1. PART 1A: sterile products
General :
Sterile products being very critical & sensitive in nature, a high degree of precautions, prevention & preparations are needed
Prescribed standards for supply of water, air, active materials, maintenance of hygienic conditions
Buildings and civil works:
Built of standardized material to avoid cracks in critical areas
Manufacturing area clearly separated into support areas, preparation areas, change areas and aseptic areas

2. Walls shall be flat & ledges and recesses can be avoided
Aseptic area:
Walls, floors and ceilings should be impervious, non-shedding & non-cracking
Walls shall be flat & ledges and recesses can be avoided
Ceilings shall be solid & joints shall be sealed
No sinks & drains in grade A & grade B areas
Doors made of aluminum or steel material & shall open towards high pressure area
Separate exit space from the aseptic areas is advisable
Change rooms to aseptic areas shall be clearly demarcated into black, grey & white rooms

3. Air handling system:
Critical areas conforming to grade B,C & D have separate air handling units
Grade
Class
Operations
Grade A
Class 100
Aseptic preparation& filling
Grade B
Class 1000
Background room conditions for activities requiring grade A
Grade C
Class 10000
Preparation of solution to be filtered
Grade D
Class
Handling of components after washing

4. Environment monitoring:
Recommended periodic monitoring include:
Particulate monitoring in air - 6 monthly
HEPA filter integrity testing – yearly
Air change rates – 6 monthly
Air pressure differentials – daily
Temperature & humidity – daily
Microbiological monitoring – daily
Garments:
Made of non-shedding & tight weave material
Outdoor clothing shall not be brought into sterile areas
Sanitation:
Employees carrying out sanitation shall be trained
Different sanitizing agents used in rotation
Records of rotational use these agents to be maintained

5. Manufacturing process
Include component washing machines, steam sterilizers, membrane filters, liquid & powder filling machine , sealing & labelling machines etc
Equipment
Potable water – microbiological specification(<500cfu/ml) &
Absence of individual pathogens per 100ml used for preparation of purified water
Steam coming in contact with products primary containers shall be sterile & pyrogen free
Water and steam system
Bulk raw materials monitored for bio-burden periodically
A limit of not more than 100cfu/ml is recommended
Finished products shall be filled in continuous operation with great care
Manufacturing process

6. Sterilization Documentation
Terminal sterilization(filling of products) - grade A
Preparation of solution(sterilized by filtration) - grade C
Sterilization process should be validated
Biological/ chemical indicators – to monitor sterilization
Documentation
Records related to manufacture of products should be maintained

7. PART 1B: oral solid dosage forms
General requirements:
Enclosed dust control manufacturing system shall be employed
Suitable environmental conditions maintained by installation of air- conditioning
Effective air-extraction system shall be provided with discharge
Filters to retain dust to protect the local environment
Sifting, mixing & granulation:
All equipments shall be fitted with dust extractors
Critical operating parameters like time &temperature shall be specified in master formula

8. Monitored during processing & recorded in batch records
Granulation & coating solution- made, stored & used in a manner to minimize contamination
Tablet compression:
Compressing machine – effective dust control facilities
Suitable labelling to prevent mix up of granules & tablets on compression machinery
Tablets examined for appearance, wt. variation, disintegration, hardness, friability & thickness
Tablet coating:
Air provided with suitable exhaust system & environmental control
Air supplied to coating pans shall be filtered & of suitable quantity

9. Filling of hard gelatin capsules
Stored in conditions which ensure safety from effects of excessive heat & moisture
Filling of hard gelatin capsules
Special care must be taken to avoid product mix-up during printing
Done using edible colors & suitable printing ink
Printing(tablets & Capsules)
Before packaging operation all ‘rogue’ tablets & capsules are removed
Strips - inspected for defects such as misprint, cut on foil, missing tablets & improper sealing
Packaging

10. PART 1C : oral liquid dosage forms
Layout & design of manufacturing area – minimize risk of contamination & mix-up
Manufacturing area – entry through double door air-lock facility
Parts of equipment – made of stainless steel
Quality of purified water used shall be specified & monitored routinely
Manufacturing personnel shall wear non- shedding clothing
Primary packaging area – air supply filtered through micron filters & temperature not exceed 30ºC

11. PART 1D : topical preparations
Suitable air-lock shall be provided at the entrance
Manufacturing area – air shall be filtered & air conditioned
These areas to be fitted with exhaust systems
Equipments designed to prevent product contamination
For cleaning or drying no rags or clusters to be used
Water used in compounding – Purified Water IP
Powders used must be properly sieved
Separate packaging section – for primary packaging

