Achieving excellence in quality and efficiency standards has become the talking point within the pharma industry according to Phil Stevenson of Sepha. Whether it's blue-chip pharmaceutical companies looking to increase their competitiveness against the threat of generics or the indigenous pharmaceutical companies in developing countries looking to increase their export product to the lucrative western market, it's on everybody’s lips.
With many big pharma companies moving production to lower labor cost economies to reduce overhead, manufacturing plants in countries such as India and China have become more aware of the quality standards that have been set by regulatory authorities and what is expected by western consumers. This has resulted in a transfer of information from many of these companies to indigenous pharmaceutical companies, which have then sought or achieved approval from regulatory authorities such as the FDA. Such approval allows the manufacture of drugs for markets in the west - a lucrative source of export revenue for the countries concerned. According to London research company Global Insight, India’s pharmaceutical drug market has the potential to reach $25 billion in 2010. The Chinese pharmaceutical industry has also seen significant growth of 16.72 percent over the last few decades.
This threat, accompanied by thin product pipelines and the rise of generics, has caused traditional pharmaceutical companies to seek new ways to become leaner and to create blocks to stop others from joining their market sector. This can be achieved through efficiency savings and a zealous concentration on quality.
It is when scrutinizing quality that package integrity comes into focus. It is vital to ensure pharmaceutical products are fit for its purpose at the point of use. If this is compromised, the product can be become ineffective, and at worst, lead to patient mortality, and, at least, potentially giving rise to very expensive recalls. Unfortunately, packaging integrity can become compromised all too easily.
Logistical failures are the simplest to detect. Packs can be printed with the wrong identification or with incorrect batch or date code information. Such errors are generally easy to spot and can be resolved using inspection systems, or costly human intervention.
Defects in the packaging itself are more difficult to detect. Blister-pack lidding material can contain micron holes created during manufacture. This is more prevalent with thin foils, less than 0.02 µm thick, where as little as 40% of the surface area is guaranteed hole free.
Even if the lidding material could be guaranteed at point of supply, damage can occur during set up or as a result of tool damage on the packing line.
According to Charles Barker, chief technical officer of Sepha, holes as small as 10 µm can cause deterioration in products sensitive to moisture, and atmospheric gasses can contaminate product whenever hole sizes reach 50 µm or more.
Producers of oncology drugs have also expressed concern that chemical substances from compromised packaged drugs could be dangerous to operators handling the drugs from production line to patient.
Given that holes less than 50 µm in packages are generally undetectable to the human eye, a method of testing is required.
Methylene Blue Dye Test
The time-honored, and by far the most popular, method of leak testing packaged product is the infamous methylene blue dye test. This test is messy, destructive, and subjective and really does not befit the technical excellence associated with modern pharmaceutical manufacturing. Yes, when appropriately set up this method can identify holes as small as 10 microns, but the subjective nature of the test and variance in setup across packaging lines can lead to validation issues. This, combined with the needless destruction of good packs and the intensive reliance on the operator, leads Sepha to believe that the time has come to replace this method with a more suitable alternative.
Research carried out by Sepha has revealed that the top pharmaceutical manufacturers are focusing their efforts on improving efficiencies and reducing labor costs throughout their production line. In this respect, the blue dye test and other destructive methods of leak testing are wholly unsatisfactory, as they are operator-intensive, time consuming, and messy.
One of the attractions of the blue dye test is the low cost of the equipment required. In it’s basic form this consists of a vacuum pump, a bucket, a stopwatch, and colored liquid. At first glance this may look very attractive, but the real cost of running the blue dye test is seen only when the cost of disposing the waste and lost production is considered.
For example, on a packaging line producing 14-tablet blisters, running two 8-hour shifts would waste $4,480 per day based on the tablets costing one dollar each and 10 packs being tested every half hour. This cost is before disposal of tested product is even considered.
Sepha identified the need to develop a leak test for packaging that would not compromise the product or the packaging. When subjected to a reduction in pressure, flexible packaging will move. This can be observed in the change in packaging shape or the force exerted by the packaging on an adjacent body. In these cases if a large (gross) hole exists, the packaged atmosphere will be quickly drawn out under vacuum and little change in packaging shape will be observed. Where small holes exist, there will be an immediate change in the packaging, but over time, as the trapped atmosphere leaks out, the package reverts back to its original shape.
For sachets and pouches, Sepha has developed the PakScan, a machine that tests multiple packs using load cells to measure the force generated by the packaging under vacuum. Sepha machines are designed to isolate this force, measuring peak force and rate of change to establish presence of both large and small holes down to 10 microns.
While effective for sachets and pouches, Sepha believes that force measurement is ineffective for blister packs, which require multiple load cells for a single pack, constraining machine capacity, flexibility, and ease of calibration.
More effective for blisters are methods that utilize cameras or high-accuracy laser measurement to monitor deflection of the lidding foil. Sepha’s BlisterScan utilizes a single laser that moves across blister pockets to measure their deflection, enhanced by altering pressure levels during testing. This system allows multiple packs to be tested in a single test
Laser Scanning Technology
Both the BlisterScan and PakScan provide a fully validatable alternative to the methylene blue dye test. Along with the cost benefits, these machines also produce useful batch data that can be used to monitor performance and improve line efficiencies.
Every pharmaceutical manufacturer is faced with the challenge of competing in a growing marketplace where quality assurance is paramount and in an economy that requires organizations to continually cut costs. When analyzing quality and efficiencies on their production line, manufacturers must come to a decision on package leak testing. As demonstrated above, Sepha believes that the subjective and wasteful methylene blue dye test has too many limitations to be acceptable in the current market. With other non-destructive means of testing available, there is no longer any need to rely on such a primitive and subjective form of testing. Up-and-coming pharmaceutical companies seeking regulatory approval can use non-destructive leak-testing machines to provide quality standards and to show a commitment to maintain and ever improve those standards. Blister, sachet, and pouch packaging are widely used throughout the industry to provide excellent product protection; therefore, it is essential that the means of testing these packages doesn’t undermine their protection. Now is the time to reduce waste and increase confidence in package leak testing.