detecting and removing poor quality medicines that harm the most vulnerable patients and damage public health

Paper Analytical Device (PAD) Project

Paper Analytical Device (PAD) project - In developing countries, customers are strongly cost-driven and the penalties for selling bad quality pharmaceuticals are small.  On this tilted playing field, unscrupulous sellers of bad quality drugs have an economic advantage.  Diversion and corruption are pervasive, and stock-outs in public clinics send patients into the private market in search of medicine.  Thus, it's critical to monitor the quality of products in the "last mile" -- the products that patients are buying and using.  

diagram

 

fake labelled as Coartem contains an unexpected "filler"
fake labelled as Coartem contains an unexpected "filler"

There is little data about the prevalence of poor quality pharmaceuticals in different markets, or how poor quality products contribute to bad health care and bad public health outcomes.  The missing information prevents development of evidence-based solutions to these problems. Yet, it is difficult to collect and analyze samples from the "last mile" of the distribution systems.    

My research group at Notre Dame has developed a "lab on paper" that can detect low quality pharmaceutical dosage forms in 7 minutes, at a cost of under $1 per sample. It is based on a library of chemical colour tests that probe functional groups present in active pharmaceutical ingredients (APIs) and excipients.  Dry reagents are stored in twelve lanes on a test card. The user smears a crushed pill across the test card, which deposits sample in each lane. When the test card is dipped into water, the water wicks up the lanes, dissolving and mixing the stored reagents and bringing the reagents into contact with the sample. The paper analytical device (PAD) carries out twelve colour tests to give a "bar code" of colours in the readout area.    

Pharmaceutical products which contain little or no active ingredient or which include substitute ingredients give different "bar codes" from authentic products.  The card can be read by eye or with an image analysis program with good sensitivity and specificity.  The photo at right shows a comparison of a fake antimalarial drug and a genuine sample which were run on two PADs; the presence of an unregistered filler is shown by the black spot in lane J.  The PADs are portable, self-contained, and testing of dosage forms can be done in minutes on the corner of a desk.  

We are currently developing a PAD for quantitative assay of beta lactam antibiotics.  See the photo at right.  The less antibiotic is present in the formulation, the more dots turn blue.     

Antibiotic PAD prelim screening resultsThe PAD project seeks strategic partnerships with globally minded foundations like Medicrime Alert International to support detection of poor quality and falsified medicines.  We want to learn how these products affect the health of patients.  This information can guide evidence-based aid programs and other donor-supported medical care.  

  • The PAD project uses covert shoppers, field screening, and confirmatory analysis to learn about what comes out at the ends of the complex pharmaceutical distribution networks.     
  • We collect and analyze dosage forms for health care providers who have noticed problems with particular medications. This approach tests the hypothesis that poor quality medicine is associated with bad health care outcomes.  
  • PADs and other analytical tools could be applied at the wholesale/retail level of the supply chain to decrease the economic advantages of poor quality products.  This approach would impact public, private, and "grey market" supply chains and could help to reduce theft, diversion, and substitution of products in protected supply chains.

More information