For pharmaceutical manufacturers in India, complying with Schedule M – the cornerstone of Good Manufacturing Practices (GMP) – has long been the game. But the winds of change have blown, ushering in a revised Schedule M, promising a more robust and globally aligned quality management system. Buckle up, because this blog post dives deep into the nitty-gritty of both versions, dissecting the revisions that reshape the pharmaceutical landscape. Revised Schedule M 2023 is a new hurdle for the pharma industry.
In this article, we tried to explore each change that happened to revised Schedule M from the existing Schedule M. The core motive of this change is to meet the standards of world-class pharmaceutical manufacturing facilities.
This new version is designed on a risk-based approach methodology where more importance is given to the Quality Risk Management principles and assessments.
Significant changes in revised Schedule M:
| Key Features | Existing Schedule M | Revised Schedule M |
| Pharmaceutical Quality System (PQS) | No section in existing Schedule M and it is also not mentioned in any sub-section/chapters. | Newly added. Separate specific requirements are mentioned. |
| Quality Risk Management | No section in existing Schedule M and also not mentioned in any sub-section/chapters. | Newly added. Separate specific requirements are mentioned. |
| Product Quality Review | No section in existing Schedule M and also not mentioned in any sub-section/chapters. | Newly added. Separate specific requirements are mentioned. |
| Good manufacturing practices (GMP) for pharmaceutical products | Requirements for the production area were mentioned but practices were not mentioned. | The title & terminology changed |
| Qualification and Validation | Product process validation requirements are specified with minimum emphasis. | Newly Added. Detailed requirements of equipment qualification along with process validation are specified. |
| Complaints and Adverse Reactions | Briefly define in existing Schedule M regarding Complaints and Adverse Reactions. | In revised Schedule M, broadly defined the complaint and Adverse Reactions and complaints section has been harmonized IQS. |
| Products Recall | Briefly define in existing Schedule M about Product Recall. | The revised Schedule M broadly defines Product recalls and this section has been harmonized with IQS |
| Product-specific manufacturing requirements | In existing Schedule M, six product-specific manufacture requirements are specified. | In revised Schedule M, another 5 categories are added. A total of 11 product-specific manufacturing requirements are specified. |
| Change Control | No separate section in existing Schedule M regarding change control management. | Newly Added. Detailed requirements of change control management are specified. |
| Production under loan license or contract and contract analysis and other activities | No section or requirements are specified in existing Schedule M. | Newly Added. Detailed requirements of contract arrangement, roles, and responsibility of product quality are specified. |
| Self-inspection, quality audits, and suppliers’ audits and approval | In existing Schedule M, the activity is limited to internal inspection. | In revised Schedule M, this activity is more clarified and extended beyond self-inspection towards supplier approval through quality audits of his premises and processes. |
| Documentation | In existing Schedule M, General principles of good documentation practices and electronic documents are mentioned. | In revised schedule M this section has been restructured and in which tried to harmonize with IQS. |
| Good manufacturing practices (GMP) for Production | In existing Schedule M, limited features have been covered. | Newly added as separate principle with specific requirements. |
| Good manufacturing practices (GMP) for Quality Control | In existing Schedule M, limited features have been covered. | Newly added as separate principle with specific requirements. |
| Computerized Systems | In existing Schedule M, limited features have been covered. | Newly added as separate principle with specific requirements complying global standards. |
| Specific Requirements For Manufacture Of Sterile Products, Parenteral Preparations | PART I-A Point 3. Air Handling System (Central AirConditioning. – Sub point 3.10 Unless there are product specific requirements, temperature and humidity in the aseptic areas shall not exceed 27 degree centigrade and relative humidity 55%, respectively. | PART II Point 4. Manufacture of sterile preparations:- Sub Point 4.7.8. Other characteristics such as temperature and relative humidity depend on the product and nature of the operations carried out. These parameters shall not interfere with the defined cleanliness standard. |
