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Congratulations to Olatunde Awosiji Awotunde, Nicholas Roseboom, and Jin Cai!

Author: Marya Lieberman

Discrimination of Substandard and Falsified Formulations from Genuine Pharmaceuticals Using NIR Spectra and Machine Learning

Near-infrared (NIR) spectroscopy is a low-cost analytical tool for rapid characterization of pharmaceuticals. Usually, it's necessary to build up a "library" of NIR spectra from authentic products in order to identify real and fake formulations.  In this paper, we developed a simple training method that uses binary mixtures of a pharmaceutical (acetaminophen) with two different cutting agents, and used several different data analysis models to extrapolate the training samples to real and fake samples of popular brands of acetaminophen tablets.   While none of the models was able to correctly classify all the samples, a simple voting algorithm was able to compensate for the weaknesses of the models and classify 93% of the samples correctly.  …

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Congratulations to Heather Whitehead, whose paper on instrument-free detection of DNA with Nile Blue was just accepted by Analytical Methods!

Author: Marya Lieberman

Many nucleic acid tests (NATs) rely on a DNA amplification step as the detection mechanism for pathogens, viral load, and so on.  Usually, DNA concentration is measured using a spectrophotometric instrument that costs tens of thousands of dollars.  In this paper, Heather Whitehead used an inexpensive dye that binds to DNA and a cell phone to measure the concentration of double stranded DNA in the same concentration range commonly used to analyze NAT results. The color of Nile Blue dye shifts from blue to blue-purple to blue  as it binds to DNA.  While it's been known for many years that Nile Blue dye changes color when it binds to DNA, and that property has been used to develop instrumental assays, Heather figured out that by using different concentrations of the Nile Blue dye and monitoring the red, green, and blue channel intensities, the concentration of double stranded DNA can be measured with an error of less than 10 ug/ml.  …

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Health systems model shows cost-effectiveness of screening amoxicillin quality

Author: Marya Lieberman

Sarah Bliese's paper with the Ozawa group at NC State is now published!  Sachiko Ozawa's group developed an agent-based model, ESTEEM (Examining Screening Technologies with Economic Evaluations for Medicines), to estimate the effectiveness and cost savings of incorporating PADs and aPADs in amoxicillin quality surveillance in Kenya. We compared the current testing scenario (batches of entire samples tested by HPLC) with an expedited HPLC scenario (testing smaller batches at a time), as well as a screening scenario using PADs/aPADs to identify poor-quality amoxicillin followed by confirmatory analysis with HPLC. The PADs/aPADs screening scenario identified and removed poor-quality antibiotics faster than the expedited or regular HPLC scenarios, and reduced costs significantly. The model estimates that use of early screening tests could avert 360-870 pneumonia deaths per year in children under age 5 while reducing the number of HPLC tests required. …

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Oopsy!

Author: Marya Lieberman

A US pharmaceutical company just announced a recall of two lots of drugs which were "inadvertently mixed up" by the manufacturer.…

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PhD defense

Author: Marya Lieberman

Congratulations to Dr. Sarah Bliese on her successful defense of her PhD thesis, entitled "DEVELOPING SCREENING TECHNOLOGIES FOR LOW RESOURCE SETTINGS".  Sarah is headed to Virginia. …

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US Pharmacopiea evaluates PADs as pharmaceutical screening technology

Author: Marya Lieberman

USP's Technology Review report on the PAD is now published.

Executive Summary

The paper analytical device (PAD) was developed as a cost-effective tool for field screening of a wide variety of pharmaceutical dosage forms in low-resource settings. The PAD is produced by wax printing on Ahlstrom 319 paper, which is a fast chromatography paper that creates separate reaction lanes and contains trace quantities of chemical reagents to create color changes in response to different pharmaceutical articles. Due to the COVID-19 pandemic, there has been continued upsurge of substandard and falsified (SF) medical products, especially those that claimed to be a possible treatment for the disease (e.g., azithromycin, chloroquine, and hydroxychloroquine), and which the PAD can be used to screen the products for quality. With the help of appropriate analytical techniques and methodologies, a preliminary laboratory study was conducted on all the samples used in the performance validation of the PAD to ascertain the quality status of each sample prior to the validation study on the PAD. The validation study was performed on the PAD by three different scientists using three different brands each of seven finished dosage forms (FDFs), their respective active pharmaceutical ingredients (APIs), SF formulations, and selected fillers (pharmaceuticals excipients). Upon evaluation of all data generated by the three scientists at the end of the validation study, the PAD was determined to be effective in identifying the active ingredients in all the samples collected for evaluation. The technology was also able to detect fillers such as corn starch present in some of the FDFs and formulations labeled to contain them. Results of the laboratory identification tests performed were consistent with those obtained with PAD by all three scientists. All SF formulations were prepared as per the study protocol, and all falsified formulations were correctly identified as falsified by the PAD. However, the PAD was incapable of distinguishing between substandard or degraded formulations (even those with 50% APIs) and good quality products and formulations and their respective pure APIs, making it impossible for the technology to be used to screen substandard products. Only falsified products were able to be identified correctly.

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DPAL project is published in J. Chem. Ed, congratulations to Sarah Bliese!

