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Glantreo Summer 2008 NewsletterWelcome to the Glantreo email newsletter. Firstly we would like to take this opportunity to thank you for your continued interest in Glantreo, and we hope you enjoy our newsletter.
Despite the best efforts of manufacturers to produce to the highest standards, there are a number of ways in which pharmaceuticals may become contaminated by foreign bodies. Such contamination may at best be unwelcome, or at worst potentially life threatening for users of pharmaceutical products such as injectables. From a production point of view, the discovery of a contaminant may render the entire batch unusable, resulting in wasted production time and raw materials. To identify a contaminant and find an explanation for its presence in the product is seldom an easy matter. It can require a significant amount of detective work on behalf of the scientist charged with investigating the problem. Very often, it requires a team effort, involving the skills of microscopists, chemists, and microbiologists working together to reach a satisfactory conclusion. Where this multi-disciplinary expertise is not available in-house, manufacturers must find a Good Manufacturing Practice compliant Partner to assist in the investigation. Many Sources ... There are many potential sources of foreign bodies in pharmaceutical products. They can include production equipment, laboratory equipment, raw materials, packaging materials and production errors, as well as deliberate act of malicious tampering. Sometimes the point at which the problem is detected will give a clue as to how the contamination occurred (e.g. glass contamination of product immediately following a known breakage of packaging materials), at other times the possible explanations will be less obvious. The Glantreo Approach has proven to be very effective and combines the collective brain of over 50 years experience with the most up to analytical equipment. The Glantreo Methodology:
Testing Microscopy is always the first line of attack in investigating foreign body incidents. There is much that can be learned even from examining the size, shape and surfaces of a foreign body with simple light microscopy. However one of the most powerful analytical tools is X-ray microanalysis linked to scanning electron microscope equipment. An alternative approach is to use X-ray Fluorescence (XRF). Both techniques can be used to reveal the elemental composition of a sample and elemental distribution within it and are especially valuable in the analysis and comparison of glass and metallic fragments Glass fragments are a potential foreign body hazard in any pharmaceutical product that uses glass packaging. Any breakage on the filling line can easily contaminate other bottles. Metal shards from machinery are another common foreign body contaminant, again arising from wear and tear on factory machinery. In a similar way, plastic fibres can also arise from the use of plastic packaging or from wear and tear on plastic fixtures in the process line. Lubricants are frequently found as co-contaminants with finely divided metal dust on tablet surfaces, but on their own may manifest as droplets within liquid pharmaceuticals. Whilst glass, metal and plastic fragments from plant and packaging constitute the majority of foreign body cases, they are by no means the only cases. Glantreo has investigated many incidents over the years and identified a wide variety of insects, mammalian hairs, pieces of paper, drops of silicone and 'black bits' (often consisting of thermally degraded product or rubber). Foreign bodies need not necessarily be of external origin. From the consumer's perspective coagulants and precipitates are also foreign bodies and clearly, their presence is liable to compromise the performance, and possibly safety, of the product. Microscopy is unlikely to be sufficient on its own to identify these foreign bodies. Chemical analysis will also be required. Always Investigate Whilst it may not be possible to prevent every foreign body incident, it is always in the interests of manufacturers to investigate every case. Continuous improvement is key in any quality systems and the information acquired by a successful investigation will offer an explanation as to how contamination occurred. It should also go a long way to helping the manufacturer to decide what measures need to be introduced to prevent a repeat occurrence and improve the reliability and safety of the manufacturing process. Continual investigation of manufacturing also allows us to build up statistical information on the process that can feed back into lean manufacturing technologies and databases.
If process analytic technology (PAT) is not at the tip of your tongue, it should be. This FDA-inspired initiative for real-time, in-process analytics, has been slowly gaining traction thanks to steadfast efforts by instrument vendors and best-in-class biomanufacturers. HPLC will be part of PAT moving forward. High-performance liquid chromatography (HPLC) has provided analytical support for biopharmaceutical research, development, and manufacturing for as long as biotech has existed. Only recently, though, have HPLC, its methods and associated instrumentation achieved the speed, reliability, and robustness sufficient to analyze process streams in real time or near-real time. Recent advances in pumping technology, mass analysers and smaller particle sizes (sub 2 micron) has led to the next generation of chromatography, so called fast LC or UPLC. Fast LC technology has dramatically reduced the time taken for complete analysis of multi component mixtures. Continued improvements in these technologies will allow LC to be carried out 'on-line' Several of the market leaders in chromatography instrumentation are developing on-line HPLC systems. In March of this year Waters Corporation unveiled its new Waters PATROL™ UPLC™ Process Analyzer, a real-time Process Analytical Technology (PAT) System able to detect and quantify complex multiple component manufacturing samples and final product on the production floor. Designed with the same enabling technology platform as Waters® ACQUITY™ Ultra-Performance Liquid Chromatography™ (UPLC) System, PATROL UPLC moves existing liquid chromatography (LC) analysis from off-line Quality Control (QC) laboratories directly to the manufacturing stream resulting in significant improvements in production efficiency with real-time analysis. Waters is currently collaborating with several global pharmaceutical companies to quantify PATROL UPLC's impact on the manufacturing process. A goal of real-time PAT is to produce more product with existing resources compared to a time-consuming, off-line QC process. Early analysis supports PATROL UPLC can enable process recovery increases during major manufacturing steps, virtually eliminating the need for any reprocessing. In general, increase in process recovery results in increase yield, which in turn translates into higher profits per batch. Pharmaceutical, biopharmaceutical, petrochemical and food manufacturers are under increased internal and external pressure to evaluate their respective PAT Programs and techniques. Global regulatory initiatives, such as US Food and Drug Administration and European Medicines Agency Critical Path and PAT Initiatives, and manufacturing total quality programs, such as Six Sigma, are driving corporations to assess and implement novel PAT solutions.
Glantreo Ltd and University College Cork (UCC) today announced the signing of a collaboration agreement, under which Glantreo will license UCC's sub2sila™ silica manufacturing technology. The sub2sila™ technology is a unique processing technology that allows the production of a highly monodispersed sub 2 micron silica porous silica particles. The particles have applications in the High performance Liquid Chromatography (HPLC) arena and also in the next generation of HPLC termed Ultra High Performance Liquid Chromatography (UPLC). The agreement has been reached following the completion of an initial feasibility study which demonstrated the ability of the sub2sila™ technology to achieve the performance characteristics required by Glantreo. Under the terms of the Licence Agreement, which were undisclosed, UCC will earn licence and fees, as well as royalties on Glantreos sales and sub-licensing revenues. The sub2sila™ process allows the controlled synthesis of highly monodispersed silica particles in the 0.2-10 µm range. By simple control of the reaction parameters (temperature, reactant concentrations etc) appropriate sized particles can be synthesized. Several method currently exist for the production of sub 2 micron silica, however, the process developed at UCC offers a number of significant benefits namely:
Glantreo is currently in negotiations with a major player in the chromatography space where this technology will be utilised. From initial interactions with several of the major OEMs in the HPLC/UPLC industry there seems to be a genuine interest in this technology. The high yield of mono dispersed particles is of major interest to these companies, and may offer significant savings in the cost of manufacturing chromatography columns. There are approximately 1.5 million HPLC columns sold each year, (average retail price ¤500.00). It is expected in 10 years time that 50% of the of the columns sold per annum will contain sub 2 micron silica. Therefore it can be envisioned that significant royalties could be generated from successful implementation of this sub 2 micron manufacturing process into a commercial entity. |
