In the pharmaceutical industry, the integrity of every vial, syringe, or cartridge is essential. A breach in a container closure system can compromise sterility, jeopardize patient safety, and trigger costly recalls or regulatory actions. For these reasons, Container Closure Integrity Testing (CCIT) has become a cornerstone of product development and quality assurance.
But not all CCIT methods are created equal. The industry is steadily moving away from archaic, probabilistic methods, like dye ingress, that provide limited data, prone to human error, and inherently subjective; factors which lead to lower levels of quality assurance. Instead, regulators and manufacturers are embracing deterministic methods, which deliver science-based, quantifiable results.
That’s where PTI’s Life Science Services program comes in. Built around the principles of USP <1207>, Life Science Services provides a complete, end-to-end framework for implementing deterministic CCIT solutions across the entire product lifecycle.
A Lifecycle Approach to CCIT through Life Science Services
1. Feasibility Studies: Every product-package system has unique challenges, from fill volume to material properties. Life Science Services begins with feasibility testing and test method selection to determine which deterministic CCIT method, such as vacuum decay, is best suited to reliably detect leaks of regulatory and clinical concern. This early stage work helps de-risk development by confirming the method’s applicability and alignment with USP <1207> before resources are heavily invested.
2. Equipment Installation and PQ (Aligned with USP <1058>): When clients deploy CCIT equipment, proper implementation is critical. Our team manages installation and qualification in full compliance with USP <1058> Analytical Instrument Qualification, covering IQ, OQ, and PQ. This ensures that instruments are installed, operated, and performing as intended, bridging the gap between laboratory feasibility and routine GMP use.
To further support compliance, the systems we implement operate on 21 CFR Part 11 compliant software, providing secure user access, audit trails, and data integrity. This makes results generated not only scientifically rigorous, but also fully defensible in global regulatory submissions.
3. Initial Recipe Creation: No two packaging configurations are the same. Recipe creation is where instrument parameters are defined that allow clear separation between conforming and leaking samples. By using both positive controls (with engineered microdefects) and negative controls (representative of finished product), we create a robust method foundation tailored to each client’s product- package.
4. Method Development: Development is where science meets rigor. Our experts stress-test the method against multiple defect sizes and package variables, using statistically appropriate control schemes, to ensure all needed method validation parameters can be met. This provides the data-driven assurance that the method is not just functional, but also resilient under real-world conditions.
5. Method Validation: Finally, PTI’s Life Science Services validates the method in alignment with USP <1207> and ICH Q2(R2), confirming that it meets critical performance attributes:
- Accuracy and Precision – Consistency in detecting and differentiating leaks
- Specificity – Clear separation between leaking and intact packages
- Detection Limit – Sensitivity down to defect sizes as small as a few microns
- Ruggedness and Robustness – Reliability across analysts, days, and deliberate parameter shifts
Validation establishes the scientific and regulatory credibility needed for routine QC and long-term lifecycle use.
Why Deterministic CCIT Matters
Adopting deterministic CCIT isn’t just about checking a regulatory box. It’s about aligning quality strategy with modern science:
- Regulatory Confidence: USP <1207>, USP <1058>, and 21 CFR Part 11 compliance provide a complete framework for global acceptance.
- Patient Safety: Reliable leak detection safeguards sterility and product efficacy.
- Operational Efficiency: Non-destructive methods reduce waste, allowing tested samples to remain in circulation.
- Lifecycle Assurance: From development through commercial stability, validated CCIT methods provide ongoing protection against integrity risks.
PTI’s Commitment
Through PTI’s Life Science Services, our mission is simple: to help safeguard sterile medicines by building CCIT programs that are scientifically sound, regulatory-ready, and operationally practical. By guiding our clients from feasibility to PQ to validation, we close the loop, ensuring that container closure integrity is not just tested, but proven.