Key Notes on Revised Schedule M: API Part-6

Last Updated on July 9, 2025 by The Health Master

API Part-6

Key notes for API Part-6 for compliance under revised Schedule M are outlined below.

Continued from: Key Notes on Revised Schedule M: API Part-5

Good Manufacturing Practices for API Part-6

Manufacturing API Part-6: A Comprehensive Guide

Navigating Schedule M Part XII: Essential Documentation and Record-Keeping for API

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-6

Schedule M Part XII: manufacturing and Control of Active Pharmaceutical Ingredients (APIs)

Key Points:

Schedule M revised requirements: API Part- 6.

Schedule-M Part- XII: Additional requirements for manufacture of Active Pharmaceutical Ingredients (APIs in India)

This article covers additional requirements for the manufacture of Active Pharmaceutical Ingredients (APIs) in India.

The key requirements are as follows:

1. Validation:

• Establish a Robust Validation Policy: This policy should encompass the company’s approach to validating production processes, cleaning procedures, analytical methods, in-process controls, computerized systems, and personnel responsibilities.

• Identify Critical Parameters: Determine the critical quality attributes of the API and identify the process parameters that can significantly impact these attributes.

• Focus on Critical Operations: Efforts for the validation must be done on operations that are crucial for the quality and efficacy of the APIs.

2. Documents for validation:

• Develop a detailed process: A written validation process is very important. Specific procedures should be mentioned for the validation of a particular process, including acceptance criteria, the type of validation (prospective, retrospective, or concurrent), and the number of process runs.

• Prepare a detailed report: A validation report should be prepared that includes summarizing the results, deviations, and conclusions.

• Variations in the documents: Any deviations from the validation process must be documented with proper justification.

3. Qualification:

• Conduct Qualification of the equipment: the qualification of critical equipment and ancillary systems must be done before initiating validation process.

This procedure involves:

o Design Qualification (DQ): Verifying that the equipment design is suitable for its intended purpose.

o Installation Qualification (IQ): Verifying that the installed equipment complies with design specifications and manufacturer recommendations.

o Operational Qualification (OQ): Verifying that the equipment performs as intended throughout its operating range.

o Performance Qualification (PQ): Verifying that the equipment performs effectively based on the approved process method.

4. Approaches to Process Validation:

• Prospective Validation: This is the preferred approach, conducted before commercial distribution of the API.

• Concurrent Validation: Applicable when limited production data is available.

• Retrospective Validation: Can be used for well-established processes with a consistent history of quality.

5. Process Validation Program:

• Determine the Number of Runs: The number of process runs for validation depends on the process complexity. Three consecutive successful batches are generally recommended for prospective and concurrent validation.

• Control Critical Parameters: Monitor and control critical process parameters during validation studies.

• Confirm Impurity Profile: Ensure the impurity profile of the API is within specified limits and comparable to historical data.

6. Periodic Review:

• Regularly Evaluate Validated Systems: Periodically review validated systems to ensure continued validity. Revalidation may not be necessary if no significant changes have occurred and the system consistently produces high-quality material.

7. Cleaning Validation:

• Validate Cleaning Procedures: Validate cleaning procedures, especially in situations where contamination risk is high.

• Reflect Actual Usage: Cleaning validation should reflect actual equipment usage patterns.

• Establish Residue Limits: Establish practical and verifiable residue limits based on the most deleterious residue.

8. Analytical Method Validation:

• Validate Analytical Methods: Validate all analytical methods unless they are included in recognized pharmacopoeias.

• Consider ICH Guidelines: Validation should consider characteristics outlined in ICH guidelines on analytical method validation.

• Qualify Analytical Equipment: Ensure appropriate qualification of analytical equipment.

9. Change Control:

• Establish a Formal System: Implement a formal change control system to evaluate all changes that may impact API production and control.

• Document All Changes: Document all changes to raw materials, specifications, analytical methods, facilities, equipment, and processing steps.

• Assess Impact: Evaluate the potential impact of each change on API quality.

• Implement Changes Effectively: Ensure all affected documents are revised after implementing approved changes.

• Evaluate First Batch: Evaluate the first batch produced under the modified process.

• Consider Stability Impact: Evaluate the potential impact of critical changes on retest or expiry dates.

• Notify Dosage Form Manufacturers: Notify manufacturers of the current dosage form about changes that may impact API quality.

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

Note: This article aims to provide a general overview of Schedule M Part XII. It is essential to consult the official guidelines and seek expert advice for specific interpretations and implementation.

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Compiled by:
Rakesh Dahiya, Asstt. State Drugs Controller, FDA Haryana

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Next: Key Notes on Revised Schedule M: API Part-7 ….coming soon

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