Detailed Comparison-New-Schedule-M-vs-Existing

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DRAFT FOR DISCUSSION

The main objective behind the revision of Schedule M is to harmonize quality standards with current global regulatory
requirements. In this revision of Schedule M a drastic attempt is made to update with International Quality Standard (IQS)
requirements.
This new version is designed on a risk-based approach methodology where more importance is given to the Quality Risk
Management principles and assessments.

Key Features Existing schedule M Revised schedule M


Pharmaceutical Quality System No section in existing Schedule M and also not Newly added. Separate specific requirements
(PQS) mentioned in any sub section/chapters. mentioned.
Quality Risk Management No section in existing Schedule M and also not Newly added. Separate specific requirements
mentioned in any sub section/chapters. mentioned.
Product Quality Review No section in existing Schedule M and also not Newly added. Separate specific requirements
mentioned in any sub section/chapters. mentioned.
Good manufacturing practices Requirements for the production area were mentioned Title & terminology changed
(GMP) for pharmaceutical but practices not mentioned.
products
Qualification and Validation Product process validation requirements are specified Newly Added. Detailed requirements of equipment
with minimum emphasis. qualification along with process validation are
specified.
Complaints and Adverse Briefly define in existing Schedule M regarding In revised Schedule M, broadly define about the
Reactions Complaints and Adverse Reactions. complaint and Adverse Reactions and complaints
section has been harmonized IQS.
Products Recall Briefly define in existing Schedule M about to products In revised Schedule M, broadly define about to Product
Recall. recalls and this section has been harmonized with IQS.
Product specific manufacturing In existing Schedule M, six product specific In revised Schedule M, another 5 categories are added.
requirements manufacture requirements are specified. Total 11 product specific manufacture requirements
are specified.
Change Control No separate section in existing Schedule M regarding Newly Added. Detailed requirements of change control
change control management. management are specified.
Production under loan license or No section or requirements specified in existing Newly Added. Detailed requirements of contract
contract and contract analysis Schedule M. arrangement, roles and responsibility of product
and other activities quality are specified.
Self-inspection, quality audits In existing Schedule M, the activity is limited upto In revised Schedule M, this activity is more clarified
and suppliers’ audits and internal inspection. and extended beyond self-inspection towards supplier
approval approval through quality audits of his premises and
processes.
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Key Features Existing schedule M Revised schedule M
Documentation In existing Schedule M, General principles of good In revised schedule M this section has been
documentation practices and electronic documents are restructured and in which tried to harmonize with IQS.
mentioned.
Good manufacturing practices In existing Schedule M, limited features have been Newly added as separate principle with specific
(GMP) for Production covered. requirements.
Good manufacturing practices In existing Schedule M, limited features have been Newly added as separate principle with specific
(GMP) for Quality Control covered. requirements.
In existing Schedule M, limited features have been Newly added as separate principle with specific
Computerized Systems
covered. requirements complying global standards.
Specific Requirements For PART I-A PART II
Manufacture Of Sterile Products, Point 3. Air Handling System (Central Air- Point 4. Manufacture of sterile preparations:-
Parenteral Preparations Conditioning. - Sub Point 4.7.8. Other characteristics such as
Sub point 3.10 Unless there are product specific temperature and relative humidity depend on the
requirements, temperature and humidity in the aseptic product and nature of the operations carried out. These
areas shall not exceed 27 degree centigrade and relative parameters shall not interfere with the defined
humidity 55%, respectively. cleanliness standard.
Raw Material (10.) Raw Materials. – 14. Materials:
10.9 Only raw materials which have been released by 14.14. Only raw materials which have been released by
the Quality Control Department and which are the QC Department and which are within their
within their shelf-life shall be used. It shall be shelf-life shall be used.
ensured that shelf life of formulation product 14.17. Only starting materials released by the QC
shall not exceed with that of active raw materials Department and within their shelf-life shall be
used. used.

