Awareness Critical for Container Closure Components

Awareness Critical for Container Closure Components
The most important takeaway for participants of PDA’s 2017 PDA Container Closure, Devices and Delivery Systems: Compatibility and Material Safety Workshop can be summed up in one word: awareness. As the complexity of delivery systems and drug/device combination products increases, the task of qualifying components fit for use becomes especially challenging, necessitating greater awareness of regulatory requirements and current trends.

Microbial Ingress No Longer an Effective CCI Test Method

Microbial Ingress No Longer an Effective CCI Test Method
In the realm of pharmaceutical sciences, ensuring the integrity of parenteral container closures is paramount to maintaining product sterility and safety.
The methods employed for container–closure integrity (CCI) testing play a crucial role in this process, influencing regulatory compliance and product quality assurance. At its core, CCI testing aims to prevent the ingress of contaminants into pharmaceutical products, particularly in parenteral formats where sterility is non-negotiable. Microbial-ingress testing was a practical mode for evaluating a container’s ability to maintain sterility. The integrity of a closure directly impacts the product's shelf life, efficacy and, overall, patient safety. Historically, the evaluation of sterility and CCI were tightly intertwined, and microbial-ingress testing was the gold standard to establish CCI and product sterility.
With the advent of new drug products, delivery systems and inspection technologies, the microbial-ingress test method has lost scientific relevance for CCI.

Container Closure Integrity Testing: CDER Perspective

Container Closure Integrity Testing: CDER Perspective
Container Closure Integrity Testing
(CCIT) in CDER
• Evolution of CCIT
• CDER’s Expectations for Microbial Ingress Testing
• Microbial Ingress Case Study

Impact of Container Closure on Drug Safety

Impact of Container Closure on Drug Safety
The following activities are expected to be conducted during the
development and validation phases:
1. Selection of container closure (CC) suitable to the product
2. Selection of the container closure integrity test method, including limit of
detection:
a. CCIT test method suitable for the type of container closure
b. CCIT limit of detection able to detect “leaks of concern” (those that may
result in impact to product quality and safety)
c. Validation of the CCIT, including selection of breached positive controls,
parameters, etc.
3. Demonstration of CCI after worst‐case process conditions:
a. Worst‐case vial crimping
b. Worst‐case sterilization cycles
4. Demonstration of CCI after secondary assembly (PFS into autoinjectors, assembly
of plunger rod, finger flange, safety device, etc.)
5. Demonstration of CCI after shipping

Non‐Destructive Container Closure Integrity Testing

Non‐Destructive Container Closure Integrity Testing
Prefilled Syringe
• 1 mL Glass Syringe, Staked Needle
• Holes laser drilled in barrel wall
– Air flow through defect correlated to standard orifices
– Grouped as either 5, 10 or 15 μm (± 2 μm)