing/ Distribution/Warehousing/Production

Shall be responsible for prompt initiation

The committee shall designate one person to co-ordinate all activities on behalf of the
Company

Page | 53

RECALL PROCEDURE

Designated member shall be responsible for taking all actions for speedy, efficient and
effective recall.

Further distribution or sale of affected batches should be stopped immediately

Confirmation should be received that stocks are frozen and kept under quarantine

If product defect is life threatening- public announcements to be made to reach retail outlets,
hospitals, Doctors and even individual users.

On receiving recall communications- responsibility of distribution to stop usage/sales

Recall co-ordination committee shall meet frequently to assess progress

Designated member of co-ordination committee shall liaise with Drug Regulatory Authorities

Recall affected as per directive from Drug Control agency on life threatening situations.
Approval for disposal/destruction to be obtained from Drug Regulatory Authorities

Recall co-ordination committee shall decide on the most effective and safe disposal of
recalled stocks, including packaging materials to make them unusable

Recall committee shall authorize the disposal/destruction of stocks recalled

Disposal/destruction of stocks shall be carried out

i.

At site approved by recall committee

ii.

Under supervision of person designated by recall committee

Appropriate documentation of Product Name- Batch No.- Date of manufacture- Date of

Expiry- Quantity destroyed- to be maintained

Recall committee shall finally review complete recall operation, including documentation and
close the recall as RECALL COMPLETED

Page | 54

18. REJECTS/SCRAP DISPOSAL

OBJECTIVE

Improper destruction procedures can cause problems

Inherent dangers of mishandling scrap/rejects

SCOPE

Guidelines dealing with rejects/scrap

RESPONSIBLITY

Mainly production, representatives of Quality assurance, shop floor, and housekeeping is

equally responsible

REJECT/SCRAP GENERATION
Rejects generated systematically collected and accounted to prevent misuse

Residues generated during sifting, milling

Product residues extracted into dust extraction system

Rejections during compression, encapsulation, coating, filling, inspection, & packing stages

Rejects from in process checks

Non volatile residues from batches

Excess of rejected printed packaging materials coded or non-coded viz. Labels, cartons,
leaflets

Excess of used stereos left over after coding

Product residues collected from floor sweepings

Obsolete printed packaging materials left over in stores

Date expired or damaged goods returned to factory

Excess sample remaining with Quality Control after testing is completed

Control samples with Quality Control after mandatory storage period

Product samples from Research & Development Laboratory at stage of Development

GENERALPRINCIPLES

Written authorized procedure for

a. Differentiating recoverable/non-recoverable rejects
b. Scrap disposed/sold- precautions to be taken to deface labels, containers.

Handling, destruction/disposal of rejects from production

Rejects collected in closed containers/labeled/segregated

Destruction carried out by authorized persons only

Page | 55

Quantities rejected and destroyed should be recorded and reconciled in relevant batch
documents

Rejected printed packaging material, not to returned to the supplier

Appropriate safety precautions to be taken while carrying out destruction

Final disposal of solid/liquid residues should comply with local requirements including effect
on environment

MODE OF DESTRUCTION: Recommended Method

S. No.

Type

Method of Destruction

1.

Empty containers

Deface Labels

2.

Powder from dusts collection

Make slurry in water/solvent.

Incinerate Solids
3.

Granules, powder, tablets, capsules

Make Slurry in water/solvent

Incinerate solids

4.

Syrups, liquids, including injectables

Drain into waste stream with/without Pre

treatment to destroy toxic waste

5.

Injectables in ampoules

Manual/mechanical crushing. Liquid Drained to

waste stream

6.

Injectables in vials

Vials de-sealed and crushed as for Ampoules

7.

Granules/tablets/liquid in bottles

De-seal pack. Destroy contents.

Destroy seal by crushing

8.

9.

Strips/blister packs including empty

Recover tablets if permitted by defoiling.

packs

Rejected tablets destroyed

Ointments/Cream

Washed into drains, with/without Special

treatment
10.

Ointment/cream tubes

Squeeze contents. Recycle if Permitted. Empty

tubes crushed or shredded or incinerated

11.

Labeled ampoules/vials

Crushed

12.

Labeled bottles

Remove labels and destroy contents and

container

13.

Printed packaging material

Incinerate and or/shredding

14.

Used stereo figures

Cutting/shredding/defacing

15.

ROPP seals

Crushing

Page | 56

19. LABORATORY CONTROLS

OBJECTIVE

Quality of Manufactured Goods depends on quality of inputs and controls during

manufacture.

Finished product testing alone is no guarantee for good quality

SCOPE

Provide guidelines for setting standards

SPECIFICATIONS
1. Written specifications for each material authorized by Quality Control and to be reviewed
periodically

2. Statutory (Pharmacopoeia) standards are minimum specifications- may not be adequate

3. If no statutory specifications are available, tests or specifications should cover identifications,

limits of purity and or potency & impurities

4. Each written specification should mention- date of issue/Revision

a. Name of material with common synonyms (if any)
b. Code reference No. if used
c. Special requirements, if any- container/pack
d. Handling hazards
e. Sampling Instruction
f.

Special storage requirements

g. Frequency of re-testing stored material

h. Approved suppliers
i.

Description of physical Form

j.

