Viewpoint: X-ray inspection – quality assurance for pharmaceuticals

The primary function of x-ray inspection is contaminant detection of a wide range of foreign bodies including metal, glass, mineral stone and high-density plastics. Simultaneously, x-ray systems perform valuable in-line quality checks including counting components, identify missing or broken products, monitoring fill levels, checking for damaged packaging and detecting agglomerates such as flavour and powder lumps.

Pharmaceutical manufacturers often express concerns about the potential impact of x-ray inspection on their products. However, studies have consistently shown that the quantity and energy of x-rays used during product inspection are minimal, and the duration of exposure is extremely brief. For example, tablets undergoing x-ray inspection are typically exposed to low-energy x-rays for less than 0.2 seconds. In comparison, the dose of background radiation that pharmaceutical products receive while on the shelf, in transit or during consumer ownership is significantly higher than the levels delivered by an end-of-production line x-ray inspection system.

The US Food and Drug Administration (FDA) acknowledges that the dose levels received by objects passing through an x-ray inspection system are lower than the dose of background radiation received in a single day. Furthermore, and perhaps most crucially, the FDA asserts that there is no known danger in consuming medicines that have undergone x-ray inspection.[1]

Scientific studies have also been conducted to evaluate the effects of x-ray inspection on pharmaceutical products. For instance, researchers at the Department of Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University in Japan conducted a study on the effect of x-rays on the pharmaceutical quality of drug tablets. The study exposed acetaminophen, ioxoprofen and mefenamic acid tablets to varying x-ray doses, ranging from 0.34mGy to 300Gy.

These doses were significantly higher than those delivered by typical x-ray inspection systems. The evaluation of samples through formulation tests revealed that exposure to x-rays did not affect the pharmaceutical quality of the drug tablets. The exposed samples exhibited similar characteristics in dissolution, disintegration and hardness tests as control samples that were not exposed to x-rays.

Additionally, when combined with accelerated temperature and humidity tests equivalent to six months of exposure, x-ray exposure did not affect the pharmaceutical quality of the samples. This study concluded that x-ray exposure at levels much higher than those encountered during product inspection had no significant effect on the efficacy or other properties of the drug tablets.[2]

Another study, conducted by Robert Bosch Packaging Technology and the PHAST Society for Pharmaceutical Quality Standards, exposed model pharmaceutical substances, tramadol HCl and nifedipine, to x-ray radiation for a period of 2 hours. This extended exposure time was significantly longer than the fraction of a second typically used during industrial x-ray inspection. However, no degradation was observed in either substance after the 2-hour exposure period.[3] 

These scientific studies collectively demonstrate that x-ray inspection at the levels used in pharmaceutical manufacturing does not significantly affect the quality or efficacy of the products. While not all formulations have been studied, the low doses of x-ray radiation involved in x-ray inspection systems are well below the levels of naturally occurring background radiation and do not pose a risk to product integrity.

Regulatory bodies worldwide have established guidelines and requirements for pharmaceutical manufacturing including the Good Manufacturing Practice (GMP), the Good Distribution Practice (GDP), and manufacturers who want to comply with these regulations while maintaining the highest level of quality assurance.

Some manufacturers may have concerns specific to their products or processes that they believe require additional scrutiny. These concerns may stem from the complexity of the formulation, sensitivity to radiation or unique packaging requirements. Conducting their own tests allows manufacturers to address these specific concerns and gain confidence in the integrity of their products.

Utilising the technology of x-ray inspection systems, manufacturers can start to see significant benefits on their production line. It eliminates the need for redundant testing, which can be costly and time-consuming, allowing manufacturers to streamline their processes and focus on other critical aspects of production. By trusting in the proven capabilities of x-ray inspection systems, manufacturers can benefit from the expertise and experience of the producers of these systems, who have a deep understanding of the technology and its application in the pharmaceutical industry.

New applications

Traditionally, x-ray inspection in the pharmaceutical industry has been primarily used for specific applications, such as verifying the presence of tablets or needles. However, when employed at the end of the production line, x-ray inspection becomes one of the most versatile and comprehensive inspection tools available to manufacturers. Unlike other inspection methods, it has the capability to inspect a diverse range of products, regardless of their shape or packaging.

One of the significant advantages of x-ray inspection is its ability to penetrate various materials, including metals, glass, high-density plastics and rubber. This capability enables the detection of dense foreign bodies that may contaminate pharmaceutical products. Metal fragments, glass shards or other foreign objects that could compromise product quality and safety can be reliably identified and removed from the production line, preventing them from reaching the consumers.

As mentioned, in addition to contaminant detection, x-ray inspection allows for other critical quality checks. It can verify the completeness and integrity of packaged products, detecting missing or damaged items within the packaging. This level of scrutiny is essential in the pharmaceutical industry, where missing components or damaged products can have severe consequences for consumers. For instance, checking the presence of needles in glucose monitoring systems, verifying their functionality is crucial, as a faulty device could have fatal implications for diabetic patients. By detecting and preventing the distribution of defective or compromised products, x-ray inspection plays a crucial role in upholding a company's brand image and reputation.

One of the notable advantages of x-ray inspection is its versatility. It is particularly beneficial for pharmaceutical manufacturers who commonly use metalised film or aluminium-backed blisters as packaging methods. X-ray inspection systems can effectively inspect products contained within these packaging materials and check their integrity and quality.

By leveraging x-ray inspection technology at the end of the production line, pharmaceutical manufacturers can enhance their quality control processes and minimise the risk of contaminated or defective products reaching the marketplace – making it an invaluable tool in upholding product safety and maintaining consumer trust.

Enhancing compliance

X-ray inspection systems also contribute to compliance with regulations and provide traceability. Manufacturers can access comprehensive quality data and export it as needed, providing transparency and accountability. It also enables creation of individual images of each product, complete with date and time stamps, providing information to support due diligence that quality checks have been completed. Easy retrieval facilitates easy tracking, while the reporting capabilities allow for detailed shift and production reports, including the number of rejected items. This level of documentation aids the validation process and ensures that approved settings remain unchanged during production, minimising the risk of errors or deviations.

By embracing x-ray inspection as an additional tool in their quality assurance processes, pharmaceutical manufacturers can elevate their standards, mitigate risks, and have confidence that high quality products are entering the market. The time has come for the industry to recognise the immense value x-ray inspection brings and embrace its potential for a safer and more reliable pharmaceutical supply chain.

Mike Pipe is head of global sales & product management, Mettler-Toledo Safeline x-ray

[1] https://www.fda.gov/radiation-emitting-products/security-systems/frequently-asked-questions-cabinet-x-ray-systems

[2] Kazuaki Uehara, Tatsuaki Tagami, Itaru Miyazaki, Norikazu Murata, Yoshifumi Takahashi, Hiroshi Ohkubo & Tetsuya Ozeki (2015) Effect of X-ray exposure on the pharmaceutical quality of drug tablets using X-ray inspection equipment, Drug Development and Industrial Pharmacy, 41:6, 953-958, DOI: 10.3109/03639045.2014.917093

[3] Martin Vogt, Elke Sternberger-Rutzel, Manuel Birke & Christoph Jacobs (2012) Influence of X-ray radiation as PAT method on the model substances tramadol HCl and nifedipine compared to the influence of UV-Vis radiation, TechnoPharm 2, Nr. 3, 1–12