| Raw Material | (10.) Raw Materials. – 10.9 Only raw materials which have been released by the Quality Control Department and which are within their shelf-life shall be used. It shall be ensured that shelf life of formulation product shall not exceed with that of active raw materials used. | 14. Materials: 14.14. Only raw materials which have been released by the QC Department and which are within their shelf-life shall be used. 14.17. Only starting materials released by the QC Department and within their shelf-life shall be used. |
| Features in Existing Schedule M | Features in Revised Schedule M |
| [SCHEDULE M] [See Rules 71, 74, 76, and 78] Good Manufacturing Practices And Requirements Of Premises, Plant And Equipment For Pharmaceutical Products. [Note: – To achieve the objectives listed below, each licensee shall evolve appropriate methodology, systems, and procedures which shall be documented and maintained for inspection and reference; and the manufacturing premises shall be used exclusively for the production of drugs and no other manufacturing activity shall be undertaken therein.] | SCHEDULE M [See rules 71, 74, 76, and 78] Good Manufacturing Practices And Requirements Of Premises, Plant, And Equipment For Pharmaceutical Products [Note.—To achieve the objectives listed below, each licensee shall evolve appropriate methodology, systems, and procedures which shall be documented and maintained for inspection and reference; and the manufacturing premises shall be used exclusively for the production of drugs and no other manufacturing activity shall be undertaken therein.] |
| PART 1 GOOD MANUFACTURING PRACTICES FOR PREMISES AND MATERIALS. | PART I GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICAL PRODUCTS: MAIN PRINCIPLES |
| Pharmaceutical Quality System (PQS), Quality Risk Management (QRM): & Good manufacturing practices for pharmaceutical products and Change Control are not available in existing schedule M. Newly addition in revised schedule M. | 1. Pharmaceutical Quality System (PQS): 2. Quality Risk Management (QRM): 3. Good manufacturing practices for pharmaceutical products: |
| GENERAL REQUIREMENTS (A) Location and surroundings.- (B) Building and premises.- (C) Water Supply. – (D) Disposal of waste. – addition Warehousing Area. – Production area. – Ancillary Areas. – Quality Control Area.- Personnel.- Health, clothing, and sanitation of workers. – Manufacturing Operations and Controls. – Sanitation in the Manufacturing Premises. – Raw Materials. – Equipment. – Documentation and Records. – Labels and other Printed Materials. – Quality Assurance. Self-Inspection and Quality audit Quality Control System. – Specification For raw materials and packaging materials. For product containers and closures. – For in-process and bulk products. – For finished products. – For preparation of containers and closures. – | 4. Sanitation and hygiene: 5. Qualification and validation: 6. Complaints and adverse reactions: 7. Product recalls: 8. Change control: 9. Production under loan license or contract and contract analysis and other activities: 9.1. Principle 9.2. General 9.3. Loan licensee or contract giver 9.4. Manufacturing facility provider or contract acceptor 9.5. Contract 10. Self-inspection, quality audits, and suppliers’ audits and approval: 10.2. Items for self-inspection 10.3. Self-inspection team 10.4. Frequency of self-inspection 10.5. Self-inspection report 10.6. Follow-up action-. 10.7. Quality audit 10.8. Suppliers’ audits and approval 11. Personnel: 11.1. Principle 11.2. General 11.3. Key personnel 11.4. Training 11.5. Personal hygiene- |
| (18) Master Formula Records – (19) Packing Records. – (20) Batch Packaging Records. (21) Batch Processing Records (22) Standard Operating Procedures (SOPs) and Records, regarding. – 22.1 Receipt of materials: 22.2 Sampling: – 22.3 Batch Numbering. – 22.4 Testing: 22.5 Records of Analysis. – (23) Reference Samples. – (24) Reprocessing and Recoveries. – (25) Distribution records: (26) Validation and process validation. – (27) Product Recalls. – (28) Complaints and Adverse Reactions. | 12. Premises: 12.1. Principle 12.2. General 12.3. Ancillary areas 12.4. Storage areas 12.5. Weighing areas 12.6. Production areas 12.7. Quality Control (QC) areas 13. Equipment: 14. Materials: 15. Reference Standards: 16. Waste materials: 17. Documentation: 17.1-Principle 17.2. General 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. Newly addition in revised schedule M. | 18. Good practices in production: 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 M. Newly addition in revised schedule M. | 19. Good practices in quality control: 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- |