Specifications for limits for purity, physical and chemical characteristics, microbial
standards and assay

k. Reference to appropriate analytical methods

l.

Signature of approving authority

5. Alternate validated method can be used but with written evidence

Page | 57

RAW MATERIAL RECEIPT, TESTING, RELEASE:

RECEIPT OF RAW MATERIAL

1. Receipt of each delivery to be recorded
2. Examine for proper labeling, damage and contamination
3. Damaged container to be segregated
4. Give control reference No. For each delivery. Should enable to get full details of each
delivery
5. Reference No. Should be indicate
a. Name of Material
b. Quantity received
c. Date of receipt
d. Name and address of supplier/manufacturer
e. Suppliers reference
f.

Results of tests carried out

6. Release of material- approval/rejection

7. Reference No. Should appear on container before processing
8. Every delivery should be held under quarantine before release by quality control
9. Quarantine by segregation or labels Under Test
10. Status labels applied by authorized personnel by Quality Control
11. Status labels- adjacent to Original labels or on top
12. Each consignment to be stored on pallets
RAW MATERIALS- TESTING
1. No material issued to production unless tested/approved
2. Detailed method of sampling and testing drawn up and approved by QCM
3. Review methods periodically- super ceded version along with current maintained
4. Sampling done as per authorized procedure
5. Samples tested for compliance of laid down specifications
6. For large deliveries- identification tests on each and every container
7. For injectable use- every container should be sampled/identified
8. Materials liable to contamination viz., dirt/microbiological/ insects should be examined
against specification for each contaminant
9. Alternative test methods can be used, but should be validated
10. Sample of approved material should be retained

Page | 58

RAW MATERIALS- RELEASE

1. Raw materials meeting with specifications are to be released
2. Ensure storage conditions in warehouse is satisfactory and not deteriorate during storage
3. Containers must have authorized PASSED labels
4. Details of PASSED LABEL
a. Name of Material
b. Code Number
c. Laboratory Reference No.
d. Date of issue/approval
e. Re-test date if any
f.

PASSED or APPROVED in bold capitals

5. Period up to materials will comply with specifications should be determined.

6. If kept for longer storage period, re-test should be done before use.
7. Rejected material should be quarantined and properly labeled.
8. Normal color code employed is GREEN for approved, RED for failed/rejected and YELLOW
for on test
RAW MATERIAL SAMPLING

RESPONSIBILITY: Quality Control Manager

SAMPLING EQUIPMENT:
1. Material of construction should not affect or contaminate sample taken- Stainless steel/
Plastic are considered suitable
2. Sampling equipment should be cleaned and dried before use
3. For microbial contamination- equipment should be sterilized before use.
4. Sample containers should be labeled and should be of right type and size
5. Suitable carriers viz. Baskets should be used
6. Containers should be wide mouth, amber or colorless bottles, with screw caps and inert
wads.
7. For hygroscopic materials- tight fitting polythene liners are used before caps are fitted
8. Containers for liquids- ladles of stainless steel with spout at right angle to the handle are
used. Valve sampling cylinders and sampling tubes of glass or metal are employed

Page | 59

SAMPLING PERSONNEL:
1. Trained for the purpose. They should be observant, meticulous and have the ability to
understand the nature of material they are handling.
2. Should be familiar with precautions to be taken while handling hazardous and sensitive
materials
3. Staff to wear protective clothing
4. Sampling staff are accountable to Quality Control Manager

PRECAUTIONS:
1. Wear proactive clothing while handling hazardous materials
2. First Aid instructions should be at place of sampling
3. Before sampling- ensure sample containers show
a. Name of material sampled
b. Identifying mark of material container from where the sample is taken
4. Open containers carefully and re seal
5. Samples should be returned to work points where taken
6. Volatile materials samples, to be filled to 70% of container volume
7. Spillage to be cleaned up immediately and disposed off safely
8. Sterile materials to be sampled in such a manner that they do not become non- sterile

SAMPLING PLAN
1. Extent of sampling depend on each consignment
2. Sample as many containers as practical, at least square root plus one of No. Of containers
in a batch. If less than 5 containers, then, each container to be sampled
3. Random sampling of containers without reference to sequence. Damaged containers to be
sampled separately
4. Every batch of material in consignment to be sampled
5. Quantity of sample taken should be sufficient for control and reference purposes. Normally
twice the requirement is taken as samples
6. Sample in two separate parts- later test, use from unopened container

SAMPLING PROCEDURE
1. Note condition of container with proper labels
2. Examine material from top and bottom for contamination. Look for variations in color,
infestation, and extraneous matter.
3. In liquids- look for presence of suspended matter or sediment

Page | 60

PACKAGING MATERIALS:

Any material used to package a drug viz., bottles, vials ampoule, tin, tube, and foil
Wrapping, cartons catch cover including stuffing used

Labels, leaflets

Primary packaging materials are those which come in direct contact

SPECIFICATIONS
1. QCM in consultation with production Manager lays down specification for all packaging
materials
2. Specifications shall include
a. Name of material
b. Description
c. Dimensions
d. Tests for compliance
e. Instructions for sampling
f.

Storage conditions

g. Frequency of re-examination
h. Date of Issue of specifications
i.