Features in Existing Schedule M Features in Revised Schedule M

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Features in Existing Schedule M Features in Revised Schedule M
[SCHEDULE M] SCHEDULE M
[See Rules 71, 74, 76 and 78] [See rules 71, 74, 76 and 78]
Good Manufacturing Practices And Requirements Of Premises, Plant And Good Manufacturing Practices And Requirements Of Premises, Plant
Equipment For Pharmaceutical Products. And Equipment For Pharmaceutical Products
Note: - To achieve the objectives listed below, each licensee shall evolve Note.—To achieve the objectives listed below, each licensee shall evolve
appropriate methodology, systems and procedures which shall be appropriate methodology, systems and procedures which shall be
documented and maintained for inspection and reference; and the documented and maintained for inspection and reference; and the
manufacturing premises shall be used exclusively for production of drugs manufacturing premises shall be used exclusively for production of drugs
and no other manufacturing activity shall be undertaken therein. and no other manufacturing activity shall be undertaken therein.
PART 1 PART I
GOOD MANUFACTURING PRACTICES FOR PREMISES AND MATERIALS. GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICAL
PRODUCTS: MAIN PRINCIPLES
Pharmaceutical Quality System (PQS), Quality Risk Management 1. Pharmaceutical Quality System (PQS):
(QRM): & Good manufacturing practices for pharmaceutical products 2. Quality Risk Management (QRM):
and Change Control are not available in existing schedule M. Newly 3. Good manufacturing practices for pharmaceutical products:
addition in revised schedule M.
(1) GENERAL REQUIREMENTS 4. Sanitation and hygiene:
(A) Location and surroundings.- 5. Qualification and validation:
(B) Building and premises.- 6. Complaints and adverse reaction:
(C) Water Supply. – 7. Product recalls:
(D) Disposal of waste. – addition 8. Change control:
(2) Warehousing Area. – 9. Production under loan licence or contract and contract analysis
(3) Production area. – and other activities:
(4) Ancillary Areas. – 9.1. Principle-
(5) Quality Control Area.- 9.2. General-
(6) Personnel.- 9.3. Loan licensee or contract giver-
(7) Health, clothing and sanitation of workers. – 9.4. Manufacturing facility provider or contract acceptor-
(8) Manufacturing Operations and Controls. – 9.5. Contract-
(9) Sanitation in the Manufacturing Premises. – 10. Self-inspection, quality audits and suppliers’ audits and approval:
(10) Raw Materials. – 10.2. Items for self-inspection
(11) Equipment. – 10.3. Self-inspection team-
(12) Documentation and Records. – 10.4. Frequency of self-inspection-
(13) Labels and other Printed Materials. – 10.5. Self-inspection report-
(14) Quality Assurance. 10.6. Follow-up action-.
(15) Self-Inspection and Quality audit – 10.7. Quality audit-
(16) Quality Control System. – 10.8. Suppliers’ audits and approval-
(17) Specification 11. Personnel:
17.1 For raw materials and packaging materials. 11.1. Principle-
17.2 For product containers and closures. – 11.2. General-
17.3 For in-process and bulk products. – 11.3. Key personnel-
17.4 For finished products. – 11.4. Training-
11.5. Personal hygiene-
17.5 For preparation of containers and closures. –
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Features in Existing Schedule M Features in Revised Schedule M
(18) Master Formula Records – 12. Premises:
(19) Packing Records. – 12.1. Principle-
(20) Batch Packaging Records. 12.2. General-
(21) Batch Processing Records 12.3. Ancillary areas-
(22) Standard Operating Procedures (SOPs) and Records, regarding. – 12.4. Storage areas-
22.1 Receipt of materials: 12.5. Weighing areas-
22.2 Sampling: - 12.6. Production areas-
22.3 Batch Numbering. – 12.7. Quality Control (QC) areas-
22.4 Testing: 13. Equipment:
22.5 Records of Analysis. - 14. Materials:
(23) Reference Samples. - 15. Reference Standards:
(24) Reprocessing and Recoveries. - 16. Waste materials:
(25) Distribution records:
17. Documentation:
(26) Validation and process validation. -
17.1-Principle-
(27) Product Recalls. -
17.2. General-
(28) Complaints and Adverse Reactions.
17.3. Documents Required:
17.3.1. Labels-
17.3.2. Specifications and testing procedures
17.3.3. Specifications for starting and packaging materials-
17.3.4. Specifications for intermediate and bulk products-
17.3.5. Specifications for finished products-
17.3.6. Master formula records-
17.3.7. Packaging instructions-
17.3.8. Batch processing records-
17.3.9. Batch packaging records-
17.3.10. Standard operating procedures and records:
Good practices in production is not available in existing schedule M. 18. Good practices in production:
Newly addition in revised schedule M. 18.1. Principle-.
18.2. General-
18.3. Prevention of cross-contamination and bacterial contamination
during production-
18.4. Processing operations-
18.5. Packaging operations:
Good practices in quality control is not available in existing schedule 19. Good practices in quality control:
M. Newly addition in revised schedule M. 19.6. Control of starting materials and intermediate, bulk and
finished products-
19.7. Test requirements-
19.8. Batch record review:
19.9. Stability studies-