| Computerized systems are not available in existing schedule M. New addition in revised schedule M. | 20. Computerised systems: |
| (29) Site Master File. –The licensee shall prepare a succinct document in the form of a Site Master File containing specific and factual Good Manufacturing Practices about the production and/or control of pharmaceutical manufacturing preparations carried out at the licensed premises. It shall contain the following: – 29.1 General information, – 29.2 Personnel. – 29.3 Premises. – 29.4 Equipment. – 29.5 Sanitation. – 29.6 Documentation. – 29.7 Production. – 29.8 Quality Control. – 29.9 Loan licence manufacture and licensee. – 29.10 Distribution, complaints, and product recall. – 29.11 Self-inspection. – 29.12 Export of drugs. – | Appendix-I Site Master File: The licensee shall prepare a succinct document in the form of a ‘Site Master File’ containing specific and factual Good Manufacturing Practices about the production or control or both of pharmaceutical manufacturing preparations carried out at the licensed premises. It shall contain the following, namely General information:- Personnel:- Premises:- Equipment:- Sanitation:- Documentation:- Production:- Quality Assurance and Control:- Manufacture under loan licence and licensee:- Distribution, complaints, and product recall:- Self-inspection:- Export of drugs:- |
| PART I-A SPECIFIC REQUIREMENTS FOR THE MANUFACTURE OF STERILE PRODUCTS, PARENTERAL PREPARATIONS (SMALL VOLUME INJECTABLES AND LARGE VOLUME PARENTERALS) AND STERILE OPHTHALMIC PREPARATIONS. | PART II SPECIFIC REQUIREMENTS FOR THE MANUFACTURE OF STERILE PRODUCTS, PARENTERAL PREPARATIONS (SMALL VOLUME INJECTABLES AND LARGE VOLUME PARENTERALS), AND STERILE OPHTHALMIC PREPARATIONS |
| General Building and Civil Works. – Air Handling System (Central Air-Conditioning). Environmental Monitoring Garments. Sanitation Equipment. Water and Steam Systems – Manufacturing Process – Form-Fill-Seal Technology or Blow, Fill-Seal Technology. – Product Containers and Closures. Documentation | General considerations:- Quality control:- Sanitation:- Manufacture of sterile preparations:- Processing: Sterilization: Personnel:- Premises: Equipment: Finishing of sterile products:- |
| Not available in existing schedule M. New addition under Part III in revised schedule M for Hazardous substances such as Sex Hormones, Steroids or | PART III Specific requirements for manufacturing of pharmaceutical products containing hazardous substances such as sex hormones, steroids (anabolic, Androgenic), or cytotoxic substances |
| Cytotoxic substances. | Introduction:- Risk assessment:- Product protection:- Personal Protection Equipment and Breathing Air Systems:- Environmental protection:- Facility layout:- Air-handling systems:- Air-Handling Units (AHU):- Personnel decontamination systems:- Effluent treatment:- Maintenance:- Qualification and validation:- |
| Not available in existing schedule M. New addition under Part IV in revised schedule M for Biological Products. | PART IV Specific Requirements For Manufacture Of Biological Products |
| Principles and general considerations:- Pharmaceutical quality system and quality risk management:- Personnel:- Starting materials:- Seed lots and cell banks:- Premises and equipment:- Containment:- Clean rooms:- Production:- Campaign production:- Labelling:- Validation:- Quality Control:- Documentation (batch processing records):- Use of animals:- Complaints:- Product recalls: | |
| Not available in existing schedule M. New addition under Part V in revised schedule M for | PART V SPECIFIC REQUIREMENTS FOR RADIOPHARMACEUTICAL |
| Radiopharmaceutical Products | PRODUCTS |
| Principles:- Personnel:- Premises and equipment:- Production:- Labelling:- Production and distribution records:- Quality assurance and quality control:- | |
| Not available in existing schedule M. New addition under Part VI in revised schedule M for Phytopharmaceuticals | PART VI SPECIFIC REQUIREMENTS FOR PHYTOPHARMACEUTICALS |
| General:- Quality assurance in the manufacture of Phytopharmaceuticals:- Good manufacturing practices for Phytopharmaceuticals:- Sanitation and hygiene:- Qualification and validation:- Complaints:- Product recalls:- Contract production and analysis:- Self-inspection:- Personnel:- Training:- Personal hygiene:- Premises:- Equipment:- Materials:- Reference samples and standards:- Documentation:- The general principles for documentation are set out in Part I. Specifications:- Finished phytopharmaceuticals:- Plant preparations:- Processing instructions:- Good practices in production:- Good practices in quality control:- | |
| Not available in existing schedule M. | PART VII |
