Positive Controls

What are Positive Controls and why are they essential?

Whenever sterile drug products are processed and packaged into containers, CCIT (Container Closure Integrity Testing) is required to confirm the products are correctly protected by their containers.

These tests are done on samples, taken from the filling line, at the start and at the end of a production batch, or at regular intervals during production.

CCIT validates the packaging process : only if the CCIT results are within specifications, the produced products can be released for distribution to patients.

CCIT itself is therefore part of the critical processes, acceptance or rejection of an entire production depends on its outcome. The validity of the testing process must therefore be verified regularly : is the CCIT instrument effectively accepting or rejecting correctly, in other words : rejecting all possible integrity flaws, and accepting all properly sealed containers ?

This is done by testing a set of Reference Parts with known defects, simulating various possible integrity breaches that may occur in the packaging process. Each of these cases must be correctly detected, i.e. return a positive test result.
These specially prepared test parts are therefore called Positive Controls.

Negative Controls are also used : these are containers that are sealed correctly and therefore should return a negative test result, no integrity flaw is detected.

Examples of Positive and Negative Controls

ASC Instrument is able to prepare Positive and Negative Controls for any drug product container type, vials, syringes, ampules, cryotubes, etc., but also for sachets, pouches, blisters.

Various techniques may be used to create these artificial defects, such as laser-drilling, insertion of capillaries and use of porous element calibrated leaks.

Each Positive Control container's leak is measured and delivered with its Certificate, stating the exact leak flow rate of the incorporated integrity flaw.

The introduced flaws are in the µm range, and potentially subject to clogging, hence the need for a yearly verification of their flow rate.