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CHEMICALS & PHARMACEUTICALS


ADDRESSING X-RAY SAFETY CONCERNS


Pharmaceutical manufacturers continue to have concerns over the effect that x-ray inspection could have on their medicines. But are they right to be concerned? Mike Pipe, Head of Global Sales of Mettler-Toledo Safeline X-ray, says research shows x-ray inspection does not compromise pharma products


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-ray technology is an effective way of inspecting pharmaceutical products for a range of factors, among them being certain kinds of contaminant, fill levels, damaged or missing components, and damaged packaging.


The European Medicines Agency (EMA) has issued rules regulating the exposure of drugs to x-ray, in its document “The use of Ionising Radiation in the Manufacture of Medicinal Products” (3AQ4a). This guidance advises that irradiation may be used for microbial decontamination, sterilisation or other treatments in the manufacture of medicinal products, and that manufacturers doing so should refer to the Guide to Good Manufacturing Practice (Volume IV of “The Rules Governing Medicinal Products in the European Union”) and in particular to Annex 12, on ionising radiation used in the manufacture of medicinal products.


The Annex explains the responsibilities and processes required for using ionising radiation with medicinal products, including different types of irradiation, validation and documentation process, and dosimetry to measure absorbed doses.


However, there is often still a sticking point – a nagging doubt that some manufacturers have about installing x-ray inspection on their pharma production and packing lines. It is the worry that inspecting products using x-rays will cause the product’s therapeutic efficacy to be compromised. This means that radiation from x-ray inspection will


28 SEPTEMBER 2024 | PROCESS & CONTROL


fundamentally alter chemical compounds and break the covalent bonds of the molecules that constitute the drug. At Mettler-Toledo, we are asked about this issue often. Any responsible manufacturer would want to ensure that its product reaches the end user in optimum condition. Our answer to this kind of query, however, is threefold. • radiation levels used in this type of inspection are incredibly low and are directed upon each product for a fraction of a second. • the research so far carried out in this area (see below) supports the hypothesis that there is no evidence of damage to pharmaceutical products after x-ray product inspection1


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• we can reassure customers that, as a responsible manufacturer, we would be happy to work with them on testing and analysing what effect, if any, our inspection technology would have upon their specific pharmaceutical product.


One aspect of this subject that needs to be understood at the outset by pharmaceutical manufacturers is the nature and intensity of the radiation produced by x-ray systems for product inspection. There are many natural sources of radiation that surround us, including uranium or radon gas. Wherever you may be, you are subjected to some level of this “background” radiation.


Alongside these natural sources of radiation are man-made sources, which include medical equipment, security scanning and inspection systems such as those used in x- ray inspection. Those created within inspection


equipment are only transmitted when the equipment is switched on. They can be turned on and off, unlike background radiation. Provided that safety guidelines are followed, there is no risk to the operators of such x-ray inspection systems.


In respect of the effect of these x-rays on pharmaceutical products, typically, products such as tablets are exposed to x-ray inspection energy of around 0.11 milligray (mGy) for less than 0.2 seconds. A frequent airline flyer will be exposed to around 200µSv (microsieverts) per year, around double the dosage size (0.1 mGy equals 100 µSv). The US Food and Drug Administration (FDA) has estimated that the dose level received by an object going through an x-ray inspection system is lower than the background radiation dose level that the same object will be exposed to over a single day. The FDA also states on its website that “there are no known adverse effects from eating food, drinking beverages, using medicine or applying cosmetics that have been irradiated by a cabinet x-ray system used for security screening”2


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There has been some scientific research into the effect of x-ray inspection on pharmaceutical products. In a study conducted and published in 2015 by scientists at the Department of Drug Delivery and Nano Pharmaceuticals, in the Graduate School of Pharmaceutical Sciences, Nagoya City University, Japan, three pharmaceutical drug tablets were exposed to x-ray doses from 0.34


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