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Features in Existing Schedule M Features in Revised Schedule M
Computerised systems are not available in existing schedule M. New
20. Computerised systems:
addition in revised schedule M.
(29) Site Master File. –The licensee shall prepare a succinct document Appendix-I
in the form of Site Master File containing specific and factual Good Site Master File:The licensee shall prepare a succinct document in the
Manufacturing Practices about the production and/or control of form of ‘Site Master File’ containing specific and factual Good
pharmaceutical manufacturing preparations carried out at the Manufacturing Practices about the production or control or both of
licensed premises. It shall contain the following: - pharmaceutical manufacturing preparations carried out at the licensed
29.1 General information, - premises. It shall contain the following, namely-
29.2 Personnel. – 1. General information:-
29.3 Premises. – 2. Personnel:-
29.4 Equipment. – 3. Premises:-
29.5 Sanitation. – 4. Equipment:-
29.6 Documentation. – 5. Sanitation:-
29.7 Production. – 6. Documentation:-
29.8 Quality Control. – 7. Production:-
29.9 Loan licence manufacture and licensee. – 8. Quality Assurance and Control:-
29.10 Distribution, complaints and product recall. – 9. Manufacture under loan licence and licensee:-
29.11 Self-inspection. – 10. Distribution, complaints and product recall:-
29.12 Export of drugs. - 11. Self-inspection:-
12. Export of drugs:-
PART I-A PART II
SPECIFIC REQUIREMENTS FOR MANUFACTURE OF STERILE SPECIFIC REQUIREMENTS FOR MANUFACTURE OF STERILE
PRODUCTS, PARENTERAL PREPARATIONS (SMALL VOLUME PRODUCTS, PARENTERAL PREPARATIONS (SMALL VOLUME
INJECTABLES AND LARGE VOLUME PARENTERALS) AND STERILE INJECTABLES AND LARGE VOLUME PARENTERALS) AND
OPHTHALMIC PREPARATIONS. STERILE OPHTHALMIC PREPARATIONS

1. General 1. General considerations:-


2. Building and Civil Works. – 2. Quality control:-
3. Air Handling System (Central Air-Conditioning). 3. Sanitation:-
4. Environmental Monitoring 4. Manufacture of sterile preparations:-
5. Garments. 5. Processing:
6. Sanitation- 6. Sterilisation:
7. Equipment. 7. Personnel:-
8. Water and Steam Systems – 8. Premises:
9. Manufacturing Process – 9. Equipment:
10. Form-Fill-Seal Technology or Blow, Fill-Seal Technology. – 10. Finishing of sterile products:-
11. Product Containers and Closures.
12. Documentation
Not available in existing schedule M. PART III
New addition under Part III in revised schedule M for Specific requirements for manufacturing of pharmaceutical products
Hazardous substances such as Sex Hormones, Steroids or containing hazardous substances such as sex hormones, steroids
(anabolic, Androgenic) or cytotoxic substances
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Features in Existing Schedule M Features in Revised Schedule M
Cytotoxic substances.
1. Introduction:-
2. Risk assessment:-
3. Product protection:-
4. Personal Protection Equipment and breathing air systems:-
5. Environmental protection:-
6. Facility layout:-
7. Air-handling systems:-
8. Air-Handling Units (AHU):-
10. Personnel decontamination systems:-
11. Effluent treatment:-
12. Maintenance:-
13. Qualification and validation:-
Not available in existing schedule M. PART IV
New addition under Part IV in revised schedule M for Biological Specific Requirements For Manufacture Of Biological Products
Products.
1. Principles and general considerations:-
2. Pharmaceutical quality system and quality risk management:-
3. Personnel:-
4. Starting materials:-
5. Seed lots and cell banks:-
6. Premises and equipment:-
7. Containment:-
8. Clean rooms:-
9. Production:-
10. Campaign production:-
11. Labelling:-
12. Validation:-
13. Quality Control:-
14. Documentation (batch processing records):-
15. Use of animals:-
16. Complaints:-
17. Product recalls:-
Not available in existing schedule M. PART V
New addition under Part V in revised schedule M for SPECIFIC REQUIREMENTS FOR RADIOPHARMACEUTICAL
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Features in Existing Schedule M Features in Revised Schedule M
Radiopharmaceutical Products PRODUCTS
1. Principles:-
2. Personnel:-
3. Premises and equipment:-
4. Production:-
5. Labelling:-
6. Production and distribution records:-
7. Quality assurance and quality control:-
Not available in existing schedule M.
PART VI
New addition under Part VI in revised schedule M for
SPECIFIC REQUIREMENTS FOR PHYTOPHARMACEUTICALS
Phytopharmaceuticals
1. General:-
2. Quality assurance in the manufacture of Phytopharmaceuticals:-
3. Good manufacturing practice for Phytopharmaceuticals:-
4. Sanitation and hygiene:-
5. Qualification and validation:-
6. Complaints:-
7. Product recalls:-
8. Contract production and analysis:-
9. Self-inspection:-
10. Personnel:-
11. Training:-
12. Personal hygiene:-
13. Premises:-
14. Equipment:-
15. Materials:-
16. Reference samples and standards:-
17. Documentation:- The general principles for documentation are set
out in Part I.
18. Specifications:-
19. Finished phytopharmaceuticals:-
20. Plant preparations:-
21. Processing instructions:-
22. Good practices in production:-
23. Good practices in quality control:-
Not available in existing schedule M. PART VII

