In a recent meeting of highly qualified medical and pharmacy professionals, discussion on storage of medicines raised several issues. One of the issues was the expiry date of medicines and every individual interpreted differently based on their own perception. Citing examples, one of the learned colleagues enquired why different manufacturers write expiry date differently causing confusion in the minds of doctors and patients. Of course, he missed to notice that one is dietary supplement (labelled as not for medicinal use) and the other is medicine. This particular dietary supplement is available as soft capsules, even containing vitamin C and vitamin A, marketed by a pharmaceutical company and was promoted through prescription. This was made available to him as sample. The issue is “even the learned professionals have different interpretation on expiry date”.
The medicines in the country are regulated by the Drugs and Cosmetics Act 1940 and the Rules 1945. The statue provides power to the central and state governments to ensure that only quality, safe and effective medicines are available for use. The regulation stipulates that every medicine must have a date of expiry of potency. The date of expiry of potency is the date that is recorded on the container, label or wrapper as the date the product may be expected to retain potency not less than or not to acquire toxicity greater than required or permitted. The minimum potency required for a medicine is specified in the pharmacopoeia or other books of standards. Rule 96 (Manner of Labelling) explains that the date of expiry is to be mentioned in terms of month and year which means medicine is recommended till the last day of the month. Though it is date of expiry, it is not the date but month and year! This means that date of expiry printed as April 2012, it can be used till 30th April 2012.
Date of expiry of medicines depends on several factors
The fact is that the date of expiry of medicines depends on several factors. The manufacturers and the distributors have the major responsibility. It is the manufacturer who predicts the expiry date of medicine based on the formulation, technology used and stability testing. The different formulations (even if same types of products) of the same drug molecule may have different date of expiry. It is the pharmaceutical art that the manufacturer uses to have a stable product with reasonable shelf life. The shelf life as predicted from stability testing is added (or directly expiry date is predicted) to the date of manufacturing to get the date of expiry. The manufacturing of pharmaceutical dosage forms takes several days to complete. For example, the tablet manufacturing commences from blending of ingredients and ends at packaging the compressed tablets. The whole process takes several days. The date of manufacturing is also expressed as month and year. The medicines manufactured in 1st April and the medicines manufactured in 30th April would have same date of expiry. Assuming a shelf life of 3 years, the date of expiry is to be printed as March 2015 for products manufactured in April 2012. This shows that the medicine manufactured on 1st April 2012 can be used beyond three years of shelf life [one month more than 3 years]. On the other hand, the medicines manufactured in 30th April 2012 would likely to have expiry date one month of ahead of calculated expiry date [still has potency, but to be discarded]. However, one month in three years may not have significance; but if the shelf life is just one year.
The expiry date is dependent on recommended storage condition. The current Indian Pharmacopoeia defines the following storage conditions: Store in a dry, well ventilated place at a temperature not exceeding 30 °C; Store in a refrigerator (2° C to 8° C). Do not freeze; store in freezer (-2 °C to -18 °C); and Store in deep freezer (below -18 °C). Heat being the main factor responsible for drug degradation, storage in controlled temperature regulated environment (also with humidity controlled) retains the potency as expected. Every 10 °C rise in temperature is likely to double the rate of decomposition. While the good manufacturing practices (GMP) in the manufacturing premises ensures the controlled humidity and temperature controlled environment for storage, there is no such assurance on such storage conditions for medicines during the distribution system. Most of the time the medicines are exposed to much higher temperature than the maximum stipulated (30°C) temperature. In such cases, the medicines expire well before expiry date. The meaning of expiry date in such cases becomes meaningless. But we continue to rely.
Though the expiry date is fixed on the basis of loss of potency, the regulation too ensures that there is no undue toxicity due to decomposed product. There are very few reports of human toxicity due to ingestion, injection or topical application of presently available medicinal products after their expiration date. There are very few examples where the products of degradation are significantly more toxic than the original active pharmaceutical ingredient. Tetracycline gets decomposed to epianhydrotetracycline and the decomposed product is shown to cause renal tubular damage. Chloroquine can produce toxic reactions attribute to photochemical degradation. Phototoxicity has also been reported following administration chlordiazepoxide and nitrazepam. Infusion of degraded Penicillin G is known to cause sensitization of lymphocytes and formation of antipenicilloyl antibodies.
While it is legally and ethically not permissible to sale medicines after expiry date, the medicines do not really retain full potency as expected when our distribution system including the retail stores does not have the appropriate storage condition as recommended by the manufacturers. The regulatory authorities must ensure appropriate storage throughout the life cycle of medicine to make the expiry date of medicines relevant in the interest of public health. [The authors thank Mr. Prafulla K Nandi, Regulatory Officer in Pharmaceutical Industry, for helping with certain information during preparation of this article].
(The authors are with Department of Pharmacy Practice, Annamalai University, Annamalai Nagar, Tamil Nadu 608 002)