How much do you know about positive sealing samples!

The definition of positive control samples in the United States Pharmacopoeia USP:

Positive control samples refer to packaging with known intentional defects. The positive control samples used for the development and validation of leak testing methods should be replicated based on material structure, packaging assembly, and component technology. Positive control samples are used during the development and validation of leak testing methods. Some methods also require the use of positive control samples during routine testing.

What are the positive samples?

1. Laser Drill

2. Glass micropipette

3. Micro tube

4. Wire

5. Type defect

Analysis of each positive sample

Laser drilling (preferred and commonly used method): It is the most capable of simulating real leaks, maintaining the geometric properties of the holes unchanged, and does not require the introduction of other substances that may affect leak detection, such as wires, pipes, epoxy resins, which can be used in various materials. Glass, stainless steel, polymers, and hole diameters can be accurately measured and calibrated, but the preparation cost is high. Commonly used for hard packaging of controlled bottles, such as color water method, microbial challenge method, quality extraction method, vacuum attenuation method, etc.

Glass micro burette: convenient preparation, with a pore size as low as 0.1 μ m. The pore size is uniform, but fragile. Before and after preparation, it is necessary to use a microscope to confirm whether the tip has been damaged. It is difficult to ensure the sealing around the glass micropipette and the packaging wall is intact, and residual air can interfere with the test. Commonly used in packaging of large infusion bottles, molded bottles, etc., such as color water method, microbial challenge method, quality extraction method, vacuum attenuation method, etc.

Microtubes: Wide aperture range, greater than 0.2 μ m. The pore size is uniform, but the length is larger than the actual leakage hole, and the geometric shape differs greatly from the actual leakage hole. It is commonly used in color water method, microbial challenge method, quality extraction method, vacuum attenuation method, etc. for packaging of large infusion bottles, molded bottles, etc.

Line: Easy to prepare, inexpensive, with a wide range of defect sizes, it can be used for the preparation of positive samples between the glass wall and piston of syringes. However, it may produce gas, liquid, and microbial leakage properties that are significantly different from actual defects. The size of the leakage hole is influenced by many factors, and it is necessary to ensure that the line is not damaged during the sealing process, and the pore size cannot be determined, making it less applicable.

In the consistency evaluation of injection generic drugs, the study of the sealing integrity of drug packaging containers requires the use of measured standard leak samples as positive control samples. The commonly used preparation method for positive control samples is also the preferred method in the pharmaceutical industry - laser drilling method.