| New addition under Part VII in revised schedule M for Investigational Pharmaceutical Products for Clinical Trials in Human | SPECIFIC REQUIREMENTS FOR THE MANUFACTURE OF INVESTIGATIONAL PHARMACEUTICAL PRODUCTS FOR CLINICAL TRIALS IN HUMANS |
| General considerations:- Quality assurance:- Validation:- Complaints:- Recalls:- Personnel:- Premises and equipment:- Materials:- Documentation:- Production:- Quality control:- Shipping, returns, and destruction: | |
| PART I-B SPECIFIC REQUIREMENTS FOR MANUFACTURE OF ORAL SOLID DOSAGE FORMS (TABLETS AND CAPSULES) | PART VIII SPECIFIC REQUIREMENTS FOR MANUFACTURE OF ORAL SOLID DOSAGE FORMS (TABLETS AND CAPSULES) |
| General Sifting, Mixing, and Granulation. Compressions (Tablets) Coating (Tablets) Filling of Hard Gelatin Capsule. Printing (Tablets and Capsules) Packaging (Strip and Blister) | General:- Sifting, Mixing, and Granulation. Compressions (Tablets) Coating (Tablets) Filling of Hard Gelatin Capsule Printing (Tablets and Capsules) Packaging (Strip and Blister) |
| General The processing of dry materials and products creates problems of dust control and cross-contamination. Special attention is, therefore, needed in the design, maintenance, and use of premises and equipment in order to overcome these problems. Wherever required, enclosed dust control manufacturing systems shall be employed. Suitable environmental conditions for the products handled shall be maintained by installation of air-conditioning wherever necessary. Effective air extraction systems, with discharge points situated to avoid contamination of other products and professes shall be provided. Filters shall be installed to retain dust and protect the factory and local environment. Special care shall be taken to protect against subsequent contamination of the product by particles of metal or wood. The use of metal detector is recommended. Wooden equipment should be avoided. Screens, sieves, punches and dies shall be examined for wear and tear or for breakage before and after each use. All ingredients for a dry product shall be sifted before use unless the quality of the input material can be assured. Such sifting shall normally be carried out at dedicated areas. Where the facilities are designed to provide special environmental conditions of pressure differentials between rooms, these conditions shall be regularly monitored and any specification results brought to the immediate attention of the Production and Quality Assurance Department which shall be immediately attended to. Care shall be taken to guard against any material lodging and remaining undetected in any processing or packaging equipment. Particular care shall be taken to ensure that any vacuum, compressed air, or air-extraction nozzles are kept clean and that there is no evidence of lubricants leaking into the product from any part of the equipment. | General:- The processing of dry materials and products creates problems of dust control and cross-contamination. Special attention is, therefore, needed in the design, maintenance, and use of premises and equipment in order to overcome these problems. Wherever required, enclosed dust control manufacturing systems shall be employed. Suitable environmental conditions for the products handled shall be maintained by installation of air conditioning, wherever necessary. Effective air extraction systems, with discharge points situated to avoid contamination of other products and processes shall be provided. Filters shall be installed to retain dust and to protect the factory and local environment. Special care shall be taken to protect against subsequent contamination of the product by particles of metal or wood. The use of metal detector is recommended. Wooden equipment shall be avoided. Screens, sieves, punches and dies shall be examined for wear and tear or for breakage before and after each use. All ingredients for a dry product shall be sifted before use unless the quality of the input material can be assured. Such sifting shall normally be carried out at dedicated areas. Where the facilities are designed to provide special environmental conditions of pressure differentials between rooms, these conditions shall be regularly monitored and any deviation shall be brought to the immediate attention of the Production and Quality assurance departments. Care shall be taken to guard against any material lodging and remaining undetected in any processing or packaging equipment. Particular care shall be taken to ensure that any vacuum, compressed air or air-extraction nozzles are kept clean and that there is no evidence of lubricants leaking into the product from any part of the equipment. 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. 