Author: Marya Lieberman

Sarah Bliese and Margaret Berta's paper on the distributed pharmaceutical analysis lab (DPAL) was just published in J. Chem. Ed. 

The distributed pharmaceutical analysis laboratory (DPAL) is a collaboration between 30 academic institutions around the world, whose goal is to determine the quality of medicines collected from partner organizations in low- and middle-income countries (LMICs).  The distributed pharmaceutical analysis lab project aims to make analytical capacity at colleges and universities around the world available to carry out preliminary HPLC tests of medicines purchased in LMICs.Over a thousand samples have been analyzed through DPAL in the last three years, and 168 samples with quality problems have been discovered, including falsified acetaminophen, adulterated amoxicillin-clavulanate and doxycycline, and substandard losartan.…

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Lancet Global Health Comment on risks to global pharma supply chain from COVID-19

Author: Marya Lieberman

A comment just published in Lancet Global Health expresses concern for the whole global supply chain due to the COVID-19 pandemic.  M. Lieberman is one of the 53 co-authors.  The comment urges the global community not to loose track of the need to provide access to good quality medical products for all the other illnesses out there.  Already, the epidemic is limiting mass gatherings for medical treatments such as vaccination, creating intense demand for drugs without a good evidence base for use in COVID-19, and curtailing regulatory efforts such as post-market surveillance. …

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Sarah's J. Chem. Ed. paper is accepted!

Author: Marya Lieberman

Paper Millifluidics Lab: Using a Library of Color Tests to Find Adulterated Antibiotics

A two to three period analytical chemistry experiment has been developed which allows second year students to explore chemical color tests used to detect adulterated pharmaceuticals. Students prepare several paper analytical devices (PADs) to generate positive and negative controls antibiotics, along with cutting agents such as starch and chalk. These PADs are used to identify the active ingredients and excipients in mystery tablets prepared by their classmates. In the second part of the lab, the students select an individual color test and design an experiment to quantify their mystery pill’s active pharmaceutical ingredient (API). Nearly all the student groups were able to successfully identify adulterants present in their mystery tablets.  The quantification of the mystery tablets was also successful with all but one group calculating the correct concentration within 6%. In a post-lab assessment, the students identified their largest gains in their ability to analyze data and other information, skill in science writing, and learning of laboratory techniques.…

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Oxford Statement published in Lancet Global Health

Author: Marya Lieberman

Every person has the right to receive safe, quality medical products – but all too often, this isn’t the case.

  • Poor-quality medical products (including medicines, vaccines, biologics and diagnostics) fall into two categories: substandard or falsified. Both negate the benefits of modern health care and put patients at risk.
    • …

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Ceftriaxone paper accepted

Author: Marya Lieberman

Congratulations to Sarah Bliese, whose paper on analysis of ceftriaxone via the 12-lane PAD was just accepted in Analytical Methods.  Sarah used principal component analysis (PCA) to differentiate good and bad products and even to figure out why a given product was bad quality.  

Graphical Abstract CeftriaxoneColor "bar codes" classify the products as good or bad.…

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No HPLC? No problem!

Author: Marya Lieberman

Nick Meyers' paper on quantitative analysis of beta lactams on a paper card was just accepted by Analytical Methods.  Congratulations Nick! The aPAD accuracy is about 5%, not quite as good as an HPLC, but then again, the aPAD doesn't cost $40,000.  

Apad Toc Jpg Full SizeThe more blue dots appear, the smaller the antibiotic content.…

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Madeline Smith won an outstanding poster award at the Gordon Conference

Author: Marya Lieberman

Madeline's poster was titled, "The chemoPAD: A Paper Analytical Device for Detection of Four Chemotherapy Drugs," and Ayenew Ashenef from Addis Ababa University is a co-author.  Congratulations to Madeline!  

 

2019 Madeline Smith Grc Poster Award

The 2019 Gordon Research Conference on Preclinical Form and Formulation for Drug Discovery focused on cutting edge research on the development, characterization and manufacture of formulations that span multiple modalities., such as …

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Kat Hayes and Vincent Schmitz awarded $30,000 in pitch competition

Author: Marya Lieberman

The Disease Diagnostic INventors Challenge provides funding to focus measurement science and engineering creativity at Purdue, IU, IBRI and Notre Dame on innovations with the potential to address unmet biomedical needs. Kathleen Hayes and Vincent Schmitz brought together the research strengths of the Whalen and Lieberman groups at Notre Dame to tackle the difficult task of detecting bad quality or fake oxytocin.  There is currently no field test available for oxytocin quality, and studies show that about 1 in 4 vials dispensed to women in Africa do not meet quality standards.  Good luck to these energetic first year grad students!…

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Heather DiLallo honored by St Mary's College

Author: Marya Lieberman

The 2019 Lumen Christi award was presented to Heather DiLallo, who has worked for many years with the PAD project at Saint Mary's. Heather is a Chemistry major who has worked to detect falsified medicines in Nepal and China through Toni Barstis's IRES program.  She is in the 5-year dual degree program, and will be continuing her engineering coursework next academic year at Notre Dame.  We look forward to seeing her around campus! …

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