SOP for Preparing Nasal Sprays for Elderly Patients

Standard Operating Procedure for Preparing Nasal Sprays for Elderly Patients

1) Purpose

This SOP provides detailed instructions for formulating nasal sprays designed for elderly patients. Elderly patients often have reduced nasal clearance, mucosal sensitivity, and may be more prone to side effects. Therefore, special attention must be paid to ensuring the formulation is both safe and effective for this demographic.

2) Scope

This SOP applies to all personnel involved in the formulation, preparation, testing, and packaging of nasal sprays for elderly patients at [Company Name].

3) Responsibilities

Operators: Responsible for following the guidelines for preparing formulations suitable for elderly patients, including proper dosing and excipient selection.
Quality Assurance (QA): Ensures the product meets efficacy and safety standards specifically for elderly patients.
Maintenance Team: Responsible for maintaining and calibrating equipment used for manufacturing nasal sprays for elderly patients.

4) Procedure

4.1 Selection of Ingredients

4.1.1 Elderly-Safe API and Excipients

Select active pharmaceutical ingredients (APIs) at doses suitable for elderly patients, who may have altered pharmacokinetics due to aging. Ensure the APIs are well tolerated and not prone to adverse effects like dizziness or hypertension.
Choose excipients that are non-irritating and compatible with the elderly’s sensitive nasal mucosa. Use preservatives and stabilizers that are generally recognized as safe (GRAS) for elderly patients.

4.1.2 Weighing of Ingredients

Weigh APIs and excipients using a calibrated balance, ensuring the accuracy of measurements within ±1%. Record all measured quantities in the Batch Manufacturing Record (BMR).

4.2 Mixing and Formulation

4.2.1 Preparing the Aqueous Phase

Dissolve excipients in Water for Injection (WFI) under gentle stirring to avoid air bubble formation, which may compromise nasal delivery.
Ensure the solution is at room temperature (20-25°C) and is free of foam.

4.2.2 Incorporating the API

Add the API to the aqueous phase while maintaining constant stirring. For hydrophobic APIs, use a surfactant to help disperse the API uniformly in the solution.
Record all mixing parameters such as stirring speed, time, and temperature in the BMR.

4.2.3 pH and Osmolality Adjustment

Measure the pH of the solution and adjust it to fall within the physiological range for nasal sprays (pH 5.5-7.0), which is safe for elderly nasal mucosa.
Ensure the osmolality is close to isotonic levels (280-320 mOsm/kg) to minimize irritation.
Document the pH and osmolality adjustment process in the BMR.

4.3 Filtration and Sterilization

4.3.1 Filtration Process

Filter the nasal spray formulation through a sterile 0.22-micron filter to ensure it is free from microbial contamination. Use a low-pressure filtration system to preserve the integrity of sensitive APIs.
Perform a filter integrity test post-filtration and record the results in the BMR.

4.4 Filling and Packaging

4.4.1 Filling Process

Fill the sterile formulation into calibrated nasal spray containers using a filling machine. Set the machine to dispense an appropriate dose volume for elderly patients (e.g., 100 µL per spray).
Check the fill accuracy by weighing 10 random filled containers. Ensure that the fill variance is within ±2% of the target volume. Record the results in the BMR.

4.4.2 Sealing and Packaging

Seal the containers with pre-sterilized caps or nozzles. Ensure that the packaging is easy to open, but child-resistant if necessary, as elderly patients may struggle with complex packaging.
Store the product in secondary packaging labeled with the appropriate storage conditions, batch number, and expiration date.

4.5 Quality Control Testing

4.5.1 API Content Testing

Test the content uniformity of the API in the nasal spray to ensure each dose delivers the correct amount of API. Perform this test on 10 randomly selected units.
Record the API content test results in the content uniformity log.

4.5.2 Stability Testing

Conduct stability testing under various environmental conditions (e.g., 25°C/60% RH and 40°C/75% RH) to ensure the formulation remains stable over its shelf life.
Document the stability test results in the stability testing log.

4.6 Documentation

Document all steps of the formulation, mixing, filtration, filling, and packaging processes in the BMR.
Ensure that QA reviews and approves all documents before the product is released for distribution.

4.7 Equipment Cleaning and Calibration

4.7.1 Equipment Calibration

Calibrate all equipment, including balances, pH meters, osmometers, and filling machines, as per the calibration schedule. Record the calibration data in the calibration log.

4.7.2 Cleaning Equipment

Follow the cleaning validation protocol to clean and sterilize all equipment used in the formulation process. Document the cleaning process in the cleaning log to ensure traceability and compliance.

5) Abbreviations, if any

API: Active Pharmaceutical Ingredient
QA: Quality Assurance
BMR: Batch Manufacturing Record
WFI: Water for Injection

6) Documents, if any

Batch Manufacturing Record (BMR)
Content Uniformity Log
Stability Testing Log
Calibration Log
Cleaning Log

7) References, if any

FDA Guidance for Drug Products for the Elderly
ICH Q1A – Stability Testing Guidelines

8) SOP Version

Version 1.0

Annexure

1. Content Uniformity Log Template


  
    Date
    Formulation
    API Content (mg/spray)
    Test Method
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Formulation Name
    API Content
    Method
    Operator Name
    QA Name

Date	Formulation	API Content (mg/spray)	Test Method	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	API Content	Method	Operator Name	QA Name

2. Stability Testing Log Template


  
    Date
    Formulation
    Storage Conditions
    Time Interval
    Stability Results
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Formulation Name
    Temperature and Humidity
    1 month, 3 months, etc.
    Pass/Fail
    Operator Name
    QA Name

Date	Formulation	Storage Conditions	Time Interval	Stability Results	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	Temperature and Humidity	1 month, 3 months, etc.	Pass/Fail	Operator Name	QA Name

3. Calibration Log Template


  
    Date
    Equipment ID
    Calibration Procedure
    Calibration Results
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Equipment Name/ID
    Procedure
    Pass/Fail
    Operator Name
    QA Name

Date	Equipment ID	Calibration Procedure	Calibration Results	Operator Initials	QA Approval
DD/MM/YYYY	Equipment Name/ID	Procedure	Pass/Fail	Operator Name	QA Name

4. Cleaning Log Template


  
    Date
    Equipment ID
    Cleaning Procedure
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Equipment Name/ID
    Procedure
    Operator Name
    QA Name