GOOD MANUFACTURING PRACTICES(GMP)

SMT.KISHORITAI BHOYAR COLLEGE

OF PHARMACY KAMPTEE
GUIDED BY: PRESENTED BY:
DR.RENUKA DAS KARISHMA DUHIJOD,
PROFESSOR HARSHA SHENDURKAR
SKBCOP DEPT.QUALITY
ASSURANCE,SKBCOP
 CONTENTS:
INTRODUCTION
WHAT IS GMP?
OBJECTIVES
WHY GMP?
PRINCIPLES OF GMP
5 MAIN COMPONENTS
SCHEDULE M
 Introduction
The Beginnings,

1900's-house-calls, Home remedies, ointments and "miracle, elixirs"

No regulations until 1902

USFAD has decide to regulation, production, distribution and consumption of

pharmaceuticals with respect to one specific regulatory requirement - Good
Manufacturing Practice (GMP)-the guidelines which govern the production,
distribution and supply of a drug.
 History
History of control of drugs, food, cosmetics sold to the public -

1905-The Jungle by Upton Sinclair - Meat packing industry led to the Food and Drug Act against
unsanitary conditions.
1937-Sulfanilamide Tragedy.

Sulfanilamide, the first "wonder drug" and a popular and effective

treatment for diseases like strap throat and gonorrhea, was formulated
into an elixir and marketed for use in children.

One company used diethylene glycol, a poisonous solvent and

chemical analog of anti-freeze, in an oral "elixir of sulfanilamide."

107 people died, many of them children,

Response: Congress passed the Federal Food, Drugs and Cosmetic (FD & C) Act of 1938.
- for the first time, companies were required to prove that their products were safe before marketing
them
 SULPHATHIAZOLE TRAGEDY:

In 1941, nearly 300 people were killed or injured by sulfathiazole tablets, a sulfa drug
tainted with the sedative phenobarbital.

That incident caused FDA to drastically revise manufacturing and quality control
requirements, leading to GMPs.
 Thalidomide tragedy:
(1962)
Thalidomide was marketed in Europe as a sleeping pill and to treat morning sickness.

Teratogenic effect: caused serious deformities

in developing fetus.

Children whose mothers took thalidomide

in the first trimester were born with severely
deformed arms and

An estimated 10,000 cases of infant deformities.

 WHAT IS GMP ?

According to WHO: GMP is that part of Quality assurance which ensures that
the products are consistently manufactured and controlled to the Quality
standards appropriate to their intended use.

Good Manufacturing Practice is a set of regulations, codes, and guidelines for

the manufacture of drug substances and drug products, medical devices, in
vivo and in vitro diagnostic products, and foods.

It is designed to minimize the risks involved in any pharmaceutical production

that cannot be eliminated through testing the final product.
 GMP Includes:

Qualification and validation are performed.

All necessary resources are provided.

Instructions and procedures are written in clear and unambiguous language,

specifically applicable to the facilities provided.

Operators are trained to carry out procedures correctly

Records are made (manually and/or by recording instruments) during manufacture.

The proper storage and distribution of the products minimizes any risk to their quality

A system is available to recall any batch of product from sale or supply

 OBJECTIVES:

GUARANTEE HIGH QUALITY PRODUCTS TO THE CONSUMER

Aim of GMP

Diminishing the risks inherent in pharmaceutical production, which may broadly be

categorized into:

1. unexpected contamination of products

2.incorrect labels on containers
3. insufficient or too much active ingredient
 WHY GMP?
A poor quality medicine may contain toxic substances that have been unintentionally added.

Final testing of the product cannot ensure the Quality, efficiency ,and safety.

