ensure dose consistency within and between units.

2. Scope

This SOP applies to all analytical scientists within the Analytical Method Development (AMD) department conducting uniformity testing of inhalation and nasal spray dosage forms during development, validation, and batch release activities.

3. Responsibilities

• Analytical Scientist: Executes the DDU testing using validated methods and approved apparatus.
• QC Analyst: Assists in sample preparation, weighing, and solution analysis.
• QA Executive: Reviews test data, validates results, and ensures compliance with regulatory limits.

4. Accountability

The Head of Analytical Method Development is accountable for the validity, reproducibility, and regulatory compliance of the DDU testing procedure.

5. Procedure

5.1 Apparatus and Equipment

1. DDU Sampling Apparatus (e.g., Dose Uniformity Sampling Apparatus – DUSA)
2. Vacuum source with flow regulator and trap
3. Analytical balance (0.1 mg sensitivity)
4. Volumetric flasks, HPLC vials, and appropriate diluent

5.2 Sample Selection and Preparation

1. Select 10–20 units from the batch based on statistical design.
2. Shake each unit as per manufacturer’s instructions (e.g., 10 times vertically).
3. Prime the device as recommended (e.g., 3 sprays to waste).

5.3 Dose Collection Procedure

1. Actuate device into DUSA for defined number of sprays (typically 1 spray per test per unit).
2. Rinse collection chamber with diluent and transfer to volumetric flask.
3. Make up to volume and analyze by validated HPLC or UV method.

5.4 Analytical Testing

1. Prepare standard solution of known concentration.
2. Run both standard and sample on validated HPLC system.
3. Calculate delivered dose using peak area ratio:
   
   Delivered Dose (mg) = (Sample Peak Area / Standard Peak Area) × Standard Concentration × Dilution Factor

5.5 Acceptance Criteria

1. All units must fall within 80–120% of label claim.
2. % RSD of delivered doses ≤ 6.0% for 10 units.
3. Any outlier to be justified or repeated as per protocol.

5.6 Validation Requirements

1. Validate method for:
   • Linearity (r ≥ 0.99)
   • Accuracy (90–110% recovery)
   • Precision (intra- and inter-day)
   • Robustness (variation in actuation, temperature)

5.7 Documentation

1. Maintain raw data printouts, chromatograms, instrument logs, and data sheets in Annexures.
2. Summarize data in DDU Validation Report with graphical representation.

6. Abbreviations

• DDU: Delivered Dose Uniformity
• DUSA: Dose Uniformity Sampling Apparatus
• HPLC: High Performance Liquid Chromatography
• RSD: Relative Standard Deviation

7. Documents

1. DDU Data Log – Annexure-1
2. DDU Sample Preparation Sheet – Annexure-2
3. DDU Validation Report – Annexure-3

8. References

• USP <601>: Aerosols, Nasal Sprays, Metered-Dose Inhalers
• FDA Guidance for Industry: Nasal Spray and Inhalation Solution Testing
• ICH Q2(R1): Validation of Analytical Procedures

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Nikita Shah	Rahul Chauhan	Sunita Reddy
Designation	Analytical Scientist	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: DDU Data Log

Unit No.	Delivered Dose (mg)	% of Label Claim	Status
1	0.101	101%	Pass
2	0.099	99%	Pass
3	0.103	103%	Pass

Annexure-2: Sample Preparation Sheet

Sample ID	Device	Number of Sprays	Diluent	Dilution Volume (mL)
DDU-NS001	NASAL-03	1	Water + MeOH	25

Annexure-3: DDU Validation Report

Delivered dose uniformity method for nasal spray metered device validated using HPLC at 220 nm. 10 units tested showed dose range 97%–104% of label claim, RSD 3.2%. Method considered suitable for routine and release testing.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Added robustness and validation criteria per FDA guidance	Annual Review and Regulatory Update	Sunita Reddy
15/04/2022	1.0	Initial SOP Release	New SOP	QA Head