|
Safety issues that have been encountered in the field of pharmaceutical ingredients over the last few decades – most recently involving heparin and glycerin – have made it hard to ignore that there is a missing element in the regulatory system for medicines. Good Manufacturing Practice (GMP) is a requirement for every component of a medicine – from the packaging to the active pharmaceutical ingredient – but excipients are an exception. This seems particularly strange when one considers these ingredients are, by weight, very often the largest constituent in a medicine.
Excipients are often perceived as low risk because they are pharmacologically inactive and, in most cases, have been in use for years. Many of them have been extensively used in the food industry, for example. However, recent history reveals a series of cases in which quality failings in excipients have led to public health catastrophes. In 2008, 84 children in Nigeria died after consuming a teething formula product containing glycerin – a commonly used excipient – which was contaminated with diethylene glycol (DEG). In 2006, 46 people died in Panama after taking a government-made cough syrup containing DEG. The list goes on, with DEG contamination often at the root of the problem. In 1996, glycerin contaminated with DEG in a cough syrup killed 85 people in Haiti, while from 1990 to 1992 paracetamol syrup contaminated with DEG from propylene to glycol led to 339 deaths in Bangladesh. In 1990, 47 people died in Nigeria after taking cough syrup contaminated with DEG.
Meanwhile, some of the incidents, such as the 2006 Panama contamination, which saw the contaminated material change hands several times between manufacturer and user, show that the problem lies not only in adherence to appropriate manufacturing standards, but also in keeping tight control of the supply chain. This shows that careful consideration of not only GMP but also Good Distribution Practice (GDP) is important, particularly as the growing presence of imported excipients from countries such as India and China is making supply chains longer, more complex and harder to monitor.
The European Commission has been looking at remedying this situation for several years, and in 2005 it published a series of amendments to Directive 2001/83/EC on medicinal products for human use, to mandate the development of a GMP system for excipients in order to bring them in line with other constituents of medicinal products (1-3). |