Final testing may always not detect contamination, error, etc

To minimize contamination eg:- microbial contamination

To produce product of consistent quality

They are designed to pharmaceutical production

 PRINCIPLES OF GMP:

1. Design and construct the facilities and equipments properly

2. Follow written procedures and Instructions
3. Document work
4. Validate work
5. Monitor facilities and equipment
6. Write step by step operating procedures and work on instructions
7.Protect against contamination
8. Control components and product related processes
9. Conduct planned and periodic audits
 5 MAIN COMPONENTS:

People Products Process

comprehend Clear specification Properly

roles and at every phase of documented ,
responsibility production simple and
consistent

Procedures(Paper work) Premises

Guidelines for Cleanliness and equipment

undertaking calibration at all times
critical processes
 Schedule "M"

Requirement of factory premises ,plant and equipment for manufacturing

drugs and pharmaceutical products.

M-1: Requirement of factory premises for the manufacture of homeopathic

preparations.

M-2: Requirement of factory premises for the manufacture of cosmetics.

M-3:Requirement of factory premises for the manufacture of medical devices.

 Part 1-GMP for premises and materials

• Part 1-A: Specific requirements for the manufacture of sterile products,

parentaral preparations and sterile opthalmic preparations.

• Part 1-B: Specific requirements for the manufacture of oral solid dosage forms
(tablets and capsules).

• Part 1-c: Specific requirements for the manufacture of oral liquids (syrups,
emulsions, suspensions, elixirs,etc).
Part 1-D: Specific requirements for the manufacture of topical products.

Part 1-E: Specific requirements for the manufacture of metered dose inhalers.

Part 1-F: Specific requirement of premises, plant and materials for the
manufacture of active pharmaceutical ingredients (bulk drugs).

Part 2 Requirements of plant and equipment.

 Materials General requirements:

1. Location and surrounding: Such as to avoid risk of contamination from external

environment.

2. Building and premises: building should be designed in such a way to permit production of
drugs under hygienic conditions.

3. Water system: validated system to produce purified water confirming to IP specifications.

Storage tanks shall be cleaned periodically and records maintained by the licensee.

4. Disposal of waste: Disposal shall be as required under EPCB and BMW.

Hazardous toxic substances and flammable substances should be stored in a segregated area.
5. Warehousing area:
Adequate and categorized areas(raw ,samples, returned, released, finished products.
Good storage for hazardous ,toxic, explosive chemicals.

6. Production area:
logical flows of materials.
Dedicatd areas for sensitive ,biological ,potent substances.

7. Ancillary areas:
Adequate ,separate space for rest and refreshments rooms should be separate from
other areas.
separate animal houses away from manufacturing area.

8. Quality control area:

to perform test for controlling quality,adequate area for preventing cross contamination.
9. personnel: adequate number of personnel; good laboratory practices and proper training of
technical staff members.

10. Health, Clothing and Sanitation of Workers.

11. Sanitation in Manufacturing Premises :

No accumulated waste; no dust particles as far as possible; proper disinfection and cleaning
of premises and no stagnant water.

12.Raw Materials:

Properly identified; analyzed; containers of raw materials inspected for any damage; stored at
optimum temperature; labeled properly; systematically sampled by quality control personnel.
13. Documentation and records:
Important part of QA system and as such shall be
related to all aspects of GMP.
Specifications for all materials, method of manufacture, quality control.

14. Labels and Other Printed Materials :Stored properly and separately.

15. Quality assurance: this section collectively influence the quality of product. it
should ensures practice with GMP,GLP,GCP.

16. Self inspection and quality audits: self inspection should be done to evaluate
compliance with GMP.
Team of independent, experienced and qualified persons for inspection.
17. Quality Control System:
Detailed instructions for quality control of raw materials and finished product; quality
control for packaging and labeling; adequacy of storage, quality control procedure .

18. Master Formula Records (MFR):

Manufactured products should be maintained. includes name of
product,reference,patent number,proprietary or generic name,dosage form,strength
,materials used,equipment,step wise procedures,intermediates,finished
products,expected yield,acceptable limits, IPQC limit,storage requirements,containers,
label,special precautions.