Approval by QCM

3. Printed packaging materials shall bear identifying code marks

4. Defects in physical attributes classified as
a. Major defects- call for rejection
b. Minor defects- rectified in subsequent supplies
5. Attach specimen

SAMPLING
1. Component materials- done a statistical basis
2. Other packaging materials- Experience of the user.

TESTING
1.

Each delivery is given a reference number

2. Testing physical inspection, dimensions, color variations, gauge, appearance

3. Check printed packaging materials against reference samples kept in up dated file for
accuracy
4. Record of test reports
a. Date of testing or inspection
b. Name of packaging material
Page | 61

c. Reference No. For identifying delivery of batch

d. Results of tests including classification of defects
e. Name of person who carried out the testing
f.

Signature of person who released from QC

TESTING OF HARD GELATIN CAPSULES

INSPECTION
1. Appearance
2. Color
3. Quality of print
4. Self locking ability
5. Dimensions- body length, cap length, body diameter, cap diameter, unclosed and closed
joined lengths
6. Smoothness of separation of unclosed capsules
7. Classification of defects- Critical/Major/Minor

TESTING
1. Moisture
2. Weight of shells- random samples of 100 capsules
3. Disintegration time- by Pharmacopoeia methods
4. Machine trials at least 1000 capsules
INSPECTION OF GLASS BOTTLES:

SAMPLING
1. Select 4 cases of boxes at random
2. Visually examine sample of all bottles
3. Dimensions- Net finish and diameter 20 bottles
Internal bore diameter- all bottles top layer
Other dimensions 20 bottles from 4 cases
4. Overflow capacity- 3 bottles at random from each case

INSPECTION
1. General conditions of cases
2. Open cases inspect requisite no. Visually
3. Check neck finish
Page | 62

4. Check internal mouth diameter/bore diameter

5. Check other dimensions
6. Thin walls, wedge bases
7. Over flow capacity
Specifications should include
1. Name of product
2. Description of physical form of Product
3. Description of product container/pack
4. Sampling instructions through stages of production
5. Safety precautions (Handling of product)
6. Tests and limits for identity/purity/physical and chemical characteristics, microbiological
standards/assay
7. Storage conditions of final product
8. Frequency of re-examination of product on storage
TESTING OF INTERMEDIATE/BULK/FINISHED PRODUCT:

Intermediate product means partly processed

Bulk product- Completed all stages but not packing

Finished Product All stages including packaging

SAMPLING

Intermediate Product
o

Sampling done based on previous experience or square root plus one of total no. Of
containers/batch

Finished product
o

Beginning and end. Preferably throughout the operation- ensure statistical control

Testing
o

Against standard specification for each category

HANDLING OF PRODUCT COMPLAINTS

PROCEDURE
1. All complaint should be brought to attention of QCM
2. Complaint Form should be used giving the following
a. Name and strength of product
b. Batch No.
Page | 63

c. Name and address of complainant

d. Nature of complaint
e. Results of investigation of the complaint
f.

Action to be taken as a follow up measure

3. The complaint form and sample sent to QCM

4. If oral complaint with no sample passed on to QCM
5. Complaint sample examined for appearance, content, evidence of deterioration/ evidence of
misuse
6. Complaint sample subjected to all tests
7. Check control samples
8. Check adjacent batches in question to reveal extent of defect
9. If inputs are same, check all relevant batches
10. Record test results
11. Reply sent to complainant by QCM or Marketing Manager
12. Convey information to production
13. If necessary, Recall Product

RECORDS
Detailed records maintained and should be available for inspection by authorities
STABILITY TESTING OF FINISHED PRODUCTS

PRE MARKETING STABILITY STUDIES

1. Stability of formulated product determined prior to marketing and also prior to adoption of
significant changes in manufacture
2. Stability studies- each package type to be sold
3. Evaluate at least 3 lots
4. If product reconstituted before use, then stability of both to be examined
5. Stability parameters
Physical
o

Tablets

Odor, friability, disintegration, dissolution

Capsules

Condition of shells, disintegration

Ointments

Odor, texture, homogeneous consistency, separation, pH

Purity
o

Moisture content of tablets and capsules, particulate matter, decomposition

Products of active ingredients

Page | 64

Potency
o

Assay of active ingredients

6. Stability of package also studied

7. Accelerated studies- preliminary information, supported by studies at ambient
Temperature
8. Continuing program of studies throughout shelf life

MANUFACTURING PROCESS CHANGES

1. Changes in manufacturing process are subjected to stability studies
2. Minor changes in raw material specification may not have adverse effect.
3. Major changes need stability studies
4. Major changes need follow up after manufacture
5. All changes should be authorized by QCM and Production Manager
RECORD OF ANALYSIS
Raw Materials
Records should comply with Drug and Cosmetic Rules 1945, schedule V
a. Date of Receipt of material
b. Name of material on invoice/challan
c. Suppliers/Manufacturers batch Ref. No.
d. No. Of containers
e. Batch identifying No. Assigned
f.

Date of sampling

g. Record of testing
a. Date of receipt of material
b. Name of material on the invoice/challan
c. Suppliers /manufacturers batch Ref. No.
d. No. Of containers
e. Batch identifying No. Assigned
f.

Date of sampling

g. Record of testing

Date of receipt of sample

Date of testing

Batch identifying No.

