Sep 20

How genotyping is aiding in the fight against malaria

3.2 billion people across 106 countries and territories, live in areas at risk of malaria transmission. The serious and sometime fatal mosquito-borne disease is caused by the Plasmodium parasite – in 2015, malaria caused 212 million clinical episodes, and 429,000 deaths.

Malaria has been a public health problem in Brazil ever since it was brought to the region during its colonization. By the 1940s it is estimated that six to eight million infections and 80,000 malaria-related deaths occurred every year in the country.

Due to a concerted series of malaria control policies, Brazil has recorded a 76.8% decrease in malaria incidence between 2000 and 2014 – and effort which the country was praised by the WHO.  In 2014, there were 143,910 of microscopically confirmed cases of malaria and 41 malaria-related deaths.

Part of Brazil’s malaria control policy involves the use of primaquine – a medication first made in 1946, to treat and prevent malaria. It is particularly effective against the Plasmodium vivax parasite that is prevalent in the Brazil.

Unfortunately primaquine can induce haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals and may lead to severe and fatal complications. 330 million people worldwide are affected with G6PD deficiency, with recent studies suggesting the prevalence of the deficiency could be as high as 10% in Brazil.

Recently, molecular biologists from LGC enabled a cutting edge study in collaboration with researchers from Brazil and the London School of Hygiene and Tropical Medicine.

The researchers looked for mutations in a sample of 516 male volunteers that could be used as clinical indicators for G6PD deficiency that could lead to complications in people prescribed with primaquine.

Blood samples were collected from around Brazil at hospitals during surgeries, as well as using the local Brazilian radio stations to ask people to come and submit blood.

Needing a fast and efficient way to generate results in high throughput, the team turned to LGC’s integrated genomics toolkit to facillitate the research. Each sample was screened against 24 KASP assays to assess the genetic bases of G6PD deficiency. In combination with the IntelliQube®,a fully automated point and click PCR system;  the team collected the data in roughly three hours of instrument time and one hour hands on time.

KASP is a flexible, highly specific genotyping technology, which can be used to determine SNPs and InDels.  KASP uses unlabelled oligonucleotide primers, which gives the technology a cost advantage and allows more data to be generated, increasing data quality.

The data indicates that approximately one in 23 males from the Alto do Juruá could be G6PD deficient and at risk of haemolytic anaemia if treated with primaquine. The authors conclude that routine G6PDd screening to personalize primaquine administration should be considered – particularly as complete treatment of patients with vivax malaria using chloroquine and primaquine, is crucial for malaria elimination.

The teams are continuing their collaboration to help further research in to treatments for malaria, and we can’t wait to see more!

To access the paper, please click here, or to see the IntelliQube in action and learn more about this automated PCR instrument click here.

Sep 08

The MIC: A Misunderstood Animal?

I read recently a paper which studied ‘relevance’ of MIC data against clinical outcomes. The conclusion of the paper as that there is no link between MIC data and clinical outcomes in the case of vancomycin for left sided endocarditis. While there may be some merit in the claim that the MIC is relied on a little too heavily for presumptive clinical outcomes, this bought into sharp contrast something that is deeply concerning for someone who works predominantly with in vitro MIC testing. It is almost always vilified by people who don’t truly understand it.

Let me start by saying this is not a direct criticism of the paper I’m referring to. It seems to be very well written and the majority of the data supports their conclusions, but there are a few decisions with study set up which as an experienced MIC scientist confuse me. For instance the fact that they have decided that the cut off for low MIC/high MIC is 1.5 mg/L. The CLSI and EUCAST breakpoint is ≤2 mg/L and the EUCAST distribution tables show a very clear end of the wild type population between 2 and 4 mg/L. So first off I’m confused why they chose 1.5 mg/L and not 2 mg/L. Also they chose to establish MIC by eTest. eTests are great in a hospital setting because they are a quick, flexible, easy option to test a rough MIC which in turn will tell you if you are dealing with a resistant infection, but if you are doing a solid comparison of the MIC value I’d argue they are not accurate enough. Also they are very easy to run and read incorrectly, providing incorrect data particularly when you are trying to read on or around the clinical breakpoints. Again I am not suggesting this is the case with the paper but is a possibility.

 

All of that is beside the point. As I say, the paper itself is not the problem. The problem is that the MIC is seen as a ‘simple’ test. That in part is due to the fact that the science behind it is inherently also very simple. Yet that simple data forms a cornerstone of drug development from early stage in vitro testing, preclinical in vivo testing alongside PK/PD work to ascertain dosage and on into clinical trials. It is also used to determine development of resistance and set clinical breakpoints through surveillance.