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. The corridor shall be maintained at a higher pressure than the cubicles, and the cubicles at a higher pressure than atmospheric pressure. Highly potent products shall be manufactured under a pressure cascade regime that is negative relative to atmospheric pressure. The pressure cascade for each facility shall be individually assessed according to the product handled and the level of protection required. The building structure shall be given special attention to accommodate the pressure cascade design. Ceilings and walls, close-fitting doors, and sealed light fittings shall be in place, to limit ingress or egress of air. 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. Low-pressure differentials may be acceptable when airlocks (pressure sinks or pressure bubbles) are used to segregate areas. The effect of room pressure tolerances shall be calculated and taken into consideration. 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. Manual control systems, where used, shall be set up during commissioning, with a set point marked, and shall not change unless other system conditions change. Airlocks can be important components in setting up and maintaining pressure cascade systems and also to limit cross-contamination. 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. 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 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. Central dust extraction systems shall be interlocked with the appropriate air-handling systems, to ensure that they operate simultaneously. Room pressure differential between adjacent cubicles, which are linked by common dust extraction ducting, shall be avoided. 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 from flowing back in the opposite direction in the event of component failure or airflow failure. 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’s 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 color 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. 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. 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. Maximum and minimum room temperatures and relative humidity shall be appropriate. Alert and action limits on temperatures and humidity shall be set, as appropriate. 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 unnecessary installation and running costs. 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. Precautions shall be taken to prevent moisture migration that increases the load on the HVAC system. Humidity control shall be achieved by removing moisture from the air or adding moisture to the air, as relevant. Dehumidification (moisture removal) may be achieved by means of either refrigerated dehumidifiers or chemical dehumidifiers. Duct material in the vicinity of the humidifier shall not add contaminants to air that will not be removed by filtration further downstream. Air filters shall not be installed immediately downstream of humidifiers, as moisture on the filters could lead to bacterial growth. Cold surfaces shall be insulated to prevent condensation within the clean area or on air-handling components. When specifying relative humidity, the associated temperature shall also be specified. Chemical driers using silica gel or lithium chloride are acceptable, provided that they do not become sources of contamination. Wherever possible, dust or vapor contamination shall be removed at the 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. Point-of-use extraction shall be either in the form of a fixed high-velocity extraction point or an articulated arm with a movable hood or a fixed extraction hood. 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 dust in the ducting. The required transfer velocity shall be determined by the density of the dust (the denser the dust, the higher the transfer velocity shall be, e.g., 15–20 m/s). 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. 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 vapors from the room. Typically, in a room operating with turbulent airflow, the air shall be introduced from ceiling diffusers, located at the door entry side of the room, and extracted from the rear of the room at a low level to help give a flushing effect in the room. Correct flushing of the rooms may be verified by airflow visualization smoke tests. When dealing with particularly harmful products, additional steps, such as handling the products in glove boxes or using barrier isolator technology, shall be used. 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. Where the powders are not highly potent, the final filters on a dust exhaust system shall be fine dust filters with a filter classification of 5μ. 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. 