12. Building & civil works:
PART 1E : MDIs
General:
Manufacture of MDI - minimum microbial & particulate contamination
Building & civil works:
Located on a solid foundation to reduce risk of cracking walls & floors
Environmental condition:
Where products or clean components are exposed, the area shall be supplied with filtered air of grade C
Equipment:
Manufacturing equipment – closed system where vessels & supply lines are stainless steel

13. Manufacture: Documentation :
Approved master formula records are required for manufacture of MDI
Primary packaging material – cleaned by compressed air filtered through 0.2 micron filter
Filled containers shall be quarantined for a suitable period to detect leaking containers
Documentation :
Temperature & humidity in the manufacturing area
Periodic filled weights of formulation
Records of rejections

14. Buildings & civil works:
PART 1F : APIs
Buildings & civil works:
Manufacture of antibiotics, steroids & cytotoxic substances – carried out in confined areas to prevent contamination of other manufactured drugs
Air filtration system – includes pre-filters & particulate matter retention air filters
Sterile products:
Filling of such products must be done aseptically
Manufacture of sterile API must include- filtration, crystallization & lyophilization

15. Utilities / Services:
Equipments used – serviced, cleaned & maintained at appropriate intervals
So as to prevent mal- function or contamination of drug product
Equipment design, size & location:
Equipment used in manufacture, processing, packaging or holding of API shall be adequate size, appropriate design &
Suitably located to facilitate operations for its intended use & for its cleaning & maintenance
Equipments - cleaned between successive batches

16. For chemical reactions include:
In- process control:
For chemical reactions include:
Reaction time
Reaction mass appearance
Reaction temperature
Concentration of reactant
Assay or purity of the product
For physical operations include:
Appearance & color
Uniformity of blend
Temperature of a process
Concentration of solution
Processing rate or time

17. Product containers & closures:
Should comply with pharmacopoeial specification
Containers & closures shall be non-reactive, additive, adsorptive or leachable
To an extent that affects quality or purity of the drug

18. External preparation: Basic installation area: 30sq.m
PART II
External preparation:
Basic installation area: 30sq.m
Ancillary area: 10sq.m
Equipments include:
Mixing & storage tank(stainless steel)
Jacketed kettle(stainless container)
Mixer
A colloidal mill or suitable emulsifier
A triple roller mill
Liquid filling equipment
Tube filling equipment

19. Oral liquid preparation: Basic installation area:30sq.m
Ancillary area:10sq.m
Equipments include:
Mixing & storage tanks
Jacketed kettle
Portable stirrer
A colloidal mill
Filtration equipment
Semi automatic filling machine
Pilfer proof cap sealing machine
Water distillation unit deionizer
Clarity testing inspection unit

20. Basic installation area :60sq.m(uncoated) 30sq.m(coated)
Tablets:
Basic installation area :60sq.m(uncoated)
30sq.m(coated)
Ancillary area :20sq.m(uncoated)
10sq.m(coated)
Tablet production department classified into four sections:
Mixing, granulation & drying section
Tablet compression section
Packaging section
Coating section (wherever required)

21. Mixing, granulation & drying section:
Disintegrator & sifter
Powder mixer
Granulator wherever required
Thermostatically controlled hot air oven
Weighing machines
Compression section:
Tablet compression machine
Punch & die storage cabinets
Tablet de-duster
Tablet inspection unit
Dissolution test apparatus
In-process testing apparatus
Air conditioning & dehumidifier

22. Packaging section: Coating section: Strip /blister packaging machine
Leak test apparatus
Tablet counters
Air-conditioner & dehumidifier
Coating section:
Jacketed kettle
Coating pan
Polishing pan
Exhaust system
Air conditioner & dehumidifier
Weighing balance

23. Basic installation area: 30sq.m Equipments include:
Powders:
Basic installation area: 30sq.m
Equipments include:
Disintegrator
Mixer (electrically operated)
Sifter
Stainless steel vessels
Filling equipment
Capsules:
Basic installation area: 25sq.m
Ancillary area:10sq.m
Mixing & blending equipment
Capsule filling unit
Capsule counters &
Polishing equipment

