Key Notes on Revised Schedule M: API Part-2

Last Updated on March 31, 2025 by The Health Master

API Part-2

Key notes for API Part-2 for compliance under revised Schedule M are outlined below.

Continued from: Key Notes on Revised Schedule M: API Part-1

Good Manufacturing Practices for API Part-2

Manufacturing API Part-2: A Comprehensive Guide

Let’s understand Schedule-M Part XII: A Guide for Active Pharmaceutical Ingredients (API) Manufacturing.

Schedule-M Part XII gives the specific requirements for Good Manufacturing Practices (GMP) guidelines for the manufacturing of Active Pharmaceutical Ingredients in India.

This specific article gives the details for ensuring the quality, safety, and efficacy of APIs used in the manufacturing of pharmaceutical products.

Key Notes on Revised Schedule M: API Part-2

Key Points

Building and Facility Requirements:

Design and Construction:

• Buildings and facilities must be designed for easy cleaning, maintenance, and safe operations.
• Adequate space is crucial to prevent contamination and mix-ups between materials.
• Outdoor equipment placement is acceptable if the equipment itself provides sufficient protection.
• The flow of materials and personnel should be carefully designed to minimize contamination risk.
• Clearly defined areas are needed for receiving raw materials, quarantining materials, sampling, storing, and conducting production, packaging, and laboratory operations.
• Proper washing and toilet facilities are essential for personnel.
• Laboratory areas should be separated from production areas to maintain accuracy and prevent contamination.

Utilities:

• Utilities like steam, gases, and air conditioning must be qualified and monitored to ensure product quality.
• Adequate ventilation, air filtration, and exhaust systems are crucial to minimize contamination.
• Recirculated air must be carefully controlled to prevent contamination risks.
• Pipework must be clearly identified to prevent contamination.
• Drains must be designed to prevent back-siphonage.

Water Quality:

• Water used in API manufacturing must meet appropriate quality standards.
• Process water should generally meet WHO drinking water guidelines.
• If higher water quality is required, specific specifications for chemical and microbial attributes must be established.
• Water treatment processes must be validated and monitored.
• Water used in the final isolation and purification steps for non-sterile APIs intended for sterile FPPs must be carefully controlled for microbial contamination.

Containment:

• Dedicated production areas are required for highly sensitizing materials like penicillins and cytotoxic drugs.
• Measures must be in place to prevent cross-contamination between dedicated areas.
• Production activities involving highly toxic non-pharmaceutical materials must be strictly separated from API production.

Lighting:

• Adequate lighting is essential in all areas to facilitate cleaning, maintenance, and proper operations.

Sewage and Refuse:

• Sewage, refuse, and other wastes must be disposed of safely and in a sanitary manner.

Sanitation and Maintenance:

• Buildings and facilities must be properly maintained and kept clean.
• Written procedures for cleaning and sanitation must be established.
• Procedures for using rodenticides, insecticides, and other pest control measures must be in place.

Process Equipment Requirements:

Design and Construction:

• Equipment must be appropriately designed, sized, and located for its intended use, cleaning, and maintenance.
• Equipment surfaces must not alter the quality of APIs.
• Equipment should only be used within its qualified operating range.
• Major equipment and processing lines must be appropriately identified.
• Substances associated with equipment operation (e.g., lubricants) must not contaminate APIs.
• Closed or contained equipment should be used whenever possible.
• Current drawings must be maintained for equipment and critical installations.

Equipment Maintenance and Cleaning:

• Schedules and procedures for equipment preventive maintenance must be established.
• Written cleaning procedures must be detailed and include information on cleaning methods, materials, and personnel.
• Equipment must be cleaned, stored, and sanitized to prevent contamination.
• Non-dedicated equipment must be thoroughly cleaned between productions of different materials.
• Acceptance criteria for cleaning residues must be defined.
• Equipment must be clearly identified as to its contents and cleanliness status.

Calibration:

• Critical equipment must be calibrated according to written procedures and an established schedule.
• Calibrations must be performed using traceable standards.
• Calibration records must be maintained.
• Instruments that do not meet calibration criteria must not be used.
• Deviations from calibration standards must be investigated.

Computerized Systems:

• GMP-related computerized systems must be validated.
• Appropriate installation and operational qualification must be demonstrated.
• Controls must be in place to prevent unauthorized access and data loss.
• Written procedures must be available for the operation and maintenance of computerized systems.
• Changes to computerized systems must be made according to a change control procedure.
• A backup system must be in place to prevent data loss.

Note: This is a summary, and manufacturers should carefully review the full text of Schedule-M Part XII for detailed guidance and specific requirements.

Disclaimer: This information is for general knowledge and informational purposes only and does not constitute legal or professional advice.

Please note: This information is for general guidance only and may not be exhaustive. Refer to the official regulations and any applicable guidance documents for specific requirements and interpretations.

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Compiled by:
Rakesh Dahiya, SDCO cum Licensing Authority, FDA Haryana

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Next: Key Notes on Revised Schedule M: API Part-3 ….coming soon

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