Other devices (e.g., the plastic-film-feeding device) and their corresponding functions (e.g., the plastic-film-feeding function)
should follow GEP but do not require qualification.
In principle, qualifications are carried out after GEP are applied. But the stages from design qualification (DQ) to operational
qualification (OQ) can be carried out in parallel with GEP according to a prior plan to avoid duplicate application or backtracking.
Direct factors are classified as dynamic factors (e.g., the plate temperature of the heating device) and static factors (e.g., the shape and size of the forming die). Dynamic factors are further classified as either being subject to process
control or not. The overall classification of direct factors is as follows:
- Class 1: Dynamic factors that affect quality
- Class 1-A: Dynamic factors subject to process control
- Class 1-B: Dynamic factors not subject to process control
- Class 2: Static factors that affect quality.
Class 1-A factors can be changed when the system is in operation. They should be observed, recorded, and adjusted so that
they stay within the predefined control range.
Class 1-B factors cannot be changed when the system is in operation. They should be set or adjusted in advance of operation.
Class 2 factors (e.g., material, configuration, and surface finish) are fixed when the system is constructed and, in principle,
do not change afterward.
Devices used to measure and control the dynamic factors and computerized control devices must be calibrated and validated,
respectively. Calibration and computerized-system validation should occur before the start of OQ, which is the third stage
The following precautions are important for constructing medical manufacturing systems and should all adhere to GMP:
- Protection against foreign substances
- Ensuring the correct product is packaged
- Protection against cross contamination.
These precautions relate chiefly to the working environment, working control, and maintenance checks. They can be taken independently
of the systems. Therefore, the functions and devices related to the items above are not subject to qualification and should
simply follow GEP.
Direct factors of blister-filling and packaging systems
Quality of blister products.
Blister packages should protect their contents (e.g., tablets) to control their stability, dissolution, and disintegration.
This article takes the protective function of blister packages as one element of the required quality for blister products.
The important elements of product protection are appropriate web thickness, which prevents vapor or oxygen-gas ingress, and
proper sealing, which maintains airtight pockets (see Figure 1).
Figure 1: The manufacturing process of a blister pocket. (All figures are courtesy of the authors and the Japan Society of
Pharmaceutical Machinery and Engineering.)
Criteria for screening the functions.
The following criteria should be used to identify the devices and parts of blister-filling and packaging systems that are
- Whether the given function affects web film thickness
- Whether the given function affects the seal quality.