Results of tests

Signature of person
performing the test

Signature of second person

checking

Signed - release/ Rejection

by QC
Page | 65

h. Records shall also include

1. Weight of sample used
2. All calculations performed
3. Graphs, charts, spectra
4. Potency assigned may vary from batch to batch

PACKAGING MATERIALS
Same as above

INTERMEDIATES, BULK AND FINISHED PRODUCTS

1. Date of manufacture
2. Date of testing
3. Signed release/rejection by QC

RETENTION OF SAMPLES
As per Drug Rules
RESERVE (RETENSION) SAMPLES
Mandatory to retain samples till designated shelf life

RAW MATERIALS
1. Sample from each batch of raw material from each delivery
2. Quantity twice than required for each test
3. Container should preserve quality and integrity
4. Period vary from two years after use or one year after expiry

PACKAGING MATERIALS
Specimen sample of printed packaging material to be maintained

FINISHED PRODUCT
1. Sample kept in same container as the one in which it is marketed
2. Quantity is twice than required for each test
3. Reserve samples to be stored at
Cold

any temperature not exceeding 8C- between 2 to 8C

Cool

between 8 and 25

Warm

above 40C

4. Samples retained for one year after expiry

Page | 66

20. IN PROCESS CONTROL

OBJECTIVE

Several tests are carried out during course of manufacture to ensure that the final product
will comply with its specification
1. Visual inspection of injection against illumination
2. Leak testing of filled ampoules
3. Testing of membranes filter
4. Tablet compression
a. Weight of tablets
b. Hardness of tablets
c. Thickness of tablet
d. Friability of tablet
e. Disintegration time
5. Strip sealing

Page | 67

21. DEVIATION PROCEDURE

OBJECTIVE

Unplanned departure from written down procedures can occur. If deviations do not affect
product quality or safety and decided to accept, a written procedure is required to be
established.

The purpose is
Inform responsible individuals of the occurrence of such deviations
Suggest method of disposition of material
Helps in initiating corrective actions

SCOPE
Applicable to all materials, packaging material, semi finished product and finished product

PROCEDURE
1. When unplanned departure from laid down specification procedure occurs, a deviation
request can be raised
2. Request from any department, except from Quality Control department
3. Request raised on Deviation Approval Form by concerned department after completing
Description of non- conformance and probable reasons for deviation
4. Following departments are consulted before accepting
a. Quality Control
b. Research and Development
c. Manufacturing
d. Marketing (when required)
e. Purchase (when required)
f.

Head of Company or his designee

5. QC shall record Recommended Disposition and proposed corrective action and return
to concerned department for action
6. The concerned department will initiate the necessary action and confirm same to Quality
control who will record the same on the Deviation Approval Form
7. Duly completed Deviation Approval Form will be retained by QC department

Page | 68

Specimen of Deviation Approval Form

Item

Request No

Quantity

Date

Value Rs
Originating department
Description of no- compliance
Reasons for deviation
Recommended disposition
Corrective action
Approvals
Department

Acceptance Y/N

Signature

Date

Disposal action Initiated by

Corrective action
Date

Page | 69

22. STABILITY STUDIES - DRUG SUBSTANCE

OBJECTIVE
To study the influence of temperature, humidity, light, on storage and establish shelf life of
any chemical, including drug substance under recommended storage conditions
SCOPE
Procedure, test criteria, method of evaluation for establishing shelf life

STABILITY STUDIES
1. Stress testing

Helps to determine intrinsic stability of molecule by establishing pathways

Helps to validate analytical procedures

2. Formal studies

Shows that drug substance will remain stable within specifications under
recommended storage conditions

3. Selection of batches

At least 3 batches are subjected to short term (accelerated) and long term
stability

4. Test procedure and criteria

Features susceptible to change during storage should be covered

5. Specifications

Acceptability criteria derived from materials used in pre-clinical batches should be

used.

Attention to upper limits of impurities and degradation products

6. Storage conditions

40C at 75+/- 5% RH for six months

25C at 60+/- 5% RH for long term

Long term beyond 12 months for reliable data

7. Frequency of testing

Initial 12 months of storage. Testing at 3 monthly intervals

For next 12 months every 6 months

Beyond 24 months - 12 monthly intervals

8. Containers

Actual packaging material planned

9. Evaluation of results

Degree of variability of individual batches shall not be such as to affect

confidence of future production
Page | 70

10. Labeling

Storage conditions should be clear and generalized

Ambient/ temperature not acceptable

Do not freeze, do not expose to sunlight, and are acceptable

22. STABILITY STUDIES - DRUG PRODUCT

OBJECTIVE
Stability behavior of a chemical (drug substance) as a raw material is only an indicator of
behavior as a part of finished product (formulation). Product stability also influenced by
method/process of formulation

SCOPE
Guide lines for conducting, evaluating and reporting stability studies

STABILITY STUDIES
1. Selection of Batches

3 batches on a pilot scale viz., 25000 to 50000 tablets or capsules.

Manufacturing process should be similar to stimulate final process proposed

2. Test procedure and test criteria

Tests should cover all features susceptible to change.

Analytical procedures should be fully validated.