19. Batch Packaging Records:

record of clean and free previous product should be documenetd.
ensure the equipment if clean ,ready,suitable for use
20.Batch Processing Records (BPR):
During the process every minute detail should be recorded like name of
product ,material batch number,equipment ,major steps,IPQC results,
operators signature ,etc

21. Standard Operating Procedures (SOPs) and Records: SOP and records for
receipts of each delivery of raw, primary and printed packing material;
sampling; instrument and equipment; internal labeling; quarantine and storage;
batch numbering; testing, records of analysis;

22. Product Containers: Compliance with pharmacopoeia requirements;

cleaning procedures and sterilization procedure should be properly followed.
There should be written schedule for programs for cleaning of container

23. Distribution Records:

Records properly maintained; records of complaints, adverse reactions and
other reactions from consumers are also maintained.
 PART I-A Specific Requirements For Manufacture Of Sterile Products, Parenteral
Preparations And Sterile Ophthalmic Preparations.
1. General
2. Building and Civil Works.
3. Air Handling System (Central Air-Conditioning).
4. Environmental Monitoring
5. Garments.
6. Sanitation
7. Equipment.
8. Water and Steam Systems
9. Manufacturing Process
10. Form-Fill-Seal Technology or Blow. Fill-Seal Technology.
11. Product Containers and Closures.
12. Documentation
1.General requirements:

These being sterile products should not be manufactured in damp, dark, dirt.
water supply, air, materials should meet requirements

2.Building and facilities:

Quality material should be used in construction, there should not be any cracks.

Pressure gradient should be maintained, furniture should not impart contaminants.

Air locks should be provided to change rooms, visual or audio warning system should be installed.
Color coded change rooms for different grade areas.
.
3.Air handling systems:

Air Handling Units for sterile product manufacturing areas shall be

different from those for other areas.

Differential pressure between areas of different environmental

standards shall be at least 15 Pascal

Temperature and humidity in the aseptic areas shall not exceed 27

degree centigrade and relative humidity 55%, respectively.
4.Environmental Monitoring:

The recommended frequencies of periodic monitoring shall be as

follows

(a) Particulate monitoring in air -6 Monthly.

(b) HEPA filter integrity testing (smoke testing) -Yearly

(c) Air change rates -6 Monthly.

(d) Air pressure differentials-Daily

(e) Temperature and humidity-Daily

5.Garments:
No out door garments, no cotton garments which shed fibers.
Clean and protective garments, gloves, masks, plastic or
rubber footwear (cleaned daily with bacteriocide).
Trained in changing garments.

6.Sanitation:
Procedures should be written and made available,
personnel specific should be trained.

7.Equipment:
Washing machines, blenders, manufacturing vessels, stem sterilizers, filter
assemblies, filling machines, vacuum chambers, lyophilizer, sealing, labeling
machines, integrated machines.
8.Water and Steam systems:
Water for injection 10CFU/ml, and should be at 70°C
temperature, continuous rotation

9.Manufacturing process:
Bio-burden of bulk materials should be checked, gases
and liquids should filtered through membrane filters
10.Product containers and closures :

Pharmacopoeial grade containers should only be used.

Type I, II glass should only be used for parenterals, type III for
sterile non parenterals.
Containers should not leak, leach, add, adsorb,
stable, non reactive.
Designed for easy cleaning and handling.

11.Documentation:

All the process employed should be documented.

Documentation of environmental monitoring, separate lines
for small and large volume preparations, glass and plastic
containers, automation.
 PART I-B Specific Requirements For Manufacture Of Oral Solid Dosage
Forms (Tablets And Capsules)

1. General
2. Sifting, Mixing and Granulation.
3. Compressions (Tablets)
4. Coating (Tablets)
5. Filling of Hard Gelatin Capsule
6. Printing (Tablets and Capsules)
7. Packaging (Strip and Blister)
1.General:
Dry substances produces lot of dust and hence building is constructed
to minimize cross contamination.
Air conditioners, dust extractors should be provided.
Pressure differences maintained.

2.Sifting, mixing and granulation:

All operations should be performed by equipping with dust extractors.
Times for mixing, blending, granulating should be mentioned in master
formula files.
Filter bags if used should not be used for another production unless
washed properly.
3.Compression:
Machines are separated into cubicles, equipped with dust
extractors or own extraction system.
Labels should be provided to prevent mix up.
In process quality control it should be performed 30 minutes.

