SOP for Preparing Lyophilized Formulations for Reconstitution

Standard Operating Procedure for Preparing Lyophilized Formulations for Reconstitution

1) Purpose

This SOP outlines the procedure for preparing lyophilized formulations that are intended to be reconstituted with a diluent before administration, ensuring the product remains stable, safe, and effective upon reconstitution.

2) Scope

This SOP applies to formulation scientists, production operators, and QA personnel involved in the preparation of lyophilized formulations for reconstitution, such as vaccines, monoclonal antibodies, and other injectable products.

3) Responsibilities

Formulation Scientists: Responsible for developing the lyophilized formulation that is stable upon reconstitution.
Operators: Responsible for the preparation and lyophilization of the formulation as outlined in the Batch Manufacturing Record (BMR).
QA: Responsible for verifying that the formulation meets specifications after reconstitution and ensuring proper documentation.

4) Procedure

4.1 Preparation of Formulation for Lyophilization

4.1.1 Equipment Setup

4.1.1.1 Ensure that all equipment (e.g., mixers, filtration systems) is cleaned, sanitized, and calibrated before use.
4.1.1.2 Prepare sterile containers for the formulation and maintain aseptic conditions throughout the process.

4.1.2 Formulation Preparation

4.1.2.1 Weigh the required active ingredient(s) and excipients using a calibrated balance according to the BMR.
4.1.2.2 Dissolve the active ingredient in a suitable buffer or solvent (e.g., saline, WFI) and stir until fully dissolved.
4.1.2.3 Add excipients, stabilizers, or cryoprotectants if necessary,

and mix until homogeneous.

4.2 Filtration and Lyophilization

4.2.1 Filtration

4.2.1.1 Filter the prepared solution using a sterile 0.22-micron filter to remove any particulates.

4.2.2 Filling and Lyophilization

4.2.2.1 Fill sterile vials with the filtered solution under aseptic conditions and freeze at -80°C before transferring to the lyophilizer.
4.2.2.2 Run the lyophilization cycle as specified in the BMR, monitoring temperature and pressure throughout.

4.3 Reconstitution Testing

4.3.1 After lyophilization, perform reconstitution tests by adding the specified diluent (e.g., saline) to ensure the product dissolves completely and quickly without visible particulates.
4.3.2 Measure pH and osmolarity of the reconstituted product to ensure it meets specifications.

4.4 Documentation

All steps, including formulation preparation, filtration, filling, lyophilization parameters, and reconstitution test results, must be recorded in the Lyophilized Formulations Logbook and verified by QA.

5) Abbreviations

BMR: Batch Manufacturing Record
WFI: Water for Injection

6) Documents

Lyophilized Formulations Logbook

7) References

Pharmacopoeial guidelines for lyophilized products and reconstitution testing

8) SOP Version

Version 1.0

Annexure

Lyophilized Formulations Logbook Template


  
    Date
    Formulation Name
    Batch No.
    Volume Filled
    pH
    Reconstitution Time
    Operator Initials
    QA Verification
  
  
    DD/MM/YYYY
    Formulation Name
    Batch Number
    Volume in mL
    pH Value
    Time in Minutes
    Operator Name
    QA Initials