Standard Operating Procedure for Management of CMC Queries From Regulatory Agencies

Department	Regulatory Affairs
SOP No.	RA/2026/731
Supersedes	NA
Page No.	1 of 10
Issue Date	14/04/2026
Effective Date	14/04/2026
Review Date	14/04/2028

Purpose

This Standard Operating Procedure (SOP) defines the systematic process for the management of Chemistry, Manufacturing, and Controls (CMC) queries received from Health Regulatory Agencies. It ensures timely, accurate, and compliant responses to regulatory queries, supporting continuous approval and market authorization maintenance of pharmaceutical products. This SOP supports regulatory compliance, document control, and quality assurance objectives by standardizing the workflow for query handling, tracking, reviewing, and archiving correspondence with regulatory authorities, thereby reducing risks of non-compliance and delays in regulatory decisions.

Scope

This SOP applies to all activities involving the receipt, assessment, drafting, reviewing, approval, submission, and archiving of CMC-related queries and deficiency letters issued by domestic and international health authorities. It covers all pharmaceutical dosage forms, product types, regulatory submission categories, and involved departments such as Regulatory Affairs, Quality Assurance, Quality Control, Manufacturing, and Technical Operations. This SOP excludes queries not related to CMC aspects and correspondence handled by other designated regulatory functions such as clinical or pharmacovigilance queries.

Responsibilities

The functional roles responsible for executing this SOP include:
– Regulatory Affairs Officers: Receive and log queries, prepare initial draft responses.
– Subject Matter Experts (e.g., QA, QC, Manufacturing): Provide technical input and review content.
– Regulatory Affairs Reviewers: Review and ensure scientific and regulatory accuracy.
– Quality Assurance: Review final responses for compliance with GMP and quality systems.
– Regulatory Affairs Manager: Provide final approval and submission authorization.
– Documentation Control Team: Ensure proper filing and record retention of all related documents.

Accountability

The Regulatory Affairs Head is accountable for ensuring the correct implementation, compliance, periodic review, escalation of issues, and effectiveness monitoring of this SOP within the organization.

Procedure

1. Receipt and Logging
Upon receipt of a CMC query or deficiency letter from a regulatory agency via official communication channels (email, eCTD platform, or courier), the Regulatory Affairs Officer shall log the document into the Query Tracking System with date/time of receipt, query origin, reference number, product details, and query deadline.

2. Preliminary Review & Assignment
Conduct an initial assessment to determine the nature and complexity of the query. Assign the query to the relevant subject matter experts (SMEs) such as QA, QC, Manufacturing, or Technical teams for input. Communicate the deadline and response format requirements to all stakeholders.

3. Preparation of Draft Response
Collect all necessary technical data, validation reports, batch records, and relevant documentation to formulate a comprehensive and evidence-based draft response. The Regulatory Affairs Officer consolidates inputs into a single coherent document, ensuring clarity, accuracy, and adherence to the regulatory format.

4. Internal Review and Quality Checks
The draft response shall be reviewed by designated reviewers from Regulatory Affairs, QA, and applicable functional departments to verify correctness and compliance with GMP, regulatory requirements, and company policy. Any comments or required corrections shall be incorporated through a formal change cycle.

5. Approval and Authorization
The final response document shall be authorized by the Regulatory Affairs Manager or designated approver before submission. Ensure all supporting documents, annexures, and required signatures are completed.

6. Submission to Regulatory Authority
Submit the approved response within the stipulated timeline using validated and secure regulatory submission platforms conforming to regulatory technology requirements. Confirm submission receipt and logging by the authority.

7. Documentation and Record Retention
Maintain all records related to the query, draft and final responses, communication logs, and evidence documents in controlled document management systems according to established retention schedules. Ensure traceability and accessibility for future audits or inspections.

8. Monitoring and Follow-up
Monitor the status of submitted responses for further feedback or closures. Escalate any non-compliance, missed deadlines, or regulatory changes impacting response strategies.

9. Continuous Improvement
Periodically review performance metrics such as response timelines, query closure rates, and audit findings to update procedures and training to enhance effectiveness and regulatory compliance.

Abbreviations

CMC – Chemistry, Manufacturing, and Controls
GMP – Good Manufacturing Practices
QA – Quality Assurance
QC – Quality Control
SME – Subject Matter Expert
eCTD – Electronic Common Technical Document
SOP – Standard Operating Procedure

Documents

Documents required specifically for managing CMC queries include:

1. CMC Query Logging Form (Annexure-1)
2. CMC Query Response Template (Annexure-2)
3. Query Tracking and Follow-up Log (Annexure-3)

References

– ICH Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
– FDA Guidance for Industry: Formal Meetings Between the FDA and Sponsors or Applicants
– EMA Guideline on the Content, Management and Archiving of the Dossier and Data Generated During the Evaluation of Medicine Applications
– Pharmaceutical Inspection Co-operation Scheme (PIC/S) GMP Guide
– Company Quality Manual and Document Control Policies

Version

1.0

Approval

Prepared By
Checked By
Approved By

Annexures

Annexure-1: CMC Query Logging Form

Purpose: To formally record receipt and tracking information for all CMC queries received from regulatory agencies.

Query Reference No.	RA2026-045
Date & Time of Receipt	10/04/2026 14:25
Regulatory Authority	Health Regulatory Agency X
Product Name	Product A – Oral Tablet
Dosage Form	Tablet
Query Deadline	24/04/2026
Query Summary	Request for additional validation batch data for manufacturing process.
Assigned To	QA Department
Logged By	Regulatory Affairs Officer
Comments	Urgent response required due to market launch timeline.

Annexure-2: CMC Query Response Template

Purpose: Standardized format for drafting responses to CMC queries ensuring clarity, completeness, and regulatory compliance.

Query Reference No.	RA2026-045
Date of Response	20/04/2026
To	Health Regulatory Agency X
From	Regulatory Affairs Department
Subject	Response to Query Regarding Validation Batch Data for Product A
Response Content	Following receipt of your letter dated 10/04/2026 requesting additional validation batch data, enclosed please find the detailed batch records, process validation reports, and stability data for Product A manufacturing process. This data confirms process consistency and product quality within specified limits. Should there be any further clarification needed, please contact our Regulatory Affairs department.
Attachments	Validation Batch Records, Stability Reports, Process Flow Diagrams
Prepared By
Reviewed By
Approved By

Annexure-3: Query Tracking and Follow-up Log

Purpose: To monitor status, follow-up actions, and closure of CMC queries throughout the lifecycle.

Query Ref No.	Date Received	Assigned To	Response Due	Response Submitted	Status	Remarks
RA2026-045	10/04/2026	QA Department	24/04/2026	20/04/2026	Closed	Response accepted by authority without further queries.
RA2026-054	05/04/2026	Manufacturing	19/04/2026	Pending	Open	Additional data collection in progress.

Revision History

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
14/04/2026	1.0	Initial issue	New SOP creation