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. When wet scrubbers are used, the dust slurry shall be removed by a suitable means, e.g., a drainage system or waste removal contractor. 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. Where necessary, additional filtration may be provided downstream of the dust collector. 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. Fumes shall be removed by means of wet scrubbers or dry chemical scrubbers (deep-bed scrubbers). Wet scrubbers for fume removal normally require the addition of various chemicals to the water to increase the adsorption efficiency. 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. The type and quantity of the vapors to be removed shall be known to enable the appropriate filter media, as well as the volume of media required to be determined. There shall be no risk of contamination or cross-contamination (including by fumes and volatiles) due to recirculation of air. 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. 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. Re-circulation of air from areas where pharmaceutical dust is not generated such as secondary packing may not require HEPA filters in the system. 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. Air-containing dust from highly toxic processes or solvents or flammable vapors shall never be recirculated into the HVAC system. 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. Areas such as airlocks, change rooms, and passages, shall be designed so that the required pressure cascades can be achieved. Detailed diagrams depicting pressure cascades, air flow directions, and flow routes for personnel and materials shall be prepared and maintained. 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). 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):- |
| 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 SPECIFIC REQUIREMENTS FOR THE MANUFACTURE OF ORAL LIQUIDS (SYRUPS, ELIXIRS, EMULSIONS, AND SUSPENSIONS) | PART IX SPECIFIC REQUIREMENTS FOR MANUFACTURE OF ORAL LIQUIDS (SYRUPS, ELIXIRS, EMULSIONS AND SUSPENSIONS) Note.- Good Manufacturing Practices for Pharmaceutical Products: The main 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 | 4. Manufacturing:- |
| PART I-D SPECIFIC REQUIREMENTS FOR MANUFACTURE OF TOPICAL PRODUCTS i.e. EXTERNAL PREPARATIONS (CREAMS, OINTMENTS, PASTES, EMULSIONS, LOTIONS, SOLUTIONS, DUSTING POWDERS AND IDENTICAL PRODUCTS) | PART X SPECIFIC REQUIREMENTS FOR MANUFACTURE OF TOPICAL PRODUCTS i.e., EXTERNAL PREPARATIONS (CREAMS, OINTMENTS, PASTES, EMULSIONS, LOTIONS, SOLUTIONS, DUSTING POWDERS 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 SPECIFIC REQUIREMENTS FOR THE MANUFACTURE OF METERED-DOSEINHALERS (MDI) | PART XI SPECIFIC REQUIREMENTS FOR MANUFACTURE OF METERED– DOSE– INHALERS (MDI) Note.– The Good Manufacturing Practices for pharmaceutical products: The 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:- |
| 6. Sanitation | 6. Sanitation:- |
| 7. Equipment | 7. Equipment:- |
| 8. Manufacture | 8. Manufacture:- |
| 9. Documentation:- | |
| PART I-F SPECIFIC REQUIREMENTS OF PREMISES, PLANT AND MATERIALS FOR MANUFACTURE OF ACTIVE PHARMACEUTIAL INGREDIENTS (BULK DRUGS). This Part has been restructured in revised schedule M with maximum requirement as the existing part was elaborated with minimum content/requirements. | PART XII SPECIFIC REQUIREMENTS FOR MANUFACTURE OF ACTIVE PHARMACEUTICAL INGREDIENTS Note — Good Manufacturing Practices for pharmaceutical products: Main principles as given in Part I shall be complied for the manufacture of API. In addition to these requirements, the following specific requirements shall also be followed, namely:— |
| Building and Civil Works. Sterile Products. Utilities / Services. Equipment Design, Size, and Location. In-Process Controls. Product Containers and Closures | Introduction:- General Scope |
| 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- 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 labeling, 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 labeling of APIs and intermediates:- 9.1. General 9.2. Packaging materials 9.3. Label issuance and control 9.4. Packaging and labeling 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- 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 REQUIREMENTS OF PLANT AND EQUIPMENT | PART XIII 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- |
| 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:- |
References:
- Medicines: Good manufacturing practices-[World Health Organization(who.int)]
- Health Ministry notifies revised Pharma manufacturing rules under schedule M to ensure quality control-[The Hindu]
- Govt notifies revised schedule M guidelines for pharma manufacturing units-[ET Healthworld(.com)]
- Gazzete Notification by CDSCO