You are literally just throwing in a culture of the test pathogen in with the test compound and if the bug is inhibited by that, it doesn’t grow and it spits out a value. Simple, right?

Having spent the past 10 years carrying out hundreds of thousands of MIC tests (mainly broth and agar dilution but the odd eTest too) I can tell you it is far from simple. Take for example the standard guideline methods for carrying out these ‘simple’ tests. Both the CLSI and EUCAST produce massive tomes and have put in countless amounts of validation and research into establishing as near to a reliable and solid method as you can get for the humble MIC. They state highly specific test conditions, quality controls, reagents and strict methods. Why do they do this? Because without them the method is not reproducible and breakpoints cannot be applied to clinical outcomes. The guidelines have to be followed as stated, otherwise all you have at the end of your testing is a value, which has no data whatsoever linking it to a clinical outcome.

There is more, in that the test is not a simple one to interpret. Okay, for the example in the paper above a guideline method dilution MIC for MSSA against vancomycin is often easy to read. For example, you need to be aware of the extended incubation period for vancomycin when compared to other test compounds (16-20 vs 24 hours). That’s because the resistance mechanisms take longer to kick in for this bug/drug combo. Sadly this is not something you’d know unless you’d done a lot of research, are following a guideline method to the letter or are experienced in the test method. Also if you are testing a worthwhile amount of clinical strains, you’ll always end up with a few ‘freaks’ which require a bit of experience to read correctly because they’ll do some strange things on the test plates. You might think that for a small number of isolates it’s not worth the concern, but remember that what you are looking for with the test are those isolates with MICs that differ from the wild type, which are usually the ‘freaks’. That makes interpreting those strains most important of all. Then there are all of the ways a test can fail. You can have failed growth for a whole host of reasons, contaminated cultures which are hard to spot with the untrained eye, trailing endpoints, bubbles in the media and/or incorrect isolate identification can happen even if the most experienced analyst has carried out the test. Still think it’s simple?

I’m not suggesting for one second that the MIC is perfect. In fact I and many others are working to develop alternative tests that may one day replace it. However right here and now, it does a better job that it is given credit for, but only if it is done right. All too frequently it isn’t and the differences between tests run by MIC experienced scientists and those who are new to the technique are significant. When the data produced is found to not match up with expected results or clinical outcomes, the method itself is blamed.

The dilution MIC is still the best method we have for determining bacterial resistance. Although other methods are popping up all over, they are commonly expensive, restricted in what they can show or unreliable. It also, despite its weaknesses, still forms a cornerstone of drug development testing. Meaning scientists time and time again come back to the MIC, which is part of the reason why it hasn’t been replaced in decades. Surely that has to stand for something?

I am begging for someone to show me a better way of accurately, affordably, reproducibly and reliably determining antimicrobial activity. But I haven’t seen it yet. That is as frustrating for me as for any other scientist, but please, don’t take it out on the MIC.

Ed

 

Ed Siegwart is a Senior Scientist for LGC’s Drug Development Services

Aug 11

Space is the place…to experiment

Bugs in Space – ATCC® Microbes are Go!

by Lauren Cracknell.

Students taking part in the ISSET programme at King’s College, London, have designed and prepared ‘micro-gravity experiments’ using ATCC’s Microbes. The intrepid microbes were launched into space on-board the Falcon 9 rocket and rendezvoused with the International Space Station on 5 June.

The aim of these experiments is to look at the impact of microgravity on bacteria. Results may potentially serve to improve patient health in clinical settings on Earth and could also be developed to improve human health and food sustainability in space. ATCC’s microbes were the ideal components for these experiments due to the diversified nature of their collection, which contains more than 18,000 well characterized strains.

 

A bit of background to the experiments can be found below:

  1. An experiment to determine the antibiotic properties of bacteriophages in microgravity

Bacteriophages are viruses that invade bacteria and have antibacterial properties. With increasing antibiotic resistance, bacteriophages offer an alternative approach to treating infections.

  1. An experiment to determine the growth of phosphate solubilising bacteria in microgravity

There is an abundance of inorganic phosphate on the surface of Mars; however plants would need it to be solubilised in order to grow. Phosphate solubilizing bacteria are able to achieve this solubilisation, but we do not yet know how effectively the bacteria will grow in microgravity. This experiment will compare growth of the bacteria (Pseudomonas putida) in microgravity compared to on earth.