Tests also indicative of loss of preservative besides, chemical, physical or

microbiological

3. Specifications

Limits of acceptance to release limit and allow acceptance and justifiable

deviations based on stability evaluation

4. Storage Test Conditions

Long term

25C +/- 2 at 60% +/- 5 RH Minimum time 12 months

Or 30C +/- 2 at 60C +/- 5 RH

Accelerated

40C +/- 2 at 75% +/- 5 RH Minimum time 6 months

5. Testing Frequency

Frequency sufficient to establish stability characteristics

Testing for every three 3 months over the first year and then annually

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6. Packaging materials

Testing to be carried out in the final packaging proposed.

Additional tests on unprotected drug product can be useful.

7. Evaluation

Should cover physical, chemical, biological and microbiological

Minimum 3 batches should be studied.

For solid dosage forms- storage under RH conditions

8. Statement/Labels

Labeling should state specific storage conditions.

Vague terms such as ambient

Temperature or Room temperature should be avoided.

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22. DOCUMENTATION
OBJECTIVE

Documentation is an integral part of GMP.

Minimizes misrepresentations and error in oral communications

Written documentation of all activities is mandatory

SCOPE
Covers all aspects of Pharmaceutical Production
1. Buildings & Premises

Installation, validation, cleaning, maintenance,

2. Personnel

Training and hygiene

3. Equipment

Installation, calibration, validation, maintenance, cleaning

4. Materials

Specifications, testing, warehousing, usage, Rejections

5. Processing

Individual steps- manufacturing and control

6. Finished Goods

Specification, testing, storage, distribution, Rejection /disposal

7. Complaint Investigations, actions, including recall, if Necessary

GENERAL
1. Designed with utmost care for effective use
2. Each document will have
a. Clear title
b. Identification No.
c. Approval of authorized person
d. Date of issue
3. Instruction given in documents should be precise and not ambiguous
Instructions shall be for each individual step and not combined
4. Document
a. Should provide sufficient space for making entries
b. Shall indicate what is to be entered,
c. Who is responsible for entries
d.

Entries shall be made in ink, clear and legible

e.

All corrections made should be initialed

5. Documents should be periodically reviewed

6. Revised versions should also be approved
7. Updated/revised versions shall super cede previous edition
8. Outdated documents should be immediately removed from active use, but copy retained
for reference
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9. Documentation through electronic media, adequate and reliable. Systems to checka. Ensure correctness of data
b. Record changes(additions/deletions)
c. Restrict access only authorized persons
10. Documents retained should permit
a. Quick, easy and reliable retrieval of data
b. Allows review up to a pre-determined time in past
c. Meets regulatory requirements

MASTER FORMULA RECORD

Product specific document, compiled, checked, authorized and approved by competent

technical personnel from development, production, packaging, and Quality control.

Should be open for review

Authorized by person responsible for Production/QC

Master Formula Record shall

1. Give patent/proprietary name of Product/strength

2. Pharmacopoeia/generic name of product and its strength
3. Give galenical/dosage form (viz., tablet, ampoule), physical characteristics viz., bi-convex
tablet, fill volume, printing on capsule etc. of a product
4. Give sufficient detailed information of product pack, primary packaging materials
5. Give identity, quality and quantity of every ingredient, including overages/assay values etc.
in respective whether or not, the material is
a. An active drug substance in the formulation/product
b. Used as a pharmaceutical aid (excipient)
c. Appears or is detected in the final product
6. Briefly describe all raw materials
7. Broad outline of process of manufacture (flow charts)
8. Brief description of equipment (machinery used for manufacture)
9. Step-wise manufacturing process
10. Critical in-process checks and controls, including limits
11. Theoretical and practical (expected) yields at different stages
12. Precautions to be taken during manufacturing for products and personal safety
13. Analytical controls, including limits to finished products
14. Stability test results- covering assigned shelf life
15. Product history data giving changes in manufacturing/packaging over the years
16. Samples of printed packaging components

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BATCH MANUFACTURING RECORD

Product and Batch Specific document giving reliable information on history of each batch
of every product.

Documents are used in the shop floor and instructions should be clear and precise

Records should include1. Status of equipment used/areas used

2. Quantities of materials used/whether appears on the final product or not
3. Quantity, source of recovered/rework materials according to Master Formula
4. Limits for every critical test to be performed
5. Theoretical and practical yields at all stages
6. Any precautions to be taken
7. Signed authorization if any, for deviation from the Master Formula
8. Reconciliation of material received, used, rejected, destroyed/ returned to warehouse
9. To ensure that operating staff are trained to appreciate importance of record keeping
10. All entries are made correctly and promptly
11. Reviewed by an independent authority from QC before cleared for distribution
12. Finally kept safely under control of QC
13. Easily retrievable
14. Retained for a period not less than the shelf life of product. Normally for a period of 5 years
or if any dispute in Court of Law, maintained till dispute is settled

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24. QUALITY ASSURANCE SELF AUDIT

OBJECTIVE

Self-inspection or self-audit systems are designed to seek any shortcomings in Quality

