It is a real honour to be appointed Chair of the CAMS Industry Advisory Board, following on from Mark Seymour. I’d like to thank Mark for all his work for CAMS and wish him a very happy retirement.
Analytical scientists in the pharmaceutical industry are being constantly challenged to work with an ever-increasing diversity of chemical and biological entities. The ongoing efforts to beat COVID-19 exemplify this, as collaborations across academia, industry and technology providers race to develop vaccines, innovative treatments and testing methodologies. And, in all these areas, analytical and measurement science will make a massive contribution.
Another hot topic that reinforces the essential role of analytical science in the pharmaceutical industry is nitrosamine trace analysis. Over the last two years the nitrosamine challenge has exponentially expanded and is one of the major issues facing the global industry. It has resulted in product recalls, has the potential to restrict the availability of some medicines and has become high profile within the media.
From the initial focus on trace nitrosamine levels in Sartans drug substance, the scope has greatly expanded. It now encompasses all synthetic and biologic drug substance, the evaluation of levels in drug product and nitrate and nitrite levels in associated excipients. More recently, the risk of nitrosamine formation in packaging processes has also come under scrutiny. As the scope has expanded, the trace analysis challenge has grown. LOQs and LODs were typically set at 15 ppb and 5 ppb respectively. However, recent regulatory challenge may drive these down further to LOQs in the region of 5 ppb and LODs at sub 1 ppb level.
Issues of method robustness, sample preparation, unexpected sources of nitrosamine contamination and associated risk of false positives have contributed to the challenge. The implications of false positives are enormous, having the potential to severely impact supply of essential medicines. Therefore, we need a high confidence in the data generated for nitrosamine to maintain public trust, as illustrated by a recent high-profile example.
The global analytical science community within the pharmaceutical industry has responded with significant investment in state-of-the-art analytical technology and collaborations with instrument and column manufacturers to advance the capability of that technology. In parallel, the demand for testing at analytical science contract research organisations (CROs) has greatly increased. It has also been essential to influence the external regulatory landscape and develop cross pharmaceutical industry collaborations.
All elements of analytical science are required to achieve the challenging LODs and LOQs. High resolution LC-MS/MS and GC-MS/MS, along with IC-MS, is being applied for quantitation and structural confirmation. Bespoke sample preparation methods are required due to the variety of drug substance and drug product sample matrices. New separation science methods and column technology are being evaluated.
Nitrosamine trace analysis again illustrates how essential it is that we develop the current and next generation of analytical scientists and innovate in many areas of technology. The importance of the skills of analytical scientists from a societal perspective is clear. Now every day is nitrosamine day and it is inspiring that analytical science is leading the charge to tackle the issue and will demonstrate the safety of medicines, for many diseases, required by the millions of patients around the world.
Chair of CAMS Industry Advisory Board,
Chemical Development, Pharmaceutical Technology and Development, AstraZeneca, Macclesfield, UK