  1. An experiment to determine the symbiotic relationship between simple plants and rhizobacteria in microgravity

Rhizobacteria are root-colonizing bacteria that form symbiotic relationships with many plants and are capable of solubilising phosphate. As an extension to experiment 2, this study will determine whether plant growth (grass) is actually increased by rhizobacteria in Space and how this compares to growth on Earth.

  1. An experiment to determine how ‘slime bacteria’ grow in microgravity

Chondromyces crocatus is a bacteria belonging to the Myxobacterial family.  This bacteria responds to a chemical signal by streaming together and producing a massive (relatively) fruitbody, which can be seen using a hand held lens. This experiment will determine whether fruit bodies are able to form the same way in microgravity as they do on Earth, which will provide important information about growth of micro-organisms in Space.

The International Space School Educational Trust (ISSET) works in partnership with some of the world’s leading space organisations to deliver unique learning opportunities for students of all ages.

Keep an eye on NASA’s ISS research page for results!

Aug 03

Antimicrobial Development: Getting Things Started

Developing antimicrobials is a war of attrition, with an unfortunate number of potential compounds falling at one of the many hurdles along the way. I’m keen to support the process and speaking as someone who is a pre-clinical in vitro drug development specialist, the obvious way for me to help is to encourage more molecules being loaded in the front end!

LGC’s Ed Siegwart

With that in mind we have launched something I’ve named ‘Project Pillar’ (not everyone liked the name, but I insisted). It was an idea based on meeting a few biochemists at the Royal Society of Chemistry Biosynthesis V meeting in Warwick earlier this year. In the meeting it was first hammered home to me that I am not a chemist and that what the synthesis guys do is hardcore science. Secondly it dawned on me just how many of them have antimicrobial molecules, and were not 100% sure what they should be doing with them next.

As part of this we are offering clinical isolate MIC screening panels to academic institutions at a very low cost, with a view to generating a broader understanding of activity of a particular molecule before it enters the next phases of pre-clinical testing. This data will only generate a small window into the potential of a particular compound, but I hope it will provide that little extra bit of buzz required to get further funding/investment for the teams working on them. It also means that we can help nudge them in the right direction of what to do next if they happen to need that little bit of industry knowledge.

We’ve had a few nibbles of interest, and we are starting to test the first few compounds soon.

This is where you can help. If you are aware of any academics who may be interested in some low cost broad panel screening, please feel free to pass on our contact details.

I’m also hoping that being academics, they might be interested in publishing the results, so watch this space!

Thanks for reading,

Ed

 

To find out more about our expertise in this area please download a copy of our fact sheet

Download fact sheet >>>

LGC Microbiology overview

Ed Siegwart will be at ASM/ESCMID Conference on Drug Development to present a poster about Project Pillar. If you would like to arrange a meeting with Ed please contact us.

Jun 08

Who is the purest of them all? The need for high quality certified reference standards

Thousands of decisions based on chemical measurements are made globally each day. This could be a clinician making a medical diagnosis, regulators identifying the presence of counterfeit drugs and removing them from sale, or a water treatment company testing their processes to ensure the water you drink is safe.

To underpin these measurements and ensure we all have confidence in them, they are calibrated through a series of reference materials – from those run on a day-to-day basis up to the highest (primary) level. The cornerstone of this reference material system is the provision of high purity reference standards as the primary calibrators, such as those produced by LGC in our role as the National Measurement Laboratory and Designated Institute for chemical and bio-measurement.

Industry increasingly requires a greater number, range and complexity of high purity reference standards to support the challenging measurements of real-world samples. This means primary calibrators must have values assigned more quickly and at significantly lower cost than traditional methods currently allow.

To address this need, scientists at LGC have been implementing the technique of quantitative nuclear magnetic resonance (qNMR). Purity determination by qNMR is much faster than traditional methods and allows for direct assay of the compound of interest rather than inferring the purity through quantitation of the myriad of minor impurities potentially present.

The use of qNMR for purity determination has been rigorously assessed and validated at LGC and its use as a primary method (with direct traceability to the international system of units, SI) has been standardised through comparison studies between National Measurement Institutes.

Earlier this year (2017) LGC became one of the few laboratories worldwide to gain ISO17025 accreditation for purity of organic materials by qNMR. The extent of the ISO17025 scope includes the determination of the purity of organic analytes of high purity (>90%) with a molecular weight of <1000 g/mol.