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Features in Existing Schedule M Features in Revised Schedule M
New addition under Part VII in revised schedule M for SPECIFIC REQUIREMENTS FOR THE MANUFACTURE OF
Investigational Pharmaceutical Products for Clinical Trials in INVESTIGATIONAL PHARMACEUTICAL PRODUCTS FOR CLINICAL
Human TRIALS IN HUMANS
1. General considerations:-
2. Quality assurance:-
3. Validation:-
4. Complaints:-
5. Recalls:-
6. Personnel:-
7. Premises and equipment:-
8. Materials:-
9. Documentation:-
10. Production:-
11. Quality control:-
12. Shipping, returns, and destruction:-
PART I-B PART VIII
SPECIFIC REQUIREMENTS FOR MANUFACTURE OF ORAL SPECIFIC REQUIREMENTS FOR MANUFACTURE OF ORAL SOLID
SOLID DOSAGE FORMS (TABLETS AND CAPSULES) DOSAGE FORMS (TABLETS AND CAPSULES)

1- General 1. General:-
2- Sifting, Mixing and Granulation. 2. Sifting, Mixing and Granulation.
3- Compressions (Tablets) 3. Compressions (Tablets)
4- Coating (Tablets) 4. Coating (Tablets)
5- Filling of Hard Gelatin Capsule. 5. Filling of Hard Gelatin Capsule.
6- Printing (Tablets and Capsules) 6. Printing (Tablets and Capsules)
7- Packaging (Strip and Blister) 7. Packaging (Strip and Blister)

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Features in Existing Schedule M Features in Revised Schedule M
1. General 1. General:-
1.1 The processing of dry materials and products creates problems of 1.1. The processing of dry materials and products creates problems of
dust control and cross-contamination. Special attention is therefore, dust control and cross contamination. Special attention is, therefore,
needed in the design, maintenance and use of premises and needed in the design, maintenance and use of premises and
equipment in order to overcome these problems. Wherever required, equipment in order to overcome these problems. Wherever required,
enclosed dust control manufacturing systems shall be employed. enclosed dust control manufacturing systems shall be employed.
1.2 1.2. Suitable environmental conditions for the products handled 1.2. Suitable environmental conditions for the products handled shall be
shall be maintained by installation of air-conditioning wherever maintained by installation of air conditioning, wherever necessary.
necessary. Effective air extraction systems, with discharge points Effective air extraction systems, with discharge points situated to
situated to avoid contamination of other products and professes shall avoid contamination of other products and processes shall be
be provided. Filters shall be installed to retain dust and protect the provided. Filters shall be installed to retain dust and to protect the
factory and local environment. factory and local environment.
1.3 Special care shall be taken to protect against subsequent 1.3. Special care shall be taken to protect against subsequent
contamination of the product by particles of metal or wood. The use contamination of the product by particles of metal or wood. The use
of metal detector is recommended. Wooden equipment should be of metal detector is recommended. Wooden equipment shall be
avoided. Screens, sieves, punches and dies shall be examined for avoided. Screens, sieves, punches and dies shall be examined for
wear and tear or for breakage before and after each use. wear and tear or for breakage before and after each use.
1.4 All ingredients for a dry product shall be sifted before use unless the 1.4. All ingredients for a dry product shall be sifted before use unless the
quality of the input material can be assured. Such sifting shall quality of the input material can be assured. Such sifting shall
normally be carried out at dedicated areas. normally be carried out at dedicated areas.
1.5 Where the facilities are designed to provide special environmental 1.5. Where the facilities are designed to provide special environmental
conditions of pressure differentials between rooms, these conditions conditions of pressure differentials between rooms, these conditions
shall be regularly monitored and any specification results brought to shall be regularly monitored and any deviation shall be brought to
the immediate attention of the Production and quality Assurance the immediate attention of the Production and Quality assurance
Department which shall be immediately attended to. departments.
1.6 Care shall be taken to guard against any material lodging and 1.6. Care shall be taken to guard against any material lodging and
remaining undetected in any processing or packaging equipment. remaining undetected in any processing or packaging equipment.
Particular care shall be taken to ensure that any vacuum, Particular care shall be taken to ensure that any vacuum,
compressed air or air-extraction nozzles are kept clean and that compressed air or air-extraction nozzles are kept clean and that
there is no evidence lubricants leaking into the product from any there is no evidence of lubricants leaking into the product from any
part of the equipment. part of the equipment.
1.7. Where different products are manufactured at the same time, in
different areas or cubicles, in a multiproduct Oral Solid Dosage
(OSD) manufacturing site, measures shall be taken to ensure that
dust cannot move from one cubicle to another.
1.8. Correct directional air movement and a pressure cascade system can
assist in preventing cross contamination. The pressure cascade shall
be such that the direction of airflow is from the clean corridor into
the cubicles, resulting in dust containment.
1.9. The corridor shall be maintained at a higher pressure than the
cubicles, and the cubicles at a higher pressure than atmospheric
pressure.
1.10. Highly potent products shall be manufactured under a pressure

