Andrea Simonetti, Director Business Development, QA & Validation Manager – Bonfiglioli Engineering S.p.A., a TASI GROUP Company
Container Closure Integrity Testing (CCIT) for pharmaceuticals, has significant relevance in terms of quality, safety and correct functionality of drug products. Also, it is linked both to financial aspects and to the image of the manufacturing company.
In this context, the use of dye solutions, such as methylene blue, in combination with extended application of negative pressure levels (vacuum), is an industrial standard named Dye Ingress Test, that is widely used, throughout the pharmaceutical field, to determine containers integrity defects and to reject containers that do not conform to specifications. Dye Ingress Test, due to its destructive nature, does not allow complete examination of the entire production; for this reason, it is generally performed on samples, at regular intervals, during the production cycle. In reason of this, when containers, that do not conform to integrity specifications, are detected, the entire batch (or at least a substantial portion of it) is rejected. Therefore, none of the containers produced, between two successive sampling stages, are placed on the market, since real testing has not been performed and it is assumed that the integrity status is equal to that of the small sample examined. Furthermore, this approach is unquestionably linked to the subjectivity of operators, who visually inspect the reference containers, to check whether there is any dye solution inside them. Finally, further limitations, linked to the use of this approach, include the randomness of the process, the total cost and the low sensitivity of the measurement.
The use of non-destructive CCIT methods, removes the aforementioned limitations, allowing a targeted, objective and holistic investigation of the production. This guarantees the reduction of costs connected to reuse of tested samples, that cannot otherwise be placed on the market, thus helping to increase productivity, quality and company image.
This article, describes an innovative method for non-destructive CCIT, which is applied to ALU-ALU “blister” type pharmaceutical containers (Figure 1) with 10 cavities, hereafter referred to as Cij cells (i=1, j=10). Each of these cells, has a diameter of 17mm and contains 1 tablet for oral use.
Below is a case study, which aims to determine the reliability, repeatability and sensitivity of the method.
Figure 1. Blister Container
Description of the machine
Carrying out the case study, required the use of a “LF-BLI” automatic machine (see Figure 2), that is designed to perform CCIT on sachets or blister pharmaceutical containers and to be installed in laboratories or research and development departments. LF-BLI, comprises a hermetic testing chamber, inside which CCIT is performed (Figure 3) and is composed of:
a top mobile part, that supports the data acquisition system (S_ACQ) and can be moved manually between two positions, respectively opening and hermetic closure conditions, for loading and unloading containers undergoing CCIT
a bottom fixed part, that holds containers to be tested in position in a housing plate.
Figure 2. LF-BLI automatic machine
Figure 3. Testing Chamber
LF-BLI, is connected to a vacuum generation system (Pump) and is equipped with an electronic pressure regulator (EPR), that allows accurate monitoring and adjustment of the vacuum levels generated inside the testing chamber.
LF-BLI, also, provides the capability to test several containers at the same time, depending on their physical and dimensional characteristics. The machine, is equipped with a user interface (HMI) which can be used to configure the whole process and display the results of the CCIT by a graphic matrix.