Schedule m

Schedule M
SRI VENKATESHWARA COLLEGE OF PHARMACY

Contents
Schedule M – Terminology
Schedule M- Good manufacturing practices for premises and
materials
Schedule M- Part 1A:Specific requirements for manufacture of
sterile products ,parenteral preparations and sterile opthalmic
preparations
Schedule M- Part 1B: Specific requirements for manufacture of oral
solid dosage forms
Any Queries & Thanks
Schedule M

SCHEDULE M
Schedule M is good manufacturing practices and requirements of
premises, plants and equipment for pharmaceutical products.
Schedule M is a part of drugs and cosmetics act, 1940.
Schedule M- І:Requirements of factory premises for manufacture of
homoeopathic preparations.
Schedule M- ІІ: :Requirements of factory premises for manufacture of cosmetics.
Schedule M- ІІІ: :Requirements of factory premises for manufacture of medical
devices.
Schedule M

Contents:
PART І : Good manufacturing practices for premises and materials.
PART ІA: specific requirements for manufacture of sterile
products, parenteral preparations and sterile ophthalmic preparations.
PART ІB: specific requirements for manufacture of solid dosage
forms.
PART ІC: specific requirements for manufacture of oral liquids.
PART ІD: specific requirements for manufacture of topical
products.
PART ІE: specific requirements for manufacture of metered dose
inhalers(MDI).
PART ІF: specific requirements for manufacture of active
pharmaceutical ingredients (Bulk drugs).
PART ІІ: requirements for plants and equipment.
SCHEDULE M
Schedule M

PART 1: GOOD MANUFACTURING PRACTICES FOR
PREMISES AND MATERIALS
1. General Requirements
2. Warehousing Area
3. Production area.
4. Ancillary Areas.
5. Quality Control Area.
6. Personnel.
7. Health, clothing and sanitation of workers.
8. Manufacturing Operations and Controls
9. Sanitation in the Manufacturing Premises.
10. Raw Materials.
11. Equipment
12. Documentation and Records
13. Labels and other Printed Materials.
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SCHEDULE M
14. Quality Assurance.
15. Self Inspection and Quality audit
16. Quality Control System
17. Specification
18. Master Formula Records
19. Packing Records
20. Batch Packaging Records
21. Batch Processing Records
22. Standard Operating Procedures (SOPs) and Records, regarding
23. Reference Samples.
24. Reprocessing and Recoveries
25. Distribution records
26. Validation and process validation
27. Product Recalls
28. Complaints and Adverse Reactions
29. Site Master File
Schedule M

General requirements (Area, Construction, Water supply, Waste
disposal):
• Location and environment – Contamination from environment
should be avoided. Avoid smoke, chemicals, odour, open drains.
• Building and premises – Designed constructed and maintained to
suit Manufacturing under hygienic conditions.
• Water – Purified water according to Pharmacopoeial standards.
Potable water for cleaning should be employed. Stored in suitable
conditions. Avoid microbial contamination.
• Waste disposal – Sewage disposal should comply environmental
control board. Biological wastes as per bio-medical waste disposal
rules 1999 Toxic chemicals, flammables should be properly
segregated.
SCHEDULE M
Schedule M

SCHEDULE M
Warehousing Area:
 Adequate and categorized areas (raw, quarantined, samples returned,
released, intermediates, finished products, machine change parts).
 Good storage conditions, restricted access to personnel.
 Separate storage for hazardous, toxic, explosive chemicals, abusive
chemicals.
 Separate dispensaries for categorically (Steroids, Hormones, Cytotoxic
substances).
 Aseptic maintenance, prevention of rodents, conducting regular
inspections.
Ancillary area :
 Adequate, separate space for rest room, refreshment room, wash rooms.
Separate for males and females.
 Separate animal houses away from manufacturing area.
 Change rooms with written instructions for disinfection.
 Separate areas for workshop, maintenance department, storage of
spares.
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SCHEDULE M
Manufacturing/ Production area :
 Logical flow of materials.
 Dedicated areas for sensitive, biological, potent substances.
 Adequate facilities, should not be interrupted by maintenance.
Quality control area:
 To perform tests for controlling quality, adequate area for preventing
cross contamination.
 Air locks and laminar air flow facilities for microbiology labs.
 Separate areas for specific products, storage of reference, test samples,
adequate instruments.
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SCHEDULE M
Personnel :
 Qualified technical staff with experience in dosage form
manufactured.
 Quality control should be done by competent staff.
 Workers proportional to work load.
 SOP’S should be provided to staff, training should be provided.
Health, clothing and sanitation of workers :
 should not be allergic to chemicals handled. Should be periodically
checked for cytotoxic or hormonal adverse effects.
 Thorough medical examination before employing, trained in personal
hygiene, inform superior authorities when sick.
 Direct contact should be avoided, change room procedures should be
followed strictly.
 Smoking drinking, eating are not permitted Plants which effect the
quality are also not permitted.
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SCHEDULE M
Manufacturing operations and controls :
 All operation should be performed by qualified staff under
supervision. Labeled with batch number, stage of process.
 Cross contamination should be prevented.
 Independent AHU for different products.
 Left over’s are completely removed after production or closing
hours.
 Packaging materials should be properly checked.
Sanitation in manufacturing premises :
 Cleaning and maintenance should be done regularly.
 No fare through, no storage of products other than manufactured
in the premises
 Should be well lit.
Schedule M