24. Basic installation area:30sq.m Equipments include:
Surgical dressing:
Basic installation area:30sq.m
Equipments include:
Rolling & trimming machine
Cutting equipment
Folding & pressing machine for gauze
Mixing tanks for processing medicated dressing
Hot air dry oven
Steam or dry heat sterilizer
Ophthalmic preparations :
Basic installation area : 25sq.m
Hot air oven
Kettle
Colloidal mill
Tube filling equipment

25. Pessaries & suppositories: Basic installation area:20sq.m
Mixing & storage tanks
Seitz filter or sintered glass filters
Liquid filling equipment
Autoclaves
Pessaries & suppositories:
Basic installation area:20sq.m
Equipments include:
Mixing & pouring equipment
Molding equipment
Weighing devices
Inhalers :
Basic installation area: 20sq.m
Mixing equipment
Graduated delivery equipment
Sealing equipment of medicament during filling

26. Repacking of drugs & pharmaceutical chemicals:
Basic installation area: 30sq.m
Equipments include:
Sifter
Stainless steel vessels
Weighing & measuring equipment
Filling equipment
Electrical sealing machine

27. Parenteral preparation:
Basic installation area: 60sq.m(partitioned into suitable sized cubicles with air lock arrangement)
Process of manufacture divided into:
Preparation of containers & closures
Preparation of solution
Filling & sealing
Sterilization & testing
Equipments include:
Manufacturing area:
Storage equipment
Washing & drying equipment

28. Dust proof storage cabinet
Water still
Preparation & mixing tanks and equipments
Filtering equipment
Hot air sterilizer
Aseptic filling & sealing room:
Benches for filling & sealing
Bacteriological filters
Filling & sealing unit under laminar flow
General room:
Inspection table
Leak testing equipment
Labelling & packaging unit
Storage equipment including cold storage & refrigeration

29. SCHEDULE M-I Requirements of factory premises of homoeopathic preparations
General Requirements: Location and Surroundings; Buildings; Water supply Health, Clothing and Sanitation of Workers; Medical Services, container management etc. comes under this.
Requirements of Plant and Equipment:
Mother tinctures and Mother solution Section- An area of 55 sq. meters is recommended for basic installations
Potentisation Section- Method of potentisation will be adopted as specified in Homoeopathic Pharmacopoeia of India Vol.I

30. SCHEDULE M-II : Requirement of premises for manufacture of cosmetics
General Requirements: Location and Surroundings; Buildings; Water supply; Health, Clothing and Sanitation of Workers; Medical Services etc
Requirements of Plant and Equipment: Specifications are given for only certain cosmetic preparations like
Powers
Creams, lotions, emulsions, pastes, cleansing milks, shampoos, pomade, brilliantine, shaving creams, and hair-oils etc
Nail Polishes and Nail lacquers
Lipsticks and lip-gloss
Depilatories
Preparations used for Eyes
Aerosol
Alcoholic Fragrance Solutions
Hair Dyes
Toilet Soaps
Tooth powders and toothpastes

31. SCHEDULE M-III Requirements of factory premises for manufacture of medical devices
General Requirements: Location and Surroundings; Buildings; Water supply; Health, Clothing and Sanitation of Workers; Medical Services etc comes under this
Requirements for Manufacture Of Medical Devices: Shall be conducted bat the licensed premises, and the process of manufacture is divided into following separate operations/Sections-
Moulding
Assembling
Raw Materials
Storage Area
Washing, drying and sealing area
Sterilization
Testing facilities

32. cGMP
What is cGMP ? : Usually see “cGMP” – where c = current, to emphasize that the expectations are dynamic 
In India it is established in 2000 & amended from July 2004
It is periodically reversed and updated

33. GMP is an important tool in quality control of drug products
Legal regulation of GMP is important to control the quality of drugs manufactured with in the country

34. REFERENCES Manual on Drugs and Cosmetics; sixth edition; 2009
Schedule M: Good Manufacturing Practices And Requirements Of Premises, Plant And Equipment For Pharmaceutical Products. Gazette Of India Extraordinary, Part II -section 3, Sub-section (I) Ministry Of Health And Family Welfare (Department Of Health)
Ansel’s Pharmaceutical Dosage forms and Drug Delivery system ;L. V. Allen et al. ; eight edition; Current good manufacturing practices and current good compounding practices;67-91
Quality Assurance of Pharmaceuticals; Good manufacturing practices and inspection; Volume – 2; WHO
Encyclopedia of pharmaceutical technology; third edition; volume – 1;Good Manufacturing Practices(GMPs): An overview;

35. Thank you -pharma street