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Features in Existing Schedule M Features in Revised Schedule M
cascade regime that is negative relative to atmospheric pressure.
1.11. The pressure cascade for each facility shall be individually assessed
according to the product handled and level of protection required.
1.12. Building structure shall be given special attention to accommodate
the pressure cascade design.
1.13. Ceilings and walls, close fitting doors and sealed light fittings shall
be in place, to limit ingress or egress of air.
1.14. The pressure differential between adjacent rooms could be
considered a critical parameter, depending on the outcome of risk
analysis. The limits for the pressure differential between adjacent
areas shall be such that there is no risk of overlap in the acceptable
operating range, e.g., 5 Pa to 15 Pa in one room and 15 Pa to 30 Pa
in an adjacent room, resulting in the failure of the pressure cascade,
where the first room is at the maximum pressure limit and the
second room is at its minimum pressure limit.
1.15. Low pressure differentials may be acceptable when airlocks
(pressure sinks or pressure bubbles) are used to segregate areas.
1.16. The effect of room pressure tolerances shall be calculated and taken
into consideration.
1.17. The pressure control and monitoring devices used shall be calibrated
and qualified. Compliance with specifications shall be regularly
verified and the results recorded. Pressure control devices shall be
linked to an alarm system set according to the levels determined by
a risk analysis.
1.18. Manual control systems, where used, shall be set up during
commissioning, with set point marked, and shall not change unless
other system conditions change.
1.19. Airlocks can be important components in setting up and
maintaining pressure cascade systems and also to limit cross-
contamination.
1.20. Airlocks with different pressure cascade regimes include the cascade
airlock, sink airlock and bubble airlock:-
(a) Cascade airlock: higher pressure on one side of the airlock and
lower pressure on the other;
(b) Sink airlock: lower pressure inside the airlock and higher pressure
on both outer sides; and
(c) Bubble airlock: higher pressure inside the airlock and lower
pressure on both outer sides.
1.21. Doors shall open to the high pressure side, so that room pressure
assists in holding the door closed and in addition self-closers shall
be provided. If the doors open to the low pressure side, the door
closer springs shall be sufficient to hold the door closed and prevent
the pressure differential from pushing the door open. There shall be

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Features in Existing Schedule M Features in Revised Schedule M
a method to indicate if both doors to airlocks are open at the same
time, or alternatively these shall be interlocked. The determination of
which doors shall be interlocked shall be the subject of a risk
assessment study.
1.22. Central dust extraction systems shall be interlocked with the
appropriate air-handling systems, to ensure that they operate
simultaneously.
1.23. Room pressure differential between adjacent cubicles, which are
linked by common dust extraction ducting, shall be avoided.
1.24. Air shall not flow through the dust extraction ducting or return air
ducting from the room with the higher pressure to the room with the
lower pressure (this would normally occur only if extract or return
systems were inoperative). Systems shall be designed to prevent dust
flowing back in the opposite direction in the event of component
failure or airflow failure.
1.25. Adequate room pressure differential indication shall be provided so
that each critical room pressure can be traced back to ambient
pressure (by summation of the room pressure differentials), in order
to determine the room actual absolute pressure. Room pressure
indication gauges shall have a range and graduation scale which
enables the reading to accuracy, as appropriate; normal operating
range, alert and action limits shall be defined and displayed at the
point of indication. A colour coding gauge may be helpful. Room
pressure indication may be either analogue or digital, and may be
represented as either pressure differentials or absolute pressures.
Whichever system is used any out-of-specification condition shall be
easily identifiable.
1.26. Material Pass-Through-Hatches (PTH) or Pass Boxes (PB) can also be
used for separating two different zones. PTHs fall into two categories,
namely a dynamic PTH or a passive PTH. Dynamic PTHs have an air
supply to or extraction from them, and can then be used as bubble,
sink or cascade PTHs.
1.27. Where appropriate, temperature and relative humidity shall be
controlled, monitored and recorded, where relevant, to ensure
compliance with requirements pertinent to the materials and
products and provide a comfortable environment for the operator
where necessary.
1.28. Maximum and minimum room temperatures and relative humidity
shall be appropriate. Alert and action limits on temperatures and
humidity shall be set, as appropriate.
1.29. The operating band or tolerance between the acceptable minimum
and maximum temperatures shall not be made too close. Tight
control tolerances may be difficult to achieve and can also add

