We recently conducted a pharmaceutical impurity webinar series with experts from LGC Standards, Broughton Laboratories and Thermo Fisher Scientific to highlight the most recent advancements in the area of pharmaceutical impurities. These webinars got us thinking: this is the current situation, but what do we predict to be the main drivers and trends in pharmaceutical impurities over the coming years? In this article we gather experts from both LGC and Thermo Fisher Scientific (biographies at the end) to give us their thoughts on future trends in the field of pharmaceutical impurities. As you can see below, there was no shortage of predications about what’s next in the sector.
“The need to characterize impurities that emanate from drug containment, or delivery devices, or as contaminants from processing lines, or machinery will be of growing importance, particularly in the emerging medicines of oligonucleotides, proteins and cells. These emerging medicines are often delivered by injection and thereby bypass the protection mechanisms of the digestive tract. The likelihood of extractable / leachable impurities is greater when drugs are in solution, allowing easier exchange and diffusion of components between the drug product and the container. Measuring these impurities is complicated and will require increasing access to reference standards and to a broad range of instrumentation and expertise, including techniques such as GC-MS; ICP-MS; FTIR microscopy, particle sizing and counting and SEM-EDX.”
“For a start we can say that as the trends towards generic products further increase, I think the testing of impurities will, of course, increase as well. A higher rate of production of generic products (and biosimilars) is necessary worldwide to keep health costs at bay. But as quality must never be compromised compared to the original products, impurity testing is done in compliance with ICH, regardless of what type of medicine you are producing. In addition, negative events like last year’s accidental detection of the genotoxic impurities NDMA and NDEA in Valsartan and similar drug substances will further raise vigilance in the marketplace, and the relevance of ICH guideline M7, resulting in more checks on impurities. By the way, while talking about NDMA and NDEA, this issue – and its general implications– will also be a topic on our May seminar agenda, which you can download here. Our goal is to provide the tools to the pharma industry for them to ensure their products are safe and of high quality and efficacy.”
‘’I believe we can all agree that we shall see an expanding repertoire of analytes that will require testing in the future, with more thorough regulatory requirements. This is coupled with the drive to minimize costs and reduce the cost-per-sample. To achieve this will require greater productivity from analytical technologies. Combining chromatography and mass spectrometry under one fully compliant software has numerous benefits, offering increased productivity, less training and data integrity. This is already possible with Thermo Scientific™ Chromeleon™ Chromatography Data System (CDS) Software in which mass spectrometry operation and data processing has been added to the existing chromatography capabilities. In the future, the prediction is that this will become commonplace and more mass spectrometry software features will be present in CDS software.’’
‘’Following on from Heiko’s comment, it is not just in the combination of chromatography and mass spectrometry software where productivity enhancements will stop. I can already see where chromatography throughput has been increased by the utilization of Dual LC and parallel ion chromatography. Tandem LC or LC-MS offers the ability for greater detector utilisation and maximizes the return on investment in the mass spectrometer. On the topic of mass spectrometry, then, there will continue to be a push towards making this much simpler to operate and becoming more of a chromatography detector than a mass spectrometer. Multi-detector approaches are likely to become more prevalent to ensure comprehensive sample characterisation in a single analytical run. Overall, the momentum will be to get more information and throughput without the associated increased in resources and to simplify workflows to become more plug-and-play.’’
“It will be interesting to see where the world of engineering biology will take us in the area of impurities. The move to ’green’ chemistry will begin to favor the use of biological catalysts that can act on natural feedstock without the need for excessive energy input. However, it will mean that even small molecules will need to be characterized for biological impurities (host cell proteins, etc.), and a potentially more complex set of chiral co-products emanating from these enzymatic processes.”
“Where quantitation of impurities in chemically defined APIs and their finished dosage forms are concerned, I think we will see RRFs (relative response factors) being used even more in the near future. The science behind the approach is robust provided your method is too, and in routine testing it saves a lot of time, and therefore money. Saving money is essential, in particular in the generic industry. Analysts should make sure, however, that they use carefully characterized reference standards when setting up the RRFs in the first place. If new to the topic, they could read our white paper featuring RRFs or check out our corresponding webinar.”
“Between the worlds of small and large molecules is an important emerging area of drug development in synthetic peptides and nucleotides. Methods and associated standards will increasingly be needed to support associated impurity identification, quantification and qualification through the process of drug development, and these will be difficult to isolate, synthesize and characterize due to their close compositional alignment with the active ingredient. To do so will require a strong knowledge in related synthesis and characterization.”
From the discussions we had, it is fair to say that the coming years the pharmaceutical impurities environment will be an exciting, but also challenging, area to be involved in and continues to grow. These are just our opinions though, we would welcome your thoughts as well – these can be exchanged in the comments box below.
For the past six years Pierre has worked within LGC's rapidly expanding Drug Development Solutions division firstly as a Principal Scientist and now a Strategic Development Director in both the UK and US. Prior to LGC, Pierre worked as a Senior Scientist for Pfizer Global R&D (13 years) providing significant contributions to drug development teams as analytical team leader for projects at varying stages of development. By maintaining effective partnerships with colleagues in Pharmaceutical Sciences, Clinical Sciences, Regulatory CMC, Legal and Manufacturing ensured key milestones for clinical studies, regulatory submissions and commercial milestones were met. Pierre’s education has been completed in parallel with his career; BSc in Chemistry, MSc in Pharmaceutical Sciences concluding with an MBA.
Dr. Christian Zeine studied chemistry at the Westphalian Wilhelms-University in Münster, Germany, where he received his doctorate in 1998 in organosilicon chemistry. After project work at the University, from 1999 on there followed activities at manufacturers of medical and in-vitro diagnostics products, including B. Braun Melsungen. Since 2002 he has worked at LGC Standards, serving now as Global Senior Product Manager for pharmaceutical reference standards.
Christian is also the author of articles introducing the general topics of impurity testing and reference standards, and lectures on these subjects during seminars and symposia.
Heiko has a PhD in Analytical Chemistry and 30 years of experience in LC, LCMS, GC and GCMS of which 19 years are with Dionex and Thermo Fisher Scientific. His current role is focused on HPLC, single quadrupole MS and Chromeleon MS products with a market focus on Pharma small molecules/routine Pharma. The role is customer and sales focused with joint sales visits on customer sites, customer demos, seminars, workshops, etc., mainly in pre-sales.
Tim has a PhD in Immunology from the University of Birmingham, UK and 20 years’ experience in the scientific industry. Initially, Tim worked in research and development, but subsequently moved in to marketing holding various different marketing management positions. He joined Thermo Fisher Scientific in 2014 and is currently the EMEA Senior Regional Marketing Manager for HPLC and life science businesses within the Chromatography and Mass Spectrometry Division.
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