in compliance with this SOP and meets regulatory requirements. QA also reviews and approves the validation reports and all associated documentation.
Production Supervisors: Oversee the validation process, ensuring all steps are properly executed and providing necessary support to operators.
Validation Team: Responsible for designing the validation protocol, executing the validation runs, and analyzing the results.
Maintenance Personnel: Ensures that all equipment used in the manufacturing process, such as filling machines, assembly equipment, and testing apparatus, is calibrated and maintained.

4) Procedure

The following steps should be followed for the process validation of MDIs and DPIs:

1. Preparation for Validation:
1.1 Review batch records to identify critical process parameters (CPPs) for each step in the MDI and DPI manufacturing process.
1.2 Develop a process validation protocol, which includes objectives, scope, equipment, process flow, and personnel involved in the validation process.
1.3 Ensure that all equipment, such as formulation tanks, filling machines, assembly lines, and testing equipment, are properly calibrated and operational before initiating the validation process.

2. Validation Protocol:
2.1 Protocol Design: The validation protocol should be based on the formulation of the MDI or DPI and the specific manufacturing process.
2.2 Defining Acceptance Criteria: Establish acceptance criteria for critical parameters such as dose uniformity, particle size distribution (for DPIs), aerosol performance (for MDIs), and packaging integrity.
2.3 Risk Assessment: Perform a risk assessment to identify critical quality attributes (CQAs) and corresponding critical process parameters (CPPs). This will ensure potential risks to product quality are identified and mitigated.

3. Execution of Validation:
3.1 Formulation: Validate the formulation process to ensure the uniform mixing of active ingredients and excipients, and to ensure that the formulation meets the specifications for both MDIs and DPIs.
3.2 Filling: Validate the filling process for MDIs and DPIs to ensure that the correct amount of product is filled in each container, with consistent dose delivery for MDIs and appropriate powder filling for DPIs.
3.3 Assembly: Validate the assembly process, ensuring that the inhalers are correctly assembled, with proper valve placement for MDIs and appropriate capsule or blister configurations for DPIs.
3.4 Aerosol Testing (MDIs): Perform aerosol testing to ensure that the MDI generates the appropriate fine particle fraction (FPF) and meets the dose delivery requirements.
3.5 Particle Size Testing (DPIs): For DPIs, validate the particle size distribution of the powder to ensure the correct aerodynamic diameter for inhalation.
3.6 Packaging: Validate the packaging process to ensure that the inhalers are securely packaged to prevent contamination and that labeling complies with regulatory requirements.

4. Documentation and Reporting:
4.1 Record all data during the validation process, including batch records, equipment logs, process parameters, and testing results.
4.2 Ensure that all forms, reports, and certificates are completed and signed by the responsible personnel.
4.3 Perform statistical analysis on the collected data to assess process capability and confirm that the process consistently meets the acceptance criteria.
4.4 Prepare a final validation report summarizing the results, including any deviations from the acceptance criteria and corrective actions taken, if necessary.

5. Revalidation:
5.1 Revalidate the process if there are significant changes to the formulation, equipment, or critical process parameters.
5.2 Periodically conduct revalidation to ensure continued compliance with regulatory requirements and to confirm that product quality remains consistent.

5) Abbreviations

• QA: Quality Assurance
• CPP: Critical Process Parameter
• CQA: Critical Quality Attribute
• SOP: Standard Operating Procedure

6) Documents

• Process Validation Protocol
• Batch Production Records
• Equipment Calibration Logs
• Process Validation Reports
• Raw Material Certificates of Analysis
• Statistical Analysis Data

7) Reference

• International Council for Harmonisation (ICH) Q7: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
• FDA Guidance for Industry: Process Validation
• ISO 9001: Quality Management Systems – Requirements

8) SOP Version

Version 1.0 – Effective Date: DD/MM/YYYY

Annexure

Template 1: Formulation Process Record

Date	Time	Operator Initials	Formulation Batch	Remarks
DD/MM/YYYY	HH:MM	Operator Name	Batch Number	Process completed as per SOP

Template 2: MDI Filling Process Record

Batch No.	Filling Date	Volume per Canister	Operator Initials	Supervisor Signature
Batch Number	DD/MM/YYYY	Volume in mL	Operator Name	Supervisor Name

Template 3: DPI Filling Process Record

Batch No.	Filling Date	Fill Weight	Operator Initials	Supervisor Signature
Batch Number	DD/MM/YYYY	Weight in mg	Operator Name	Supervisor Name

Template 4: Aerosol Performance Testing Record (MDI)

Batch No.	Test Date	Fine Particle Fraction (FPF)	Delivered Dose	Operator Initials
Batch Number	DD/MM/YYYY	FPF in %	Delivered Dose in µg	Operator Name

Template 5: Particle Size Distribution (DPI)

Batch No.	Test Date	Particle Size Distribution	Operator Initials	Remarks
Batch Number	DD/MM/YYYY	Distribution Range (µm)	Operator Name	Pass/Fail

Template 6: Statistical Analysis Data

Sample ID	Test Type	Mean	Standard Deviation	Result
Sample Number	Test Name	Mean Value	Standard Deviation	Pass/Fail