Standard Operating Procedure for Selection of Container Closure Systems for Prefilled Syringes
| Department | Formulation & Development |
|---|---|
| SOP No. | SOP/SIM/117/2025 |
| Supersedes | SOP/SIM/117/2022 |
| Page No. | Page 1 of 12 |
| Issue Date | 18/06/2025 |
| Effective Date | 20/06/2025 |
| Review Date | 18/06/2026 |
1. Purpose
To establish a standardized approach for evaluating and selecting appropriate container closure systems (CCS) for prefilled syringe (PFS) formulations to ensure product quality, safety, and compliance with regulatory requirements.
2. Scope
This procedure is applicable to
all sterile injectable products intended for filling in prefilled syringes at the formulation development and scale-up stage.
3. Responsibilities
- Formulation Development: Conducts compatibility studies and proposes appropriate container materials.
- Packaging Development: Sources, evaluates, and documents CCS materials.
- Quality Assurance: Reviews and approves CCS selection documentation.
4. Accountability
The Head of Formulation Development is accountable for initiating CCS studies. Head QA ensures compliance with applicable regulatory standards.
5. Procedure
5.1 Identify Product Requirements
- Review formulation properties: pH, ionic strength, viscosity, sensitivity to light/oxygen/moisture.
- Determine route of administration and dosage form characteristics.
5.2 Select Preliminary CCS Candidates
- Choose materials such as Type I borosilicate glass or cyclic olefin polymer (COP).
- Evaluate plungers, tip caps, and needle shields compatible with syringe barrel.
- Document vendor specifications and material certificates.
5.3 Compatibility Studies
- Conduct extractables and leachables (E&L) studies.
- Perform adsorption/absorption tests with API and excipients.
- Assess container closure integrity (CCI) and dimensional fit.
5.4 Functional Testing
- Verify glide force, break-loose force, needle retraction (if applicable), and needle guard mechanism.
- Conduct syringe plunger leakage and ease of assembly testing.
5.5 Regulatory and Pharmacopeial Compliance
- Ensure materials comply with USP <381>, USP <660>, EP 3.2.1, and relevant ISO standards.
- Request DMF (Drug Master File) from vendor wherever available.
5.6 Documentation
- Prepare CCS Selection Report (Annexure-1) with data from all studies.
- Maintain vendor qualification file and E&L profiles (Annexure-2).
- Archive compatibility test protocols, certificates of analysis, and test reports.
6. Abbreviations
- CCS: Container Closure System
- PFS: Prefilled Syringe
- CCI: Container Closure Integrity
- E&L: Extractables and Leachables
7. Documents
- CCS Selection Report – Annexure-1
- Vendor Qualification and E&L File – Annexure-2
- Compatibility Study Data Sheets – Annexure-3
8. References
- ICH Q3D – Elemental Impurities
- USP <1664>, <381>, <660>
- ISO 11040, ISO 11607
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | Formulation Scientist | Packaging Executive | Head QA |
| Department | Formulation Development | Packaging Development | Quality Assurance |
11. Annexures
Annexure-1: CCS Selection Report
Summarizes evaluation of different materials, compatibility data, and justification of selected system.
Annexure-2: Vendor Qualification and E&L File
Includes supplier details, certificates, E&L data, regulatory status, and reference documents.
Annexure-3: Compatibility Study Data Sheets
Comprehensive results of pH stability, interaction testing, light/moisture barrier studies, and plunger performance.
Revision History
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 15/12/2022 | 1.0 | Initial release | New development of prefilled syringe products | Head QA |
| 18/06/2025 | 2.0 | Incorporated ISO and extractables/leachables testing elements | Regulatory alignment | Head QA |