SCHEDULE M
Raw materials :
 Records should be maintained according to schedule U.
 Immediately quarantined, stored under appropriate conditions.
 First in – first out principle should be followed.
 Damaged or received condition should be noted.
 Approved by QC should only be dispensed.
 Separate storage for quarantined, stored, rejected materials.
 Always stored on racks, not on bare ground/ floor.
Equipment:
 Properly designed, place according to layout, minimum risk of errors.
 Qualified, validated equipment.
 Do not add contaminants, should be cleaned thoroughly.
 Defectives are separated and labeled.
Schedule M

SCHEDULE M
Labels and printed matter :
 Labels should be given to indicate the status of process, avoid mix up’s
Labels should be legibly printed, dark colored.
 Before dispatch quality control dept. should ensure of proper labeling
and Checked for inserts, leaflets placed.
 Adequate number of samples should be collected.
 Records of received labels should be maintained, unused codes should
be documented.
Documentation:
 It is essential part of quality assurance, required for audits, inspections.
 It should contain all the details, any alteration at time of operation
should be noted and signed by authorities responsible.
 Electronic documentation should be easily available, password
protected.
Schedule M

SCHEDULE M
Quality assurance :
 It influences the quality of the product.
 It should ensure practice of GMP, GLP, GCP.
 Should have control on raw materials, intermediates, finished products,
validation, calibration.
 No product should be distributed unless assured by the department.
Self inspection and quality audits :
 Separate experienced team for inspection of quality, evaluate practice of
GMP.
 Procedure of inspection, results, recommendations, actions should be
documented.
 Performed routinely or specifically when product recall or repeated
reprocessing.
 Premises, building, raw materials, storage area, equipment, IPQC,
sanitation, hygiene, validation, recall procedures, complaint management,
results, corrective actions implemented should be documented.
Schedule M

Quality control system :
 Duties are to perform sampling, testing, documenting, validating
instruments, implementing control procedures.
 Should have adequate area, equipment, qualified and experienced
personnel.
 Sop’s beside the equipment, for sampling, testing, packaging etc.,
 Access to all the areas of the premises.
 Availability of Pharmacopoeial reference standards, reference
spectra, relevant reference standards.
Specifications :
 Raw materials – name, code reference, Pharmacopoeial
requirements
 Containers and closures – cleaning, compliance.
 In process – authenticated specifications for bulk, finished products.
 Finished products – name, formula, qualitative, quantitative
requirements, shelf life, storage etc.
SCHEDULE M
Schedule M

SCHEDULE M
Master formula record :
Manufactured products should be documented. It
should include name of product, reference, patent number, proprietary or
generic name, dosage form, strength, materials used, equipment, step wise
processes, intermediates, finished product, expected yield, acceptable limits,
IPQC limits, storage requirements, containers, labels, special precautions.
Packaging record:
 Detailed instruction of packaging should be written.
 It should have name of the product, dosage form, codes or reference
number, packaging description, in process control, sampling, acceptance
criteria.
 After completion reconcile issued, packed, returned, missing labels and
careful investigation should be done.
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SCHEDULE M
Batch packaging record:
 Record of clean and free from previous product should be
documented
 Ensure the equipment if clean, ready, suitable for use.
Batch processing record
 Before the process beginning work station should be clean of
previous product.
 During the process every minute detail should be recorded like
name of product, material batch number, date of commencement,
equipment, major steps, intermediate stages, IPQC results,
operator’s signature, etc.,
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SCHEDULE M
Reprocessing and Recovery:
 Quality assurance personnel are concerned with the reprocessing. They
should establish and give limitations for reprocessing.
 The problem should be investigated and rectified in reprocessing.
 Residual solvents can be recovered according to master formula.
Distribution records :
 Pretests should be done before dispatch for assuring quality, QC should
certify the product.
 Records of distribution should be maintained for efficient recall of
products.
Validation and Process Validation:
 It is essential part of GMP, records and reports for validation should be
maintained.
 Any small changes which reflect the quality of the product should be
validated.
Schedule M