This accreditation provides demonstrable evidence of LGC’s expertise and supports our new qNMR facility in providing reference material characterisation and quantitative measurement research for customers across the AgBio, biopharmaceutical, chemicals, consumer products and forensic industries.

 

If you would like to find out how we could use our NMR expertise to address your measurement challenges, please contact LGC’s Measurement Services.

LGC is accredited to ISO Guide 34 for the production of reference materials.

 

May 26

Accurate MIC endpoints with automation

LGC’s drug development team regularly assess new methods to refine and strengthen our existing analytical services across all disciplines.

 

An old-school stalwart of microbiology testing, minimum inhibitory concentration (MIC) testing identifies the lowest concentration of a substance that prevents visible growth of a bacterial strain.

 

The MIC is the bacteria’s tipping point and is the mainstay of in vitro antimicrobial susceptibility testing (AST) for any new antimicrobial drug or treatments or for monitoring the emergence of resistant strains against existing antibiotics.

 

LGC-Anti-infective-drug-development_services

 

At LGC,MIC testing is done in line with CLSI M100-S27E Performance Standards for Antimicrobial Susceptibility Testing (2017) and CLSI M07-A10 (2015) using a MIC endpoint broth microdilution test. A serial dilution of an antimicrobial stock solution is dispensed into microtitre plates. Bacterial suspensions are made in broth culture to a standard density of colony forming units (cfu) this is then added to the plates and the effect on growth observed. The same test can be repeated for multiple culturable bacteria with multiple antimicrobials and the MICs compared.

 

Traditionally these measurements are done by eye, but optical density readings (OD600) to determine MIC endpoints are a promising alternative – reducing error and time and permitting high-volume screening in the laboratory.

 

Download our poster on “Alternative Minimum Inhibitory Concentration (MIC) Test Methods: The Use of Optical Density Readings to Determine an MIC Endpoint” to read more about the results from side-by-side comparisons of visual MIC testing with automated endpoint determination on a range of aerobic bacteria and antibiotics.

 

Alternative Minimum Inhibitory Concentration (MIC) Test Methods poster

Authors; April Taylor, Scientist, LGC and Ed Siegwart, Senior Scientist, LGC

 

To find out more about our anti-infective drug development and surveillance expertise, please contact us

 

 

 

May 19

Measurement and alcohol: it’s World Metrology Day!

Tomorrow (20 May) is World Metrology Day, the birthday of the signing of the Metre Convention in 1875. This convention set the framework for global collaboration in the science of measurement (metrology).

Its aim – to ensure we use uniform measurements across the globe ­– remains as important for industry, trade and society today as it was over 140 years ago.

The theme for World Metrology Day 2017 is ‘Measurements for transport’, chosen because transport plays such an important role in the modern world: we travel but so does the food we eat, the clothes we wear, the goods we use and the raw materials they are made from. Ensuring all this travelling happens safely, efficiently and with minimal environmental impact requires a surprising range of measurements.

Calibration to save lives

As the National Measurement Laboratory and Designated Institute for chemical and bio-measurement, LGC forms part of the UK National Measurement System (NMS) that provides the core measurement infrastructure for the UK. The measurements we make support manufacture and trade, protect consumers and enhance quality of life.

LGC’s certified reference alcohol standards play a crucial role in supporting the safe transport of people and goods. The number of people estimated to have been killed in drink drive accidents in Great Britain has decreased from 1,640 in 1979 to 240 in 2013 and routine work-place testing for alcohol use also prevents accidents. LGC ethanol primary reference standards and LGC ethanol calibration services now support 50% of the breathalyser market. In addition, our standards supply 150+ clients for clinic-based work-place testing.

Furthermore, with tax revenues from alcohol sales contributing £10.5 bn to HMRC, the accurate measurement of the alcohol percentage in wines and spirits is critical to correctly calculate duty liability. To support the calibration of automatic density meters routinely used in industry to determine alcoholic strength, LGC supplies certified reference materials to over 40 distilleries, councils and testing laboratories.

 

Our certified reference materials to support measurement for transport

Contact LGC Standards for more information on these and other materials

 

Our impact

In our role as a National Measurement Laboratory we develop innovative capabilities to address measurement challenges of the future, supporting government, academia and industry to promote productivity and economic growth. Find out more about the impact of our work.

 

If you would like to find out how you could use measurement expertise to address your measurement challenges, contact LGC’s Measurement Services.