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unnecessary installation and running costs.
1.30. Cubicles or suites, in which products requiring low relative humidity
are processed, shall have well sealed walls and ceilings and shall
also be separated from adjacent areas with higher relative humidity
by means of suitable airlocks.
1.31. Precautions shall be taken to prevent moisture migration that
increases the load on the HVAC system.
1.32. Humidity control shall be achieved by removing moisture from the
air, or adding moisture to the air, as relevant.
1.33. Dehumidification (moisture removal) may be achieved by means of
either refrigerated dehumidifiers or chemical dehumidifiers.
1.34. 1.34. Duct material in the vicinity of the humidifier shall not add
contaminants to air that will not be removed by filtration further
downstream.
1.35. Air filters shall not be installed immediately downstream of
humidifiers, as moisture on the filters could lead to bacterial growth.
1.36. Cold surfaces shall be insulated to prevent condensation within the
clean area or on air-handling components.
1.37. When specifying relative humidity, the associated temperature shall
also be specified.
1.38. Chemical driers using silica gel or lithium chloride are acceptable,
provided that they do not become sources of contamination.
1.39. Wherever possible, dust or vapour contamination shall be removed
at source. Point-of-use extraction, i.e., as close as possible to the
point where the dust is generated, shall be employed. Spot
ventilation or capture hoods may be used as appropriate.
1.40. Point-of-use extraction shall be either in the form of a fixed high
velocity extraction point or an articulated arm with movable hood or
a fixed extraction hood.
1.41. Dust extraction ducting shall be designed with sufficient transfer
velocity to ensure that dust is carried away and does not settle in the
ducting. Periodic checks shall be performed to ensure that there is
no build-up of the dust in the ducting.
1.42. The required transfer velocity shall be determined on the density of
the dust (the denser the dust, the higher the transfer velocity shall
be, e.g., 15–20 m/s).
1.43. Airflow direction shall be carefully chosen to ensure that the
operator does not contaminate the product and also so that the
operator is not put at risk by the product.
1.44. Point extraction alone is usually not sufficient to capture all of the
contaminants, and general directional airflow shall be used to assist
in removing dust and vapours from the room.
1.45. Typically, in a room operating with turbulent airflow, the air shall be

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introduced from ceiling diffusers, located at the door entry side of
the room and extracted from the rear of the room at low level to help
give a flushing effect in the room. Correct flushing of the rooms may
be verified by airflow visualisation smoke tests.
1.46. When dealing with particularly harmful products, additional steps,
such as handling the products in glove boxes or using barrier
isolator technology, shall be used.
1.47. Exhaust air discharge points on pharmaceutical equipment and
facilities, such as from fluid bed driers and tablet-coating
equipment, and exhaust air from dust extraction systems, carry
heavy dust loads and shall be provided with adequate filtration to
prevent contamination of the ambient air.
1.48. Where the powders are not highly potent, final filters on a dust
exhaust system shall be fine dust filters with a filter classification of
5μ.
1.49. Where reverse-pulse dust collectors are used for removing dust from
dust extraction systems, they shall usually be equipped with
cartridge filters containing a compressed air lance, and be capable of
continuous operation without interrupting the airflow.
1.50. Mechanical-shaker dust collectors shall not be used for applications
where continuous airflow is required, in order to avoid unacceptable
fluctuations in room pressures, except in the case where room
pressures are automatically controlled.
1.51. When wet scrubbers are used, the dust-slurry shall be removed by a
suitable means, e.g., a drainage system or waste removal contractor.
1.52. The quality of the exhaust air shall be determined to see whether the
filtration efficiency is adequate with all types of dust collectors and
wet scrubbers.
1.53. Where necessary, additional filtration may be provided downstream
of the dust collector.
1.54. The systems for fume, dust and effluent control shall be designed,
installed and operated in such a manner that they do not become
possible sources of contamination or cross-contamination, e.g., an
exhaust air discharge point located close to the HVAC system fresh
air inlet.
1.55. Fumes shall be removed by means of wet scrubbers or dry chemical
scrubbers (deep-bed scrubbers).
1.56. Wet scrubbers for fume removal normally require the addition of
various chemicals to the water to increase the adsorption efficiency.
1.57. Deep-bed scrubbers shall be designed with activated carbon filters
or granular chemical adsorption media. The chemical media for
deep-bed scrubbers shall be specific to the effluent being treated.
1.58. The type and quantity of the vapours to be removed shall be known