SCHEDULE M
Standard operating procedures :
 Receipt of Raw materials – Product name, receipt details, quantity.
 Sampling – Sampling methods, plans, quantity, containers used, precautions
taken to prevent contamination of sensitive products.
 Batch numbering – issue a number, should be able to track at any stage.
 Testing – written procedures to proceed on different equipments.
 Record of analysis – all details required to fill forms during analysis like
product details, validation records, calibration records etc.
Reference material :– Reference materials should be stored till 3 months after
the expiry of the product, in same conditions, final packed form.
Schedule M

Product recall :
 Products should be distributed only after approval of quality control
and quality assurance departments.
 If any problem is discovered the product should be recalled from
the market form all levels of distribution
 Written procedures should be available for recall.
 Electronic and print media can be used for recalls.
 Quantities recovered should be compared with distribution and
stored separately till final report is issued.
Complaints and adverse reactions :
 Complaints should be seriously reviewed and remedies shall be
taken and recorded.
 Serious complaints should be reported to authorities.
SCHEDULE M
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Site master file :
Licensee shall maintain sufficient information in the site master file.
 General information – premises, licensed products, no. of employees,
activities, quality control, storage, distribution, etc
 Premises – layout, materials used for construction, ventilation, special
area, sanitation, preventive maintenance programs etc.,
 Personnel – records of employees, health, hygienic, responsibilities.
 Equipment – list, description, validation, calibration of equipment.
 Sanitation – written procedures and specifications.
 Documentation – preparation and revision of documents, documents
related to product quality,
 Production
 Quality control activity
 Distribution, complaint management – recording of distribution,
arrangements for handling complaints, product recalls.
 Self inspection
 Export
Schedule M

SCHEDULE M
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
Schedule M

SCHEDULE M
General requirements:
These being sterile products should not be manufactured in damp, dark, dirt,
water supply, air, materials should meet requirements
Building and facilities :
 Quality material should be used in construction, there should not be any
cracks, facilities maintenance & repair should not interfere with integrity.
 Separate areas like supporting area, change rooms, preparation area, aseptic
area. Materials suspected for contamination are not allowed. In aseptic area,
flooring should be unbroken, joints should be coved, light fittings, air
vent/grills, windows should flush with the walls. No sinks in grade A, B
rooms
 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
 Intercom and pass box for communication and passage of materials. Drains
should be periodically monitored.
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Schedule M
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.
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
(f) Microbiological monitoring by settle plates and/or swabs in aseptic areas - daily,
and at decreased frequency in other areas

SCHEDULE M
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.
Sanitation :
Procedures should be written and made available, personnel specific should be
trained. Agents should be used in rotation, combination, concentrations.
Equipment :
Washing machines, blenders, manufacturing vessels, stem sterilizers, filter
assemblies, filling machines, vacuum chambers, lyophilizer, sealing, labeling
machines, integrated machines. Effectiveness of sterilizers , temperature
mapping of sterilizers, fill volume of filling machines should be validated and
done once a year.
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SCHEDULE M
Water and Steam systems :
 Should be checked for Bio-burden , ≯500 in potable ,
≯100CFU/ml.
 Water for injection 10CFU/ml, and should be at 70˚C temperature ,
continuous rotation .
Manufacturing process :
 Bio-burden of bulk materials should be checked , ≯100CFU/ml,
gases and liquids should filtered through membrane filters .
 Each lot should be prepared at one time ,one lot prepared at
different times shall be evaluated differently for sterility .
Form fill seal, Blow fill seal technology :
 Thermoplastic granules are used for forming, filled and sealed in the
same line.
 Blowing or formation of container is done in a separate area and
then filled and sealed.
 Terminally sterilized products should be filled in class A
environment.
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SCHEDULE M
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.
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.
Schedule M

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)
SCHEDULE M
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SCHEDULE M
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.
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.
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 .
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SCHEDULE M
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.
Filling of hard gelatin capsules:
 Considered as drug components.
 Temperature, humidity should be properly maintained.
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.
Packaging :
 Care to avoid previous batch products when using automated machines.
 Checked for defects, misprint, cuts, missing doses, improper sealing.
Schedule M

1. Dr.B.S.Kuchekar, Mr.M.Khadatare, Mr.Sachin C.Itkar et.al; Forensic
Pharmacy : Textbook : ISBN NO. 85790 – 01 – 9, Fourth Edition , Page
No: 149 – 185.
Schedule M

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