Counterfeit pharmaceutical products may often cause serious public health problems. It is thus the responsibility of the drug regulatory authority to ensure that such products are taken off the market, and that sources of these products are found and dismantled.
The first step in detecting potential counterfeit products is inspection. Visual inspection can be conducted by examining the packaging, sealing, labelling, printing, size, shape and colour of the product. Any differences with the legitimate product will indicate a potential counterfeit. During an investigation in 1994, several fake drugs were detected in this way. For example, vials of an antibiotic for injection with a metal seal but without the flip-off top and with a punctured rubber stopper were found. In this case, the fake drug was filled into vials which had been used and which still exhibited the original label. When the content of the vial was dissolved in water, it produced a colourless solution without any precipitate, while the genuine product would have produced a yellowish solution with white precipitation. In cases of fake antibiotics in capsule form, differences were noticed in the foil cover, label printing, size of the lettering on the packaging, and a strange colour of the capsule cap. Products had no lot number, or expiry date and were packaged differently to the legitimate product.
In order to monitor the quality of drugs in areas where full laboratory analysis is not possible, a document of simple tests has now been compiled by WHO for use when a product is suspected of being counterfeit. These tests serve to determine the identity of a product, and very little training is needed to use them. They may also conveniently be used to detect substandard drugs. These simple tests cannot replace pharmacopoeial analysis and other approved methods which are necessary to provide proof in the case of counterfeiting activities and all samples suspected of being counterfeit or substandard should therefore be subjected to the correct laboratory analysis to confirm any suspicion.
WHO has also published very useful manuals on Basic Tests which identify the active ingredients of common pharmaceutical substances and dosage forms. These manuals describe the colour and precipitation reactions and identification tests of 150 dosage forms and 112 drug products, most of which are included in the WHO Model List of Essential Drugs. In many cases the Basic Tests are specific enough to confirm the identity of drugs. However, they cannot distinguish between certain drugs with similar chemical structure features, such as beta-lactam antibiotics, sulfonamides or corticosteroid hormones. In addition, excipients may interfere or mask the colour reaction. Being qualitative, these tests are not designed to detect substandard drugs and complementary techniques need to be developed.
One such technique is thin-layer chromatography (TLC), which is simple and rapid and also more specific and selective. There is little interference from excipients with TLC. It can be used for the identification and semi-quantitative estimation of the active ingredient. It will also determine degraded products and contaminated substances. Nonetheless, TLC procedures are more dependent on the ambient temperature and humidity than basic tests and it is necessary to test against a reference substance. It may therefore be desirable to make use of TLC combined with basic tests depending on the circumstances. WHO is now preparing guidelines for developing education and training programmes for drug inspectors and analysts for use of these tests in country situations.
* * *