Applying PAT Principles to Blister Packaging
FEA Modeling, 3-D Scanning, and SEM are all part of a “right first time” approach to pharmaceutical packaging.
By Peter J. Schmitt, President, Montesino Associates, LLC
Blister packaging is a key component of pharmaceutical packaging globally as well as in the U.S. However, traditional or legacy pharmaceutical process control systems are not easily applied to blister packaging.
At a time when the need for higher barrier packaging, and equipment speed and precision is growing exponentially, legacy tools are two-dimensional and of low resolution. It’s a classic case of 20th century technology being used to address 21st century problems.
Only by developing robust three-dimensional, high resolution processes and controls can blister packaging move to a more scientific basis and to a full and robust implementation of the principles of process analytical technology (PAT). Montesino aims to bring PAT to pharmaceutical packaging and has allied itself with several companies in both materials and equipment as it seeks to develop three-dimensional, high resolution services for pharmaceutical packaging.
Prodieco Pharmaceutical Components (PPC) of Dublin, Ireland, a company whose focus has shifted from computer industry tooling to pharmaceutical tooling, introduced Montesino to 3D scanning, measuring and rendering and to a better understanding of the manufacture of high quality tooling for blister packaging. Amcor Flexibles licensed Montesino Black Box FEA simulation software for pharmaceutical blister packaging.
A wide variety of materials and equipment companies including Honeywell are working with Montesino to increase the scientific base of blister packaging and move out of the dark ages into a three-dimensional, high-resolution universe.Legacy Packaging
Until very recently, blister packaging relied on legacy process controls best thought of as two-dimensional and of low-resolution. Material barrier data was primarily discussed in terms of flat or unformed sheet data, tooling and machine drawings were two-dimensional and of very low-resolution (typically, they did not even include tolerances or the other crucial specifications required in any engineering drawing). Process control tests were either compendial like USP 671 which requires time and often is quite "low resolution" in terms of what the data finally means or very limited like the methylene-blue vacuum leak testing for seal integrity.
These tests offer neither the three-dimensional details nor the resolutions that would allow them to ensure package integrity. Two factors drove these conditions beyond their limits:
- A rise in the use of ICH accelerated stability testing conditions at 40°C, 65% relative humidity
- The development of new types of active pharmaceutical ingredients (APIs) and formulations that are highly sensitive to moisture and even to oxygen, UV, and other elements.
In other words, getting the barrier right is the single most important factor in developing packaging that will be able to pass stability tests the first time, every time.
While high barrier materials have been further developed and enhanced in recent years to satisfy the need for increased barrier, the tools used to form those materials and their barriers into the blister cavity or pocket lagged behind.
Specifically, the complex relationship between cavity or pocket design, tooling construction and materials, sealing technology and the impact of process conditions has been poorly understood due to limitations of available process control tools.The 3 Ds of Blister Packaging
Montesino first began to explore 3-D packaging in a joint development with PPC called 3DSmart
Starting with a scanning technology developed by PPC to qualify tooling cavities and dimensional tolerances, the two companies developed a technology that can scan, measure, and render tools or components of the blister packaging process into high-resolution three-dimensional drawings that can be compared to a much more robust set of specifications.
The second step in this process is to apply finite element analysis (FEA; see Figure 1 below), a technique that is practically unknown in the pharmaceutical industry, but widely applied in discrete manufacturing.
Just as most people will fly in airplanes that haven’t been “crash tested,” but developed almost entirely via simulation, “right first time” blister packaging can now be developed via modeling.
FEA, in particular, analysis using the Black Box platform, allows barrier and barrier conditions to be modeled precisely before any stability testing is done.
In the final step within the process, using an SEM microscope, microtome cross sections are used to measure and analyze the structure of high barrier formed blisters in a precise, visual and high resolution presentation.
Using this process, one no longer starts with a "flat sheet barrier" number and prays that the actual barrier formed in a cavity or pocket is correct. That barrier number and the decisions based on that number are now readily accessible.
It is widely known that chamfers, flat bottoms and sharp radii in tooling can all have an impact on the formed barrier of a blister cavity or pocket. However, the combination of 3DSmart, microtome cross- sections (see Figure 2 below) and FEA analysis has demonstrated that simple changes in these three areas can result in 40% more barrier in the formed cavity.
Applying science to blister packaging requires taking the tooling and package development process into three dimensions, and applying the “Three Ds” of blister packaging:
PAT and the Future of Packaging
- Designing the blister pack correctly from the beginning, using robust specifications for minimum sealing areas and dimensions, cavity or pocket design, or types of materials to be used in the tooling, pharmaceutical packaging can reach a new level of precision and quality.
- Debugging that design using 3-D scanning tools, pharmaceutical packaging can use science to verify that the designed blister is actually the manufactured blister.
- And by using the rendering of that blister pack in an industry standard 3-D format, pharmaceutical packaging can deploy a design across multiple sites, multiple machines, even multiple geographical locations.
The FDA-encouraged drive towards PAT and a scientific and risk-based approach to manufacturing will continue to drive change in blister packaging. While the three Ds of blister packaging are a huge step towards high-resolution, three-dimensional quality, PAT demands more. Packaging technology must evolve to meet these demands in the future.
|Figure 1. FEA, especially analysis using the Black Box platform, allows barrier and barrier conditions to be modeled precisely before stability testing is done.|
|Figure 2. Microtome cross-sections help to demonstrate that simple changes in chamfers, flat bottoms and sharp radii in tooling can result in 40% more barrier in the formed cavity.|