 

May 08

How do you give coffee authentication an extra shot?

With a high market value and commercial importance coffee is in the top 10 products most at risk of food fraud.

A recent paper by the Government Chemist team at LGC, and the Institute of Global Food Security in Queen’s University, Belfast (QUB), tackles the question of where and how to analytically check the coffee supply chain.

Analysing the results of several studies in the scientific literature Dr Michael Walker and a team from QUB have produced key instructions for probing the authenticity of coffee.

Michael Walker, Referee Analyst, Government Chemist Programme, LGC, said, “Coffee is one of the most widely traded tropical products and is produced in over 50 developing countries around the world. Because of its high market value and commercial importance it is increasingly the target of adulteration by dilution of cheaper materials. This fraud can take many forms, from swapping cheaper materials – e.g. coffee husks, chicory, cereal grains, woody tissue, cocoa or soya beans, acai berries or exogenous sugars – or substituting the more expensive Arabica species with cheaper beans.

M Cup Coffee IStock 000012881314Medium[1]“Adulteration of coffee has been around for a long time. Indeed, one of the first large scale samplings of foodstuff performed by the Laboratory of the Government Chemist, which was set up in 1842, was of coffee for adulteration and ceased in 1863. At that time adulterants included chicory, and, later, orange pips and iron oxide, burnt sugar or caramel, locust beans, ground acorns, and even date stones being found in 1878. (Weighed in the balance, PW Hammond and Harold Egan, HMSO, 1992, pp 40-43) But the food fraud episode of 2013 has reiterated that consumers need clear and accurate information so they can make informed choices about their diet and the foods they buy. This choice might reflect lifestyle, economic or health concerns but, in a multicultural society, it can also reflect religious practices.”

The full paper contains outline experimental details and references to the key studies so that any laboratory wishing to check coffee in the supply chain can make a good start.

Most of the common modern adulterants can be detected by chromatography of marker carbohydrates as detailed in standard methods (BS ISO 24114 and BS 5752-15) with the help of chromatograms of authentic coffee/ adulterant mixtures. Looking at DNA by Real Time PCR is a viable alternative to the chemical methods.

Claims for specific coffee bean geographic origin can be checked by discriminant molecular markers, although these are not as yet available for all coffee growing areas. Solvent extraction and Fourier Transform Infrared spectroscopy, FTIR, for the markers has the advantage that the FTIR spectra for authentic dichloromethane extracts are freely available online.

Discrimination between Arabica and Robusta species in coffee samples is possible via the marker compounds kahweol and 16-O-cafestol, predominant in Robusta. Determination of the latter by Nuclear magnetic Resonance, NMR, spectroscopy has the advantage of speed and relative simplicity.

Perhaps the most intriguing coffee authenticity problem is posed by Kopi Luwak, coffee beans harvested from the faeces of the palm civet cat. Processing in the digestive tract of this cat indigenous to Indonesia contributes to Kopi Luwak’s mystique and price. Although proof of identity of Kopi Luwak has been made more difficult by the possibility of mimicking the effect of the cat’s gut on beans by the use of microorganisms and enzymes, discriminant markers identified by Gas Chromatography – Mass Spectrometry, GC-MS, has proved successful. The question as to whether or not any residual civet cat DNA can be detected on ground roast coffee can be detected remains unanswered.

Thorburn Burns, D., Tweed, L. & Walker, M.J., 2017, Ground Roast Coffee: Review of Analytical Strategies to Estimate Geographic Origin, Species Authenticity and Adulteration by dilution,  Food Anal. Methods  doi:10.1007/s12161-016-0756-3

If you would like to find out how you could use our dPCR expertise to address your measurement challenges, please contact LGC’s Measurement Services.

Apr 20

Transplant care: ensuring consistency across the globe

Reference materials (RMs) are the cornerstone of accurate and traceable measurements – they are measurement standards which can be used to validate analytical methods, establish traceability and support quality control.

A month ahead of World Metrology Day, we look at the use of our certified reference materials (CRMs, reference materials with evidence of metrological traceability and a statement of measurement uncertainty) to support measurements in the clinic. CRMs help remove measurement variation between hospitals, ensure more precise prognoses and ultimately improve patient care.

CRMs allow manufacturers to establish the traceability of calibrators supplied with diagnostic equipment and they support medical and clinical laboratories to validate their methods in line with the traceability and uncertainty requirements as defined in the International Organisation for Standardization (ISO) standard 15189 (Medical laboratories – Requirements for quality and competence).

