These results provide a strong indication FDC-ALU is a far more robust medicine in uncontrolled African conditions (i.e. tropical conditions) than is currently credited. Of 70 samples, the authors found that all of them contained an acceptable amount of active ingredients by the TLC method. Only one sample failed by the more exacting method of Raman spectrometry on initial testing, and another one sample failed disintegration testing. Overall on initial testing, 68/70 (97%) samples passed, including samples that were up to 33 months past their expiry date.
A limitation of this study is that its findings are generally only valid for Coartem/Riamet. The limitation is as expected: Coartem/Riamet was the first FDC-ALU to have entered the marketplace, and owing to a not-for-profit distribution agreement between Novartis AG and the WHO, it remains dominant. Few generic manufacturers, such as GVS Labs, Ajanta Pharma Ltd. and Jiangsu Yixing Forward Pharmaceutical Factory were manufacturing large quantities of FDC-ALU prior to 2006, and as such, their products are less available in the marketplace, and when they are encountered, are usually too recent to have passed their expiry date. The authors located two expired samples of Lumartem, manufactured by Cipla Ltd, which passed the battery of initial tests.
These data are useful, but not sufficient for a shelf-life extension. A more complete protocol would entail high performance liquid chromatography (HPLC) and/or tandem mass spectrometry analysis of degradation products; testing of package stability; testing for biological contamination; and possibly other tests as would be mandated by a drug regulator. However, while these studies are often done on medicines that have aged in controlled laboratory conditions, the advantage of this study is that it examines medicines kept in uncontrolled real-world conditions in tropical Africa. Since these conditions cannot always be accurately emulated in the laboratory – for example, a test designed to mimic stability of a product in a pharmacy's enclosed shelf may not approximate an open-air market pharmacy's presentation in full sunlight – these data should be viewed as complementary to the future laboratory studies previously recommended.
An advantage of this study is that it demonstrates reliable drug quality testing can be done without advanced analytical laboratories. The TLC and Raman techniques utilized in this study are not a substitute for the laboratory-based "gold standard" of HPLC or mass spectrometry, but are validated as "silver standard", which is easily field-deployable and which reliably detects deviations from a known reference medicine – and unlike an HPLC laboratory, the TruScan used in this study runs on battery power and fits in a person's hands. Drug quality surveillance from manufacturer to point-of-use likely requires both the gold and silver standard; it is not one or the other.
Until now, it has been assumed that supply-and-demand management for ACT could be simplified by stock-piling artemisinin or its derivatives, rather than finished products, as these tend to be over 99% stable when stored at 25 degrees Centigrade and 60% relative humidity . While that is an attractive option, it also may not be necessary, as the stability of FDC-ALU is reasonably stable for about this same duration. The authors encountered apparently stable samples of 57 months in age on initial testing (= 24 months shelf-life + 33 months post-expiry).
A problem that all manufacturers of FDC-ALU have is that a 24-month shelf-life requires extraordinarily tight and difficult control over production schedules and supply chains. At the front end, the lead time is 14 months to cultivate and extract Artemesia annua and to carry out the manufacturing process; and at the back end, purchasers' demand 18 or more months of remaining product life upon receipt of product . The former fact means that unless the manufacturer holds some product in inventory, then a purchaser who experiences a sudden rise in demand (as during an epidemic or complex emergency) cannot have that need met. The latter fact means that if the manufacturer actually holds product in inventory, it runs a serious financial risk because at only six months of age the product becomes unsalable. This is an invidious situation for manufacturers of FDC-ALU, who must choose between erring on the side of over-production and possible financial loss, or under-production and possible health crises. Such a tight market is also prone to price excursions, as have occurred for artemisinin before .
The unexpected observation of product diversion suggests that there is also scope to improve public sector medicine logistics in Africa. Such instances of diversion, besides being illegal, suggest that the public sector controls over FDC-ALU stocks are inaccurate. Inaccurate controls in this instance meant theft, but are also likely to be associated with mismanagement of medicines with a short shelf-life, leading to wastage.
The authors' findings argue for a reevaluation of the shelf-life of FDC-ALU, if confirmed by future studies using more advanced analytical techniques, which for the policy reasons already described would be very desirable. Improving access to medicines will require many different interventions that will vary from country to country. However, extending the shelf-life of ACTs would be of benefit in every country, which is why it should be a high priority, with hopefully many more lives saved as a result.