4.Coating:
Coating solutions should be immediately prepared to minimize
microbial contamination.
Air used for drying should be filtered, exhaust should be
provided to prevent environmental contamination.
5.Filling of hard gelatin capsule
Temperature, humidity should be properly maintained.

6.Printing tablets and capsules:

Care to prevent mix up while performing with different
batches, different products.
Edible grade colors, suitable printing ink should be used.
Quality control department should assure its quality before
dispatch.
PART I-C

SPECIFIC REQUIREMENTS FOR MANUFACTURE OF ORAL

LIQUIDS (SYRUPS, ELIXIRS, EMULSIONS AND SUSPENSIONS)

1. Building and Equipment

2. Purified Water

3. Manufacturing
 1. Building and Equipment

Manufacuring area shall have entry through double door air lock facility and made fly proof
by use of "Fly catcher " and /or "air -curtain".

Drainage shall be of adequate size and have adequate traps, without open channels and
design shall be such as to prevent back flow.

Tanks, containers, pipe work and pumps shall be designed and installed so that they can
be easily cleaned and sanitized.

Equipment design shall be such as to prevent accumulation of residual microbial growth

or cross-contamination.
2. Purified Water

The chemical and microbiological quality of purified water used shall be

specified and monitored routinely.

There shall be a written procedure for operation and maintenance of the

purified water system.

Care shall be taken to avoid the risk of microbial proliferation with

treatment like heat and sanitizing agent.

After any chemical sanitisation of the water systems, a flushing shall be

done to ensure that the sanitizing agent has been effectively removed.
3. Manufacturing

Manufacturing personnel shall wear non-fiber

shedding clothing to prevent contamination of the product.

Materials likely to shed fiber like gunny bags, or

wooden pallets shall not be carried into the area where
products or cleaned-containers are exposed.

Care shall be taken to maintain the homogenecity of emulsion by use

of appropriate emulsifier and suspensions by use of appropriate stirrer
during filling.

Mixing and filling processes shall be specified and monitored.

PART 1 - D

SPECIFIC REQUIREMENTS FOR MANUFACTURE OF TOPICAL PRODUCTS i.e.

EXTERNAL PREPARATIONS

1. The entrance to the area where topical products are manufactured should be
through a suitable airlock, Outside the airlock, insectocutors shall be installed

2. The air to this manufacturing area shall be filtered through at least 20μ air filters
and shall be air-conditioned. The area shall be ventilated.

3. The area shall be fitted with an exhaust system of suitable capacity to effectively
remove vapours, fumes, smoke, floating dust particles.
4. Water used in compounding shall be Purified Water IP.

5. Powders, wherever used, shall be suitably sieved before use.

6. Heating vehicles and a base like petroleum jelly shall be done in separate mixing area in
suitable stainless steel vessels, using steam, gas, electricity, solar energy, etc.

7. A separate packing section may be provided for primary packaging of the products.

8.No rags or dusters shall be used in the process of cleaning and drying the process
equipment or accessories used.
PARTI - E SPECIFIC REQUIREMENTS FOR MANUFACTURE OF METERED - DOSE
INHALERS (MDI)

1. General
2. Building and Civil Works
3. Environmental Conditions
4. Garments
5. Sanitation
6. Equipment
7. Manufacture
8. Documentation
1.General

Manufacture of Metered-Dose-Inhalers shall be

done under conditions which shall ensure minimum
microbial and particulate contamination.

2.Building and Civil Works

The building shall be located on a slid foundation to
reduce risk of cracking walls and floor due to the movement
of equipment and machinery

3.Environmental Conditions

Where products or clean components are exposed,

the res shall be supplied with filtered air of Grade C
4.Documentation

In addition to the routine good manufacturing practices

documentation, manufacturing records shall show the following
additional informations.

Temperature and humidity in the manufacturing area.

Periodic filled weights of the formulation.

Records of rejections during on line check weighing.

Records of rejection during spray testing.