One area where standardisation is necessary is the monitoring of immunosuppressants, the therapeutic drugs used to prevent patients rejecting a donor organ after a transplant. With 4,500 organ transplants carried out in the UK each year, there are tens of thousands of people for whom monitoring the dosages of these drugs is crucial in order to allow the donor organs to remain functional for as long as possible.

Whilst life-saving at the right doses, immunosuppressants have a very narrow therapeutic range. Too little and the body rejects the organ. Too much and unnecessary toxic effects occur, potentially causing diabetes, skin cancer or even resulting in kidney failure, leading to a need for dialysis or even further organ donation.

Improving the accuracy of immunosuppressant monitoring through the use of higher order reference standards could reduce the number of rejections and give patients the best possible chance of an improved quality of life, away from hospital beds and dialysis machines.

Over the past few years LGC, as the UK National Measurement Laboratory and Designated Institute for chemical and bio-measurement, has been producing certified reference materials for two commonly prescribed immunosuppressants (tacrolimus, sirolimus) to underpin the standardisation of existing or in-development assays.

A new material has recently been released to extend the current portfolio and support a greater number of laboratories, secondary standards producers and assay developers ensure compliance with ISO 15189, ultimately helping ensure consistent care across transplant centres globally.

 

Immunosuppressant certified reference materials (CRMs) available from LGC Standards

These materials are produced under LGC’s accreditation to ISO Guide 34 and accredited to ISO 17025. ERM-AC021a and ERM-DA110a are both listed on the JCTLM database of higher order reference materials.

Apr 05

The new ICH Q3D Elemental Impurities Guideline – nothing to fear if you act now

The ICH Q3D Guideline on Elemental Impurities has been adopted by the European and US Pharmacopoeias, meaning that by the end of 2017 all new and existing products in Europe and the US will need to be assessed.

Initially it was thought that every marketed product would require full testing for trace metals. However, the risk based nature of ICH Q3D means that many elements can be eliminated from consideration if sufficient data are available. Elemental Impurities are rarely seen at levels that require control measures. This means that screening alone may be sufficient to satisfy the ICH Q3D requirements. Screening can fill the knowledge gap and allow an informed risk assessment to be completed prior to committing to full quantitative validation.

 

LEnElementalImpurities

 

What are elemental impurities and how do they get there?

Elemental impurities are traces of metals that can end up in finished drug products. Elemental impurities can come from multiple points in the manufacturing process, such as deliberate addition as reaction catalysts during product synthesis, or from contact with manufacturing equipment and containers. These impurities do not typically contribute to a drugs therapeutic effect, and can cause patients harm if the levels are not monitored and controlled. Therefore, for evaluation, manufacturers need to consider all potential sources of trace metals in the final formulation and product packaging. The permitted daily exposure of each element varies, but overall, no elemental impurity should be present at more than 30% of the Permitted Daily Exposure (PDE) in the final product.

 

Testing required? Consider this

The wide variation in pharmaceutical material composition and the requirement for simultaneous multi-elemental determination across a wide concentration range can lead to analytical challenges.

The product, 30% PDE level, dosage route and ICH Q3D option selected all affect the sample preparation method, solvent and instrumental detection methods chosen. Each available method has a range in sensitivity and response and these must be aligned carefully with each specific product’s requirements taking into consideration the targeted elements impurities and their documented risk and exposure limits.

 

Help is at hand!

USP <231> Heavy Metals test is being replaced with two new chapters, USP<232> Elemental Impurities (Limits) and USP<233> Elemental Impurities (Procedures). As a consequence, the use of Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES) and Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS) will become the preferred standard approach for the determination of heavy metals in drug products, replacing wet chemical tests. This means tests with better specificity, accuracy and sensitivity are now available to help sponsors confirm that their materials meet the new compliance criteria.

The implementation deadline for the new USP directive is scheduled for January 2018 and LGC is already prepared for what will be a very significant industry requirement for additional ICP-OES / ICP-MS testing of new products.

To find out more about the new guidelines and LGC’s expertise, please download the fact sheet and view our webinar.

 

LEnElementalImpuritiesFS

Download fact sheet >>>

 

 View LGC webinar on In Vitro Antimicrobial Efficacy Testing: Potential Pitfalls and Future Methods

View webinar >>>

 

Author: Sarah James, Principal Scientist, CMC Analytical Services, LGC

 

 

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