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CHEMICALS & PHARMACEUTICALS MEETING THE STANDARD USING ANALYSERS


Dr Simone B. Moos, product manager for the pharma, chemicals and energy markets at Elementar, explains how using the right tools helps tackle the pharmaceutical sector’s regulatory challenges


welfare and fundamental changes in the way we live our lives. Innovative vaccines, chemotherapy drugs, beta blockers, birth control pills and more have expanded our freedoms, improved our lifespans and underpin the stability of the modern world. As such, it is essential that we are able to put


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our full trust in the regulatory systems and checks that are used to affirm and safeguard the quality and safety of these medicines. When producing pharmaceutical drugs, manufacturers need to follow guidelines known as Good Manufacturing Practice (GMP), a vital safeguard designed to help prevent harm from occurring to patients, which apply to aspects that affect manufacturing, including facilities, starting materials and processes, as well as equipment validation and hygiene. In this context, manufacturers are also required to document their actions using clear and unambiguous language. Regulatory agencies such as the US Food &


Drug Administration (FDA) and European Medicine Agency (EMA) regularly conduct audits, sometimes unannounced, to check whether manufacturers are complying with GMP guidelines. If violations are noticed, it could result in anything from a warning letter and an improvement request through to a full import ban for the products in question. As a result, it is absolutely essential that


drugmakers are making full use of the tried- and-tested analytical tools that can help them comply with GMP. One of the key responsibilities that


manufacturers have under GMP is to check that the containers they use to produce their medications are cleaned properly between uses. The goal is to avoid cross-contamination - especially between batches of different medications or medications with different levels of active pharmaceutical ingredient (API). For this kind of cleaning validation, the FDA


recommends total organic carbon (TOC) analysis, since TOC is a screening parameter for organic contamination and will detect cleaning detergent or API residue reliably. There are two ways of sampling the containers for TOC analysis: by taking a swab sample, or by taking


he advent of modern pharmaceuticals has played a crucial role in reshaping our societies for the better, leading to increased


an aliquot of the rinse solution. A swab sample is


taken from the container walls. The swab is then screened for organic contamination, with the TOC level of the swab needing to fall below a certain threshold in order to declare the container clean. Instead of swabbing the surface, TOC can


also be determined by analysing the water used during the rinsing process. Because containers used in drug production need to be rinsed multiple times to clean them, an aliquot of the final rinse can be analysed for TOC. Efficient analysis of swab samples or final


rinse aliquots can be accomplished effectively with modern TOC analysers, which are designed to provide quick results, easy calibration, and user-friendly performance. For example, Elementar’s acquray system utilises a wet-chemical oxidation process, supported by highly energetic UV radiation (254 nm and 185 nm). This UV radiation is so strong that there is no need for an oxidising agent - which always carries the potential to be a source of contamination - in the lower TOC range. Additionally, the acquray allows injection volumes of up to 40 mL, combined with a precise infrared detector, for low detection limits of only a few ppb. In addition to making sure containers used in


the drug production process are clean, pharmaceutical manufacturers are also required by GMP regulations to ensure that their drug products meet established specifications in terms of composition, strength, quality and purity. This is another area in which an elemental analysis technique - in this case, CHNS (carbon, hydrogen, nitrogen


and sulphur) analysis - can make a significant difference. For example, lyophilised peptide powder


typically contains only 60% to 80% in peptidic material, and determining this net peptide content is crucial to incorporating the correct quantity of a peptide into a therapeutic drug. Because the peptidic material is the only source of nitrogen in the powder, it means the net peptide content can be calculated once the nitrogen content of the powder is known. Using a combustion analyser - such as


Elementar’s UNICUBE - nitrogen and other elements can be measured in just a few minutes. Samples are weighed and wrapped in tin foil, and are then placed in the analyser’s autosampler, delivering measurements of the absolute elemental amounts within a few minutes. The sample is combusted within a high-temperature furnace and completely converted into the target gas analytes, which are separated with the help of a column and sent into a thermal conductivity detector, with the recorded peak areas translated into absolute elemental amounts. In order to meet the standards required


by regulators, drug manufacturers need to be able to demonstrate that the analysers used for quality control purposes function properly, and that the results that they deliver can be relied upon. This is the value of turning to proven, established methods such as TOC and CHNS. As analysers such as the acquray and the UNICUBE have been installed at numerous pharmaceutical production facilities, proven IQ/OQ/PQ protocols and 21 CFR part 11 software options exist for these analysers. Using elemental analysers, companies will


be able to consistently meet the high quality standards expected of them by international regulators.


Elementar www.elementar.com/en-gb/


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