 PARTI-F SPECIFIC REQUIREMENTS OF PREMISES, PLANT AND
MATERIALS FOR MANUFACTURE OF ACTIVE PHARMACEUTICAL
INGREDIENTS (BULK DRUGS)

1. Building and Civil Works

2. Sterile Products

3. Utilities / Services

4. Equipment Design, Size and Location

5. In-Process Controls

6. Product Containers and Closures

Part-II requirements of plant and equipment

External Preparations
Oral liquid Preparation
Tablets
Powders
Capsules
Surgical dressing Ophthalmic preparation
Repacking of Drugs and Pharmaceutical
Chemicals
Parenteral preparations
Inhalers and vitrallae
Parenteral preparations in glass containers
1)External Preparation

External Preparation :

Mixing and storage tanks (stainless steel)

Jacketed Kettle (steam, gas or electrically heated), Mixer(electrically operated)
Planetary mixer
A colloid mill or a suitable emulsifier.
A triple roller mill or an ointment mill.
Liquid filling equipment (electrically operated).
Jar or tube filling equipment (electrically operated)

Area. A minimum area of 30 sq. m. for basic installation of ten square meters for Ancillary area
is recommended
2)Oral liquid Preparations

• The following equipment's are commended for the manufacture of oral/internal use
preparations namely: -

1. Mixing and storage tanks (stainless steel)

2. Jacketed Kettle / Stainless steel tank (steam, gas or electrically heated)
3. Portable stirrer (electrically operated)
4. A colloid mill or suitable emulsifier (electrically operated)
5. Suitable filtration equipment (electrically operated)
6. Semi-automatic/automatic bottle filling machine 77
7. Pilfer proof cap sealing machine.
8. Water distillation unit or deioniser
9. Clarity testing inspection units
3) Tablets 4) Powders

The tableting section shall be free from • The following equipment is

dust and floating particles and may be recommended for the manufacture of
air-conditioned. powders,
Connected to a vacuum dust collector or
an exhaust system.
(1) Disintegrator
For effective operations, tablet
(2) Mixer (electrically operated)
production department shall be divided
(3) Sifter.
into four distinct and separate sections
(4) Stainless steel vessels and scoops of
as follows: -
suitable sizes.
1. Mixing, Granulation and Drying
section.
(5) Filling equipment (electrically
2. Tablet compression section. operated). (6) Weighing balance.
3. Packaging section (strip/blister
machine wherever required). Coating Area. - A minimum area of thirty square
section (wherever required). meters is recommended
 6) Surgical Dressing
5)Capsules Surgical Dressing The following equipment is
Capsules separate enclosed area suitably air- recommended for the manufacture of Surgical
conditioned and dehumidified with an airlock Dressings other than Absorbent Cotton Wool,
arrangement shall be provided. The following namely:
equipment is recommended for filling Hard 1. Rolling machine
Gelatin Capsules, namely: - 2. Trimming machine
1. Mixing and blending equipment 3. Cutting equipment.
(electrically or power driven). 4. Folding and pressing machine for gauze.
2. Capsules filling units (preferably semi 5. Mixing tanks for processing medicated dressing.
automatic or automatic filling machines). 6. Hot air dry oven.
3. Capsules counters 7. Steam sterilizer or dry heat sterilizer or other
4. Weighing balance. suitable equipment.
5. Disintegration test apparatus. 8. Work tables/benches for different operations
6. Capsule polishing equipment.
Area. - A minimum area of thirty square meters is
recommended to allow for the basic installations.
8) Pessaries and Suppositories

(i) The following equipment is recommended for manufacture of Pessaries and

Suppositories, namely: -

1. Mixing and pouring equipmen

2. Moulding equipment.
3. Weighing devices.

Area. - A minimum area of twenty

square meters is recommended to
allow for the basic installation.

(ii) In the case of Pessaries manufactured by granulation and compression, the

requirements as indicated under Item 3 of Tablet, shall be provided.
Thankyou !!
THIS WAS IT FROM MYSIDE.

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Karishma Duhijod

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