Assurance Systems, to suggest corrective actions

SCOPE

All operations directly connected with manufacture of Pharmaceutical products

RESPONSIBILITIES

A TEAM OF EXPERTS DRAWN FROM Production, Engineering, Quality Control

independently responsible to the Company

Each member of team independent and equal in performing self-audit

Independent audits by external experts/agencies also to be considered

METHODS
1. Self inspection/Audit shall be independent and impartial
2. Check list shall be drawn for each audit
3. Check list shall be area specific/Operation specific so as to make the exercise of self audit
more focused
4. Self audits shall be conducted at reasonable intervals, but should cover area at least once a
year
5. If need arises. A specific area/operation shall be audited more frequently
6. Findings of Self audit shall be recorded
7. Self-Audit reports suggest corrective actions and assign responsibilities for implementation
8. Systems should provide status of implementation
CHECK LIST- SELF AUDIT- DISPENSING OF RAW MATERIALS
ANNEXURE I

YES/NO

1. Area is neat and clean

2. Effective dust extractions in place
3. Weighing scales in order
4. Written documentation on scale accuracy
5. Materials issued only against authorized requisitions
6. All materials weighed in clean, labeled containers
7. Each weighing is signed
8. SOP in place for equipment use, including cleaning
9. All equipment in order
10. Air circulation system does not lead to cross contamination
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CHECK LIST- SELF AUDIT- PACKAGING MATERIAL STORES

OBSERVATION

RECOMMENDATION
ANNEXURE II

1. No Quarantined Labels

All goods pending approval shall carry

Quarantine Labels

2. Packaging material samples are

Returned by QC to stores

Samples once taken out by QC shall

not be returned to stores

3. Packaging materials returned by

Packaging dept. is not securely

all materials returned by Packaging

Dept. shall be wrapped and labeled

Wrapped
4. Rejected packaging materials are
Stored in the same area along

Rejected material shall be clearly

identified and stored separately

Approved stock in secured area

SELF AUDIT REPORT

ANNEXURE III
Department Audited
Audit Date
Audit Team
Mr.

Manager Production

Mr. Manager Quality Assurance

Mr. Manager Engineering
*Audit Report date

Manager- Tab letting

Action Plan

Manager- Production

Report Date

Manager- Quality Control

Manager Engineering

CC Plant Manager for Information

For action

Compliance Report: Schedule date

*Finalized after discussion between Audit team and Area Supervisor/ Manager
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25. CONTRACT MANUFACTURING

OBJECTIVE
To ensure quality of products manufactured, both Principal Manufacturer (Contract giver) and
Contract Manufacturer (Contract acceptor) shall understand and agree

SCOPE
To recommend
1. General conditions, both technical and commercial as part of contract
2. Technical guide lines for selecting a Contract Manufacturer
3. Quality assurance systems to be considered while drawing a contract

GENERAL REQUIREMENTS & RESPONSIBILITIES

1. Principal Manufacturer whose labels appear on Product manufactured is primarily
responsible for technical issues
2. To avoid misunderstanding a written contract should be drawn between the two parties
3. Contract should cover
a. Technical know-how and safeguards for secrecy
b. Supply of materials
c. Quality specifications for inputs and finished products
d. Quality Assurance systems, documentation audits by either or both parties
e. Responsibility for batch release
f.

Responsibility, accountability and redress should a failure occur

g. Compliance with cGMP and statutory requirements

h. Commercial terms
i.

Reviewing agreement in part or whole

4. Responsibilities for non-technical (commercial) aspects, production planning, billing.

Etc.

SELECTION OF A CONTRACT MANUFACTURER

1. Statutory clearance/license
2. Adequate facilities for storage, handling, manufacturing, testing of in-puts
3. Competence and experience of employees directly/indirectly responsible
4. Competence and experience of Quality assurance/ Quality Control staff
5. Previous experience of manufacture of similar products
6. Ability to document and adhere to cGMP requirements

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7. Audit the prospective Contract Manufacturer prior to contract

8. Prepare a written report
9. Short comings highlighted and plan steps for corrective action

QUALITY ASSURANCE
1. Manufacturing procedure to be fully documented
2. Materials and product specifications
3. In process controls
4. Responsibilities, individual or joint assigned
5. Documentation system to be discussed and agreed
6. Equipment and facilities, testing procedures to be validated

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26. GOOD LABORATORY PRACTICE

OBJECTIVE
To derive benefits suitable and properly trained and motivated staff is essential

BUILDINGS AND SURROUNDINGS

1. Testing laboratories should be designed or equipped to suit the operations
2. Special attention should be given to
a. Avoidance of cross contamination within the laboratory and between laboratory
And manufacturing areas
b. Proper disposal of waste, effluents, from fume cupboards
c. Provision for space for storing reagents, equipment, retention samples and records
d. Provision of separate laboratories for biological and microbiological testing

STAFF AND TRAINING

1. Laboratory staff should have demonstrated ability to carry out assigned task
2. Training to be provided to staff at all levels. Training also to non-laboratory staff who do in
process testing

EQUIPMENT
1. Should be serviced and calibrated at suitable intervals and records maintained
2. Instructions available for operating each item of specialized equipment
3. Suitable arrangements made for protecting sensitive apparatus against humidity,
temperature, vibration
4. Warning provide to indicate failure of important services viz., fume
Cupboard extract

SPECIFICATION AND RECORDS

1. Specifications, records, documentation as per details mentioned in GMP
Retention samples are regarded as part of Laboratory records
2. Records of test results are so maintained that results of consecutive batches can be
compared

SAMPLING
1. Samples taken should be representative from which they are taken, and should as
Per written instructions
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2. Sampling instructions should include

a. Method of sampling and the equipment to be used
b. Amount of sample to be taken and instructions for any sub division required
c. Any precautions to be taken
3. Each sample container should bear a label, indicating its contents, batch, lot or
Reference number
4. Sampling equipment should be cleaned after each use

TESTING

Sample to be tested in accordance with the analytical methods detailed or retained or

referred to, in the relevant specification.