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to enable the appropriate filter media, as well as the volume of media
required to be determined.
1.59. There shall be no risk of contamination or cross-contamination
(including by fumes and volatiles) due to recirculation of air.
1.60. Depending on the airborne contaminants in the return air system it
may be acceptable to use recirculated air, provided that HEPA filters
are installed in the supply air stream to remove contaminants and
thus, prevent cross-contamination.
1.61. HEPA filters may not be required where the air handling system is
serving a single product facility and there is evidence that cross-
contamination would not be possible.
1.62. Re-circulation of air from areas where pharmaceutical dust is not
generated such as secondary packing may not require HEPA filters
in the system.
1.63. HEPA filters may be located in the air handling unit or placed
terminally. Where HEPA filters are terminally mounted they shall
preferably not be connected to the ducting by means of flexible
ducting. Due to the high air pressure required for the terminal filter;
this connection shall preferably be a rigid duct connection. Where
flexible ducting is used, it shall be as short as possible and properly
fixed to withstand duct pressure.
1.64. Air containing dust from highly toxic processes or solvents or
flammable vapours shall never be recirculated to the HVAC system.
1.65. Adequate airlocks, such as personnel airlocks (PAL), material
airlocks (MAL), change rooms and passages shall be provided to
protect passage between different cleanliness conditions. These shall
have supply and extract air systems as appropriate.
1.66. Areas such as airlocks, change rooms and passages, shall be
designed so that the required pressure cascades can be achieved.
1.67. Detailed diagrams depicting pressure cascades, air flow directions
and flow routes for personnel and materials shall be prepared and
maintained.
1.68. Where possible, personnel and materials shall not move from a
higher cleanliness zone to a lower cleanliness zone and back to a
higher cleanliness zone; (if moving from a lower cleanliness zone to a
higher cleanliness zone, changing or decontamination procedures
shall be followed).
1.69. The final stage of the changing room shall, in the “at rest” state, be
the same good manufacturing practices classification grade as the
area into which it leads.
2. Sifting, Mixing and Granulation. 2. Sifting, mixing and granulation:-
3. Compression (Tablets):- 3. Compression (Tablets):-

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Features in Existing Schedule M Features in Revised Schedule M
4. Coating (Tablets):- 4. Coating (Tablets):-
5. Filling of Hard Gelatin Capsule:- 5. Filling of Hard Gelatin Capsule:-
6. Printing (Tablets and Capsules):- 6. Printing (Tablets and Capsules):-
7. Packaging (Strip and Blister):- 7. Packaging (Strip and Blister):-
PART I-C PART IX
SPECIFIC REQUIREMENTS FOR MANUFACTURE OF ORAL SPECIFIC REQUIREMENTS FOR MANUFACTURE OF ORAL LIQUIDS
LIQUIDS (SYRUPS, ELIXIRS, EMULSIONS AND (SYRUPS, ELIXIRS, EMULSIONS AND SUSPENSIONS)
Note.- Good Manufacturing Practices for pharmaceutical products: Main
SUSPENSIONS) principles as given in Part I shall be complied with, mutatis mutandis, for
the manufacture of Syrups, Elixirs, Emulsions and Suspensions. In
addition to these requirements, the following specific requirements shall
also be followed, namely:-
1. Building and Equipment. 1. Principle:-
2. Purified Water. 2. Building and Equipment:-
3. Manufacturing 3. Purified Water:-
4. Manufacturing:-
PART I-D PART X
SPECIFIC REQUIREMENTS FOR MANUFACTURE OF TOPICAL SPECIFIC REQUIREMENTS FOR MANUFACTURE OF TOPICAL
PRODUCTS i.e. EXTERNAL PREPARATIONS (CREAMS, OINTMENTS, PRODUCTS i.e., EXTERNAL PREPARATIONS (CREAMS, OINTMENTS,
PASTES, MULSIONS, LOTIONS, SOLUTIONS, DUSTING POWDERS AND PASTES, EMULSIONS, LOTIONS, SOLUTIONS, DUSTING POWDERS
IDENTICAL PRODUCTS) AND IDENTICAL PRODUCTS)
Note.- Good Manufacturing Practices for pharmaceutical products: Main
principles as given in Part I shall be complied with, mutatis mutandis, for
the manufacture of Topical Products i.e., External Preparations (Creams,
Ointments, Pastes, Emulsions, Lotions, Solutions, Dusting powders and
identical products used for external applications). In addition to these
requirements, the following specific requirements shall also be followed,
namely:—
PART I-E PART XI
SPECIFIC REQUIREMENTS FOR MANUFACTURE OF METERED-DOSE- SPECIFIC REQUIREMENTS FOR MANUFACTURE OF METERED–
INHALERS (MDI) DOSE– INHALERS (MDI)
Note.– The Good Manufacturing Practices for pharmaceutical products:
Main principles as given in Part I shall be complied with, mutatis
mutandis, for the manufacture of Metered-Dose-Inhalers (MDI). In
addition to these requirements, the following specific requirements shall
also be followed, namely:—
1. Documentation- 1. Principle:-
2. General 2. General:-
3. Building and Civil Works 3. Building and civil works:-
4. Environmental Conditions 4. Environmental conditions:-
5. Garments 5. Garments:-
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Features in Existing Schedule M Features in Revised Schedule M
6. Sanitation 6. Sanitation:-
7. Equipment. 7. Equipment:-
8. Manufacture.- 8. Manufacture:-
9. Documentation:-
PART I-F PART XII
SPECIFIC REQUIREMENTS OF PREMISES, PLANT AND SPECIFIC REQUIREMENTS FOR MANUFACTURE OF ACTIVE
MATERIALS FOR MANUFACTURE OF ACTIVE PHARMACEUTIAL PHARMACEUTICAL INGREDIENTS
INGREDIENTS (BULK DRUGS). Note — Good Manufacturing Practices for pharmaceutical products: Main
principles as given in Part I shall be complied for the manufacture of API.
This Part has been restructured in revised schedule M with In addition to these requirements, the following specific requirements
shall also be followed, namely:—
maximum requirement as the existing part was elaborated with
minimum content/requirements.
1. Building and Civil Works. 1. Introduction:-
2. Sterile Products. 1.1. General-
1.2. Scope-
3. Utilities / Services.
4. Equipment Design, Size and Location.
5. In-Process Controls.
6. Product Containers and Closures
2. Quality management:-
2.1. Principles-
2.2. Responsibilities of the quality units-
2.3. Responsibility for production activities-
2.4. Internal audits (self-inspection)-
2.5. Product quality review-
3. Personnel-
3.1. Personnel qualifications-
3.2. Personnel hygiene-
3.3. Consultants-
4. Buildings and facilities-
4.1 Design and construction-
4.2. Utilities-
4.3. Water-
4.4. Containment-
4.5. Lighting
4.6. Sewage and refuse-
4.7. Sanitation and maintenance:—
5. Process equipment:-
5.1. Design and construction-
5.2. Equipment maintenance and cleaning-
5.3. Calibration-
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Features in Existing Schedule M Features in Revised Schedule M
5.4. Computerised systems-
6. Documentation and records:-
6.1. Documentation system and specifications-
6.2. Equipment cleaning and use record-
6.3. Records of raw materials, intermediates, API labelling and
packaging materials-
6.4. Master production instructions (master production and control
records):-
6.5. Batch production records (batch production and control records)-
6.6. Laboratory control records-
6.7. Batch production record review-
7. Materials management:-
7.1. General controls-
7.2. Receipt and quarantine-
7.3. Sampling and testing of incoming production materials-
7.4. Storage-
7.5. Re-evaluation-
8. Production and in-process controls:-
8.1. Production operations-
8.2. Time limits-
8.3. In-process sampling and control-
8.4. Blending batches of intermediates or APIs-
8.5. Contamination control-
9. Packaging and identification labelling of APIs and intermediates:-
9.1. General-
9.2. Packaging materials-
9.3. Label issuance and control-
9.4. Packaging and labelling operations-
10. Storage and distribution:-
10.1. Warehousing procedures-
10.2. Distribution procedures-
11. Laboratory controls:-
11.1. General controls-
11.2. Testing of intermediates and APIs-
11.3. Certificates of analysis-
11.4. Stability monitoring of APIs-
11.5. Expiry and retest dating-
11.6. Reserve or retention samples-
12. Validation:-
12.1. Validation policy-
12.2. Validation documentation-

