following storage or interruption.

2. Scope

This SOP applies to Analytical Method Development (AMD) scientists evaluating the performance of nasal sprays, metered-dose inhalers (MDIs), or other pressurized or pump-based delivery devices under initial and post-interruption usage conditions.

3. Responsibilities

• Analytical Scientist: Conducts the priming and repriming tests and records results.
• QC Analyst: Assists in dose collection and ensures environmental conditions are controlled.
• QA Executive: Reviews the test data and validates the method for implementation.

4. Accountability

The Head of Analytical Method Development is accountable for ensuring method accuracy, adherence to regulatory guidance, and fitness-for-purpose in evaluating device readiness after storage.

5. Procedure

5.1 Definitions

1. Priming: Initial activation of the device to fill metering chamber and enable consistent dose delivery.
2. Repriming: Re-activation of the device after an extended period of non-use to restore uniform dosing.

5.2 Apparatus and Setup

1. Dose collection system (e.g., DUSA)
2. Analytical balance and HPLC system (if applicable)
3. Controlled room temperature and humidity (23 ±2°C, 50 ±5% RH)

5.3 Priming Evaluation

1. Select 3–6 units from the batch for testing.
2. Shake device and actuate into a waste container until consistent spray is observed (usually 3–5 actuations).
3. Start dose collection from the first actuation after priming is complete.
4. Collect next 3 actuations and measure delivered dose.
5. Compare these doses with the labeled claim.

5.4 Repriming Evaluation

1. After priming, store devices horizontally for 14 days (or label-specific duration).
2. Without shaking, actuate and record first spray — should show reduction in dose.
3. Reprime as per label instructions and collect 3 doses after repriming.
4. Evaluate recovery of uniformity in doses post-repriming.

5.5 Analytical Measurement

1. Analyze collected samples using validated HPLC method or gravimetric analysis (for spray weight).
2. Calculate:
   
   Delivered Dose (mg) = Sample Peak Area / Standard Peak Area × Standard Concentration × Dilution Factor

5.6 Acceptance Criteria

1. Dose after priming: 85–115% of label claim.
2. Reprimed dose recovery within ±10% of primed dose values.
3. RSD of triplicate sprays ≤ 6.0%.

5.7 Documentation

1. Record device ID, actuation count, duration of storage, and assay results.
2. Include observations of spray pattern or anomalies.

6. Abbreviations

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

7. Documents

1. Priming and Repriming Data Log – Annexure-1
2. Storage Log Sheet – Annexure-2
3. Validation Summary Report – Annexure-3

8. References

• FDA Guidance: Nasal Spray and Inhalation Solution Product Quality Testing
• USP <601>: Aerosols, Nasal Sprays, and Metered-Dose Inhalers
• 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	Reema Joshi	Anil Verma	Sunita Reddy
Designation	Analytical Scientist	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: Priming and Repriming Data Log

Device ID	Primed Dose (mg)	Reprimed Dose (mg)	% Difference	RSD (%)	Status
NS-PRM-001	0.102	0.099	2.9%	3.5	Pass

Annexure-2: Storage Log Sheet

Device ID	Storage Start Date	Storage End Date	Condition	Verified By
NS-PRM-001	01/05/2025	15/05/2025	23°C / 50% RH	QA Officer

Annexure-3: Validation Summary Report

Priming and repriming evaluation method validated for nasal spray NS-25. Results met acceptance limits. Doses recovered after 14-day storage showed 98% of initial dose. Method deemed robust and reproducible.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Revised to include RSD criteria and storage log annexure	Annual Review & Compliance Update	Sunita Reddy
14/03/2022	1.0	Initial SOP Release	New SOP	QA Head