Validity of results obtained should be checked (Any calculations) before material is

released or rejected by authorized person

CONTRACT ANALYSIS
1. Although analysis may be undertaken by a Contract Analyst responsibility for Quality Control
cannot be delegated
2. Nature and extent of any contract analysis to be undertaken should be agreed and clearly
defined, and sampling procedure should be set.
3. Contract Analyst to be supplied with details of test methods relevant to the material under
examination.
4. Formal arrangement to be made for retention of samples and of records of test results

Page | 81

27. ISO 9000

ISO 9000 defines
Quality policy as Overall quality intention and direction of Organization as regards to quality

Quality management

As aspect of overall management function that determines and implements the quality policy

Organization accomplish three objectives of quality

1. Achieve and maintain quality of products/services to meet customer needs

2.

Gain confidence of customers that quality has been or will be achieved and maintained

3. Support managements confidence that quality system has been installed and is effective.

IMPLEMENTATION OF TOTAL QUALITY MANAGEMENT (TQM) AND ISO 9000

ADVANTAGES
1. Can become profitable
Poor quality cost billions of Rupees each year.
Getting it right for the FIRST TIME is cost effective
2. Motivation of Staff: No rectification of defects.
Setting up standards by involving staff
Higher productivity results in higher earning
3. When approved- Company appears in Department of Trade and Industrys Register of
Approved Firms
4. Certified Companies are permitted to use Approved Firm Logo
Attracts fresh business
5. Gives international recognition

DISADVANTAGES
1. Implementation of formal quality system is demanding on resources. Involves considerable
expense and is time consuming
2. Unless carefully planned it can become non-cost effective and burdensome.
3. In the absence of an attitude conducive to change and improvement, the process can become
traumatic
4. Need to change attitude and accept new working practices may strain the management
capability of Company beyond its ability to cope.
5. ISO 9000 certification is expected to eliminate second party assessment- may not be the case
initially.
6. ISO 9000 only supplements and compliments product quality- but does not replace them.
Page | 82

QUALITY VOCUBULARY:

Quality
Quality is the totality of characteristics of an entity that bare on its ability to satisfy stated and implied
needs
Inspection
Inspection is the activity such as measuring, examining, testing, or gauging one or more
characteristics of an entity and comparing the results with specified requirements in order to
establish whether conformity is achieved for each characteristic.
Quality Control
Quality Control is the operational techniques and activities that are used to fulfill requirements of
quality
Quality Assurance
All the planned and systematic activities implemented within the quality system and demonstrated
as needed to provide adequate confidence that an entity will fulfill requirements of quality.
Quality Planning
Activities that establish the objectives and requirements for quality and for the application of quality
system elements
Quality Policy
The overall intention and direction of an organization with regards quality, as formally expressed by
top management

Quality Plan
Document setting out the specific quality practices, resources and sequences of activities relevant
to particular product, project or contract
Quality Management
All activities of the overall management function that determine the quality policy, objectives, and
responsibilities and implement tem by means such as quality planning, quality control, quality
assurance and quality improvement within the quality system

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Quality system
The organized structure, procedures, processes and resources needed to implement quality
management
Quality audit
A systematic and independent examination to determine whether quality activities and related
results comply with planned arrangements and whether these arrangements are implemented
effectively and are suitable to achieve objectives

Quality surveillance
The continuous monitoring and verification of status of an entity and analysis of records that
specified requirement and fulfilled
Non- conformity
Non-fulfillment of an intended usage requirements or reasonable expectations, including one
concerned with safety
Management Review
Formal evaluation by top management of the status and adequacy of the quality system in relation
to quality policy and objectives
Validation
Confirmation by examination and provision of objective evidence that specified requirements of a
specific intended use have been fulfilled
Verification
Confirmation by examination and provision of objective evidence that specified requirements have
been fulfilled
Process
Set of interrelated resources and activities, which transforms inputs to outputs.
Procedure
Specified way to perform an activity
Product
Result of activities or processes
Page | 84

Requirements of Society
Obligations resulting from laws, rules codes, statutes or other considerations
Production Permit/Deviation Permit
Written authorization to depart from the originally specified requirements for a product prior
production
Quality Manual
Document stating the quality policy and describing the quality system of an organization

Record
Document which furnishes objective evidence of activities performed or results achieved
Total Quality Management
Management approach of an organization centered on quality based on participation of all its
members of the organization and to society
Quality Improvements
Action taken throughout the organization to increase the effectiveness and efficiency of activities
and processes in order to provide added benefits to both organization and its customers
ISO 9000 STANDARDS AND ITS CLAUSES
Principles of ISO 9000