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Features in Existing Schedule M Features in Revised Schedule M
12.3. Qualification-
12.4. Approaches to process validation-
12.5. Process validation programme-
12.6. Periodic review of validated systems-.
12.7. Cleaning validation-
12.8. Validation of analytical methods-
13. Change control:
14. Rejection and reuse of materials:-
14.1. Rejection-.
14.2. Reprocessing-
14.3. Reworking-
14.4. Recovery of materials and solvents-
14.5. Returns-
15. Complaints and recalls-
16. Contract manufacturers (including laboratories):-
17. Specific guidance for APIs manufactured by cell culture or
fermentation:-
17.1. General-
17.2. Cell bank maintenance and record keeping-
17.3. Cell culture or fermentation-
17.4. Harvesting, isolation and purification-
17.5. Viral removal or inactivation steps:
18. APIs for use in clinical trials:-
18.1. General-
18.2. Quality-
18.3. Equipment and facilities-
18.4. Control of raw materials-
18.5. Production-
18.6. Validation-
18.7. Changes-
18.8. Laboratory controls-
18.9. Documentation-
PART- II PART XIII
REQUIREMENTS OF PLANT AND EQUIPMENT REQUIREMENTS OF PLANT AND EQUIPMENT
1. External Preparations. - 1. External preparations:-
2. Oral Liquid Preparations. - 2. Oral Liquid Preparations:-
3. Tablets 3. Tablets-
4. Powders 4. Powders:-
5. Capsules 5. Capsules:-
6. Surgical Dressing 6. Surgical dressing-

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Features in Existing Schedule M Features in Revised Schedule M
7. Ophthalmic Preparations. 7. Ophthalmic preparations:-
8. Pessaries and Suppositories 8. Pessaries and Suppositories:-
9. Inhalers and Vitralle 9. Inhalers and Vitrallae:-
10. Repacking of Drugs and Pharmaceutical Chemicals. 10. Repacking of drugs and pharmaceutical chemicals:-
11. Parenteral Preparations 11. Parenteral Preparations:-

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