CCIT Regulatory Background:
On October 21, 2020, CDE issued a notice on the "Technical Guidelines for Sealing Research of Chemical Injection Packaging Systems (Trial)".
Clear requirements are put forward for the verification of packaging sealing systems. No less than two methods (one of which is the microbial challenge method) are required to verify the sealing of the packaging. At the same time, continuous testing is carried out during the process verification and stability stages of the packaging products to ensure that the sealing of the packaging system is intact throughout the entire life cycle of the product.
How to choose a reliable deterministic detection method? We will maximize the product's scope of application and detection limit sensitivity!
The five deterministic methods recommended in the Technical Guide are introduced and compared:
| Detection Methods | Rationale | Scope of application | Common packaging types | Detection limit | shortcoming |
| High voltage discharge method | By releasing 8-30KV high voltage electricity to the package and detecting the current changes at both ends of the package | The product is conductive and the packaging is relatively non-conductive | Soft bags, BFS, ampoules | ≧1μm | The scope of application is limited and the detection limit is affected by the packaging form and product conductivity |
| Laser headspace analysis | Based on headspace gas detection and analysis, it can indirectly reflect packaging leakage | It has certain headspace conditions, such as N2, CO2 or vacuum packaging, and the packaging container needs to be transparent | Controlled vials and ampoules | ≧0.1 μm |
Indirect response to packaging leakage, requiring multiple/multiple time point detection and analysis |
| Mass extraction method | Detection of packaging leakage rate under vacuum conditions μg/min | Applicable to all packaging forms and products of conventional chemical injections | Vials, ampoules, infusion bags, prefilled, BFS and almost all other packaging types | ≧1μm | Single supplier brand |
| Vacuum decay method | Detecting package leakage pressure difference under vacuum conditions | Applicable to most chemical injection packaging forms and products. Not applicable to solution preparations containing oils, organic solvents, and high viscosity products | Almost all rigid containers such as vials, ampoules, prefilled bottles and some PP infusion bottles | ≧2μm | The detection limit is greatly affected by the large size of the packaging and the soft bag packaging. Usually the detection limit of the soft bag is >15μm |
| Pressure decay method | Detecting package leakage under pressurized conditions | Only applicable to solid preparations in rigid containers, not applicable to solution preparations | Freeze-dried/powder injection vials | ≧2μm | Limited scope of application |
Technical reference: USP1207.2