ISO 9000 sets forth basic elements of a Quality System within the organization

PLAN- the means by which quality- the user- customer defines it is achieved

DOCUMENT converts these plans into operating procedures

COMMUNICATE- the procedure to everyone in the organization whose work affects quality

MONITOR- success of the effort

MODIFY- the procedure on a controlled basis to improve based on feedback of monitoring

Organization following ISO 9000 has another principle

PROVE- to others the existence of efficacy of quality system
PLAN WHAT YOU DO
DO WHAT YOU PLAN
PROVE IT
Find out what went wrong- Learn from itDO not let it happen again
Page | 85

PURCHASING STANDARDS

Guidance for ISO 9000 in subsection (4.6.1)

To ensure that purchased sub-contracted products (including services) conform to specified

purchaser requirements as well as regulatory requirements

Assessments of sub-contractors- Section (4.6.2)

Ways of choosing sub- contractors

Verification of Purchased Products Section (4.6.2)

DOCUMENTATION
QA MANUAL
PROCEDURES
AUDIT SYSTEM

Page | 86

28. TOTAL QUALIY MANAGEMENT (TQM)

THE COMMON PERCEPTION
It is often uneconomical to make quality improvement since it brings down productivity, increases
cost and investment
IN REALITY
It may be possible to improve continuously without reducing productivity and increasing cost
As W.E Deming says:
Productivity goes up and cost comes down as quality goes up. This fact is well known, but only to
selected few
QUALITY THEN IS TO SATIFY CUSTOMER NEEDS

IT IS INFACT TO DELIGHT THE CUSTOMER

TOTAL QUALITY MANAGEMENT (TQM) = TOTAL + QUALITY+ MANAGEMENT

TQM - DEFINITION
TQM is an integrated organizational approach in delighting customers (both external and internal)
by meeting their expectations on a continuous basis through every one involved within the
organization working on a continuous improvement in all products, services and processes along
with problem solving methodology

ELEMENTS OF TQM:

PEOPLE

APPROPIATE TECHNOLOGY

PROBLEM SOLVING TOOLS/PROCEDURES

CONTINUOUS IMPROVEMENT

TQM Total Quality Management and TQS Total quality service are two sides of the same coin.
TQM and TQS are inseparable

ORGANIZATION AND PEOPLE

Organization consists of a number of people working for a purpose

Each and every employee, each and every department has a role to play.

Page | 87

Everybodys role is equally important

Organization becomes most effective when all employees and all departments work together
and harmoniously towards common company objectives

THE ISSUES ARE

How do we get everybody to work together

How do we maintain their involvement

How do we make them contribute their best

How do we create their satisfaction and How do we continuously improve

THE BELIEFS ARE

Employees are not resources, they are the very purpose

Company hires the total man with body, mind and intellect, and not just hands

Problems are with systems and not with people

Variance analysis focuses on what how-why (and who)

People will be able to improve systems and solve problems

Aim is to utilize the full potential of all employees

Total employee involvement is essential for customer satisfaction

PEOPLE ORIENTATION
Individual

Team

Managing

Involving and leading

Delegation

Participation, Consensus

Control

Empowerment

Problem Management

Problem solving

Traditional Pyramid structure

Flattened Structure

ELEMENTS OF EI- (EMPLOYEE INVOLVEMENT)

Problem solved at the lowest level

Meet conditions for enfranchisement (empowerment)

Team Building

Revised organizational structures (flattened hierarchy, area Management)

Congruence/design V-A-M-R (Value- Action- Measurement- Reward)

Note: EI is a misnomer as it is pertinent to others (viz., Suppliers)

Page | 88

AT WHAT LEVEL IN THE ORGANIZATION ARE PROBLEM BEST SOLVED? WHY?

Most Timely

Best for future prevention

Lowest Cost

Least Political involvement

Solution at source of problem

Provides direct satisfaction

Shortest path of communication

Action visible reinforces

Data not distorted

KAI-ZEN (Composition of Two Japanese Words)

Change for the better

Transformation

Continuous Improvement

Kai-zen is defined in various ways

KAI-ZEN: CHANGE

Is a human process

Is a social or collective process

Is effected by a process of learning

One perceives the deficiency, tries to find a way around it, eventually changes

One cannot change any human system unless he/she is prepared to change himself/herself

Change is essential for organization growth and continuous improvement

KAI-ZEN
Improvement

A continuous improvement

Accumulation of small steps

Involving everyone (Top Management, Managers, and Workers)

CHANGING ENVIRONMENT

Customer Expectations

People

Product Design

Competition

Product Quality

Government Rules and Regulations

We must change Our way of thinking

Our way of doing jobs

If dont move forward, we will move backwards

Page | 89

CUSTOMERS HAVE 3 DEMANDS

1. HIGH QUALITY

(Q)

2. REASONABLE PRICE

(P)

3. ON-LINE DELIVERY

(D)

SIX BASIC ELEMENTS OF WORK PLACE MANAGEMENT

1. PRODUCTIVITY

(P)

2. QUALITY

(Q)

3. COST

(C)

4. DELIVERY

(D)

5. SAFETY

(S)

6. MORALE

(M)

AREAS OF KAIZEN

Preventing Defect Recurrence

Cost

Safety

Inadequacy

Present Conditions

Waste

Inconsistency

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